Open Biology[JOURNAL]
Sun
200 papers
Deep learning in tumour genomics: from multi-omics integration to precision oncology.
Zhou Z, Li Z, Wang S … +3 more , Ang MY, Xiao J, Choo SW
Open Biol · 2026 Jul · PMID 42379586 · Publisher ↗
Cancer remains a leading cause of death globally, with nearly 10 million deaths in 2020. Advances in genomic technologies have revolutionized cancer research, shifting focus towards precision medicine based on comprehens...
Cancer remains a leading cause of death globally, with nearly 10 million deaths in 2020. Advances in genomic technologies have revolutionized cancer research, shifting focus towards precision medicine based on comprehensive tumour genomic profiling. Concurrently, deep learning (DL) has emerged as a powerful paradigm for complex biological data. This review critically assesses recent advances in DL applications for tumour genomics, emphasizing four key domains: DNA sequencing analysis for mutation detection, gene expression profiling for cancer subtype classification, methylation function prediction for epigenetic characterization and integrative multi-omics approaches for comprehensive tumour profiling. We systematically analyse how different DL architectures-including convolutional neural networks, recurrent neural networks, graph neural networks, autoencoders and transformers-address specific challenges in cancer genomics. Our review highlights how these approaches significantly enhance detection sensitivity for genomic alterations, improve cancer subtype stratification, identify novel biomarkers and optimize therapeutic target selection. We examine technical challenges in DL implementation, including model interpretability, data scarcity, computational requirements and integration issues, alongside emerging solutions such as explainable AI, federated learning, and multi-modal frameworks. By synthesizing methodological innovations and identifying research directions, this review provides bioinformaticians and cancer researchers with a roadmap for leveraging DL to advance precision oncology.
Understanding GnRH: local systems, signalling mechanisms and implications in female health.
Tosh L, Tinto K, Cunningham M … +2 more , Mulheran P, Ferro V
Open Biol · 2026 Jul · PMID 42379585 · Publisher ↗
Gonadotropin-releasing hormone (GnRH) is a peptide hormone forming a central component of the hypothalamic-pituitary-gonadal axis and is critical for controlling reproductive functions. Dysregulated GnRH is implicated in...
Gonadotropin-releasing hormone (GnRH) is a peptide hormone forming a central component of the hypothalamic-pituitary-gonadal axis and is critical for controlling reproductive functions. Dysregulated GnRH is implicated in many steroid hormone-dependent diseases, and its receptor, GnRHR, is an attractive and clinically exploited therapeutic target. Mounting evidence suggests that beyond the hypothalamus and pituitary, GnRH and GnRHR are expressed in reproductive and non-reproductive, healthy and malignant peripheral tissues, where they act in an autocrine and paracrine manner. This review provides an updated overview of GnRH and GnRHR signalling with a focus on extrapituitary autocrine and paracrine roles in female reproductive health. We examine the molecular and cellular mechanisms of extrapituitary GnRHR signalling, including G-protein coupling profiles, and alternative cell-specific mechanisms that differ from pituitary signalling. We highlight recent data surrounding the (patho) physiological functions of local GnRH systems, including in the endometrium, ovary, placenta and breast, and their implications for hormone-dependent gynaecological conditions and cancers. Finally, we consider implications of peripheral GnRH/GnRHR systems for therapeutic innovation, including avenues for targeted or biased GnRH-based therapeutics, GnRH/GnRHR-mediated 'off target' effects of GnRH analogues, and explore future translational avenues for the treatment of both hormone-dependent and hormone-refractory diseases.
The evolution and functional significance of neuropeptide cocktails: insights from SALMFamides in asteroid echinoderms.
Escudero Castelán N, Elphick MR
Open Biol · 2026 Jun · PMID 42336389 · Publisher ↗
Neuropeptides derived from larger precursor proteins are neuronal signalling molecules that regulate physiological processes and behaviour. Some precursors, particularly in invertebrates, give rise to 'cocktails' of stru...
