Current Biology最新文献

{"title":"The histone H3.3 K27M mutation suppresses Ser31phosphorylation and mitotic fidelity, which can directly drive gliomagenesis.","authors":"Charles A Day, Florina Grigore, Faruck L Hakkim, Souren Paul, Alyssa Langfald, Molly Weberg, Sela Fadness, Paiton Schwab, Leslie Sepaniac, Jason Stumpff, Kevin T Vaughan, David J Daniels, James P Robinson, Edward H Hinchcliffe","doi":"10.1016/j.cub.2024.11.035","DOIUrl":"10.1016/j.cub.2024.11.035","url":null,"abstract":"<p><p>Serine 31 is a phospho-site unique to the histone H3.3 variant; mitotic phospho-Ser31 is restricted to pericentromeric heterochromatin, and disruption of phospho-Ser31 results in chromosome segregation defects and loss of p53-dependant G₁ cell-cycle arrest.¹^,²^,³^,⁴ Ser31 is proximal to the H3.3 lysine 27-to-methionine (K27M) mutation that drives ∼80% of pediatric diffuse midline gliomas.⁵^,⁶^,⁷^,⁸^,⁹^,¹⁰^,¹¹^,¹² Here, we show that expression of the H3.3 K27M mutant in normal, diploid cells results in increased chromosome missegregation and failure to arrest in the following G₁. Expression of a non-phosphorylatable S31A mutant also drives chromosome missegregation, while the expression of a double K27M + phosphomimetic S31E mutant restores mitotic fidelity and the p53 response to chromosome missegregation. We show that patient-derived H3.3 K27M tumor cells have decreased mitotic Ser31 phosphorylation and increased frequency of chromosome missegregation. CRISPR reversion of the K27M mutation to wild type (WT) restores phospho-Ser31 levels and results in a decrease in chromosome missegregation. However, inserting an S31A mutation by CRISPR into these revertant cells disrupts mitotic fidelity. In vitro and in vivo analyses reveal that Chk1-the mitotic Ser31 kinase-is preferentially retained at pericentromeres in K27M-expressing tumor cells, compared with MLysine27-to-methionine mutation (M27K) isogenic revertants, correlating with both diminished phospho-Ser31 and mitotic defects. Interestingly, whereas M27K revertant cells do not form xenograft tumors in mice, H3.3 S31A cells do, similar to those formed by H3.3 K27M cells. Replication-competent avian leukosis virus splice-acceptor (RCAS)/cellular receptor for subgroup A avian sarcoma and leukosis virus (TVA) mice expressing S31A also form diffuse midline gliomas morphologically indistinguishable from K27M tumors. Together, our results reveal that the H3.3 K27M mutant alters H3.3 Ser31 phosphorylation, which, in turn, has profound impacts on chromosome segregation/cell-cycle regulation.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"354-362.e7"},"PeriodicalIF":8.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emily Shepard.","authors":"Emily Shepard","doi":"10.1016/j.cub.2024.12.018","DOIUrl":"https://doi.org/10.1016/j.cub.2024.12.018","url":null,"abstract":"<p><p>Interview with Emily Shepard, who studies the effects of the aerial environment on bird behaviour, energetics and space use at Swansea University.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":"35 2","pages":"R48-R49"},"PeriodicalIF":8.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Itch.","authors":"Lillian N Murphy, Ellen A Lumpkin, Diana M Bautista","doi":"10.1016/j.cub.2024.12.021","DOIUrl":"https://doi.org/10.1016/j.cub.2024.12.021","url":null,"abstract":"<p><p>A camping trip will quickly become unpleasant if a horde of mosquitoes descends while you pitch your tent, or you find yourself in a patch of poison oak. Whether due to an insect bite, a poisonous plant, or a chronic skin disease, everyone has experienced the urgent sensation of itch and the sweet relief of scratching. The itch-scratch cycle is so powerful that just reading about itch or seeing someone scratching elicits a strong desire to scratch. Itch is a unique sensation that is mediated by specialized neurons that innervate the skin. In this primer, we will discuss recent advancements that define the molecules and cells that mediate acute itch and that promote chronic itch associated with inflammatory diseases.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":"35 2","pages":"R51-R57"},"PeriodicalIF":8.