Pub Date : 2024-07-16DOI: 10.1101/2024.07.15.603503
Kohei Ito, Yutaro Ito
Latilactobacillus sakei, a lactic acid bacterium in diverse environments such as fermented foods, meat, and the human gastrointestinal tract, exhibits significant genetic diversity and niche-specific adaptations. This study conducts a comprehensive comparative genomic analysis of 30 complete L. sakei genomes to uncover the genetic mechanisms underlying these adaptations. Phylogenetic analysis divided the species into three distinct clades that did not correlate with the source of isolation and did not suggest any niche-specific evolutionary direction. The pan-genome analysis revealed a substantial core genome alongside a diverse genetic repertoire, indicating both high genetic conservation and adaptability. Predicted growth rates based on codon use bias analysis suggest that L. sakei strains have an overall faster growth rate and may be able to efficiently dominant in competitive environments. Plasmid analysis revealed a variety of plasmids carrying genes essential for carbohydrate metabolism, enhancing L. sakei’s ability to thrive in various fermentation substrates. It was also found that the number of genes belonging to the GH1 family among sugar metabolism-related genes present on chromosomes and plasmids varies between strains, and that AA1, which is involved in alcohol oxidation, has been acquired from plasmids. BLAST analysis revealed that some strains have environmental adaptation gene clusters of cell surface polysaccharides that may mediate attachment to food and mucosa. These findings not only underscore the genetic and functional diversity of L. sakei but also highlight its potential as a potent starter culture in fermentation and as a probiotic. The knowledge gleaned from this study lays a solid foundation for future research aimed at harnessing the genetic traits of L. sakei strains for industrial and health-related applications.
{"title":"Comparative genomic analysis of Latilactobacillus sakei strains provides new insights into their association with different niche adaptations","authors":"Kohei Ito, Yutaro Ito","doi":"10.1101/2024.07.15.603503","DOIUrl":"https://doi.org/10.1101/2024.07.15.603503","url":null,"abstract":"Latilactobacillus sakei, a lactic acid bacterium in diverse environments such as fermented foods, meat, and the human gastrointestinal tract, exhibits significant genetic diversity and niche-specific adaptations. This study conducts a comprehensive comparative genomic analysis of 30 complete L. sakei genomes to uncover the genetic mechanisms underlying these adaptations. Phylogenetic analysis divided the species into three distinct clades that did not correlate with the source of isolation and did not suggest any niche-specific evolutionary direction. The pan-genome analysis revealed a substantial core genome alongside a diverse genetic repertoire, indicating both high genetic conservation and adaptability. Predicted growth rates based on codon use bias analysis suggest that L. sakei strains have an overall faster growth rate and may be able to efficiently dominant in competitive environments. Plasmid analysis revealed a variety of plasmids carrying genes essential for carbohydrate metabolism, enhancing L. sakei’s ability to thrive in various fermentation substrates. It was also found that the number of genes belonging to the GH1 family among sugar metabolism-related genes present on chromosomes and plasmids varies between strains, and that AA1, which is involved in alcohol oxidation, has been acquired from plasmids. BLAST analysis revealed that some strains have environmental adaptation gene clusters of cell surface polysaccharides that may mediate attachment to food and mucosa. These findings not only underscore the genetic and functional diversity of L. sakei but also highlight its potential as a potent starter culture in fermentation and as a probiotic. The knowledge gleaned from this study lays a solid foundation for future research aimed at harnessing the genetic traits of L. sakei strains for industrial and health-related applications.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"5 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.11.603062
Yan Zhao, Hanshuo Zhu, Jinqian Li, Li Sun
Type III secretion system (T3SS) is a virulence apparatus existing in many bacterial pathogens. Structurally, T3SS consists of the base, needle, tip, and translocon. The NLRC4 inflammasome is the major receptor for T3SS needle and basal rod proteins. Whether other T3SS components are recognized by NLRC4 is unclear. In this study, using Edwardsiella tarda as a model intracellular pathogen, we examined T3SS−inflammasome interaction and its effect on cell death. E. tarda induced pyroptosis in a manner that required the bacterial translocon and the host inflammasome proteins of NLRC4, NLRP3, ASC, and caspase 1/4. The translocon protein EseB triggered NLRC4/NAIP-mediated pyroptosis by binding NAIP via its C-terminal region, particularly the terminal 6 residues (T6R). EseB homologs exist widely in T3SS-positive bacteria and share high identities in T6R. Like E. tarda EseB, all of the representatives of the EseB homologs exhibited T6R-dependent NLRC4 activation ability. Together these results revealed the function and molecular mechanism of EseB to induce host cell pyroptosis and suggested a highly conserved inflammasome-activation mechanism of T3SS translocon in bacterial pathogens.
