Doulathunnisa Ahamed Younis, Mason Marosvari, Wei Liu, Sunitha Pulikkot, Ziming Cao, Beiyan Zhou, Anthony T. Vella, Sara McArdle, Liang Hu, Yunfeng Chen, Wenqi Gan, Ji Yu, Emanuela M. Bruscia, Zhichao Fan
Monocytes are critical in controlling tissue infections and inflammation. Monocyte dysfunction contributes to the inflammatory pathogenesis of cystic fibrosis (CF) caused by CF transmembrane conductance regulator (CFTR) mutations, making CF a clinically relevant disease model for studying the contribution of monocytes to inflammation. Although CF monocytes exhibited adhesion defects, the precise mechanism is unclear. Herein, superresolution microscopy showed that an integrin clustering but not an integrin activation defect determines the adhesion defect in CFTR-deficient monocytes, challenging the existing paradigm emphasizing an integrin activation defect in CF patient monocytes. We further found that the clustering defect is accompanied by defects in CORO1A membrane recruitment, actin cortex formation, and CORO1A engagement with integrins. Complementing canonical studies of leukocyte adhesion focusing on integrin activation, we highlight the importance of integrin clustering in cell adhesion and report that integrin clustering and activation are distinctly regulated, warranting further investigation for selective targeting in therapeutic strategy design involving leukocyte-dependent inflammation.
{"title":"CFTR dictates monocyte adhesion by facilitating integrin clustering but not activation","authors":"Doulathunnisa Ahamed Younis, Mason Marosvari, Wei Liu, Sunitha Pulikkot, Ziming Cao, Beiyan Zhou, Anthony T. Vella, Sara McArdle, Liang Hu, Yunfeng Chen, Wenqi Gan, Ji Yu, Emanuela M. Bruscia, Zhichao Fan","doi":"10.1073/pnas.2412717122","DOIUrl":"https://doi.org/10.1073/pnas.2412717122","url":null,"abstract":"Monocytes are critical in controlling tissue infections and inflammation. Monocyte dysfunction contributes to the inflammatory pathogenesis of cystic fibrosis (CF) caused by CF transmembrane conductance regulator (CFTR) mutations, making CF a clinically relevant disease model for studying the contribution of monocytes to inflammation. Although CF monocytes exhibited adhesion defects, the precise mechanism is unclear. Herein, superresolution microscopy showed that an integrin clustering but not an integrin activation defect determines the adhesion defect in CFTR-deficient monocytes, challenging the existing paradigm emphasizing an integrin activation defect in CF patient monocytes. We further found that the clustering defect is accompanied by defects in CORO1A membrane recruitment, actin cortex formation, and CORO1A engagement with integrins. Complementing canonical studies of leukocyte adhesion focusing on integrin activation, we highlight the importance of integrin clustering in cell adhesion and report that integrin clustering and activation are distinctly regulated, warranting further investigation for selective targeting in therapeutic strategy design involving leukocyte-dependent inflammation.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"18 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Long Lin, Danyu Shen, Xiaolong Shao, Yicheng Yang, Li Li, Caihong Zhong, Jiandong Jiang, Mengcen Wang, Guoliang Qian
Bacterial–fungal interaction (BFI) has significant implications for the health of host plants. While the diffusible antibiotic metabolite-mediated competition in BFI has been extensively characterized, the impact of intercellular contact remains largely elusive. Here, we demonstrate that the intercellular contact is a prevalent mode of interaction between beneficial soil bacteria and pathogenic filamentous fungi. By generating antibiotics-deficient mutants in two common soil bacteria, Lysobacter enzymogenes and Pseudomonas fluorescens , we show that antibiotics-independent BFI effectively inhibits pathogenic fungi. Furthermore, transcriptional and genetic evidence revealed that this antibiotics-independent BFI relies on intercellular contact mediated by the type VI secretion system (T6SS), which may facilitate the translocation of bacterial toxic effectors into fungal cells. Finally, by using a “conidia enrichment” platform, we found that T6SS-mediated fungal inhibition resulting from intercellular contact naturally occurs within the soil microbiome, particularly represented by Pseudomonas fulva . Overall, these results demonstrate that bacteria from the soil microbiome can protect host plants from fungal infection through antibiotics-independent intercellular contacts, thus revealing a naturally occurring and ecologically important mode of BFI in agricultural contexts.
