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A Nature-Inspired Ion Trap for Parallel Manipulation of Ions on a Massive Scale. 一个受自然启发的离子阱,用于大规模的离子并行操作。
bioRxiv : the preprint server for biology Pub Date : 2025-09-30 DOI: 10.1101/2025.08.21.671534
Andrew N Krutchinsky, Brian T Chait
{"title":"A Nature-Inspired Ion Trap for Parallel Manipulation of Ions on a Massive Scale.","authors":"Andrew N Krutchinsky, Brian T Chait","doi":"10.1101/2025.08.21.671534","DOIUrl":"10.1101/2025.08.21.671534","url":null,"abstract":"<p><p>Parallelization has revolutionized computing and DNA sequencing but remains largely unexploited in mass spectrometry (MS), which typically analyzes ions sequentially. Inspired by nuclear cytoplasmic transport, where diffusion governs transport to multiple gated channels (nuclear pore complexes), we introduce an ion trap (MultiQ-IT) that enables massively parallel MS. The device comprises a cubic array of small quadrupoles forming multiple ion entry and exit ports, allowing >10⁹ ions to be cooled, confined and manipulated simultaneously. This architecture enables selective depletion of singly charged ions, greatly improving signal-to-noise ratios and detection sensitivity. The trap also functions as a parallel ion splitter, transmitting ions into multiple m/z-specific beams. We demonstrate scalable ion throughput, real-time charge discrimination, and parallel beam separation, suggesting a path toward truly parallel MS. Our results establish a foundation for next-generation, high-throughput proteomic and metabolomic analyses.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Uncovering the electrical synapse proteome in retinal neurons via in vivo proximity labeling. 通过体内接近标记揭示视网膜神经元的电突触蛋白质组。
bioRxiv : the preprint server for biology Pub Date : 2025-09-30 DOI: 10.1101/2024.11.26.625481
Stephan Tetenborg, Eyad Shihabeddin, Elizebeth Olive Akansha Manoj Kumar, Crystal Sigulinsky, Karin Dedek, Ya-Ping Lin, Fabio Echeverry, Hannah Hoff, Alberto Pereda, Bryan William Jones, Christophe Ribelayga, Klaus Ebnet, Ken Matsuura, John O'Brien
{"title":"Uncovering the electrical synapse proteome in retinal neurons via in vivo proximity labeling.","authors":"Stephan Tetenborg, Eyad Shihabeddin, Elizebeth Olive Akansha Manoj Kumar, Crystal Sigulinsky, Karin Dedek, Ya-Ping Lin, Fabio Echeverry, Hannah Hoff, Alberto Pereda, Bryan William Jones, Christophe Ribelayga, Klaus Ebnet, Ken Matsuura, John O'Brien","doi":"10.1101/2024.11.26.625481","DOIUrl":"10.1101/2024.11.26.625481","url":null,"abstract":"<p><p>Electrical synapses containing Connexin 36 (Cx36) represent the main means for communication in the mammalian nervous system. However, little is known about the protein complexes that constitute these synapses. In the present study, we applied different BioID strategies to screen the interactomes of Connexin 36 the major neuronal connexin and its zebrafish orthologue Cx35b in retinal neurons. For in vivo proximity labeling in mice, we took advantage of the Cx36-EGFP strain and expressed a GFP-nanobody-TurboID fusion construct selectively in AII amacrine cells. For in vivo BioID in zebrafish, we generated a transgenic line expressing a Cx35b-TurboID fusion under control of the Cx35b promoter. Both strategies allowed us to capture a plethora of molecules that were associated with electrical synapses and showed a high degree of evolutionary conservation in the proteomes of both species. Besides known interactors of Cx36 such as ZO-1 and ZO-2 we have identified more than 50 new proteins, such as scaffold proteins, adhesion molecules and regulators of the cytoskeleton. Moreover, we determined the subcellular localization of these proteins in AII amacrine and tested potential binding interactions with Cx36. Amongst these new interactors, we identified signal induced proliferation associated 1 like 3 (SIPA1L3), a protein that has been implicated in cell junction formation and cell polarity as a new scaffold of electrical synapses. Interestingly, SIPA1L3 was able to interact with ZO-1, ZO-2 and Cx36, suggesting a pivotal role in electrical synapse function. In summary, our study provides the first detailed view of the electrical synapse proteome in retinal neurons, which is likely to apply to electrical synapses elsewhere.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Human sand fly challenge elicits saliva-specific innate and TH1-polarized immunity that promotes Leishmania killing. Lutzomyia longipalpis唾液蛋白可激发人类先天性和适应性免疫反应,从而抑制利什曼原虫寄生。