Neuropeptides derived from larger precursor proteins are neuronal signalling molecules that regulate physiological processes and behaviour. Some precursors, particularly in invertebrates, give rise to 'cocktails' of structurally related neuropeptides, but the functional significance of this phenomenon is poorly understood. Here, we investigate this by analysing the evolution and receptor pharmacology of SALMFamide-type neuropeptides in starfish (class Asteroidea, phylum Echinodermata). Two types of SALMFamide precursors occur in echinoderms: L-type and F-type, which contain neuropeptides that typically have C-terminal LxF-NH2 and FxF-NH2 motifs (x is variable), respectively. In starfish, L-type and F-type precursors typically contain seven and nine neuropeptides, respectively, but taxon-specific loss/gain of neuropeptides has occurred. Experimental tests revealed that most neuropeptides derived from L-type and F-type precursors in the starfish Asterias rubens exhibit similar potency/efficacy as ligands for their kisspeptin-type receptors, ArKPR7 and ArKPR6, respectively. However, the N-terminally positioned neuropeptide in each precursor has lower potency/efficacy. Furthermore, one neuropeptide derived from the F-type precursor exhibits convergent similarity with L-type precursor-derived neuropeptides, but it has low potency as a ligand for ArKPR7. Our findings indicate that structurally related neuropeptides derived from the same precursor are functionally redundant as receptor ligands; therefore, loss of neuropeptides and/or neuropeptide bioactivity can occur.
Structural basis of Drosophila insulin receptor activation by DILP2 hormone.
Shafi T, Moroz OV, Jenkins HT … +6 more , Chechik M, Iusupov MN, Lubos M, Jiráček J, De Meyts P, Brzozowski AM
Open Biol · 2026 Jun · PMID 42303271 · Publisher ↗
Insulin-related hormones regulate key life processes in the animal kingdom, from metabolism to growth, lifespan and ageing, through an evolutionarily conserved insulin and insulin-like hormones signalling axis (IIS). In...
Insulin-related hormones regulate key life processes in the animal kingdom, from metabolism to growth, lifespan and ageing, through an evolutionarily conserved insulin and insulin-like hormones signalling axis (IIS). In humans, the IIS axis is controlled by insulin, two insulin-like growth factors, two isoforms of the insulin receptor (hIR-A and -B), and its homologous IGF-1R. In Drosophila, this signalling engages seven insulin-like hormones (DILP1-7) and a single receptor (dmIR) that follows the blueprint of hIR/hIGF-1R. This report describes two cryo-EM structures of the dmIR ectodomain (dmIR-ECD) in complex with DILP2, revealing their relationship to other known DILP5/2/1 complexes. A high excess of DILP2 yielded two dmIR-ECD complexes in asymmetric conformations, similar to that observed in some complexes of hIR and in the dmIR-ECD:DILP5 complex. This stoichiometric and structural heterogeneity was not observed in DILP5:dmIR-ECD and DILP2 full-length dmIR assemblies. Also, in contrast to DILP5, the resistance of DILP2 to form more dmIR-ECD-saturated complexes, despite very high 40 : 1 excess of this hormone, suggests some structural bases for DILP1-7 specificities. This work expands understanding of the dmIR conformational flexibility, indicating that insect dmIR follows a more hIR:IGF-1R receptor hybrid mode of structural signal transduction pattern induced by various two-chains DILPs.
Parental rearing shapes brain functional networks and socio-sexual behaviours in the prairie vole.
López-Gutiérrez MF, Gracia-Tabuenca Z, Ortiz-Retana JJ … +5 more , Camacho FJ, Paredes RG, Díaz NF, Alcauter S, Portillo W
Open Biol · 2026 Jun · PMID 42268208 · Publisher ↗
Animal models with natural variation in family structure, like the prairie vole (Microtus ochrogaster), offer valuable insight into how parental care shapes offspring behaviour. While prior studies have linked early care...