{"title":"Soil microbiome bacteria protect plants against filamentous fungal infections via intercellular contacts","authors":"Long Lin, Danyu Shen, Xiaolong Shao, Yicheng Yang, Li Li, Caihong Zhong, Jiandong Jiang, Mengcen Wang, Guoliang Qian","doi":"10.1073/pnas.2418766122","DOIUrl":"https://doi.org/10.1073/pnas.2418766122","url":null,"abstract":"Bacterial–fungal interaction (BFI) has significant implications for the health of host plants. While the diffusible antibiotic metabolite-mediated competition in BFI has been extensively characterized, the impact of intercellular contact remains largely elusive. Here, we demonstrate that the intercellular contact is a prevalent mode of interaction between beneficial soil bacteria and pathogenic filamentous fungi. By generating antibiotics-deficient mutants in two common soil bacteria, <jats:italic>Lysobacter enzymogenes</jats:italic> and <jats:italic>Pseudomonas fluorescens</jats:italic> , we show that antibiotics-independent BFI effectively inhibits pathogenic fungi. Furthermore, transcriptional and genetic evidence revealed that this antibiotics-independent BFI relies on intercellular contact mediated by the type VI secretion system (T6SS), which may facilitate the translocation of bacterial toxic effectors into fungal cells. Finally, by using a “conidia enrichment” platform, we found that T6SS-mediated fungal inhibition resulting from intercellular contact naturally occurs within the soil microbiome, particularly represented by <jats:italic>Pseudomonas fulva</jats:italic> . Overall, these results demonstrate that bacteria from the soil microbiome can protect host plants from fungal infection through antibiotics-independent intercellular contacts, thus revealing a naturally occurring and ecologically important mode of BFI in agricultural contexts.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"23 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Interferon regulatory factor 3 (IRF3) is the key transcription factor in the type I IFN signaling pathway, whose activation is regulated by multiple posttranslational modifications. Here, we identify SMYD3, a lysine methyltransferase, as a negative regulator of IRF3. SMYD3 interacts with IRF3 and catalyzes the dimethylation of IRF3 at lysine 39. This modification reduces IRF3 phosphorylation, dimerization, and subsequent nuclear translocation, leading to the inhibition of downstream type I interferon production. In addition, Smyd3 -deficient mice are more resistant to RNA and DNA viral infections. Zebrafish lacking smyd3 or treated with the inhibitor BCI121 are also more resistant to viral infection. Our findings reveal a role for SMYD3 in the regulation of antiviral innate immunity and provide insight into a specific modulation of IRF3 that affects its activation.
