Biology Open最新文献

Muscle structure is dynamically shaped by mechanical use, yet how distinct locomotor behaviors influence sarcomere organization remains poorly understood. In Caenorhabditis elegans, crawling and swimming constitute discrete gaits that differ in curvature, frequency, and mechanical load, providing a tractable model for studying activity-dependent remodeling. Using confocal imaging of phalloidin-stained body-wall myocytes, we quantified myocyte geometry, sarcomere length, and sarcomere number across anterior, mid-body, and posterior regions in animals reared exclusively under crawling or swimming conditions. Quantification and hypothesis testing used linear mixed models that accounted for repeated myocyte measurements within animals, with interaction terms testing region-specific effects of locomotor condition after interquartile range (IQR)-based outlier removal. Swimming produced characteristic remodeling of body-wall muscles. Myocytes elongated globally, while selectively thinning in the mid-body, reducing cell area by ∼13% relative to crawlers. Shape metrics confirmed this shift: circularity declined at mid- and tail-regions and anisotropy increased by ∼2-3 units. Sarcomere architecture exhibited parallel remodeling. Average sarcomere length shortened across the body (-0.19 µm in head, -0.35 µm in mid-body, -0.20 µm in tail), while sarcomere number increased in anterior and mid-body regions (+0.77 and +0.65 sarcomeres per myocyte). The mid-body region also showed a significant rise in sarcomere density, indicating tighter serial packing. These adaptations mirror functional compartmentalization predicted from gait kinematics and parallel fast-fiber remodeling observed in vertebrate muscles. The results indicate that C. elegans muscles adapt their contractile lattice to sustained mechanical demand, linking neural gait selection and mechanosensitive signaling to long-term structural plasticity. This work establishes C. elegans as a model for dissecting the conserved pathways that couple muscle use to cellular architecture and provides a foundation for future comparisons of healthy and diseased muscle remodeling.

Moderate exercise is recommended by health experts across the globe to maintain health. Exercise induces a range of physiological changes, often shifting body composition towards increased muscle mass. To investigate the genetic factors controlling exercise responses, particularly altered body composition, we measured protein levels, as a proxy for muscle mass, in 32 genetically distinct strains from the Drosophila melanogaster Genetic Reference Panel (DGRP) that underwent a 5-day exercise treatment. At baseline, the protein levels varied significantly across genotypes and between sexes. The effects of exercise on protein content also were highly variable: some strains showed increased levels, others decreased levels, and many strains showed no significant change. A genome-wide association study (GWAS) identified multiple loci linked to both baseline and exercise-induced protein levels, as well as the change in protein levels after exercise. Many of these loci are involved in morphogenesis, neuronal development, and cell signaling. Notably, there was no correlation between protein concentration and measures of activity levels or climbing speed, suggesting muscle mass and function may be regulated independently. A modest positive correlation between protein levels and lifespan was observed in exercise-treated females, but not in other groups. These findings highlight the complex, context-dependent genetic architecture underlying exercise responses and underscore the need to consider both genotype and sex in physiological exercise studies. The genes identified here provide targets for future work aimed at elucidating the molecular mechanisms of exercise response.

ZNF16 (also known as HZF1 and KOX9) is a multi-C2H2 zinc finger protein first identified via its expression in human T-cells and shown to have a role in blood cell differentiation. ZNF16 was later shown to be ubiquitously expressed in a variety of fetal and adult tissues, suggesting a broader function. In this study, we confirm the ubiquitous expression of ZNF16 in a variety of cancer and non-cancer cell lines and show that ZNF16 depletion reduces cell viability in all cell lines tested. Furthermore, we show that ZNF16 localizes to the nucleolus in a transcription-dependent manner, interacts with the intergenic spacer region of the rDNA and promotes rDNA transcription. Additionally, RNA-sequencing experiments after ZNF16 depletion revealed that ZNF16 also has roles in a variety of pathways including extracellular matrix-receptor interaction, focal adhesions, cytokine-cytokine receptor interactions, human papillomavirus infection and cancer pathways. These findings are consistent with broader roles for ZNF16, including the regulation of nucleolar function, a process that is essential for all cells, and provide evidence at the cellular/molecular level of its role in the regulation of cancer-associated genes (e.g. NRAS, BIRC3, EGFR).