Animal models with natural variation in family structure, like the prairie vole (Microtus ochrogaster), offer valuable insight into how parental care shapes offspring behaviour. While prior studies have linked early care to long-term behavioural outcomes, the underlying brain network adaptations remain unclear. Using resting-state functional magnetic resonance imaging, we examined how monoparental (single-parent) versus biparental rearing influences brain connectivity and socio-sexual behaviour. Offspring raised by a single parent received less licking and grooming, and monoparentally reared males failed to form pair bonds after 48 h of cohabitation. Functional connectivity analysis revealed distinct networks shaped by early parental care. One network was linked specifically to monoparental upbringing, while another correlated with the amount of care received. During cohabitation, additional networks associated with prosocial behaviour and pair bonding were also modulated by early-life care. These results demonstrate that parental rearing has long-term effects on brain functional organization and social behaviour in adulthood.
The periosteum as an endocrine organ: historical foundations and new insights.
Nijsure M, Rosen CJ
Open Biol · 2026 Jun · PMID 42264469 · Publisher ↗
Anatomists have recognized the periosteum as essential for bone growth and repair, and yet its broader physiological roles have remained underappreciated. Emerging evidence now positions the periosteum not only as a stru...
Anatomists have recognized the periosteum as essential for bone growth and repair, and yet its broader physiological roles have remained underappreciated. Emerging evidence now positions the periosteum not only as a structural membrane, but also as a dynamic interface that integrates mechanical load, nutritional status, metabolic cues and systemic hormones to regulate skeletal homeostasis. In this review, we trace the historical foundations that first revealed periosteal function and synthesize modern insights into the cellular and molecular pathways that enable this tissue to sense and respond to its environment. We highlight nutrient- and energy-sensing mechanisms, alongside classical endocrine pathways. We also discuss mechanical load sensing, neural, vascular and immune signals within the periosteum. By uniting historical observations with single-cell and spatial omics datasets, we propose a modern framework in which the periosteum is reconsidered as an endocrine organ with implications for bone growth, homeostasis and regeneration.
NudC moonlights in ribosome biogenesis and homeostasis in polyploid cells of Drosophila melanogaster.
Shi D, Shimada-Niwa Y, Okamoto N … +6 more , Nakamura A, Ohhara Y, Shichino Y, Iwasaki S, Sun W, Niwa R
Open Biol · 2026 Jun · PMID 42229917 · Publisher ↗
Ribosomes, the cellular machinery responsible for protein synthesis, are fundamental across all kingdoms of life. Disruption of ribosome biogenesis (RiBi) can cause severe ribosomopathies, underscoring the need for preci...
Ribosomes, the cellular machinery responsible for protein synthesis, are fundamental across all kingdoms of life. Disruption of ribosome biogenesis (RiBi) can cause severe ribosomopathies, underscoring the need for precise regulatory mechanisms. In this study, we identified a role for the gene nuclear distribution C, dynein complex regulator (NudC) in RiBi within polyploid cells of Drosophila melanogaster larvae. Depletion of NudC in polyploid salivary gland cells led to a significant reduction in ribosome abundance, accompanied by the loss of ribosome-binding sites on the rough endoplasmic reticulum and impaired translation. These defects are linked to decreased ribosomal RNA levels. Notably, NudC knockdown also triggered a homeostatic response, characterized by increased transcription and translation of ribosome biogenesis factors and ribosomal proteins. This response is similar to that observed in cells with defective ribosomal activity, suggesting that the ribosomal impairment triggers transcriptional feedback to maintain ribosome function. Meanwhile, NudC-deficient cells exhibited chromosome abnormalities, JNK signalling activation and autophagy-resembling defects from ribosome dysfunction. Finally, our findings suggest that the role of NudC in RiBi is independent of its established function in dynein regulation, indicating its moonlighting role in RiBi. Together, these results uncover a new, fundamental function for NudC in maintaining RiBi and homeostasis in polyploid cells.
Pan-resistome and genomic plasticity analysis of antibiotic resistance in Aeromonas: new vaccine targets for A. caviae, A. veronii and A. hydrophila through reverse vaccinology.
Tristão CLAM, Felice AG, Prado LCDS … +4 more , Mattiuzi M, Veneron G, Marques PH, Soares SC
Open Biol · 2026 May · PMID 42191148 · Publisher ↗
Aeromonas species are globally significant pathogens. However, the mechanisms driving their antimicrobial resistance patterns remain unclear. This study addresses the spread of resistance genes in the Aeromonas genus thr...