bioRxiv : the preprint server for biology Pub Date : 2025-09-30 DOI: 10.1101/2025.02.25.640210
Maha Abdeladhim, Clarissa Teixeira, Roseanne Ressner, Kelly Hummer, Ranadhir Dey, Regis Gomes, Waldionê de Castro, Fernanda Fortes de Araujo, George W Turiansky, Eva Iniguez, Claudio Meneses, Fabiano Oliveira, Naomi Aronson, Joshua R Lacsina, Jesus G Valenzuela, Shaden Kamhawi
{"title":"Human sand fly challenge elicits saliva-specific innate and T<sub>H</sub>1-polarized immunity that promotes <i>Leishmania</i> killing.","authors":"Maha Abdeladhim, Clarissa Teixeira, Roseanne Ressner, Kelly Hummer, Ranadhir Dey, Regis Gomes, Waldionê de Castro, Fernanda Fortes de Araujo, George W Turiansky, Eva Iniguez, Claudio Meneses, Fabiano Oliveira, Naomi Aronson, Joshua R Lacsina, Jesus G Valenzuela, Shaden Kamhawi","doi":"10.1101/2025.02.25.640210","DOIUrl":"10.1101/2025.02.25.640210","url":null,"abstract":"<p><p>In <i>Leishmania</i>-endemic areas, humans are constantly exposed to sand fly bites. To explore the immune consequences of this chronic vector exposure, we performed a human challenge study with the sand fly <i>Lutzomyia longipalpis</i>. Peripheral blood mononuclear cells were collected from fifteen healthy volunteers who underwent multiple controlled exposures to sand fly bites. We identified two <i>Lu. longipalpis</i> salivary proteins, LJM19 and LJL143, which elicited T<sub>H</sub>1-polarized cytokine responses in cells from exposed individuals and which correlated with enhanced killing of <i>Leishmania</i> parasites in co-cultured macrophages. Interestingly, LJM19 also exerted this parasite-killing effect in cells from unexposed individuals, consistent with innate immune activation. In support of this, both LJM19 and LJL143 stimulated the production of the innate cytokines IL-1β and IFN-α. Our results demonstrate that repeated exposure to sand fly bites induces innate and adaptive cytokine responses to vector salivary proteins that can be co-opted to protect humans against <i>Leishmania</i> infection.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants. 刺突突变影响最近的kp .3.1.1样SARS-CoV-2变体的功能和抗原性
bioRxiv : the preprint server for biology Pub Date : 2025-09-30 DOI: 10.1101/2025.08.18.671001
Bernadeta Dadonaite, Sheri Harari, Brendan B Larsen, Lucas Kampman, Alex Harteloo, Anna Elias-Warren, Helen Y Chu, Jesse D Bloom
{"title":"Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants.","authors":"Bernadeta Dadonaite, Sheri Harari, Brendan B Larsen, Lucas Kampman, Alex Harteloo, Anna Elias-Warren, Helen Y Chu, Jesse D Bloom","doi":"10.1101/2025.08.18.671001","DOIUrl":"10.1101/2025.08.18.671001","url":null,"abstract":"<p><p>SARS-CoV-2 is under strong evolutionary selection to acquire mutations in its spike protein that reduce neutralization by human polyclonal antibodies. Here we use pseudovirus-based deep mutational scanning to measure how mutations to the spike from the recent KP.3.1.1 SARS-CoV-2 strain affect cell entry, binding to ACE2 receptor, RBD up/down motion, and neutralization by human sera and clinically relevant antibodies. The spike mutations that most affect serum antibody neutralization sometimes differ between sera collected before versus after recent vaccination or infection, indicating these exposures shift the neutralization immunodominance hierarchy. The sites where mutations cause the greatest reduction in neutralization by post-vaccination or infection sera include receptor-binding domain (RBD) sites 475, 478 and 487, all of which have mutated in recent SARS-CoV-2 variants. Multiple mutations outside the RBD affect sera neutralization as strongly as any RBD mutations by modulating RBD up/down movement. Some sites that affect RBD up/down movement have mutated in recent SARS-CoV-2 variants. Finally, we measure how spike mutations affect neutralization by three clinically relevant SARS-CoV-2 antibodies: VYD222, BD55-1205, and SA55. Overall, these results illuminate the current constraints and pressures shaping SARS-CoV-2 evolution, and can help with efforts to forecast possible future antigenic changes that may impact vaccines or clinical antibodies.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12393327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Deep Neural Network Trained on Congruent Audiovisual Speech Reports the McGurk Effect. 基于一致视听语音训练的深度神经网络报告了McGurk效应。