{"title":"Direct lysine dimethylation of IRF3 by the methyltransferase SMYD3 attenuates antiviral innate immunity","authors":"Zixuan Wang, Xiaoyun Chen, Chunchun Zhu, Sijia Fan, Jinhua Tang, Hongyan Deng, Xueyi Sun, Xing Liu, Wuhan Xiao","doi":"10.1073/pnas.2320644122","DOIUrl":"https://doi.org/10.1073/pnas.2320644122","url":null,"abstract":"Interferon regulatory factor 3 (IRF3) is the key transcription factor in the type I IFN signaling pathway, whose activation is regulated by multiple posttranslational modifications. Here, we identify SMYD3, a lysine methyltransferase, as a negative regulator of IRF3. SMYD3 interacts with IRF3 and catalyzes the dimethylation of IRF3 at lysine 39. This modification reduces IRF3 phosphorylation, dimerization, and subsequent nuclear translocation, leading to the inhibition of downstream type I interferon production. In addition, <jats:italic>Smyd3</jats:italic> -deficient mice are more resistant to RNA and DNA viral infections. Zebrafish lacking <jats:italic>smyd3</jats:italic> or treated with the inhibitor BCI121 are also more resistant to viral infection. Our findings reveal a role for <jats:italic>SMYD3</jats:italic> in the regulation of antiviral innate immunity and provide insight into a specific modulation of IRF3 that affects its activation.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"209 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rodrigo Telles, Arda Kotikian, Guillaume Freychet, Mikhail Zhernenkov, Patryk Wąsik, Benjamin M. Yavitt, Jorge-Luis Barrera, Caitlyn C. Cook, Ronald Pindak, Emily C. Davidson, Jennifer A. Lewis
Liquid crystal elastomers (LCEs) exhibit reversible shape morphing behavior when cycled above their nematic-to-isotropic transition temperature. During extrusion-based 3D printing, LCE inks are subjected to coupled shear and extensional flows that can be harnessed to spatially control the alignment of their nematic director along prescribed print paths. Here, we combine experiment and modeling to elucidate the effects of ink composition, nozzle geometry, and printing parameters on director alignment. From rheological measurements, we quantify the dimensionless Weissenberg number ( Wi ) for the flow field each ink experiences as a function of printing conditions and demonstrate that Wi is a strong predictor of LCE alignment. We find that director alignment in LCE filaments printed through a tapered nozzle varies radially when Wi < 1, while it is uniform when Wi ≫ 1. Based on COMSOL simulations and in operando X-ray measurements, we show that LCE inks printed through nozzles with an internal hyperbolic geometry exhibit a more uniform director alignment for a given Wi compared to those through tapered nozzles. Concomitantly, the stiffness along the print direction and actuation strain of printed LCEs increases substantially under such conditions. By varying Wi during printing through adjusting the flow rate “on the fly”, LCE architectures with uniform composition, yet locally encoded shape morphing transitions can be realized.
{"title":"Spatially programmed alignment and actuation in printed liquid crystal elastomers","authors":"Rodrigo Telles, Arda Kotikian, Guillaume Freychet, Mikhail Zhernenkov, Patryk Wąsik, Benjamin M. Yavitt, Jorge-Luis Barrera, Caitlyn C. Cook, Ronald Pindak, Emily C. Davidson, Jennifer A. Lewis","doi":"10.1073/pnas.2414960122","DOIUrl":"https://doi.org/10.1073/pnas.2414960122","url":null,"abstract":"Liquid crystal elastomers (LCEs) exhibit reversible shape morphing behavior when cycled above their nematic-to-isotropic transition temperature. During extrusion-based 3D printing, LCE inks are subjected to coupled shear and extensional flows that can be harnessed to spatially control the alignment of their nematic director along prescribed print paths. Here, we combine experiment and modeling to elucidate the effects of ink composition, nozzle geometry, and printing parameters on director alignment. From rheological measurements, we quantify the dimensionless Weissenberg number ( <jats:italic>Wi</jats:italic> ) for the flow field each ink experiences as a function of printing conditions and demonstrate that <jats:italic>Wi</jats:italic> is a strong predictor of LCE alignment. We find that director alignment in LCE filaments printed through a tapered nozzle varies radially when <jats:italic>Wi</jats:italic> < 1, while it is uniform when <jats:italic>Wi</jats:italic> ≫ 1. Based on COMSOL simulations and in operando X-ray measurements, we show that LCE inks printed through nozzles with an internal hyperbolic geometry exhibit a more uniform director alignment for a given <jats:italic>Wi</jats:italic> compared to those through tapered nozzles. Concomitantly, the stiffness along the print direction and actuation strain of printed LCEs increases substantially under such conditions. By varying <jats:italic>Wi</jats:italic> during printing through adjusting the flow rate “on the fly”, LCE architectures with uniform composition, yet locally encoded shape morphing transitions can be realized.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"119 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marco S. Messina, Laura Torrente, Aidan T. Pezacki, Hanna I. Humpel, Erin L. Li, Sophia G. Miller, Odette Verdejo-Torres, Teresita Padilla-Benavides, Donita C. Brady, David W. Killilea, Alison N. Killilea, Martina Ralle, Nathan P. Ward, Jun Ohata, Gina M. DeNicola, Christopher J. Chang