Aeromonas species are globally significant pathogens. However, the mechanisms driving their antimicrobial resistance patterns remain unclear. This study addresses the spread of resistance genes in the Aeromonas genus through a large-scale genomic analysis of all complete Aeromonas genomes in the RefSeq database. The emergence of next-generation genomic sequencing enabled the sequencing, assembling and annotation of numerous genomes with a description and characterization of the genomic plasticity and the pan-resistome, through bioinformatics programmes, of each species in the Aeromonas genus, and revealed species-specific patterns of resistance determinants. Leveraging these genomic insights, we applied a reverse vaccinology approach with a subtractive genomic workflow to select novel in silico vaccine targets for the three main pathogens: A. veronii, A. hydrophila and A. caviae. These protein candidates offer a potential alternative to prevent the spread of antibiotic resistance genes. Our findings underscore that continuous genomic surveillance is essential for monitoring established and emerging pathogens. While further in vitro and in vivo validation is pending, this work provides a robust framework for understanding Aeromonas resistance and developing new strategies to protect public and environmental health.
Shaping the microvascular network: insights into skeletal muscle angiogenesis.
Gustafsson T, Nwadozi E, Tryfonos A … +1 more , Haas TL
Open Biol · 2026 Apr · PMID 42156063 · Publisher ↗
Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a complex and tightly regulated biological process that plays a fundamental role in both physiological and pathological tissue remodeling...
Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a complex and tightly regulated biological process that plays a fundamental role in both physiological and pathological tissue remodeling by facilitating the delivery of oxygen and nutrients. Over recent decades, extensive research has identified a wide array of factors that regulate the balance between endothelial cell quiescence and activation. This review discusses the cellular events and molecular mechanisms that regulate angiogenesis within skeletal muscle, considering dynamic interactions with the extracellular matrix and highlighting the critical involvement of multiple resident and infiltrating cell types-including myofibres, satellite cells, fibro-adipogenic progenitors, immune cells and pericytes. The current understanding of these regulatory networks is examined in both healthy muscle tissue as part of the phenotype changes that occur during exercise and in pathological conditions that affect skeletal muscle angiogenesis. Particular attention is given to introduce data of emerging high-resolution techniques, especially omics-based approaches such as single-cell RNA sequencing (scRNA-seq) of skeletal muscle tissue. These methodologies hold significant promise for elucidating cell-type-specific roles and intercellular interactions that drive angiogenic processes in both physiological and disease contexts. Despite substantial progress, the precise mechanisms governing angiogenesis in skeletal muscle remain only partially understood.
Investigating how changes in the levels of kinesins impact neuronal health in Drosophila and human iPSC-derived neurons AD model.
Francis D, Paonessa F, Hewitt VL … +6 more , Southall M, Peset I, Whitworth AJ, Livesey FJ, Fabre CCG, Palacios IM
Open Biol · 2026 May · PMID 42120060 · Publisher ↗
Alzheimer's disease (AD) is the leading cause of dementia and the most common neurodegenerative disorder. Understanding the molecular pathology of AD may help identify new ways to reduce neuronal damage. In the past deca...
Alzheimer's disease (AD) is the leading cause of dementia and the most common neurodegenerative disorder. Understanding the molecular pathology of AD may help identify new ways to reduce neuronal damage. In the past decades, Drosophila has become a powerful tool in modelling mechanisms underlying human diseases. Here, we investigate how the expression of the human 42-residue β-amyloid (Aβ) carrying the E22G pathogenic 'Arctic' mutation (Aβ42Arc) affects axonal health and behaviour in Drosophila. We find that Aβ42Arc flies present aberrant neurons, with altered axonal transport of mitochondria and aberrant terminal boutons at neuromuscular junctions. We demonstrate that the motor proteins kinesin-1 and kinesin-3 are essential for the correct development of neurons in Drosophila larvae and in human induced pluripotent stem cell-derived cortical neurons. We then show that the overexpression of kinesin-1 or kinesin-3 restores the correct number and morphology of boutons in Aβ42Arc-expressing neurons and rescues neuronal function measured by negative geotaxis locomotor behavioural assay. We therefore provide new evidence towards understanding the mechanisms of axonal transport defects in AD, and our results support the idea that kinesins should be considered as potential drug targets to help reduce dementia-associated disorders.