bioRxiv : the preprint server for biology Pub Date : 2025-09-30 DOI: 10.1101/2025.08.20.671347
Haotian Ma, Zhengjia Wang, Xiang Zhang, John F Magnotti, Michael S Beauchamp
{"title":"A Deep Neural Network Trained on Congruent Audiovisual Speech Reports the McGurk Effect.","authors":"Haotian Ma, Zhengjia Wang, Xiang Zhang, John F Magnotti, Michael S Beauchamp","doi":"10.1101/2025.08.20.671347","DOIUrl":"10.1101/2025.08.20.671347","url":null,"abstract":"<p><p>In the McGurk effect, incongruent auditory and visual syllables are perceived as a third, illusory syllable. The prevailing explanation for the effect is that the illusory syllable is a consensus percept intermediate between otherwise incompatible auditory and visual representations. To test this idea, we turned to a deep neural network known as AVHuBERT that transcribes audiovisual speech with high accuracy. Critically, AVHuBERT was trained only with <i>congruent</i> audiovisual speech, without exposure to McGurk stimuli or other incongruent speech. In the current study, when tested with congruent audiovisual \"ba\", \"ga\" and \"da\" syllables recorded from 8 different talkers, AVHuBERT transcribed them with near-perfect accuracy, and showed a human-like pattern of highest accuracy for audiovisual speech, slightly lower accuracy for auditory-only speech, and low accuracy for visual-only speech. When presented with incongruent McGurk syllables (auditory \"ba\" paired with visual \"ga\"), AVHuBERT reported the McGurk fusion percept of \"da\" at a rate of 25%, many-fold greater than the rate for either auditory or visual components of the McGurk stimulus presented on their own. To examine the individual variability that is hallmark of human perception of the McGurk effect, 100 variants of AVHuBERT were constructed. Like human observers, AVHuBERT variants was consistently accurate for congruent syllables but highly variable for McGurk syllables. Similarities between the responses of AVHuBERT and humans to congruent and incongruent audiovisual speech, including the McGurk effect, suggests that DNNs may be a useful tool for interrogating the perceptual and neural mechanisms of human audiovisual speech perception.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12393562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lymph node contraction links sex-biased naive CD8 T cell decline to compromised antigen recognition. 淋巴结将性别偏见免疫老化与抗原识别受损联系起来。
bioRxiv : the preprint server for biology Pub Date : 2025-09-30 DOI: 10.1101/2025.02.11.637693
Lutz Menzel, Maria Zschummel, Meghan J O'Melia, Marten Sandstedt, Hengbo Zhou, Pin-Ji Lei, Lingshan Liu, Hang Lee, Debattama R Sen, Lance L Munn, Lena Jonasson, Timothy P Padera
{"title":"Lymph node contraction links sex-biased naive CD8 T cell decline to compromised antigen recognition.","authors":"Lutz Menzel, Maria Zschummel, Meghan J O'Melia, Marten Sandstedt, Hengbo Zhou, Pin-Ji Lei, Lingshan Liu, Hang Lee, Debattama R Sen, Lance L Munn, Lena Jonasson, Timothy P Padera","doi":"10.1101/2025.02.11.637693","DOIUrl":"10.1101/2025.02.11.637693","url":null,"abstract":"<p><p>A diverse naive CD8 T cell repertoire is essential to provide broad protection against infection and cancer. Here, we uncover a sex-biased mechanism of immune aging in which male mice exhibit early depletion of naive CD8 T cells through accelerated, antigen-agnostic differentiation into virtual memory cells. This depletion, compounded by androgen-driven thymic atrophy, leads to contraction of lymph nodes and a reduced local naive T cell repertoire, limiting antigen recognition capacity. Therapeutic thymus regeneration via androgen ablation repopulates naive CD8 T cells in lymph nodes and reinvigorates tumor recognition in middle-aged male mice. These findings reveal the crucial impact of sex and age on locoregional naive T cell repertoires in lymph nodes and suggest strategies to restore immune competence in aging males.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Beyond Blacklists: A Critical Assessment of Exclusion Set Generation Strategies and Alternative Approaches. 超越黑名单:排除集生成策略和替代方法的关键评估。