Copper is an essential nutrient for sustaining vital cellular processes spanning respiration, metabolism, and proliferation. However, loss of copper homeostasis, particularly misregulation of loosely bound copper ions which are defined as the labile copper pool, occurs in major diseases such as cancer, where tumor growth and metastasis have a heightened requirement for this metal. To help decipher the role of copper in the etiology of cancer, we report a histochemical activity-based sensing approach that enables systematic, high-throughput profiling of labile copper status across many cell lines in parallel. Coppermycin-1 reacts selectively with Cu(I) to release puromycin, which is then incorporated into nascent peptides during protein translation, thus leaving a permanent and dose-dependent marker for labile copper that can be visualized with standard immunofluorescence assays. We showcase the utility of this platform for screening labile Cu(I) pools across the National Cancer Institute’s 60 (NCI-60) human tumor cell line panel, identifying cell types with elevated basal levels of labile copper. Moreover, we use Coppermycin-1 to show that lung cancer cells with heightened activation of nuclear factor-erythroid 2-related factor 2 (NRF2) possess lower resting labile Cu(I) levels and, as a result, have reduced viability when treated with a copper chelator. This work establishes that methods for labile copper detection can be used to assess cuproplasia, an emerging form of copper-dependent cell growth and proliferation, providing a starting point for broader investigations into the roles of transition metal signaling in biology and medicine.
{"title":"A histochemical approach to activity-based copper sensing reveals cuproplasia-dependent vulnerabilities in cancer","authors":"Marco S. Messina, Laura Torrente, Aidan T. Pezacki, Hanna I. Humpel, Erin L. Li, Sophia G. Miller, Odette Verdejo-Torres, Teresita Padilla-Benavides, Donita C. Brady, David W. Killilea, Alison N. Killilea, Martina Ralle, Nathan P. Ward, Jun Ohata, Gina M. DeNicola, Christopher J. Chang","doi":"10.1073/pnas.2412816122","DOIUrl":"https://doi.org/10.1073/pnas.2412816122","url":null,"abstract":"Copper is an essential nutrient for sustaining vital cellular processes spanning respiration, metabolism, and proliferation. However, loss of copper homeostasis, particularly misregulation of loosely bound copper ions which are defined as the labile copper pool, occurs in major diseases such as cancer, where tumor growth and metastasis have a heightened requirement for this metal. To help decipher the role of copper in the etiology of cancer, we report a histochemical activity-based sensing approach that enables systematic, high-throughput profiling of labile copper status across many cell lines in parallel. Coppermycin-1 reacts selectively with Cu(I) to release puromycin, which is then incorporated into nascent peptides during protein translation, thus leaving a permanent and dose-dependent marker for labile copper that can be visualized with standard immunofluorescence assays. We showcase the utility of this platform for screening labile Cu(I) pools across the National Cancer Institute’s 60 (NCI-60) human tumor cell line panel, identifying cell types with elevated basal levels of labile copper. Moreover, we use Coppermycin-1 to show that lung cancer cells with heightened activation of nuclear factor-erythroid 2-related factor 2 (NRF2) possess lower resting labile Cu(I) levels and, as a result, have reduced viability when treated with a copper chelator. This work establishes that methods for labile copper detection can be used to assess cuproplasia, an emerging form of copper-dependent cell growth and proliferation, providing a starting point for broader investigations into the roles of transition metal signaling in biology and medicine.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"53 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fang-Yuan Chen, Wen-Chao Geng, Meng-Meng Chen, Rong Fu, Han Han, Zhan-Zhan Zhang, Wen-Bo Li, Yuan-Qiu Cheng, Juan-Juan Li, J. Fraser Stoddart, Kang Cai, Dong-Sheng Guo
On the one hand, nature utilizes hierarchical assemblies to create complex biological binding pockets, enabling ultrastrong recognition toward substrates in aqueous solutions. On the other hand, chemists have been fervently pursuing high-affinity recognition by constructing covalently well-preorganized stereoelectronic cavities. The potential of noncovalent assembly, however, for enhancing molecular recognition has long been underestimated. Inspired by (strept)avidin, an amphiphilic azocalix[4]arene derivative capable of assembly in aqueous solutions has been explored by us and demonstrated to exhibit ultrahigh binding affinity (up to 10 12 M −1 ), which is almost four orders of magnitude higher than those reported for nonassembled azocalix[4]arenes. An ultrastable azocalix[4]arene/photosensitizer complex has been applied in hypoxia-targeted photodynamic therapy for tumors. These findings highlight the immense potential of an assembly-enhanced recognition strategy in the development of the next generation of artificial receptors with appropriate functionalities and extraordinary recognition properties.