Macrophages warrant Mauthner cell axon regrowth by preventing late-stage hyperglycemia in zebrafish.
Bai J, Lai S, Huang Y … +3 more , Liu J, Huang Z, Xu J
Open Biol · 2026 May · PMID 42089279 · Publisher ↗
Axonal regeneration in the central nervous system is imperative for functional restoration following spinal cord injury (SCI). Myeloid cells are key regulators of axonal regeneration, yet their roles are not fully reveal...
Axonal regeneration in the central nervous system is imperative for functional restoration following spinal cord injury (SCI). Myeloid cells are key regulators of axonal regeneration, yet their roles are not fully revealed. SCI perturbs glucose metabolism; however, its precise impact on axonal regeneration remains undefined. Moreover, whether myeloid cells orchestrate glucose metabolic responses to facilitate regeneration is unclear. Here, using the zebrafish Mauthner cell axon transection model, we demonstrate that following SCI, myeloid cell deficiency leads to a late-stage glucose surge, which leads to impaired axonal regeneration. We further identify glucagon signalling as a critical molecular determinant of this metabolic dysregulation and show that targeted mutations in gcga or its receptors (gcgra, gcgrb) rescue the axonal regeneration defects caused by myeloid cell deficiency. Finally, cell-depletion experiments demonstrated that macrophages are responsible for the late-stage hyperglycemia and defective axon regeneration of Mauthner cells. These findings suggest that glucose metabolism plays a critical role in macrophage-warranted axon regeneration in the spinal cord, positioning glucose homeostasis as a potential therapeutic target for enhancing axon regeneration and recovery.
Is the alpha-amylase paralogue Amyrel dispensable in Drosophila melanogaster?
Da Lage JL, Bonneau M, Moreno C … +1 more , Le Rouzic A
Open Biol · 2026 Apr · PMID 42049209 · Publisher ↗
Divergent duplicated gene copies are considered to get new or variant function or regulation through sub- or neofunctionalization. In Drosophila and other flies (Muscomorpha), the alpha-amylase paralogue Amyrel is known...
Divergent duplicated gene copies are considered to get new or variant function or regulation through sub- or neofunctionalization. In Drosophila and other flies (Muscomorpha), the alpha-amylase paralogue Amyrel is known to have peculiar enzymological properties compared with the classical enzyme Amy. Yet, its real function in fly biology is unclear. Here, we show that Amyrel and Amy share similar regulation patterns such as sugar downregulation and midgut-specific expression in Drosophila melanogaster. Most regulatory information lies within 500 bp of the upstream sequence, as enhanced green fluorescent protein expression under the Amyrel promoter mimics Amyrel expression quite well. To get an insight into Amyrel function, we knocked out the gene using CRISPR-Cas9. Setting a competition experiment between wild-type (wt) and null alleles over 40 generations, we estimated the selective advantage of the wt to be 2%. However, Amyrel-null mutant lines exhibited no clear defect in several life history traits. Interestingly, while Amyrel had very low expression in young adults, it was significantly upregulated in females aged two months; however, lifespan was not affected. Overall, we were able to document substantial functional and regulatory differences between the Amyrel copy and the regular amylase, and we showed that carrying an Amyrel gene conferred a competitive fitness advantage.
Oocyst: knowns and unknowns about the lengthiest life stage of the malaria parasite.
Bailey AJ, Vlachou D, Christophides GK
Open Biol · 2026 Apr · PMID 42014057 · Publisher ↗
The oocyst is the longest life stage of Plasmodium, the causative agent of malaria, one of the most persistent and devastating infectious diseases of humankind. Following ingestion during blood feeding, parasites reprodu...