bioRxiv : the preprint server for biology Pub Date : 2025-09-30 DOI: 10.1101/2025.02.06.636968
Brydon P G Wall, Jonathan D Ogata, My Nguyen, Amy L Olex, Konstantinos V Floros, Anthony C Faber, Joseph L McClay, Chuck Harrell, Mikhail G Dozmorov
{"title":"Beyond Blacklists: A Critical Assessment of Exclusion Set Generation Strategies and Alternative Approaches.","authors":"Brydon P G Wall, Jonathan D Ogata, My Nguyen, Amy L Olex, Konstantinos V Floros, Anthony C Faber, Joseph L McClay, Chuck Harrell, Mikhail G Dozmorov","doi":"10.1101/2025.02.06.636968","DOIUrl":"10.1101/2025.02.06.636968","url":null,"abstract":"<p><p>Short-read sequencing data can be affected by alignment artifacts in certain genomic regions. Removing reads overlapping these exclusion regions, previously known as Blacklists, help to potentially improve biological signal. Tools like the widely used Blacklist software facilitate this process, but their algorithmic details and parameter choices are not always clearly documented, affecting reproducibility and biological relevance. We examined the Blacklist software and found that pre-generated exclusion sets were difficult to reproduce due to variability in input data, aligner choice, and read length. We also identified and addressed a coding issue that led to over-annotation of high-signal regions. We further explored the use of \"sponge\" sequences - unassembled genomic regions such as satellite DNA, ribosomal DNA, and mitochondrial DNA - as an alternative approach. Aligning reads to a genome that includes sponge sequences reduced signal correlation in ChIP-seq data comparably to Blacklist-derived exclusion sets while preserving biological signal. Sponge-based alignment also had minimal impact on RNA-seq gene counts, suggesting broader applicability beyond chromatin profiling. These results highlight the limitations of fixed exclusion sets and suggest that sponge sequences offer a flexible, alignment-guided strategy for reducing artifacts and improving functional genomics analyses.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cross-species brain circuitry from diffusion MRI tractography and mouse viral tracing. 扩散核磁共振成像和小鼠病毒追踪的跨物种脑回路。
bioRxiv : the preprint server for biology Pub Date : 2025-09-30 DOI: 10.1101/2025.09.07.674762
Siva Venkadesh, Wen-Jieh Linn, Yuhe Tian, G Allan Johnson, Fang-Cheng Yeh
{"title":"Cross-species brain circuitry from diffusion MRI tractography and mouse viral tracing.","authors":"Siva Venkadesh, Wen-Jieh Linn, Yuhe Tian, G Allan Johnson, Fang-Cheng Yeh","doi":"10.1101/2025.09.07.674762","DOIUrl":"10.1101/2025.09.07.674762","url":null,"abstract":"<p><p>We integrated tracer-derived projection polarity from ~1,200 mouse injections with species-specific diffusion MRI (dMRI) tractography to construct directed connectomes for mouse, marmoset, rhesus macaque, and human. Brain circuitry was modeled as a directed connectome, where asymmetric pathways capture forward neuronal signal flow. Using a common cross-species atlas as a scaffold, we introduced a path efficiency metric balancing projection strength against axonal length and applied shortest-path algorithms to quantify inter-regional influence. This framework revealed conserved and divergent organization. The entorhinal-hippocampal projection remained the most efficient in all species, underscoring memory-circuit preservation. In humans, anterior insula-superior temporal paths gained efficiency, strengthening a temporal-insula-frontal circuit while olfactory pathways ranked lower. Macaques showed peak efficiencies in inferior temporal outflows, whereas marmosets maintained high olfactory influence. Together, these results establish a scalable framework for directed connectomics and show how conserved and lineage-specific circuits shaped association and sensory systems.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pleiotropic mutational effects on function and stability constrain the antigenic evolution of influenza hemagglutinin. 流感血凝素功能和稳定性的多效性突变影响制约了其抗原性进化。
