Pub Date : 2024-11-04DOI: 10.1038/s42003-024-07150-0
Moonsup Lee, Christina Carpenter, Yoo-Seok Hwang, Jaeho Yoon, Quanlong Lu, Christopher J. Westlake, Sally A. Moody, Terry P. Yamaguchi, Ira O. Daar
Motile cilia are critical structures that regulate early embryonic development and tissue homeostasis through synchronized ciliary motility. The formation of motile cilia is dependent on precisely controlled sequential processes including the generation, migration, and docking of centrioles/basal bodies as well as ciliary growth. Using the published proteomics data from various organisms, we identified proliferation-associated 2G4 as a novel regulator of ciliogenesis. Loss-of-function studies using Xenopus laevis as a model system reveal that Pa2G4 is essential for proper ciliogenesis and synchronized movement of cilia in multiciliated cells (MCCs) and the gastrocoel roof plate (GRP). Pa2G4 morphant MCCs exhibit defective basal body docking to the surface as a result of compromised Rac1 activity, apical actin network formation, and immature distal appendage generation. Interestingly, the regions that include the RNA-binding domain and the C-terminus of Pa2G4 are necessary for ciliogenesis in both MCCs and GRP cells. Our findings may provide insights into motile cilia-related genetic diseases such as Primary Ciliary Dyskinesia. The study on the role of Proliferation-associated 2G4 in motile cilia formation and synchronized cilia movement offers valuable insights into research on motile cilia-related genetic diseases.
{"title":"Proliferation associated 2G4 is required for the ciliation of vertebrate motile cilia","authors":"Moonsup Lee, Christina Carpenter, Yoo-Seok Hwang, Jaeho Yoon, Quanlong Lu, Christopher J. Westlake, Sally A. Moody, Terry P. Yamaguchi, Ira O. Daar","doi":"10.1038/s42003-024-07150-0","DOIUrl":"10.1038/s42003-024-07150-0","url":null,"abstract":"Motile cilia are critical structures that regulate early embryonic development and tissue homeostasis through synchronized ciliary motility. The formation of motile cilia is dependent on precisely controlled sequential processes including the generation, migration, and docking of centrioles/basal bodies as well as ciliary growth. Using the published proteomics data from various organisms, we identified proliferation-associated 2G4 as a novel regulator of ciliogenesis. Loss-of-function studies using Xenopus laevis as a model system reveal that Pa2G4 is essential for proper ciliogenesis and synchronized movement of cilia in multiciliated cells (MCCs) and the gastrocoel roof plate (GRP). Pa2G4 morphant MCCs exhibit defective basal body docking to the surface as a result of compromised Rac1 activity, apical actin network formation, and immature distal appendage generation. Interestingly, the regions that include the RNA-binding domain and the C-terminus of Pa2G4 are necessary for ciliogenesis in both MCCs and GRP cells. Our findings may provide insights into motile cilia-related genetic diseases such as Primary Ciliary Dyskinesia. The study on the role of Proliferation-associated 2G4 in motile cilia formation and synchronized cilia movement offers valuable insights into research on motile cilia-related genetic diseases.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07150-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-04DOI: 10.1038/s42003-024-07138-w
Emanuele Fornasier, Simone Fabbian, Haidi Shehi, Janine Enderle, Barbara Gatto, Daniele Volpin, Barbara Biondi, Massimo Bellanda, Gabriele Giachin, Alice Sosic, Roberto Battistutta
Many enzymes work as homodimers with two distant catalytic sites, but the reason for this choice is often not clear. For the main protease Mpro of SARS-CoV-2, dimerization is essential for function and plays a regulatory role during the coronaviral replication process. Here, to analyze a possible allosteric mechanism, we use X-ray crystallography, native mass spectrometry, isothermal titration calorimetry, and activity assays to study the interaction of Mpro with three peptide substrates. Crystal structures show how the plasticity of Mpro is exploited to face differences in the sequences of the natural substrates. Importantly, unlike in the free form, the Mpro dimer in complex with these peptides is asymmetric and the structures of the substrates nsp5/6 and nsp14/15 bound to a single subunit show allosteric communications between active sites. We identified arginines 4 and 298 as key elements in the transition from symmetric to asymmetric dimers. Kinetic data allowed the identification of positive cooperativity based on the increase in the processing efficiency (kinetic allostery) and not on the better binding of the substrates (thermodynamic allostery). At the physiological level, this allosteric behavior may be justified by the need to regulate the processing of viral polyproteins in time and space. Structural, biophysical, and kinetic analyses of the interaction of SARS-CoV-2 Mpro with peptide substrates shed light on the allosteric properties of the enzyme, which is based on kinetics rather than thermodynamics.