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Balbiani body is formed by microtubule-controlled molecular condensation of Buc in early oogenesis.","authors":"Swastik Kar, Rachael Deis, Adam Ahmad, Yoel Bogoch, Avichai Dominitz, Gal Shvaizer, Esther Sasson, Avishag Mytlis, Ayal Ben-Zvi, Yaniv M Elkouby","doi":"10.1016/j.cub.2024.11.056","DOIUrl":"10.1016/j.cub.2024.11.056","url":null,"abstract":"<p><p>Vertebrate oocyte polarity has been observed for two centuries and is essential for embryonic axis formation and germline specification, yet its underlying mechanisms remain unknown. In oocyte polarization, critical RNA-protein (RNP) granules delivered to the oocyte's vegetal pole are stored by the Balbiani body (Bb), a membraneless organelle conserved across species from insects to humans. However, the mechanisms of Bb formation are still unclear. Here, we elucidate mechanisms of Bb formation in zebrafish through developmental biomolecular condensation. Using super-resolution microscopy, live imaging, biochemical, and genetic analyses in vivo, we demonstrate that Bb formation is driven by molecular condensation through phase separation of the essential intrinsically disordered protein Bucky ball (Buc). Live imaging, molecular analyses, and fluorescence recovery after photobleaching (FRAP) experiments in vivo reveal Buc-dependent changes in the Bb condensate's dynamics and apparent material properties, transitioning from liquid-like condensates to a solid-like stable compartment. Furthermore, we identify a multistep regulation by microtubules that controls Bb condensation: first through dynein-mediated trafficking of early condensing Buc granules, then by scaffolding condensed granules, likely through molecular crowding, and finally by caging the mature Bb to prevent overgrowth and maintain shape. These regulatory steps ensure the formation of a single intact Bb, which is considered essential for oocyte polarization and embryonic development. Our work offers insight into the long-standing question of the origins of embryonic polarity in non-mammalian vertebrates, supports a paradigm of cellular control over molecular condensation by microtubules, and highlights biomolecular condensation as a key process in female reproduction.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"315-332.e7"},"PeriodicalIF":8.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a tetrahedral apical cell preserved within a fossilized fern fiddlehead.","authors":"Rafael Cruz, Alexander J Hetherington","doi":"10.1016/j.cub.2024.10.076","DOIUrl":"10.1016/j.cub.2024.10.076","url":null,"abstract":"<p><p>The gradual unfurling of fronds from tightly coiled tips, termed fiddleheads or croziers, is one of the most recognizable features of the fern lineage, but its evolutionary origin remains unclear. Here, we identify that fiddleheads and their development, termed circinate vernation,¹^,² are not ubiquitous across ferns. Instead, they are a synapomorphy of a clade we term the circinatophytes that includes extant marattioid and leptosporangiate ferns. Circinatophytes encompass the vast majority of extant ferns,³ and fossil evidence demonstrates the antiquity of the group at over 315 million years. Despite their overall conservation, a comparative investigation of extant species suggests that during fiddlehead evolution, there was a transition from a tetrahedral to a wedge-shaped apical cell in the leaf meristem. We predict that a tetrahedral leaf apical cell was likely ancestral in circinatophytes, despite being present in less than 2% of modern species,³ and that this cell mirrored the tetrahedral cell found in the shoots of all major groups of ferns. This is supported by our description of a tetrahedral apical cell in, to our knowledge, the oldest preserved fossil fern leaf meristem of the ca. 315-million-year-old fern Ankyropteris corrugata. We conclude that fiddleheads have been highly conserved in the circinatophytes, and the similarities in leaf and shoot apical cells in early diverging groups of ferns add support to the hypothesis that fern leaves evolved through the modification of shoots, as proposed by the telome theory.⁴.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"383-390.e2"},"PeriodicalIF":8.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant physiology: Rethinking CRY photoreceptors.","authors":"Gaoping Qu, Chentao Lin","doi":"10.1016/j.cub.2024.11.050","DOIUrl":"https://doi.org/10.1016/j.cub.2024.11.050","url":null,"abstract":"<p><p>The CRY2 photoreceptor is known to form homotetramers that bind to transcription regulators to affect gene expression in response to light. A new study provides evidence that the CRY2 monomer binds different transcription regulators to affect gene expression in darkness, suggesting that photoreceptors change activity in response to light.