{"title":"T3SS translocon induces pyroptosis by direct interaction with NLRC4/NAIP inflammasome","authors":"Yan Zhao, Hanshuo Zhu, Jinqian Li, Li Sun","doi":"10.1101/2024.07.11.603062","DOIUrl":"https://doi.org/10.1101/2024.07.11.603062","url":null,"abstract":"Type III secretion system (T3SS) is a virulence apparatus existing in many bacterial pathogens. Structurally, T3SS consists of the base, needle, tip, and translocon. The NLRC4 inflammasome is the major receptor for T3SS needle and basal rod proteins. Whether other T3SS components are recognized by NLRC4 is unclear. In this study, using Edwardsiella tarda as a model intracellular pathogen, we examined T3SS−inflammasome interaction and its effect on cell death. E. tarda induced pyroptosis in a manner that required the bacterial translocon and the host inflammasome proteins of NLRC4, NLRP3, ASC, and caspase 1/4. The translocon protein EseB triggered NLRC4/NAIP-mediated pyroptosis by binding NAIP via its C-terminal region, particularly the terminal 6 residues (T6R). EseB homologs exist widely in T3SS-positive bacteria and share high identities in T6R. Like E. tarda EseB, all of the representatives of the EseB homologs exhibited T6R-dependent NLRC4 activation ability. Together these results revealed the function and molecular mechanism of EseB to induce host cell pyroptosis and suggested a highly conserved inflammasome-activation mechanism of T3SS translocon in bacterial pathogens.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"21 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.10.602558
Art Riddle, Taasin Srivastava, Kang Wang, Eduardo Tellez, Hanna O’Neill, Xi Gong, Abigail O'Niel, Jaden A Bell, Jacob Raber, Matthew Lattal, James Maylie, Stephen A. Back
Objective Although nearly half of preterm survivors display persistent neurobehavioral dysfunction including memory impairment without overt gray matter injury, the underlying mechanisms of neuronal or glial dysfunction, and their relationship to commonly observed cerebral white matter injury are unclear. We developed a mouse model to test the hypothesis that mild hypoxia during preterm equivalence is sufficient to persistently disrupt hippocampal neuronal maturation related to adult cellular mechanisms of learning and memory. Methods: Neonatal (P2) mice were exposed to mild hypoxia (8%O2) for 30 min and evaluated for acute injury responses or survived until adulthood for assessment of learning and memory and hippocampal neurodevelopment. Results Neonatal mild hypoxia resulted in clinically relevant oxygen desaturation and tachycardia without bradycardia and was not accompanied by cerebral gray or white matter injury. Neonatal hypoxia exposure was sufficient to cause hippocampal learning and memory deficits and abnormal maturation of CA1 neurons that persisted into adulthood. This was accompanied by reduced hippocampal CA3-CA1 synaptic strength and LTP and reduced synaptic activity of calcium-sensitive SK2 channels, key regulators of spike timing dependent neuroplasticity, including LTP. Structural illumination microscopy revealed reduced synaptic density, but intact SK2 localization at the synapse. Persistent loss of SK2 activity was mediated by altered casein kinase 2 (CK2) signaling. Interpretation Clinically relevant mild hypoxic exposure in the neonatal mouse is sufficient to produce morphometric and functional disturbances in hippocampal neuronal maturation independently of white matter injury. Additionally, we describe a novel persistent mechanism of potassium channel dysregulation after neonatal hypoxia. Collectively our findings suggest an unexplored explanation for the broad spectrum of neurobehavioral, cognitive and learning disabilities that paradoxically persist into adulthood without overt gray matter injury after preterm birth.