{"title":"Allostery in homodimeric SARS-CoV-2 main protease","authors":"Emanuele Fornasier, Simone Fabbian, Haidi Shehi, Janine Enderle, Barbara Gatto, Daniele Volpin, Barbara Biondi, Massimo Bellanda, Gabriele Giachin, Alice Sosic, Roberto Battistutta","doi":"10.1038/s42003-024-07138-w","DOIUrl":"10.1038/s42003-024-07138-w","url":null,"abstract":"Many enzymes work as homodimers with two distant catalytic sites, but the reason for this choice is often not clear. For the main protease Mpro of SARS-CoV-2, dimerization is essential for function and plays a regulatory role during the coronaviral replication process. Here, to analyze a possible allosteric mechanism, we use X-ray crystallography, native mass spectrometry, isothermal titration calorimetry, and activity assays to study the interaction of Mpro with three peptide substrates. Crystal structures show how the plasticity of Mpro is exploited to face differences in the sequences of the natural substrates. Importantly, unlike in the free form, the Mpro dimer in complex with these peptides is asymmetric and the structures of the substrates nsp5/6 and nsp14/15 bound to a single subunit show allosteric communications between active sites. We identified arginines 4 and 298 as key elements in the transition from symmetric to asymmetric dimers. Kinetic data allowed the identification of positive cooperativity based on the increase in the processing efficiency (kinetic allostery) and not on the better binding of the substrates (thermodynamic allostery). At the physiological level, this allosteric behavior may be justified by the need to regulate the processing of viral polyproteins in time and space. Structural, biophysical, and kinetic analyses of the interaction of SARS-CoV-2 Mpro with peptide substrates shed light on the allosteric properties of the enzyme, which is based on kinetics rather than thermodynamics.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07138-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-04DOI: 10.1038/s42003-024-07048-x
Lihui Wang, Runda Xu, Daosheng Huang, Pai Peng, Keyong Sun, Jie Hu, Bei-zhong Liu, Liang Fang, Liwen Zhang, Xin Sun, Fei Gu, Ni Tang, Ai-long Huang, Xin Lin, Xun Lan
Identifying epitopes and their corresponding T-cell receptor (TCR) sequences is crucial in the face of rapidly mutating viruses. Peptide synthesis is often required to confirm the exact epitope sequences, which is time-consuming and expensive. In this study, we introduce a scalable workflow to identify the exact sequences of virus epitopes and reactive TCRs targeting the epitopes from memory T cells. Following the narrowing down of epitopes to specific regions via the tandem minigene (TMG) system, our workflow incorporates the utilization of peptide-major histocompatibility complex-displaying yeasts (pMHC-displaying yeasts) to rapidly screen immunogenic epitopes’ precise sequences, obviating the necessity for the chemical synthesis of peptides. Focusing on SARS-CoV-2, we identify the precise sequences of reactive TCRs, targeting conserved epitopes across the Coronaviridae family, from the blood of COVID-19-recovered individuals over 8 months. Notably, we reveal that at least 75% (6/8) of the tested donors harbor T cells targeting a shared epitope, KTFPPTEPK, derived from the N protein. Furthermore, several identified TCRs exhibit cross-reactivity to mutant epitopes, suggesting a potential mechanism for sustained T-cell responses against emerging SARS-CoV-2 variants. A scalable workflow involving a pMHC-displaying yeast system is introduced to identify precise virus epitope sequences and corresponding T-cell receptor (TCR) sequences from memory T cells.