The oocyst is the longest life stage of Plasmodium, the causative agent of malaria, one of the most persistent and devastating infectious diseases of humankind. Following ingestion during blood feeding, parasites reproduce sexually and traverse the mosquito midgut epithelium to differentiate into oocysts on the basal lamina, where they undergo prolonged development, ultimately giving rise to thousands of sporozoites capable of infecting a new human host. Oocyst formation represents a severe population bottleneck, resulting in the lowest parasite numbers observed across the parasite life cycle. Given its extended duration and pronounced numerical vulnerability, it is striking that the oocyst remains one of the least explored stages of Plasmodium development. Major gaps persist in our understanding of the molecular and cellular processes governing oocyst growth and differentiation, including transcriptional and epigenetic regulation, nutrient acquisition and metabolic remodelling, cell cycle control and interactions with the mosquito immune system and physiology. Recent technological advances and renewed interest in mosquito-stage biology provide an opportunity to dissect these processes at unprecedented resolution. In this review, we synthesize knowledge of oocyst biology, highlight key unresolved questions and discuss how deeper insight into this critical stage could inform the development of next-generation transmission-blocking strategies and accelerate progress towards malaria elimination.
Unveiling karyoskeletal dynamics in chromatin organization and gene regulation in haematopoietic cell physiology and pathology.
Kamran M, Nassar N, Cancelas JA
Open Biol · 2026 Apr · PMID 42014056 · Publisher ↗
Chromatin organization and gene regulation are essential for maintaining homeostatic haematopoiesis, the tightly regulated process by which haematopoietic stem and progenitor cells generate diverse blood lineages. Growin...
Chromatin organization and gene regulation are essential for maintaining homeostatic haematopoiesis, the tightly regulated process by which haematopoietic stem and progenitor cells generate diverse blood lineages. Growing evidence identifies karyoskeletal proteins, particularly nuclear actin and its associated scaffolding networks, as central regulators of nuclear function. These proteins influence transcription through interactions with chromatin-remodelling complexes, shape three-dimensional genome architecture, facilitate DNA repair and modulate polycomb-mediated gene repression, thereby governing blood cell identity and lineage commitment. Dysregulation of nuclear structural proteins contributes to haematological malignancies, including leukaemia and myelodysplastic syndromes. In this review, we synthesize current understanding of how karyoskeletal proteins integrate structural and regulatory roles to control chromatin dynamics and gene expression in the lympho-haematopoietic system. We highlight recent insights into their roles in three-dimensional genome organization, epigenetic regulation, polycomb-dependent repression and stemness in both normal and pathological contexts and discuss how nuclear actin modulates these processes in cancer pathogenesis. Collectively, this review underscores how emerging concepts in nuclear architecture reveal karyoskeletal proteins as pivotal determinants of transcriptional regulation and haematopoietic function.
tRNA modification landscapes in streptococci: shared losses and clade-specific adaptations.
Tsui HT, Chan CK, Yuan Y … +15 more , Elias R, Sun J, Marchand V, Jaroch M, Sun G, Manzoor I, Kutchuashvili A, Leszczynska G, Seaton K, Motorin Y, Rice K, Swairjo M, Dedon PC, Winkler ME, de Crécy-Lagard V
Open Biol · 2026 Apr · PMID 41980722 · Publisher ↗
tRNA modifications are central to bacterial translational control. Here, we integrated genetics, mass spectrometry, epitranscriptomics and comparative genomics to map the tRNA modification genes of the Gram-positive path...
tRNA modifications are central to bacterial translational control. Here, we integrated genetics, mass spectrometry, epitranscriptomics and comparative genomics to map the tRNA modification genes of the Gram-positive pathogens Streptococcus mutans and Streptococcus pneumoniae. Both species show a marked loss of modifications dependent on Fe-S enzymes, consistent with a broader trend of Fe-S enzyme reduction in Streptococcus central metabolism. In addition, the D, m1A, m7G, t6A and i6A modifications were mapped in S. pneumoniae tRNAs, and we confirmed that a unique DusB1 enzyme is responsible for the insertion of all the detectable D modifications. We uncovered differences in queuosine (Q) metabolism: while S. mutans synthesizes Q de novo, S. pneumoniae instead salvages preQ₁ and accumulates the epoxy-Q precursor, a strategy shared with multiple other streptococci as revealed by analysis of Q pathways in 1599 sequenced streptococcal genomes. Comparative essentiality profiling of modification genes revealed notable differences, including the essentiality of the N⁶-threonylcarbamoyladenosine (t⁶A) synthesis enzyme TsaE in S. pneumoniae but not in S. mutans, which was confirmed by genetic studies. We found that suppressor mutations in asnS encoding asparaginyl-tRNA synthetase (AsnRS) restored viability to ∆tsaE mutants, albeit with reduced growth. Our finding highlights the functional importance of modifications in the recognition of tRNAs by aminoacyl-tRNA synthetases.
