Biology Open最新文献

Prostate cancer management faces significant challenges in distinguishing indolent from aggressive disease, particularly since most patients are intermediate-risk and therefore hinders the ability to recommend standardized treatment recommendations. Moreover, current prognostic tools including Gleason scoring and tumor staging demonstrate limited accuracy for predicting disease progression and tumor recurrence. DNA methylation serves as a stable epigenetic modification that directly regulates gene expression, making it an ideal biomarker for cancer prognosis. Therefore, this study leveraged whole-genome enzymatic methylation sequencing on 120 patients to develop a novel prognostic signature for aggressive prostate cancer progression. We analyzed 20,849 differentially methylated regions (DMRs) and employed multiple machine learning approaches to identify optimal biomarkers. This revealed a 14-region DNA methylation signature that can serve as independent prognostic prediction factors outperforming traditional clinical indices. Further, when combined into a risk score it achieved a clinically meaningful odds ratio. This methylation-based approach provides actionable information for treatment decisions and surveillance strategies, representing a significant advancement toward precision medicine in prostate cancer management through biologically informed risk stratification.

Cleft lip with or without cleft palate (CL/P) represents one of the most common congenital craniofacial anomalies. Its complex genetic etiology remains incompletely understood. This study investigated compound inheritance of mutations in the EHHADH and MASP1 genes in a Polish family with three affected individuals using whole-genome sequencing and bioinformatic analysis, followed by zebrafish functional validation. We identified mutations in both genes that segregated with the CL/P phenotype. Network analysis demonstrated significant functional associations between these genes, with enrichment for innate immune response pathways. Using zebrafish models, we validated the phenotypic consequences of these mutations through mRNA injection experiments. Individual or combined injections of mutant EHHADH and MASP1 mRNAs resulted in craniofacial abnormalities, with co-injection producing the most severe phenotypes, including cleft formation. Alcian Blue staining revealed significant alterations in cartilage development, particularly in the ceratohyal angle and chondrocyte morphology. These changes may affect extracellular matrix composition and cartilage biomechanics, potentially disrupting the structural integrity and mechanical properties essential for proper craniofacial morphogenesis. Our findings suggest the possibility of a novel genetic mechanism for nonsyndromic CL/P involving the interaction between metabolic processes regulated by EHHADH and immune signaling pathways controlled by MASP1. This study expands our understanding of the genetic complexity underlying CL/P and highlights the potential intersection of immune regulation and metabolic processes in craniofacial development.

Water intakes entrain large numbers of fish larvae in waterways where drift coincides with large-scale extraction. While modern fish-protection screens can reduce these losses, many are not designed for larvae and were developed or evaluated primarily for juveniles and adults. This study evaluated the effectiveness of Australia's fish screen design criteria (which specify a maximum approach velocity of 0.1 m s-¹ and slot widths of 2-3 mm) for protecting drifting larval Murray cod (Maccullochella peelii). Larvae were tested in a large flume under combinations of approach velocity (0.1 or 0.2 m s-¹), slot width (2 or 3 mm), and proximity. Entrainment rose sharply with velocity; slot size had a smaller interactive effect. The most protective combination (0.1 m s-¹ and 2 mm) reduced entrainment by up to 94% relative to unscreened conditions. Three-dimensional flow measurements helped explain how velocity vectors interact to influence larval fate. The results demonstrate that Australia's current standards, although developed for juveniles, can provide strong larval protection when strictly followed, but that even modest departures can sharply increase risk. More broadly, since the criteria tested here are less conservative than those adopted in many other countries, where empirical evidence on larval behaviour does not exist, targeted research could determine whether existing guidelines warrant revision.

Hosted in the scenic surroundings of the High Tatras, the V4SDB Meeting 2025 represented the fourth biennial conference of the Visegrád Group Society for Developmental Biology. The meeting brought together over 170 researchers covering a multidisciplinary range of topics, from early development and organogenesis to non-traditional model systems and evo-devo, as well as stem cells and plasticity. With its numerous high-level talks and rich poster sessions, complemented by social and outreach activities, the meeting provided an excellent platform for networking, knowledge exchange, and initiating new collaborations. Moreover, the organizers arranged the Young Developmental Biologists Workshop, focused on data analysis, soft-skills training and community strengthening, which further enhanced early-career researchers' participation and support at the meeting. Altogether, the event underscored the V4SDB's commitment to nurturing the developmental biology community within the region.

Skeletal muscle formation involves the fusion of myocytes into precisely aligned, multinucleated myofibres. These fibres continue to grow through reiterative rounds of myocyte fusion, incorporating new myonuclei and supporting muscle growth, repair and regeneration over organismal life span. The vertebrate-specific myocyte fusogens, Myomaker (Mymk) and Myomixer (Mymx), are crucial for generating multinucleated skeletal muscles. Here, using quantitative imaging and a mymx knockout strain, we explored the impact on myogenesis at different life stages of the zebrafish. We demonstrate that during the initial phase of muscle formation, mymx has a spatiotemporally varied expression across all axes of the developing myotome, not just along the anterior-posterior axis. On Mymx loss, myotome morphogenesis is disrupted, with both cell and tissue structure impacted. In particular, the shape of the resulting myotome segments is altered. Moreover, we show differential effects of Mymk versus Mymx loss on myocyte fusion and muscle growth. Finally, we report that perturbation to adult muscle multinucleation and size impacted bone development, again with different phenotypic severities among the two fusogen mutants. Together, our work provides insights into the interplay between myocyte fusion, myotome morphogenesis and acquisition of final adult form.