面对快速变异的病毒，识别表位及其相应的 T 细胞受体（TCR）序列至关重要。通常需要合成多肽来确认表位的确切序列，这既耗时又昂贵。在本研究中，我们介绍了一种可扩展的工作流程，用于识别病毒表位的准确序列以及记忆 T 细胞中靶向表位的反应性 TCR。在通过串联微型基因（TMG）系统将表位缩小到特定区域后，我们的工作流程结合了利用多肽-主要组织相容性复合体显示酵母（pMHC-显示酵母）来快速筛选免疫原表位的精确序列，从而避免了化学合成多肽的必要性。我们以 SARS-CoV-2 为重点，从 COVID-19 恢复者 8 个月的血液中确定了反应性 TCR 的精确序列，这些 TCR 针对的是冠状病毒家族中的保守表位。值得注意的是，我们发现至少 75%（6/8）的受检供体携带有靶向来自 N 蛋白的共享表位 KTFPPTEPK 的 T 细胞。此外，一些已确定的 TCR 对突变表位表现出交叉反应，这表明针对新出现的 SARS-CoV-2 变体的持续 T 细胞反应具有潜在的机制。
{"title":"Identification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesis","authors":"Lihui Wang, Runda Xu, Daosheng Huang, Pai Peng, Keyong Sun, Jie Hu, Bei-zhong Liu, Liang Fang, Liwen Zhang, Xin Sun, Fei Gu, Ni Tang, Ai-long Huang, Xin Lin, Xun Lan","doi":"10.1038/s42003-024-07048-x","DOIUrl":"10.1038/s42003-024-07048-x","url":null,"abstract":"Identifying epitopes and their corresponding T-cell receptor (TCR) sequences is crucial in the face of rapidly mutating viruses. Peptide synthesis is often required to confirm the exact epitope sequences, which is time-consuming and expensive. In this study, we introduce a scalable workflow to identify the exact sequences of virus epitopes and reactive TCRs targeting the epitopes from memory T cells. Following the narrowing down of epitopes to specific regions via the tandem minigene (TMG) system, our workflow incorporates the utilization of peptide-major histocompatibility complex-displaying yeasts (pMHC-displaying yeasts) to rapidly screen immunogenic epitopes’ precise sequences, obviating the necessity for the chemical synthesis of peptides. Focusing on SARS-CoV-2, we identify the precise sequences of reactive TCRs, targeting conserved epitopes across the Coronaviridae family, from the blood of COVID-19-recovered individuals over 8 months. Notably, we reveal that at least 75% (6/8) of the tested donors harbor T cells targeting a shared epitope, KTFPPTEPK, derived from the N protein. Furthermore, several identified TCRs exhibit cross-reactivity to mutant epitopes, suggesting a potential mechanism for sustained T-cell responses against emerging SARS-CoV-2 variants. A scalable workflow involving a pMHC-displaying yeast system is introduced to identify precise virus epitope sequences and corresponding T-cell receptor (TCR) sequences from memory T cells.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07048-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicroRNAs (miRNAs) are post-transcriptional, non-coding regulatory RNAs that function coordinately with transcription factors (TFs) in gene regulatory networks. TFs and their targets are often co-regulated by miRNAs, forming composite feedforward circuits (cFFCs) with varying degrees of redundancy, primarily mediated by miRNAs. However, the maintenance of miRNA-mediated regulatory redundancy and its impact on gene expression evolution remain elusive. By integrating ChIP-seq data from ENCODE and miRNA targeting from TargetScanFly, we quantified miRNA-mediated cFFC redundancy in Drosophila melanogaster embryos and larvae, revealing more than three quarters of miRNA targets are involved in redundant cFFCs. Higher cFFC redundancy, where more miRNAs target the same gene within a cFFC, is correlated with stronger purifying selection, reduced expression divergence between species, and increased expression stability under heat shock stress. Redundant cFFCs primarily regulate older or broadly expressed young genes. These findings highlight the role of miRNA-mediated cFFC redundancy in enhancing gene expression robustness through natural selection. Network analysis reveals miRNAs mediate high redundancy of composite feedforward circuits (cFFCs) in Drosophila, correlating with strong purifying selection, reduced interspecies expression divergence, and increased stability under stress.