Non-cell-autonomous regulation of testicular stem cell niche homeostasis by the 20S proteasome core particle through cell adhesion and cyclin proteins.
Li J, Wang C, Qian W … +14 more , He L, Huang Q, Zhao J, Cao Z, Huang Y, Wang Y, Wang X, Du Y, Li X, Zhu G, Li Y, Yu J, Tan X, Li Z
Open Biol · 2026 Apr · PMID 41980721 · Publisher ↗
The Drosophila stem cell niche harbours two principal stem cell populations: germline stem cells (GSCs) and cyst stem cells (CySCs), whose self-renewal and differentiation are stringently governed by niche-derived regula...
The Drosophila stem cell niche harbours two principal stem cell populations: germline stem cells (GSCs) and cyst stem cells (CySCs), whose self-renewal and differentiation are stringently governed by niche-derived regulatory factors. Nevertheless, the mechanistic role of the 20S core particle (CP)-the catalytic core of the 26S proteasome-within this niche remains poorly elucidated. In this study, we reveal that three 20S CP subunits, Prosα5, Prosβ2 and Prosβ5, mediate non-cell autonomous effects in the niche. Loss of function of Prosα5, Prosβ2 or Prosβ5 in cyst cells disrupts CySC differentiation, impairs early-stage germline differentiation and culminates in testicular dysgenesis, aberrant GSC-like cluster formation and male sterility. Moreover, we establish that diminished levels of these proteasome subunits trigger the accumulation of cell adhesion molecules and Cyclin proteins. Collectively, our findings offer novel insights into the regulatory functions of the 20S CP within the Drosophila testicular stem cell niche.
Mechanical bone loading effects on morphology and mechanobiology in the coronal suture of Crouzon mice.
Steacy M, Didziokas M, Qiu T … +7 more , Chathuranga DS, Liang C, Alazmani A, Moulding D, Gardner O, Moazen M, Pauws E
Open Biol · 2026 Apr · PMID 41980720 · Publisher ↗
Craniosynostosis is a congenital condition characterized by the premature fusion of the craniofacial sutures. The Crouzon mouse (Fgfr2cC342Y/+) is a well-established model of this condition which shows premature fusion o...
Craniosynostosis is a congenital condition characterized by the premature fusion of the craniofacial sutures. The Crouzon mouse (Fgfr2cC342Y/+) is a well-established model of this condition which shows premature fusion of the coronal suture. Our group has recently shown that postnatal, cyclic loading can potentially rescue the coronal suture and normalize skull morphology in Crouzon mice. This study aimed to investigate the underlying biological mechanism of the treatment. Wild-type (WT) and Crouzon (MUT) mice underwent in vivo loading sessions. Loading did not significantly affect skull shape. The patency across the coronal suture did not change between treated and untreated MUT animals. Orientation and coherence of the coronal suture collagen fibres were statistically different when comparing WT untreated with MUT untreated and WT treated with MUT treated. Treatment increases the number of proliferative cells in both the WT and MUT sutures compared to their untreated counterparts. The mechanobiological mechanisms driving the differences need further investigation into molecular mechanotransduction pathways. Understanding the biological principles affected during bone loading, a more refined cyclical bone loading protocol can be developed and refined for potential clinical use.
Epigenomic and transcriptomic analyses reveal cnidocyte specialization in a sea anemone.
Kozlovski I, Jaimes-Becerra A, Aleshkina D … +2 more , Levy M, Moran Y
Open Biol · 2026 Apr · PMID 41946505 · Publisher ↗
Cnidarians, including corals, hydras, jellyfish and sea anemones, possess specialized stinging cells called cnidocytes that function in prey capture and defense. These cells represent a striking evolutionary innovation a...