bioRxiv : the preprint server for biology Pub Date : 2025-09-30 DOI: 10.1101/2025.05.24.655919
Timothy C Yu, Caroline Kikawa, Bernadeta Dadonaite, Andrea N Loes, Janet A Englund, Jesse D Bloom
{"title":"Pleiotropic mutational effects on function and stability constrain the antigenic evolution of influenza hemagglutinin.","authors":"Timothy C Yu, Caroline Kikawa, Bernadeta Dadonaite, Andrea N Loes, Janet A Englund, Jesse D Bloom","doi":"10.1101/2025.05.24.655919","DOIUrl":"10.1101/2025.05.24.655919","url":null,"abstract":"<p><p>The evolution of human influenza virus hemagglutinin (HA) involves simultaneous selection to acquire antigenic mutations that escape population immunity while preserving protein function and stability. Epistasis shapes this evolution, as an antigenic mutation that is deleterious in one genetic background may become tolerated in another. However, the extent to which epistasis can alleviate pleiotropic conflicts between immune escape and protein function/stability is unclear. Here, we measure how all amino acid mutations in the HA of a recent human H3N2 influenza strain affect its cell entry function, acid stability, and neutralization by human serum antibodies. We find that epistasis has entrenched certain mutations so that reverting to the ancestral amino acid identity in earlier strains is no longer tolerated. Epistasis has also enabled the emergence of antigenic mutations that were detrimental to HA's cell entry function in earlier strains. However, epistasis appears insufficient to overcome the pleiotropic costs of antigenic mutations that impair HA's stability, explaining why some mutations that strongly escape human antibodies never fix in nature. Our results refine our understanding of the mutational constraints that shape recent H3N2 influenza evolution: epistasis can enable antigenic change, but pleiotropic effects can restrict its trajectory.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A single-nucleus transcriptomic atlas of the adult Aedes aegypti mosquito. 蚊子细胞图谱:成年埃及伊蚊的单核转录图谱。
bioRxiv : the preprint server for biology Pub Date : 2025-09-30 DOI: 10.1101/2025.02.25.639765
Olivia V Goldman, Alexandra E DeFoe, Yanyan Qi, Yaoyu Jiao, Shih-Che Weng, Brittney Wick, Leah Houri-Zeevi, Priyanka Lakhiani, Takeshi Morita, Jacopo Razzauti, Adriana Rosas-Villegas, Yael N Tsitohay, Madison M Walker, Ben R Hopkins, Maximilian Haeussler, Omar S Akbari, Laura B Duvall, Helen White-Cooper, Trevor R Sorrells, Roshan Sharma, Hongjie Li, Leslie B Vosshall, Nadav Shai
{"title":"A single-nucleus transcriptomic atlas of the adult <i>Aedes aegypti</i> mosquito.","authors":"Olivia V Goldman, Alexandra E DeFoe, Yanyan Qi, Yaoyu Jiao, Shih-Che Weng, Brittney Wick, Leah Houri-Zeevi, Priyanka Lakhiani, Takeshi Morita, Jacopo Razzauti, Adriana Rosas-Villegas, Yael N Tsitohay, Madison M Walker, Ben R Hopkins, Maximilian Haeussler, Omar S Akbari, Laura B Duvall, Helen White-Cooper, Trevor R Sorrells, Roshan Sharma, Hongjie Li, Leslie B Vosshall, Nadav Shai","doi":"10.1101/2025.02.25.639765","DOIUrl":"10.1101/2025.02.25.639765","url":null,"abstract":"<p><p>The female <i>Aedes aegypti</i> mosquito's remarkable ability to hunt humans and transmit pathogens relies on her unique biology. Here, we present the <i>Aedes aegypti</i> Mosquito Cell Atlas, a comprehensive single-nucleus RNA sequencing dataset of more than 367,000 nuclei from 19 dissected tissues of adult female and male <i>Aedes aegypti</i>, providing cellular-level resolution of mosquito biology. We identify novel cell types and expand our understanding of sensory neuron organization of chemoreceptors to all sensory tissues. Our analysis uncovers male-specific cells and sexually dimorphic gene expression in the antenna and brain. In female mosquitoes, we find that glial cells in the brain, rather than neurons, undergo the most extensive transcriptional changes following blood feeding. Our findings provide insights into the cellular basis of mosquito behavior and sexual dimorphism. The <i>Aedes aegypti</i> Mosquito Cell Atlas resource enables systematic investigation of cell type-specific expression across all mosquito tissues.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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