{"title":"MicroRNA-mediated network redundancy is constrained by purifying selection and contributes to expression robustness in Drosophila melanogaster","authors":"Aimei Dai, Wenqi Lan, Yang Lyu, Xuanyi Zhou, Xin Mi, Tian Tang, Zhongqi Liufu","doi":"10.1038/s42003-024-07162-w","DOIUrl":"10.1038/s42003-024-07162-w","url":null,"abstract":"MicroRNAs (miRNAs) are post-transcriptional, non-coding regulatory RNAs that function coordinately with transcription factors (TFs) in gene regulatory networks. TFs and their targets are often co-regulated by miRNAs, forming composite feedforward circuits (cFFCs) with varying degrees of redundancy, primarily mediated by miRNAs. However, the maintenance of miRNA-mediated regulatory redundancy and its impact on gene expression evolution remain elusive. By integrating ChIP-seq data from ENCODE and miRNA targeting from TargetScanFly, we quantified miRNA-mediated cFFC redundancy in Drosophila melanogaster embryos and larvae, revealing more than three quarters of miRNA targets are involved in redundant cFFCs. Higher cFFC redundancy, where more miRNAs target the same gene within a cFFC, is correlated with stronger purifying selection, reduced expression divergence between species, and increased expression stability under heat shock stress. Redundant cFFCs primarily regulate older or broadly expressed young genes. These findings highlight the role of miRNA-mediated cFFC redundancy in enhancing gene expression robustness through natural selection. Network analysis reveals miRNAs mediate high redundancy of composite feedforward circuits (cFFCs) in Drosophila, correlating with strong purifying selection, reduced interspecies expression divergence, and increased stability under stress.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07162-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Victims of explosive events frequently suffer from blast lung injuries. Immune system has been implicated in the pathogenesis of this disease. However, systemic immune responses underlying the progression and recovery of injury repair remain poorly understood. Here, we depict the systemic landscape of immune dysregulation during blast lung injury and uncover immune recovery patterns. Single-cell analyses reveal dramatic changes in neutrophils, macrophages, monocytes, dendritic cells, and eosinophils after a gas explosion, along with early involvement of CD4 T, CD8 T, and Th17 cells. We demonstrate that myeloid cells primarily exert functions during the acute phase, while the spleen serves as an alternative source of granulocytes. Granulopoiesis is initiated in the bone marrow at a later stage during blast lung injury recovery, rather than at the acute stage. These findings contribute to a better understanding of the pathogenesis and provide valuable insights for potential immune interventions in blast lung injury. Single-cell proteomics using mass cytometry reveals the systemic landscape of immune dysregulation during blast lung injury and uncovers patterns of immune recovery, offering valuable insights for potential interventions in blast lung injury.
爆炸事件的受害者经常受到爆炸造成的肺部伤害。免疫系统与这种疾病的发病机制有关。然而，人们对损伤修复的进展和恢复所依赖的全身免疫反应仍然知之甚少。在这里，我们描绘了爆炸性肺损伤期间免疫失调的系统状况，并揭示了免疫恢复模式。单细胞分析揭示了气体爆炸后中性粒细胞、巨噬细胞、单核细胞、树突状细胞和嗜酸性粒细胞的巨大变化，以及 CD4 T、CD8 T 和 Th17 细胞的早期参与。我们证明，髓系细胞主要在急性期发挥功能，而脾脏则是粒细胞的替代来源。粒细胞生成是在爆炸性肺损伤恢复的后期阶段而不是急性阶段从骨髓开始的。这些发现有助于更好地了解发病机制，并为爆炸性肺损伤的潜在免疫干预提供了宝贵的见解。利用质控细胞仪进行的单细胞蛋白质组学研究揭示了爆炸性肺损伤期间免疫失调的系统情况，并发现了免疫恢复的模式，为爆炸性肺损伤的潜在干预措施提供了宝贵的见解。
{"title":"Single-cell proteomics delineates murine systemic immune response to blast lung injury","authors":"Long Li, Zhongrui Liu, Linqiang Tian, Sanqiao Yao, Lili Feng, Feng Lai, Kunxi Wang, Yue Zhang, Yanyan Li, Jinheng Wang, Wenjie Ren","doi":"10.1038/s42003-024-07151-z","DOIUrl":"10.1038/s42003-024-07151-z","url":null,"abstract":"Victims of explosive events frequently suffer from blast lung injuries. Immune system has been implicated in the pathogenesis of this disease. However, systemic immune responses underlying the progression and recovery of injury repair remain poorly understood. Here, we depict the systemic landscape of immune dysregulation during blast lung injury and uncover immune recovery patterns. Single-cell analyses reveal dramatic changes in neutrophils, macrophages, monocytes, dendritic cells, and eosinophils after a gas explosion, along with early involvement of CD4 T, CD8 T, and Th17 cells. We demonstrate that myeloid cells primarily exert functions during the acute phase, while the spleen serves as an alternative source of granulocytes. Granulopoiesis is initiated in the bone marrow at a later stage during blast lung injury recovery, rather than at the acute stage. These findings contribute to a better understanding of the pathogenesis and provide valuable insights for potential immune interventions in blast lung injury. Single-cell proteomics using mass cytometry reveals the systemic landscape of immune dysregulation during blast lung injury and uncovers patterns of immune recovery, offering valuable insights for potential interventions in blast lung injury.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07151-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The widespread bacterial genus Sulfurimonas is metabolically versatile and occupies a key ecological niche in different habitats, but its interaction with bacteriophages remains unexplored. Here we systematically investigated the genetic diversity, taxonomy and interaction patterns of Sulfurimonas-associated phages based on sequenced microbial genomes and metagenomes. High-confidence phage contigs related to Sulfurimonas were retrieved from various ecosystems, clustered into 61 viral operational taxonomic units across three viral realms, including Duplodnaviria, Monodnaviria and Varidnaviria. Head-tail phages of Caudoviricetes were assigned to 19 genus-level viral clusters, the majority of which were distantly related to known viruses. Notably, diverse double jelly-roll viruses and inoviruses were also linked to Sulfurimonas, representing two commonly overlooked phage groups. Historical and current phage infections were revealed, implying viral impact on the evolution of host adaptive immunity. Additionally, phages carrying auxiliary metabolic genes might benefit hosts by compensating or augmenting sulfur metabolism. This study highlights the diversity and novelty of Sulfurimonas-associated phages with divergent tailless lineages, providing basis for further investigation of phage-host interactions within this genus. A catalog of phages associated with Sulfurimonas reveals unexplored diversity and potential viral impacts, providing new insight into the phage-host coevolution.