The inaugural UK Zebrafish Meeting 2025 (UKZF2025) hosted by the Living Systems Institute (LSI) at the University of Exeter, was held from 10 to 12 September 2025 in Exmouth and Exeter. The organising committee comprised LSI Group Leaders Steffen Scholpp, Soojin Ryu, Nikolas Nikolaou and Yu Hsuan Carol Yang, and the Facility Manager of Exeter's Aquatic Resources Centre, Greg Paull. The event brought together over 150 zebrafish researchers from across the UK to present their latest discoveries, share resources and expertise, and discuss strategies to strengthen the UK zebrafish research community. This Meeting Review highlights the key scientific themes showcased during the meeting, including developmental biology, human disease modelling, toxicology, neuroscience, technology development and alternative fish models. Furthermore, it provides a summary of the community session led by zebrafish facility managers from across the UK, emphasising potential opportunities for enhancing collaboration and resource sharing within the community.

Chytridiomycosis is a contributor to amphibian population declines. Diseased amphibians show symptoms of lethargy and loss of righting reflexes, likely due to an ion imbalance across the skin. However, it is possible developing zoosporangia release toxins that affect neuromuscular activity. Using Xenopus laevis as a model, we hypothesized that locomotor performance would be affected by injection of Bd supernatant factors. X. laevis were injected and then filmed performing a swimming escape response with high-speed cameras at 4 h, 24 h, and 1-week post-injection. Average maximum swimming velocity and escape latency were digitized using high-speed video. Despite no difference in escape velocity, there was a significant difference in escape latency 24 h post injection at both concentrations tested, 106 and 107 cell equivalents, though only differences at 106 cell equivalents/ml supernatant persisted 1 week post injection. Changes in specific locomotor function suggest that there may be neurotoxins present, though the potential neurotoxins may exhibit neural circuit specificity across escape behavior. This study provides a method to test more purified extracts to determine whether Bd produces neurotoxic factors that could enter the blood stream and alter locomotion during a natural skin infection.

Nociception, a phenomenon crucial for animal survival, deploys evolutionarily conserved molecular mechanisms. Among invertebrate species, cephalopods are of particular interest as they possess a well-developed brain speculated to be able to encode pain-like states. This has led to their inclusion in the Directive 2010/63 EU for welfare protection. However, the molecular mechanisms of nociception in cephalopods are still poorly characterised and it is important to address this knowledge gap to better understand cephalopods' capacity to express pain states. Here we describe a bioinformatic strategy utilising conserved nociceptive genes, to identify the orthologous candidates in the Octopus vulgaris transcriptome. We identified 51 genes we predict to function in nociception. These add to the mechanosensory TRPN and the unique chemotactile receptors recently identified in octopus suckers, thus expanding the set of genes that merit further functional characterisation in cephalopods. We therefore selected 38 orthologues in Caenorhabditis elegans, a tractable experimental platform and tested loss of function mutant strains of distinct functional gene classes (e.g. osm-9, egl-3, frpr-3) in a low pH avoidance paradigm. This identified 19 nociceptive-related genes to be prioritised for further functional characterisation in O. vulgaris.

Mitophagy is essential for mitochondrial quality control, selectively removing damaged or superfluous mitochondria to maintain cellular health and metabolic homeostasis. While positive regulators of mitophagy are relatively well characterized, the mechanisms governing its downregulation remain less understood. In this study, we investigate the role of Saccharomyces cerevisiae Slm35 - a protein previously involved in oxidative stress response - in the regulation of mitophagy. We discovered that Slm35 is a soluble mitochondrial matrix protein and functions as a novel negative regulator of mitophagy and the mitochondrial retrograde (RTG) signaling pathway. Our results show that Slm35 modulates mitophagy through the RTG pathway, independently of Atg32 proteolytic processing by Yme1 or mitochondrial membrane potential dissipation. Notably, Slm35 is crucial for the dynamic regulation of the RTG pathway in mitophagy-inducing conditions. These findings highlight the importance of Slm35 in fine-tuning mitochondrial quality control in response to metabolic cues and suggest a critical role for dynamic RTG pathway regulation in mitophagy control.