The Genetics Society Non-Seed Plant meeting brought together researchers embracing the diversity of plants and using emerging and established model systems covering hornworts, mosses, liverworts, lycophytes and ferns. This growing community of researchers is exploring fundamental questions on plant development, evolution and environmental responses. Highlights included cutting-edge work in bryophytes on meristem development, hormonal signalling and chromatin regulation, as well as advances in charophyte algae, illuminating the evolutionary origins of key plant traits. The meeting emphasized how non-seed plants, often overlooked in mainstream plant science, are now providing transformative insights into gene regulation, plant-environment interactions and crop improvement potential. These developments reflect a broader shift in plant biology, where diverse model systems are essential for reconstructing the evolutionary history of plants and addressing modern agricultural challenges.

Egg-sac brooding is a costly maternal strategy for which evolutionary persistence hinges on clear offspring benefits and effective maternal tactics to offset those costs. Using the wolf spider Pardosa pusiola, we examined (1) whether hatchling emergence depends on the presence of a conspecific mother, (2) whether egg sac opening is a flexible response to embryonic cues, and (3) how mothers modulate locomotor performance under different ecological risks (sun exposure, flooding, predation). Conspecific foster mothers matched biological mothers in synchronizing egg-sac opening with embryonic development, whereas interspecific foster mothers (Pardosa astrigera) mistimed opening in most cases. Motherless egg sacs contained fully developed but un-emerged hatchlings, confirming that maternal presence is indispensable for emergence, not for hatching itself. Under moderate sun exposure, egg-sac-carrying females escaped slower than non-carrying females. Under high sun exposure or predator stimulus, carrying females escaped as fast as or faster than non-carrying females. Under simulated flooding, carrying females suffered higher mortality, yet survivors showed no difference in escape speed compared to non-carrying females. These results demonstrate flexible egg-sac management coupled with adaptive maternal locomotion, illustrating how costly parental care can be maintained when parents adjust their behavior according to environmental risk.

The extracellular matrix (ECM) is a critical component of embryonic development, providing both structural support and a dynamic signaling environment for cell migration, adhesion, and tissue organization. Collagen, the most abundant protein in the ECM, is crosslinked by the enzyme lysyl oxidase (LOX), and that activity plays a pivotal role in creating support throughout the ECM. Dysregulated LOX activity disrupts the mechanical integrity of the ECM. Sea urchins offer a robust model for studying LOX function and ECM dynamics in embryonic development due to their rapid, transparent development and traceable cell lineages. Previous studies using the pan-monoamine oxidase/LOX inhibitor β-aminopropionitrile suggested an essential role of LOX activity in sea urchin gastrulation and maintenance of ECM integrity. Here, we integrate newly developed and traditional LOX inhibitors, with a translation blocking morpholino antisense oligonucleotide to a specific lysyl oxidase, and chemoselective fluorescent probes to LOX oxidation products, all to test the role of the ECM in development and germ cell formation. The primordial germ cells in this animal are believed to be committed at the fifth cell division as small micromeres by inheritance of yet unknown molecular constituency. We find that LOX activity is essential for an instructive environment in the development of a germ line, even though the fate of that germ line in the sea urchin is predetermined. Our findings provide insight into the dynamic interplay between ECM remodeling, gene expression, and metabolism, offering a more profound understanding of the role of the ECM in development and germ cell identity.

Skippers (Hesperiidae) form a distinct lineage of butterflies where the developmental mechanisms of color patterning have seldom been studied. Skipper wing patterns often consist of median stripes, and studies from the mid-twentieth century suggested these elements are homologous to the central symmetry system (CSS) found in nymphalid butterflies. Here we examined the expression of the signaling ligand gene WntA, known to mark the presumptive CSS patterns in nymphalids, in the silver-spotted skipper Epargyreus clarus, and found support for the homology of the CSS across 95 MY of evolutionary divergence. We generated an annotated genome for E. clarus and used RNAseq to profile gene expression along the wing proximo-distal (P-D) axis. These data suggest that the transcription factor genes lobe, u-shaped, and odd-paired are expressed in restricted P-D sections of the wing similarly to WntA, indicating potential roles in CSS patterning. In addition, developmental genes involved in wing P-D patterning in Drosophila - dachsous, four-jointed, homothorax, tiptop/teashirt, vestigial, scalloped - reveal similar expressions between Diptera and Lepidoptera on the wing P-D axis, suggesting a deep conservation of P-D patterning in insect wings. This work expands our understanding of the mechanisms shaping wing pattern evolution in butterflies.