{"title":"Genomic diversity of phages infecting the globally widespread genus Sulfurimonas","authors":"Xiaofeng Li, Ruolin Cheng, Chuanxi Zhang, Zongze Shao","doi":"10.1038/s42003-024-07079-4","DOIUrl":"10.1038/s42003-024-07079-4","url":null,"abstract":"The widespread bacterial genus Sulfurimonas is metabolically versatile and occupies a key ecological niche in different habitats, but its interaction with bacteriophages remains unexplored. Here we systematically investigated the genetic diversity, taxonomy and interaction patterns of Sulfurimonas-associated phages based on sequenced microbial genomes and metagenomes. High-confidence phage contigs related to Sulfurimonas were retrieved from various ecosystems, clustered into 61 viral operational taxonomic units across three viral realms, including Duplodnaviria, Monodnaviria and Varidnaviria. Head-tail phages of Caudoviricetes were assigned to 19 genus-level viral clusters, the majority of which were distantly related to known viruses. Notably, diverse double jelly-roll viruses and inoviruses were also linked to Sulfurimonas, representing two commonly overlooked phage groups. Historical and current phage infections were revealed, implying viral impact on the evolution of host adaptive immunity. Additionally, phages carrying auxiliary metabolic genes might benefit hosts by compensating or augmenting sulfur metabolism. This study highlights the diversity and novelty of Sulfurimonas-associated phages with divergent tailless lineages, providing basis for further investigation of phage-host interactions within this genus. A catalog of phages associated with Sulfurimonas reveals unexplored diversity and potential viral impacts, providing new insight into the phage-host coevolution.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07079-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1038/s42003-024-07114-4
Marius Grabow, Wiebke Ullmann, Conny Landgraf, Rahel Sollmann, Carolin Scholz, Ran Nathan, Sivan Toledo, Renke Lühken, Joerns Fickel, Florian Jeltsch, Niels Blaum, Viktoriia Radchuk, Ralph Tiedemann, Stephanie Kramer-Schadt
In wildlife populations, parasites often go unnoticed, as infected animals appear asymptomatic. However, these infections can subtly alter behaviour. Field evidence of how these subclinical infections induce changes in movement behaviour is scarce in free-ranging animals, yet it may be crucial for zoonotic disease surveillance. We used an ultra-high-resolution tracking system (ATLAS) to monitor the movements of 60 free-ranging swallows every 8 seconds across four breeding seasons, resulting in over 1 million localizations. About 40% of these swallows were naturally infected with haemosporidian parasites. Here, we show that infected individuals had reduced foraging ranges, foraged in lower quality habitats, and faced a lowered survival probability, with an average reduction of 7.4%, albeit with some variation between species and years. This study highlights the impact of subclinical infections on movement behaviour and survival, emphasizing the importance of considering infection status in movement ecology. Our findings provide insights into individual variations in behaviour and previously unobservable local parasite transmission dynamics. Subclinical infections in wild swallows reduce foraging ranges, alter habitat use, and decrease survival rates. A study using ultra-high-resolution tracking reveals overlooked impacts of infection on movement behaviour and links them to demography.