{"title":"Mild neonatal hypoxia disrupts adult hippocampal learning and memory and is associated with CK2-mediated dysregulation of synaptic calcium-activated potassium channel KCNN2","authors":"Art Riddle, Taasin Srivastava, Kang Wang, Eduardo Tellez, Hanna O’Neill, Xi Gong, Abigail O'Niel, Jaden A Bell, Jacob Raber, Matthew Lattal, James Maylie, Stephen A. Back","doi":"10.1101/2024.07.10.602558","DOIUrl":"https://doi.org/10.1101/2024.07.10.602558","url":null,"abstract":"Objective Although nearly half of preterm survivors display persistent neurobehavioral dysfunction including memory impairment without overt gray matter injury, the underlying mechanisms of neuronal or glial dysfunction, and their relationship to commonly observed cerebral white matter injury are unclear. We developed a mouse model to test the hypothesis that mild hypoxia during preterm equivalence is sufficient to persistently disrupt hippocampal neuronal maturation related to adult cellular mechanisms of learning and memory. Methods: Neonatal (P2) mice were exposed to mild hypoxia (8%O2) for 30 min and evaluated for acute injury responses or survived until adulthood for assessment of learning and memory and hippocampal neurodevelopment. Results Neonatal mild hypoxia resulted in clinically relevant oxygen desaturation and tachycardia without bradycardia and was not accompanied by cerebral gray or white matter injury. Neonatal hypoxia exposure was sufficient to cause hippocampal learning and memory deficits and abnormal maturation of CA1 neurons that persisted into adulthood. This was accompanied by reduced hippocampal CA3-CA1 synaptic strength and LTP and reduced synaptic activity of calcium-sensitive SK2 channels, key regulators of spike timing dependent neuroplasticity, including LTP. Structural illumination microscopy revealed reduced synaptic density, but intact SK2 localization at the synapse. Persistent loss of SK2 activity was mediated by altered casein kinase 2 (CK2) signaling. Interpretation Clinically relevant mild hypoxic exposure in the neonatal mouse is sufficient to produce morphometric and functional disturbances in hippocampal neuronal maturation independently of white matter injury. Additionally, we describe a novel persistent mechanism of potassium channel dysregulation after neonatal hypoxia. Collectively our findings suggest an unexplored explanation for the broad spectrum of neurobehavioral, cognitive and learning disabilities that paradoxically persist into adulthood without overt gray matter injury after preterm birth.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"91 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.11.603013
Noam Saadon-Grosman, Tsahi Asher, Y. Loewenstein
It is well-known that cortical areas specializing in the processing of somatosensory information from different parts of the body are arranged in an orderly manner along the cortex. It is also generally accepted that in the cortex, somatosensory information is initially processed in the primary somatosensory cortex and from there, it is hierarchically processed in other cortical regions. Previous studies have focused on the organization of representation at a level of a single or few cortical regions, identifying multiple body maps. However, the question of the large-scale organization of these different maps, and their relation to the hierarchical organization has received little attention. This is primarily because the highly convoluted shape of the cortical surface makes it difficult to characterize the relationship between cortical areas that are centimeters apart. Here, we used functional MRI to characterize cortical responses to full-body light touch stimulation. Our results indicate that the organization of both body representation and hierarchy is radial, with a small number of extrema that reign over a large number of cortical regions. Quantitatively computing the local relationship between the gradients of body and hierarchy maps, we show that the interaction between these two radial geometries, body representation and hierarchy in S1 are approximately orthogonal. However, this orthogonality is restricted to S1. Similar organizational patterns in the visual and auditory systems suggest that radial topography may be a common feature across sensory systems. Significance statement The sensation of touch on our skin is represented in the brain as a map, where body parts are organized sequentially from head to toe. In the cerebral cortex, multiple body maps are distributed across numerous regions, processing signals at different hierarchical levels. Is there a large-scale organization of these body maps in the cerebral cortex? We show that all previously known body maps and their hierarchies are organized with a radial geometry. Similar radial geometry may also characterize the visual and auditory systems, indicating that radial geometry is a common organizational principle of sensory processing in the cortex.