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":"35 2","pages":"R65-R66"},"PeriodicalIF":8.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An intrinsic hierarchical, retinotopic organization of visual pulvinar connectivity in the human neonate.","authors":"Vladislav Ayzenberg, Chenjie Song, Michael J Arcaro","doi":"10.1016/j.cub.2024.11.042","DOIUrl":"10.1016/j.cub.2024.11.042","url":null,"abstract":"<p><p>The thalamus plays a crucial role in the development of the neocortex, with the pulvinar being particularly important for visual development due to its involvement in various functions that emerge early in infancy. The development of connections between the pulvinar and the cortex constrains its role in infant visual processing and the maturation of associated cortical networks. However, the extent to which adult-like pulvino-cortical pathways are present at birth remains largely unknown, limiting our understanding of how the thalamus may support early vision. To address this gap, we investigated the organization of pulvino-cortical connections in human neonates using probabilistic tractography analyses on diffusion imaging data. Our analyses identified white matter pathways between the pulvinar and areas across occipital, ventral, lateral, and dorsal visual cortices at birth. These pathways exhibited specificity in their connections within the pulvinar, reflecting both an intra-areal retinotopic organization and a hierarchical structure across areas of visual cortical pathways. This organization suggests that even at birth, the pulvinar could facilitate detailed processing of sensory information and communication between distinct processing pathways. Comparative analyses revealed that while the large-scale organization of pulvino-cortical connectivity in neonates mirrored that of adults, connectivity with the ventral visual cortex was less mature than other cortical pathways, consistent with the protracted development of the visual recognition pathway. These findings advance our understanding of the developmental trajectory of thalamocortical connections and provide a framework for how subcortical structures may support early perceptual abilities and scaffold the development of cortex.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"300-314.e5"},"PeriodicalIF":8.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental and evolutionary controls in animal-sediment interactions at the onset of the Cambrian explosion.","authors":"Romain Gougeon, Luis A Buatois, M Gabriela Mángano, Guy M Narbonne, Brittany A Laing, Maximiliano Paz, Nicholas J Minter","doi":"10.1016/j.cub.2024.11.028","DOIUrl":"10.1016/j.cub.2024.11.028","url":null,"abstract":"<p><p>The Cambrian explosion was a time of groundbreaking ecological shifts related to the establishment of the Phanerozoic biosphere. Trace fossils, which are the products of animals interacting with their substrates, provide a key record of the diversification of the benthos and the evolution of behavioral complexity through this interval. The Chapel Island Formation of Newfoundland in Canada hosts the most extensive trace-fossil record from the latest Ediacaran to Cambrian Age 2, spanning about 20 million years continuously. To elucidate the relative roles of environmental changes as opposed to evolutionary trajectories, we gathered the largest trace-fossil dataset to date and designed fourteen high-resolution time-environment matrices on bioturbation intensity, burrow width and depth, tiering (i.e., the vertical partitioning of trace fossils within the substrate), ichnodiversity, ichnodisparity (i.e., the development of novel architectural designs in ichnotaxa), ecospace utilization (i.e., the development of ecological niches by benthic animals), and other trends related to specific trace-fossil types. Ecosystem engineering by early animals resulted in three stages identified in the Chapel Island Formation that are probably global-an Ediacaran matground ecology, a Fortunian matground/firmground ecology, and a latest Fortunian/Cambrian Age 2 mixground ecology. Time-environment matrices further imply that the lower offshore was the cradle of diversification for animal behavior, which later expanded inshore and led to a novelty evolutionary event, refining our understanding of the early stages of the Cambrian explosion.