{"title":"Assembly-enhanced recognition: A biomimetic pathway to achieve ultrahigh affinities","authors":"Fang-Yuan Chen, Wen-Chao Geng, Meng-Meng Chen, Rong Fu, Han Han, Zhan-Zhan Zhang, Wen-Bo Li, Yuan-Qiu Cheng, Juan-Juan Li, J. Fraser Stoddart, Kang Cai, Dong-Sheng Guo","doi":"10.1073/pnas.2414253122","DOIUrl":"https://doi.org/10.1073/pnas.2414253122","url":null,"abstract":"On the one hand, nature utilizes hierarchical assemblies to create complex biological binding pockets, enabling ultrastrong recognition toward substrates in aqueous solutions. On the other hand, chemists have been fervently pursuing high-affinity recognition by constructing covalently well-preorganized stereoelectronic cavities. The potential of noncovalent assembly, however, for enhancing molecular recognition has long been underestimated. Inspired by (strept)avidin, an amphiphilic azocalix[4]arene derivative capable of assembly in aqueous solutions has been explored by us and demonstrated to exhibit ultrahigh binding affinity (up to 10 <jats:sup>12</jats:sup> M <jats:sup>−1</jats:sup> ), which is almost four orders of magnitude higher than those reported for nonassembled azocalix[4]arenes. An ultrastable azocalix[4]arene/photosensitizer complex has been applied in hypoxia-targeted photodynamic therapy for tumors. These findings highlight the immense potential of an assembly-enhanced recognition strategy in the development of the next generation of artificial receptors with appropriate functionalities and extraordinary recognition properties.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"31 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-14Epub Date: 2025-01-02DOI: 10.1073/pnas.2405086121
Lars Kaestner, Stephane Egée, Philippe Connes, Anna Yu Bogdanova, Michael J Simmonds
{"title":"Splenic filtration of red blood cells: Physics, chemistry, and biology need to go hand in hand.","authors":"Lars Kaestner, Stephane Egée, Philippe Connes, Anna Yu Bogdanova, Michael J Simmonds","doi":"10.1073/pnas.2405086121","DOIUrl":"https://doi.org/10.1073/pnas.2405086121","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 2","pages":"e2405086121"},"PeriodicalIF":9.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-14Epub Date: 2024-12-20DOI: 10.1073/pnas.2424805121
{"title":"Correction for Alboreggia et al., Targeted degradation of Pin1 by protein-destabilizing compounds.","authors":"","doi":"10.1073/pnas.2424805121","DOIUrl":"https://doi.org/10.1073/pnas.2424805121","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 2","pages":"e2424805121"},"PeriodicalIF":9.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-14Epub Date: 2025-01-02DOI: 10.1073/pnas.2411917121
Jeffrey W Lockhart, Agustín Fuentes, Gina Rippon, Lise Eliot
{"title":"Not so binary or generalizable: Brain sex differences with artificial neural networks.","authors":"Jeffrey W Lockhart, Agustín Fuentes, Gina Rippon, Lise Eliot","doi":"10.1073/pnas.2411917121","DOIUrl":"https://doi.org/10.1073/pnas.2411917121","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"122 2","pages":"e2411917121"},"PeriodicalIF":9.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annika Freudiger, Vladimir M. Jovanovic, Yilei Huang, Noah Snyder-Mackler, Donald F. Conrad, Brian Miller, Michael J. Montague, Hendrikje Westphal, Peter F. Stadler, Stefanie Bley, Julie E. Horvath, Lauren J. N. Brent, Michael L. Platt, Angelina Ruiz-Lambides, Jenny Tung, Katja Nowick, Harald Ringbauer, Anja Widdig