{"title":"On the Geometry of Somatosensory Representations in the Cortex","authors":"Noam Saadon-Grosman, Tsahi Asher, Y. Loewenstein","doi":"10.1101/2024.07.11.603013","DOIUrl":"https://doi.org/10.1101/2024.07.11.603013","url":null,"abstract":"It is well-known that cortical areas specializing in the processing of somatosensory information from different parts of the body are arranged in an orderly manner along the cortex. It is also generally accepted that in the cortex, somatosensory information is initially processed in the primary somatosensory cortex and from there, it is hierarchically processed in other cortical regions. Previous studies have focused on the organization of representation at a level of a single or few cortical regions, identifying multiple body maps. However, the question of the large-scale organization of these different maps, and their relation to the hierarchical organization has received little attention. This is primarily because the highly convoluted shape of the cortical surface makes it difficult to characterize the relationship between cortical areas that are centimeters apart. Here, we used functional MRI to characterize cortical responses to full-body light touch stimulation. Our results indicate that the organization of both body representation and hierarchy is radial, with a small number of extrema that reign over a large number of cortical regions. Quantitatively computing the local relationship between the gradients of body and hierarchy maps, we show that the interaction between these two radial geometries, body representation and hierarchy in S1 are approximately orthogonal. However, this orthogonality is restricted to S1. Similar organizational patterns in the visual and auditory systems suggest that radial topography may be a common feature across sensory systems. Significance statement The sensation of touch on our skin is represented in the brain as a map, where body parts are organized sequentially from head to toe. In the cerebral cortex, multiple body maps are distributed across numerous regions, processing signals at different hierarchical levels. Is there a large-scale organization of these body maps in the cerebral cortex? We show that all previously known body maps and their hierarchies are organized with a radial geometry. Similar radial geometry may also characterize the visual and auditory systems, indicating that radial geometry is a common organizational principle of sensory processing in the cortex.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"87 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.12.603135
A. García Jiménez, T. Gaboriau, L. M. Fitzgerald, Sara Heim, A. Marcionetti, S. Schmid, Joris A. M. Bertrand, G. Litsios, Abigail Shaughnessy, Carl Santiago, Ploypallin Rangseethampanya, Phurinat Ruttanachuchote, Wiphawan Aunkhongthong, Sittiporn Pengsakun, M. Sutthacheep, B. Frédérich, Fabio Cortesi, Thamasak Yemin, N. Salamin
Fluctuating sea levels during the Pleistocene led to habitat loss and fragmentation, impacting the evolutionary trajectories of reef fishes. Species with specialized ecological requirements or habitat preferences, like clownfishes (Amphiprioninae), may have been particularly vulnerable due to their intricate dependence on sea anemones. The diverse host specializations within this group likely contributed distinct responses to sea-level fluctuations, differentially shaping their recent evolutionary histories. Leveraging a comprehensive genomic dataset, we reveal demographic patterns and connectivity dynamics across multiple populations of ten clownfish species under different host specializations. Host-generalist species demonstrated strong resilience to habitat perturbations, while those specialized on single hosts suffered dramatic bottlenecks linked to sea-level fluctuations. Spatial analyses revealed the significant role of oceanic currents in shaping clownfish genetic diversity landscapes. Dispersal barriers were driven by environmental variables, with the Coral Triangle emerging as a hub of genetic diversity. Our results reveal how clownfish associative behavior influences their population dynamics, holding major implications for their conservation such as the need to consider their mutualism with sea anemones, particularly on host-specialists, to ensure their survival in the face of climate threats. These findings extend broader principles of conservation, improving our understanding of species’ responses to ecological constraints and environmental changes over evolutionary timescales.