Cnidarians, including corals, hydras, jellyfish and sea anemones, possess specialized stinging cells called cnidocytes that function in prey capture and defense. These cells represent a striking evolutionary innovation and produce distinct types of organelles such as venom-injecting nematocysts and mechanically entangling spirocysts. While their biomechanics and transcriptional regulation have been studied extensively, little is known about their epigenetic regulation. Here, we combined epigenetic profiling with RNA sequencing in the sea anemone Nematostella vectensis to explore regulatory programs underlying cnidocyte diversity. We identified cell-type-specific H3K27ac-marked regulatory elements in promoter-proximal and distal regions and linked them to distinct gene expression programs. This analysis revealed fundamental differences between nematocytes and spirocytes and uncovered a previously unrecognized nematocyte population that expresses the Nep3 toxin but lacks most other toxins. These findings highlight the complexity of cnidocyte regulation and suggest greater cellular diversity within this defining cnidarian cell type than previously appreciated.
Pre-cheliceral region patterning in a spider provides new insights into the development and evolution of arthropod neurosecretory centres.
Harper A, Sumner-Rooney L, Janssen R … +1 more , McGregor AP
Open Biol · 2026 Apr · PMID 41946504 · Publisher ↗
Comparing head development among arthropods has helped identify ancestral aspects of brain patterning and structure in animals more generally. Most understanding of arthropod head patterning has been learned from insects...
Comparing head development among arthropods has helped identify ancestral aspects of brain patterning and structure in animals more generally. Most understanding of arthropod head patterning has been learned from insects and the myriapod Strigamia maritima. Chelicerates represent an outgroup to mandibulate arthropods and can provide a valuable perspective to arthropod evolution and development. We assayed the expression of key markers of head patterning and neurosecretory centres from mandibulates in the pre-cheliceral region of embryos of the spider Parasteatoda tepidariorum. We found that, like mandibulates, this spider likely has a pars intercerebralis, marked by six3.2 and visual system homeobox/chx. We also found some evidence for another neurosecretory centre, the pars lateralis, marked by six3.2 and fasciclin 2. Furthermore, we identified anterior-medial cells in the spider pre-cheliceral region that express six3.2, foxQ2 and collier1, suggesting they may be pioneer neurons. However, these spider cells do not appear to be equivalent to the central pioneer neuronal cells identified in S. maritima because they lack expression of other key markers. Taken together, our study of spider pre-cheliceral region patterning adds a new chelicerate perspective to understanding the development and evolution of the arthropod head.
Autophagy in the arms race: how pathogen effectors rewire immunity in plants.
Yuen ELH, Bozkurt TO
Open Biol · 2026 Apr · PMID 41920023 · Publisher ↗
Autophagy is an evolutionarily conserved recycling process that underpins cellular homeostasis and stress resilience in eukaryotes. In the context of plant-pathogen interactions, autophagy has emerged as a key regulatory...
Autophagy is an evolutionarily conserved recycling process that underpins cellular homeostasis and stress resilience in eukaryotes. In the context of plant-pathogen interactions, autophagy has emerged as a key regulatory hub linking immunity, metabolism and programmed cell death. Recent discoveries reveal that diverse virulence factors, or effectors, from a wide range of pathogens target the host autophagy machinery to manipulate cellular responses for their own benefit. On the one hand, selective autophagy functions as a critical component of plant immunity by directly eliminating intracellular pathogens and pathogen-derived molecules, while also degrading negative regulators of immune pathways, thereby strengthening host defences. On the other hand, many pathogens subvert autophagic processes through their effector arsenal: some suppress autophagic degradation to evade immune clearance or maintain host cell viability, whereas others hijack autophagic membranes and signalling components to promote replication and nutrient acquisition. Together, these findings establish autophagy as a central battleground in the molecular arms race between plants and their pathogens. Understanding how effector-autophagy interfaces shape infection outcomes will be critical for engineering disease resistance and for redefining the multifaceted roles of autophagy in plant immunity.
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