Biological relatedness is a key consideration in studies of behavior, population structure, and trait evolution. Except for parent–offspring dyads, pedigrees capture relatedness imperfectly. The number and length of identical-by-descent DNA segments (IBD) yield the most precise relatedness estimates. Here, we leverage different methods for estimating IBD segments from low-depth whole genome resequencing data to demonstrate the feasibility and value of resolving fine-scaled gradients of relatedness in free-living animals. Using primarily 4 to 6× depth data from a rhesus macaque ( Macaca mulatta ) population with long-term pedigree data, we show that we can infer the number and length of IBD segments across the genome with high accuracy even at 0.5× sequencing depth. In line with expectations based on simulation, the resulting estimates demonstrate substantial variation in genetic relatedness within kin classes, leading to overlapping distributions between kin classes. By comparing the IBD-based estimates with pedigree and short tandem repeat-based methods, we show that IBD estimates are more reliable and provide more detailed information on kinship. The inferred IBD segments also identify cryptic genetic relatives not represented in the pedigree and reveal elevated recombination rates in females relative to males, which enables the majority of close maternal and paternal kin to be distinguished with genotype data alone. Our findings represent a breakthrough in the ability to study the predictors and consequences of genetic relatedness in natural populations, contributing to our understanding of a fundamental component of population structure in the wild.
{"title":"Estimating realized relatedness in free-ranging macaques by inferring identity-by-descent segments","authors":"Annika Freudiger, Vladimir M. Jovanovic, Yilei Huang, Noah Snyder-Mackler, Donald F. Conrad, Brian Miller, Michael J. Montague, Hendrikje Westphal, Peter F. Stadler, Stefanie Bley, Julie E. Horvath, Lauren J. N. Brent, Michael L. Platt, Angelina Ruiz-Lambides, Jenny Tung, Katja Nowick, Harald Ringbauer, Anja Widdig","doi":"10.1073/pnas.2401106122","DOIUrl":"https://doi.org/10.1073/pnas.2401106122","url":null,"abstract":"Biological relatedness is a key consideration in studies of behavior, population structure, and trait evolution. Except for parent–offspring dyads, pedigrees capture relatedness imperfectly. The number and length of identical-by-descent DNA segments (IBD) yield the most precise relatedness estimates. Here, we leverage different methods for estimating IBD segments from low-depth whole genome resequencing data to demonstrate the feasibility and value of resolving fine-scaled gradients of relatedness in free-living animals. Using primarily 4 to 6× depth data from a rhesus macaque ( <jats:italic>Macaca mulatta</jats:italic> ) population with long-term pedigree data, we show that we can infer the number and length of IBD segments across the genome with high accuracy even at 0.5× sequencing depth. In line with expectations based on simulation, the resulting estimates demonstrate substantial variation in genetic relatedness within kin classes, leading to overlapping distributions between kin classes. By comparing the IBD-based estimates with pedigree and short tandem repeat-based methods, we show that IBD estimates are more reliable and provide more detailed information on kinship. The inferred IBD segments also identify cryptic genetic relatives not represented in the pedigree and reveal elevated recombination rates in females relative to males, which enables the majority of close maternal and paternal kin to be distinguished with genotype data alone. Our findings represent a breakthrough in the ability to study the predictors and consequences of genetic relatedness in natural populations, contributing to our understanding of a fundamental component of population structure in the wild.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"312 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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