{"title":"Specialization into Host Sea Anemones Impacted Clownfish Demographic Responses to Pleistocene Sea Level Changes","authors":"A. García Jiménez, T. Gaboriau, L. M. Fitzgerald, Sara Heim, A. Marcionetti, S. Schmid, Joris A. M. Bertrand, G. Litsios, Abigail Shaughnessy, Carl Santiago, Ploypallin Rangseethampanya, Phurinat Ruttanachuchote, Wiphawan Aunkhongthong, Sittiporn Pengsakun, M. Sutthacheep, B. Frédérich, Fabio Cortesi, Thamasak Yemin, N. Salamin","doi":"10.1101/2024.07.12.603135","DOIUrl":"https://doi.org/10.1101/2024.07.12.603135","url":null,"abstract":"Fluctuating sea levels during the Pleistocene led to habitat loss and fragmentation, impacting the evolutionary trajectories of reef fishes. Species with specialized ecological requirements or habitat preferences, like clownfishes (Amphiprioninae), may have been particularly vulnerable due to their intricate dependence on sea anemones. The diverse host specializations within this group likely contributed distinct responses to sea-level fluctuations, differentially shaping their recent evolutionary histories. Leveraging a comprehensive genomic dataset, we reveal demographic patterns and connectivity dynamics across multiple populations of ten clownfish species under different host specializations. Host-generalist species demonstrated strong resilience to habitat perturbations, while those specialized on single hosts suffered dramatic bottlenecks linked to sea-level fluctuations. Spatial analyses revealed the significant role of oceanic currents in shaping clownfish genetic diversity landscapes. Dispersal barriers were driven by environmental variables, with the Coral Triangle emerging as a hub of genetic diversity. Our results reveal how clownfish associative behavior influences their population dynamics, holding major implications for their conservation such as the need to consider their mutualism with sea anemones, particularly on host-specialists, to ensure their survival in the face of climate threats. These findings extend broader principles of conservation, improving our understanding of species’ responses to ecological constraints and environmental changes over evolutionary timescales.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"25 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.15.603602
Anusha D. Bhatt, Madeleine G. Brown, Aurora B. Wackford, Yuki Shindo, Amanda A. Amodeo
Early embryos often have relatively unstructured chromatin that lacks active and inactive domains typical of differentiated cells. In many species, these regulatory domains are established during zygotic genome activation (ZGA). In Drosophila, ZGA occurs after 13 fast, reductive, syncytial nuclear divisions during which the nuclear to cytoplasmic (N/C) ratio grows exponentially. These divisions incorporate maternally-loaded, cytoplasmic pools of histones into chromatin. Previous work found that chromatin incorporation of replication-coupled histone H3 decreases while its variant H3.3 increases in the cell cycles leading up to ZGA. In other cell types, H3.3 is associated with sites of active transcription as well as heterochromatin, suggesting a link between H3.3 incorporation and ZGA. Here, we examine the factors that contribute to H3.3 incorporation at ZGA. We identify a more rapid decrease in the nuclear availability of H3 than H3.3 over the final pre-ZGA cycles. We also observe an N/C ratio-dependent increase in H3.3 incorporation in mutant embryos with non-uniform local N/C ratios. We find that chaperone binding, not gene expression, controls incorporation patterns using H3/H3.3 chimeric proteins at the endogenous H3.3A locus. We test the specificity of the H3.3 chaperone pathways for H3.3 incorporation using Hira (H3.3 chaperone) mutant embryos. Overall, we propose a model in which local N/C ratios and specific chaperone binding regulate differential incorporation of H3.3 during ZGA. Graphical abstract
{"title":"Local nuclear to cytoplasmic ratio regulates chaperone-dependent H3 variant incorporation during zygotic genome activation","authors":"Anusha D. Bhatt, Madeleine G. Brown, Aurora B. Wackford, Yuki Shindo, Amanda A. Amodeo","doi":"10.1101/2024.07.15.603602","DOIUrl":"https://doi.org/10.1101/2024.07.15.603602","url":null,"abstract":"Early embryos often have relatively unstructured chromatin that lacks active and inactive domains typical of differentiated cells. In many species, these regulatory domains are established during zygotic genome activation (ZGA). In Drosophila, ZGA occurs after 13 fast, reductive, syncytial nuclear divisions during which the nuclear to cytoplasmic (N/C) ratio grows exponentially. These divisions incorporate maternally-loaded, cytoplasmic pools of histones into chromatin. Previous work found that chromatin incorporation of replication-coupled histone H3 decreases while its variant H3.3 increases in the cell cycles leading up to ZGA. In other cell types, H3.3 is associated with sites of active transcription as well as heterochromatin, suggesting a link between H3.3 incorporation and ZGA. Here, we examine the factors that contribute to H3.3 incorporation at ZGA. We identify a more rapid decrease in the nuclear availability of H3 than H3.3 over the final pre-ZGA cycles. We also observe an N/C ratio-dependent increase in H3.3 incorporation in mutant embryos with non-uniform local N/C ratios. We find that chaperone binding, not gene expression, controls incorporation patterns using H3/H3.3 chimeric proteins at the endogenous H3.3A locus. We test the specificity of the H3.3 chaperone pathways for H3.3 incorporation using Hira (H3.3 chaperone) mutant embryos. Overall, we propose a model in which local N/C ratios and specific chaperone binding regulate differential incorporation of H3.3 during ZGA. Graphical abstract","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"5 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.11.603064
Anna Rudnitsky, Hanna Oh, Joanathan Talmor, Ranit Kedmi
To efficiently absorb nutrients and facilitate microbial commensalism, the host establishes tolerogenic immune programs against dietary and commensal antigens, promoted by peripheral regulatory T cells (pTregs)1,2. Previous research into which antigen-presenting cells (APCs) initiate dietary pTreg responses focused on type 1 DCs (cDC1)3. However, we now report that food-specific pTreg cells are exclusively induced by the recently identified RORγt+ APCs4–8, and not by cDC1. Instead, pTregs interact with cDC1 to regulate the response of food-specific CD8αβ T cells that accumulate in the lamina propria (LP) and epithelial layer of the small intestine (SI) and express memory markers. Upon infection with pathogens that mimic dietary antigens, food-specific CD8αβ cells activate an effector program to potentially guard against ‘Trojan horse’ attacks. Uniquely, after the infection resolves, these cells do not respond to their corresponding dietary antigens, allowing for safe food consumption. Based on our findings, we propose that in response to dietary antigens, dedicated antigen-presenting cells direct a unique CD8αβ response that is coupled to the pTreg program to facilitate protective acute effector responses within the overall strategy of tolerance.
{"title":"Coordinated network of T cells and antigen presenting cells regulate tolerance to food","authors":"Anna Rudnitsky, Hanna Oh, Joanathan Talmor, Ranit Kedmi","doi":"10.1101/2024.07.11.603064","DOIUrl":"https://doi.org/10.1101/2024.07.11.603064","url":null,"abstract":"To efficiently absorb nutrients and facilitate microbial commensalism, the host establishes tolerogenic immune programs against dietary and commensal antigens, promoted by peripheral regulatory T cells (pTregs)1,2. Previous research into which antigen-presenting cells (APCs) initiate dietary pTreg responses focused on type 1 DCs (cDC1)3. However, we now report that food-specific pTreg cells are exclusively induced by the recently identified RORγt+ APCs4–8, and not by cDC1. Instead, pTregs interact with cDC1 to regulate the response of food-specific CD8αβ T cells that accumulate in the lamina propria (LP) and epithelial layer of the small intestine (SI) and express memory markers. Upon infection with pathogens that mimic dietary antigens, food-specific CD8αβ cells activate an effector program to potentially guard against ‘Trojan horse’ attacks. Uniquely, after the infection resolves, these cells do not respond to their corresponding dietary antigens, allowing for safe food consumption. Based on our findings, we propose that in response to dietary antigens, dedicated antigen-presenting cells direct a unique CD8αβ response that is coupled to the pTreg program to facilitate protective acute effector responses within the overall strategy of tolerance.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"12 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.16.603680
Spiros Palikyras, Vassiliki Varamogiani-Mamatsi, Yajie Zhu, Shyam Ramasamy, Athanasia Mizi, Isabel Liebermann, Athanasia Stavropoulou, Ioanna Papadionysiou, Deniz Bartsch, Yulia Kargapolova, K. Sofiadis, Christoforos Nikolaou, Leo Kurian, A. M. Oudelaar, Mariano Barbieri, A. Papantonis