The 'French flag' model has long served as the prevailing framework for explaining how morphogen gradients generate spatial domains during embryonic development. However, recent evidence indicates that many tissues establish patterns by translating the sequential activation of genes into spatial domains. While the sequential nature of this process is becoming clear, the mechanisms that mediate these temporal dynamics and translate them into stable spatial boundaries remain debated. Using the gap gene network in the flour beetle Tribolium castaneum [which mediates the regionalization of the anterior-posterior (AP) axis into different axial fates through the regulation of downstream Hox genes] as a model, we combined hybridization chain reaction in situ hybridization, parental RNA interference (RNAi), and computational modeling to dissect these mechanisms. Our high-resolution spatiotemporal analysis indicates that gap genes initially function as a genetic cascade in the posterior growth zone. Specifically, RNAi perturbations reveal that the disruption of upstream genes prevents the initiation of downstream targets in the posterior rather than merely affecting their anterior maintenance. Conversely, the knockdown of downstream repressors leads to the posterior persistence of upstream genes. Furthermore, we investigated the relationship between this dynamic initiation phase and anterior maintenance. We observe that in milles-pattes (mlpt) RNAi embryos, the gap gene shavenbaby (svb) fails to propagate anteriorly out of the growth zone, indicating that the anterior maintenance of svb is actively mediated by other genes in the network. Computational simulations demonstrate that a gene network switching framework, where regulatory interactions reconfigure across the AP axis, successfully reproduces these complex phenotypes. These findings provide definitive spatiotemporal evidence that Tribolium gap gene initialization is driven by a genetic cascade, and support a model in which dynamic network rewiring converts this cascade into stable spatial patterns more anteriorly.

Ocean warming is reshaping marine ecosystems and shifting species distributions. Resilient habitat-forming species help stabilize conditions for other organisms, supporting community structure under change. The tube-worm Lanice conchilega is such a habitat-former, enhancing species richness in sandy environments. Its thermal performance range remains unknown, partly because standard methods are poorly suited for this species. We present a new experimental approach to assess thermal performance based on tube-building activity, an important trait for physical protection, feeding, and habitat engineering. Spring-collected individuals were exposed in the laboratory to an ecologically relevant temperature range. Tube-building activity matched spring field conditions with a thermal minimum, optimum, and maximum at 3.6, 12.4, and 21.4°C, respectively. Performance depended strongly on recent thermal history. Because thermal tolerance can shift through acclimation, seasonal performance curves are needed to determine whether cold winters or hot summers may constrain this ecosystem engineer with potential consequences for intertidal community structure.

Maintenance of proteostasis is critical for neuronal functions, as the accumulation of misfolded or damaged proteins leads to neurodegeneration. Cooling is generally neuroprotective and is used in various clinical settings. However, how it impacts neuronal proteostasis remains unclear. In rodents, the neuroprotective effects of cold have been largely attributed to the cold-inducible RNA-binding motif protein 3 (RBM3). Here, studying the human RBM3 in cultured neurons subjected to profound hypothermia, we observed its cold-induced aggregation. These RBM3 aggregates are distinct from stress granules, occur specifically in differentiated neurons, and form also at physiological temperature upon proteasomal inhibition. Thus, in humans, RBM3 aggregation may be normally counteracted by the proteasome to maintain neuronal health. Exploring the natural variation between RBM3 proteins in hibernating versus non-hibernating mammals, we discuss how the aggregation could be prevented in animals with fluctuating body temperature. These findings are important for the understanding of RBM3 functions and neuronal proteostasis and have implications for medical treatments involving incidental and induced hypothermia.