{"title":"Sick without signs. Subclinical infections reduce local movements, alter habitat selection, and cause demographic shifts","authors":"Marius Grabow, Wiebke Ullmann, Conny Landgraf, Rahel Sollmann, Carolin Scholz, Ran Nathan, Sivan Toledo, Renke Lühken, Joerns Fickel, Florian Jeltsch, Niels Blaum, Viktoriia Radchuk, Ralph Tiedemann, Stephanie Kramer-Schadt","doi":"10.1038/s42003-024-07114-4","DOIUrl":"10.1038/s42003-024-07114-4","url":null,"abstract":"In wildlife populations, parasites often go unnoticed, as infected animals appear asymptomatic. However, these infections can subtly alter behaviour. Field evidence of how these subclinical infections induce changes in movement behaviour is scarce in free-ranging animals, yet it may be crucial for zoonotic disease surveillance. We used an ultra-high-resolution tracking system (ATLAS) to monitor the movements of 60 free-ranging swallows every 8 seconds across four breeding seasons, resulting in over 1 million localizations. About 40% of these swallows were naturally infected with haemosporidian parasites. Here, we show that infected individuals had reduced foraging ranges, foraged in lower quality habitats, and faced a lowered survival probability, with an average reduction of 7.4%, albeit with some variation between species and years. This study highlights the impact of subclinical infections on movement behaviour and survival, emphasizing the importance of considering infection status in movement ecology. Our findings provide insights into individual variations in behaviour and previously unobservable local parasite transmission dynamics. Subclinical infections in wild swallows reduce foraging ranges, alter habitat use, and decrease survival rates. A study using ultra-high-resolution tracking reveals overlooked impacts of infection on movement behaviour and links them to demography.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07114-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1038/s42003-024-07121-5
Olga S. Strelkova, Richard T. Osgood, Chunjie Tian, Xinyuan Zhang, Evan Hale, Pedro De-la-Torre, Daniel M. Hathaway, Artur A. Indzhykulian
Polycystic Kidney and Hepatic Disease 1-Like 1 (PKHD1L1) is a human deafness gene, responsible for autosomal recessive deafness-124 (DFNB124). Sensory hair cells of the cochlea are essential for hearing, relying on the mechanosensitive stereocilia bundle at their apical pole for their function. PKHD1L1 is a stereocilia protein required for the formation of the developmentally transient stereocilia surface coat. In this study, we carry out an in depth characterization of PKHD1L1 expression in mice during development and adulthood, analyze hair-cell bundle morphology and hearing function in aging PKHD1L1-deficient mouse lines, and assess their susceptibility to noise damage. Our findings reveal that PKHD1L1-deficient mice display no disruption to bundle cohesion or tectorial membrane attachment-crown formation during development. However, starting from 6 weeks of age, PKHD1L1-deficient mice display missing stereocilia and disruptions to bundle coherence. Both conditional and constitutive PKHD1L1 knockout mice develop high-frequency hearing loss progressing to lower frequencies with age. Furthermore, PKHD1L1-deficient mice are susceptible to permanent hearing loss following moderate acoustic overexposure, which induces only temporary hearing threshold shifts in wild-type mice. These results suggest a role for PKHD1L1 in establishing robust sensory hair bundles during development, necessary for maintaining bundle cohesion and function in response to acoustic trauma and aging. Characterization of hearing function and sensory hair-cell morphology in mice deficient in the developmental stereocilia protein PKHD1L1, reveal it is required for the formation of robust sensory hair bundles, resilient to noise exposure and aging.
{"title":"PKHD1L1 is required for stereocilia bundle maintenance, durable hearing function and resilience to noise exposure","authors":"Olga S. Strelkova, Richard T. Osgood, Chunjie Tian, Xinyuan Zhang, Evan Hale, Pedro De-la-Torre, Daniel M. Hathaway, Artur A. Indzhykulian","doi":"10.1038/s42003-024-07121-5","DOIUrl":"10.1038/s42003-024-07121-5","url":null,"abstract":"Polycystic Kidney and Hepatic Disease 1-Like 1 (PKHD1L1) is a human deafness gene, responsible for autosomal recessive deafness-124 (DFNB124). Sensory hair cells of the cochlea are essential for hearing, relying on the mechanosensitive stereocilia bundle at their apical pole for their function. PKHD1L1 is a stereocilia protein required for the formation of the developmentally transient stereocilia surface coat. In this study, we carry out an in depth characterization of PKHD1L1 expression in mice during development and adulthood, analyze hair-cell bundle morphology and hearing function in aging PKHD1L1-deficient mouse lines, and assess their susceptibility to noise damage. Our findings reveal that PKHD1L1-deficient mice display no disruption to bundle cohesion or tectorial membrane attachment-crown formation during development. However, starting from 6 weeks of age, PKHD1L1-deficient mice display missing stereocilia and disruptions to bundle coherence. Both conditional and constitutive PKHD1L1 knockout mice develop high-frequency hearing loss progressing to lower frequencies with age. Furthermore, PKHD1L1-deficient mice are susceptible to permanent hearing loss following moderate acoustic overexposure, which induces only temporary hearing threshold shifts in wild-type mice. These results suggest a role for PKHD1L1 in establishing robust sensory hair bundles during development, necessary for maintaining bundle cohesion and function in response to acoustic trauma and aging. Characterization of hearing function and sensory hair-cell morphology in mice deficient in the developmental stereocilia protein PKHD1L1, reveal it is required for the formation of robust sensory hair bundles, resilient to noise exposure and aging.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1038/s42003-024-07062-z