Senescence —the endpoint of replicative lifespan for normal cells— is established via a complex sequence of molecular events. One such event is the dramatic reorganization of CTCF into senescence-induced clusters (SICCs). However, the molecular determinants, genomic consequences, and functional purpose of SICCs remained unknown. Here, we combine functional assays, super-resolution imaging, and 3D genomics with computational modelling to dissect SICC emergence. We establish that the competition between CTCF-bound and non-bound loci dictates clustering propensity. Upon senescence entry, cells repurpose SRRM2 —a key component of nuclear speckles— and BANF1 —a ‘molecular glue’ for chromosomes— to cluster CTCF and rewire genome architecture. This CTCF-centric reorganization in reference to nuclear speckles functionally sustains the senescence splicing program, as SICC disruption fully reverts alternative splicing patterns. We therefore uncover a new paradigm, whereby cells translate changes in nuclear biochemistry into architectural changes directing splicing choices so as to commit to the fate of senescence. GRAPHICAL ABSTRACT HIGHLIGHTS HMGB2-bound loci compete with CTCF-bound ones for nuclear speckle association Senescent cells repurpose SRRM2 and BANF1 to cluster CTCF on speckles BANF1 is essential, but not sufficient for CTCF clustering The SRRM2 RNA-binding domain directs CTCF clustering SICCs rewire chromatin positioning to sustain the senescence splicing program
{"title":"Senescent cells cluster CTCF on nuclear speckles to sustain their splicing program","authors":"Spiros Palikyras, Vassiliki Varamogiani-Mamatsi, Yajie Zhu, Shyam Ramasamy, Athanasia Mizi, Isabel Liebermann, Athanasia Stavropoulou, Ioanna Papadionysiou, Deniz Bartsch, Yulia Kargapolova, K. Sofiadis, Christoforos Nikolaou, Leo Kurian, A. M. Oudelaar, Mariano Barbieri, A. Papantonis","doi":"10.1101/2024.07.16.603680","DOIUrl":"https://doi.org/10.1101/2024.07.16.603680","url":null,"abstract":"Senescence —the endpoint of replicative lifespan for normal cells— is established via a complex sequence of molecular events. One such event is the dramatic reorganization of CTCF into senescence-induced clusters (SICCs). However, the molecular determinants, genomic consequences, and functional purpose of SICCs remained unknown. Here, we combine functional assays, super-resolution imaging, and 3D genomics with computational modelling to dissect SICC emergence. We establish that the competition between CTCF-bound and non-bound loci dictates clustering propensity. Upon senescence entry, cells repurpose SRRM2 —a key component of nuclear speckles— and BANF1 —a ‘molecular glue’ for chromosomes— to cluster CTCF and rewire genome architecture. This CTCF-centric reorganization in reference to nuclear speckles functionally sustains the senescence splicing program, as SICC disruption fully reverts alternative splicing patterns. We therefore uncover a new paradigm, whereby cells translate changes in nuclear biochemistry into architectural changes directing splicing choices so as to commit to the fate of senescence. GRAPHICAL ABSTRACT HIGHLIGHTS HMGB2-bound loci compete with CTCF-bound ones for nuclear speckle association Senescent cells repurpose SRRM2 and BANF1 to cluster CTCF on speckles BANF1 is essential, but not sufficient for CTCF clustering The SRRM2 RNA-binding domain directs CTCF clustering SICCs rewire chromatin positioning to sustain the senescence splicing program","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"9 47","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141640412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.12.603213
Evelin Iseli, Nathan Diaz Zeugin, Camille Brioschi, Jake M. Alexander, J. Lenoir
Global warming is pushing species to shift their ranges towards higher latitudes and elevations, causing a reassembly of plant communities potentially accompanied by community thermophilization (i.e., an increasing number or cover of thermophilic species, sometimes at the expense of mesic or cold-adapted species). Given the large variation typically observed in the magnitude and direction of range shifts, quantifying community thermophilization might provide a sensitive method to detect range shifts within short time periods and across limited spatial extents. Assessing changes in plant community composition as a whole might integrate early signs of range shifts across co-occurring species while accounting for changes in both occurrence and abundance. Here, we combine an assessment of (i) species-level range shifts, (ii) changes in species richness and (iii) changes in community-inferred temperatures along three