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"249-264.e4"},"PeriodicalIF":8.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple mechanisms of action for an extremely painful venom.","authors":"Lydia J Borjon, Luana C de Assis Ferreira, Jonathan C Trinidad, Sunčica Šašić, Andrea G Hohmann, W Daniel Tracey","doi":"10.1016/j.cub.2024.11.070","DOIUrl":"10.1016/j.cub.2024.11.070","url":null,"abstract":"<p><p>Evolutionary arms races can lead to extremely specific and effective defense mechanisms, including venoms that deter predators by targeting nociceptive (pain-sensing) pathways. The venom of velvet ants (Hymenoptera: Mutillidae) is notoriously painful. It has been described as \"Explosive and long lasting, you sound insane as you scream. Hot oil from the deep fryer spilling over your entire hand.\"¹ The effectiveness of the velvet ant sting against potential predators has been shown across vertebrate orders, including mammals, amphibians, reptiles, and birds.²^,³^,⁴ This leads to the hypothesis that velvet ant venom targets a conserved nociception mechanism, which we sought to uncover using Drosophila melanogaster as a model system. Drosophila larvae have peripheral sensory neurons that sense potentially damaging (noxious) stimuli such as high temperature, harsh mechanical touch, and noxious chemicals.⁵^,⁶^,⁷^,⁸ They share features with vertebrate nociceptors, including conserved sensory receptor channels.⁹^,¹⁰ We found that velvet ant venom strongly activated Drosophila nociceptors through heteromeric Pickpocket/Balboa (Ppk/Bba) ion channels, through a single venom peptide, Do6a. Drosophila Ppk/Bba is homologous to mammalian acid-sensing ion channels (ASICs).¹¹ However, Do6a did not produce behavioral signs of nociception in mice, which was instead triggered by other venom peptides that are non-specific and less potent on Drosophila nociceptors. This suggests that Do6a has an insect-specific function. In fact, we further demonstrated that the velvet ant's sting produced aversive behavior in a predatory praying mantis. Together, our results indicate that velvet ant venom acts through different molecular mechanisms in vertebrates and invertebrates.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"444-453.e4"},"PeriodicalIF":8.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Climatic forcing of the Southern Ocean deep-sea ecosystem.","authors":"Moriaki Yasuhara, Huai-Hsuan May Huang, Raine Wing Ki Chong, Yuanyuan Hong, Hokuto Iwatani, Jingwen Zhang, Katsunori Kimoto, Minoru Ikehara","doi":"10.1016/j.cub.2024.11.026","DOIUrl":"10.1016/j.cub.2024.11.026","url":null,"abstract":"<p><p>The deep-time development of the Southern Ocean's deep-sea ecosystem remains poorly understood, despite being a key region in global ecological, climatological, and oceanographic systems, where deep water forms and biodiversity is unexpectedly high.¹^,² Here, we present an ∼500,000-year fossil record of the deep-sea Southern Ocean ecosystem in the subantarctic zone. The results indicate that changes in surface productivity and the resulting food supply to the deep sea, driven by eolian dust input and iron fertilization, along with changes in bottom-water temperature influenced by deep-water circulation, have controlled the deep-sea ecosystem in the Southern Ocean on orbital (10⁴-10⁵ years) timescales following the Mid-Brunhes event (MBE), a major climatic transition ∼430,000 years ago.³ However, before the MBE, the deep-sea Southern Ocean ecosystem was distinct from the present-day, post-MBE one. The present-day form of the deep-sea Southern Ocean ecosystem was established following the MBE, likely because of a stronger incursion of the warm North Atlantic deep water into the Southern Ocean after the MBE. Before that, the deep-sea Southern Ocean ecosystem lacked typical deep-sea faunal components and resembled deep, marginal sea fauna, likely because of the stronger thermal isolation of the Southern Ocean from the Atlantic Ocean. This result suggests that if future human-induced climatic warming weakens global deep-water circulation from the Atlantic through the Southern Ocean to the Pacific,⁴ a deep-sea biodiversity hotspot in the Southern Ocean may diminish or even vanish.</p>","PeriodicalId":11359,"journal":{"name":"Current Biology","volume":" ","pages":"347-353.e1"},"PeriodicalIF":8.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}