Heiko Meyer, Judith Bossen, Maren Janz, Xenia Müller, Sven Künzel, Thomas Roeder, Achim Paululat
Drosophila nephrocytes are specialised cells that share critical functional, morphological, and molecular features with mammalian podocytes. Accordingly, nephrocytes represent a preferred invertebrate model for human glomerular disease. Here, we established a method for cell-specific isolation of the two types of Drosophila nephrocytes, garland and pericardial cells, from animals of different developmental stages and ages. Mass spectrometry-based proteomics and RNA-Seq-based transcriptomics were applied to characterise the proteome and transcriptome of the respective cells in an integrated and complementary manner. We observed characteristic changes in the proteome and transcriptome due to cellular ageing. Furthermore, functional enrichment analyses suggested that larval and adult nephrocytes, as well as garland and pericardial nephrocytes, fulfil distinct physiological functions. In addition, the pericardial nephrocytes were characterised by transcriptomic and proteomic profiles suggesting an atypical energy metabolism with very low oxidative phosphorylation rates. Moreover, the nephrocytes displayed typical signatures of extensive immune signalling and showed an active antimicrobial response to an infection. Factor-specific comparisons identified novel candidate proteins either expressed and secreted by the nephrocytes or sequestered by them. The data generated in this study represent a valuable basis for a more specific application of the Drosophila model in analysing renal cell function in health and disease. Combined transcriptomic and proteomic analyses of the two types of Drosophila nephrocytes – pericardial cells and garland cells – provide information on their individual physiological significance.
{"title":"Combined transcriptome and proteome profiling reveal cell-type-specific functions of Drosophila garland and pericardial nephrocytes","authors":"Heiko Meyer, Judith Bossen, Maren Janz, Xenia Müller, Sven Künzel, Thomas Roeder, Achim Paululat","doi":"10.1038/s42003-024-07062-z","DOIUrl":"10.1038/s42003-024-07062-z","url":null,"abstract":"Drosophila nephrocytes are specialised cells that share critical functional, morphological, and molecular features with mammalian podocytes. Accordingly, nephrocytes represent a preferred invertebrate model for human glomerular disease. Here, we established a method for cell-specific isolation of the two types of Drosophila nephrocytes, garland and pericardial cells, from animals of different developmental stages and ages. Mass spectrometry-based proteomics and RNA-Seq-based transcriptomics were applied to characterise the proteome and transcriptome of the respective cells in an integrated and complementary manner. We observed characteristic changes in the proteome and transcriptome due to cellular ageing. Furthermore, functional enrichment analyses suggested that larval and adult nephrocytes, as well as garland and pericardial nephrocytes, fulfil distinct physiological functions. In addition, the pericardial nephrocytes were characterised by transcriptomic and proteomic profiles suggesting an atypical energy metabolism with very low oxidative phosphorylation rates. Moreover, the nephrocytes displayed typical signatures of extensive immune signalling and showed an active antimicrobial response to an infection. Factor-specific comparisons identified novel candidate proteins either expressed and secreted by the nephrocytes or sequestered by them. The data generated in this study represent a valuable basis for a more specific application of the Drosophila model in analysing renal cell function in health and disease. Combined transcriptomic and proteomic analyses of the two types of Drosophila nephrocytes – pericardial cells and garland cells – provide information on their individual physiological significance.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07062-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1038/s42003-024-07149-7
Sishi Liu, Man Gao, Xue Zhang, Jun Wei, Hong Cui
Preeclampsia (PE) is a common pregnancy disorder characterized by hypertension and proteinuria. Trophoblast behavior severely affect PE progression. Transcription factor Forkhead box protein P2 (FOXP2) was involved in cell migration and invasion, but its role in PE progression remains unknown. Laminin subunit alpha 4 (LAMA4) was predicted as a downstream gene of FOXP2 and related to PE. Thus, we supposed that FOXP2 might regulate PE by regulating LAMA4. We found the decreased FOXP2 expression in patients with PE compared with healthy pregnant women. The rat model of PE was induced by L-NAME oral gavage. FOXP2 overexpression lowered systolic and diastolic blood pressure and restored pathological changes of rats with PE. Trophoblasts under the hypoxia/reoxygenation (H/R) treatment were used to mimic PE in vitro. The results revealed that FOXP2 overexpression inhibited apoptosis but promoted migration, invasion, and angiogenesis of H/R-treated trophoblasts. Dual luciferase and chromatin immunoprecipitation-polymerase chain reaction assays confirmed that FOXP2 transcriptionally upregulated the LAMA4 expression in trophoblasts. LAMA4 knockdown reversed the migration and invasion-promoting role of FOXP2 overexpression in trophoblasts with H/R treatment. Collectively, our findings suggest that the FOXP2/LAMA4 axis regulates PE by suppressing trophoblast apoptosis and promoting its migration, invasion, and angiogenesis. Overexpression of FOXP2-mediated LAMA4 expression provides an insight on the preeclampsia treatment by suppressing trophoblast apoptosis and promoting its migration, invasion, and angiogenesis.
子痫前期（PE）是一种以高血压和蛋白尿为特征的常见妊娠疾病。滋养层细胞的行为严重影响子痫前期的进展。转录因子叉头盒蛋白 P2（FOXP2）参与了细胞迁移和侵袭，但其在子痫前期进展中的作用仍不清楚。层粘连蛋白亚基α4（LAMA4）被认为是 FOXP2 的下游基因，与 PE 有关。因此，我们认为 FOXP2 可能通过调节 LAMA4 来调控 PE。我们发现，与健康孕妇相比，PE 患者的 FOXP2 表达降低。用 L-NAME 口服诱导大鼠 PE 模型。过表达 FOXP2 可降低 PE 大鼠的收缩压和舒张压，恢复病理变化。用缺氧/再氧合（H/R）处理下的滋养细胞在体外模拟 PE。结果发现，FOXP2的过表达抑制了H/R处理的滋养细胞的凋亡，但促进了其迁移、侵袭和血管生成。双荧光素酶和染色质免疫沉淀聚合酶链反应实验证实，FOXP2转录上调滋养细胞中LAMA4的表达。LAMA4 的敲除逆转了 FOXP2 在 H/R 处理下过表达对滋养细胞迁移和侵袭的促进作用。总之，我们的研究结果表明，FOXP2/LAMA4轴通过抑制滋养细胞凋亡和促进其迁移、侵袭和血管生成来调控PE。
{"title":"FOXP2 overexpression upregulates LAMA4 expression and thereby alleviates preeclampsia by regulating trophoblast behavior","authors":"Sishi Liu, Man Gao, Xue Zhang, Jun Wei, Hong Cui","doi":"10.1038/s42003-024-07149-7","DOIUrl":"10.1038/s42003-024-07149-7","url":null,"abstract":"Preeclampsia (PE) is a common pregnancy disorder characterized by hypertension and proteinuria. Trophoblast behavior severely affect PE progression. Transcription factor Forkhead box protein P2 (FOXP2) was involved in cell migration and invasion, but its role in PE progression remains unknown. Laminin subunit alpha 4 (LAMA4) was predicted as a downstream gene of FOXP2 and related to PE. Thus, we supposed that FOXP2 might regulate PE by regulating LAMA4. We found the decreased FOXP2 expression in patients with PE compared with healthy pregnant women. The rat model of PE was induced by L-NAME oral gavage. FOXP2 overexpression lowered systolic and diastolic blood pressure and restored pathological changes of rats with PE. Trophoblasts under the hypoxia/reoxygenation (H/R) treatment were used to mimic PE in vitro. The results revealed that FOXP2 overexpression inhibited apoptosis but promoted migration, invasion, and angiogenesis of H/R-treated trophoblasts. Dual luciferase and chromatin immunoprecipitation-polymerase chain reaction assays confirmed that FOXP2 transcriptionally upregulated the LAMA4 expression in trophoblasts. LAMA4 knockdown reversed the migration and invasion-promoting role of FOXP2 overexpression in trophoblasts with H/R treatment. Collectively, our findings suggest that the FOXP2/LAMA4 axis regulates PE by suppressing trophoblast apoptosis and promoting its migration, invasion, and angiogenesis. Overexpression of FOXP2-mediated LAMA4 expression provides an insight on the preeclampsia treatment by suppressing trophoblast apoptosis and promoting its migration, invasion, and angiogenesis.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07149-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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