mountain roads in Switzerland to ask whether plant communities have responded to warming climate over a 10 year period, and whether community thermophilization is an appropriate metric for early detection of these changes. We found a community thermophilization signal of +0.13°C over the 10-year study period based on presence-absence data only. Despite significant upward shifts of species’ upper range limits in the lower part of the studied elevational gradient and a decrease in species richness at high elevations, significant thermophilization was not detectable if community- inferred temperatures were weighted by species’ covers. Low cover values of species that were gained or lost over the study period and their similar species-specific temperatures to resident species explained the discrepancy between the thermophilization detected in either cover-weighted or unweighted models. Synthesis. Our work shows that plant species are shifting to higher elevations along roadsides in the western Swiss Alps and that this translates into a detectable warming signal of plant communities within 10 years. However, the species-level range shifts and the community-level warming effect are mostly based on low cover values of gained/lost species, preventing the detection of community thermophilization signals when incorporating cover changes. We therefore recommend using unweighted approaches for early detection of community-level responses to changing climate, ideally set into context by also assessing species-level range shifts.
{"title":"Early signs of plant community responses to climate warming along mountain roads in Switzerland","authors":"Evelin Iseli, Nathan Diaz Zeugin, Camille Brioschi, Jake M. Alexander, J. Lenoir","doi":"10.1101/2024.07.12.603213","DOIUrl":"https://doi.org/10.1101/2024.07.12.603213","url":null,"abstract":"Global warming is pushing species to shift their ranges towards higher latitudes and elevations, causing a reassembly of plant communities potentially accompanied by community thermophilization (i.e., an increasing number or cover of thermophilic species, sometimes at the expense of mesic or cold-adapted species). Given the large variation typically observed in the magnitude and direction of range shifts, quantifying community thermophilization might provide a sensitive method to detect range shifts within short time periods and across limited spatial extents. Assessing changes in plant community composition as a whole might integrate early signs of range shifts across co-occurring species while accounting for changes in both occurrence and abundance. Here, we combine an assessment of (i) species-level range shifts, (ii) changes in species richness and (iii) changes in community-inferred temperatures along three mountain roads in Switzerland to ask whether plant communities have responded to warming climate over a 10 year period, and whether community thermophilization is an appropriate metric for early detection of these changes. We found a community thermophilization signal of +0.13°C over the 10-year study period based on presence-absence data only. Despite significant upward shifts of species’ upper range limits in the lower part of the studied elevational gradient and a decrease in species richness at high elevations, significant thermophilization was not detectable if community- inferred temperatures were weighted by species’ covers. Low cover values of species that were gained or lost over the study period and their similar species-specific temperatures to resident species explained the discrepancy between the thermophilization detected in either cover-weighted or unweighted models. Synthesis. Our work shows that plant species are shifting to higher elevations along roadsides in the western Swiss Alps and that this translates into a detectable warming signal of plant communities within 10 years. However, the species-level range shifts and the community-level warming effect are mostly based on low cover values of gained/lost species, preventing the detection of community thermophilization signals when incorporating cover changes. We therefore recommend using unweighted approaches for early detection of community-level responses to changing climate, ideally set into context by also assessing species-level range shifts.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"10 38","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141640463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.10.602938
Rachel A. Tinkey, Brandon C. Smith, Maria L. Habean, Jessica L. Williams
Astrocytic interferon (IFN)γ signaling is associated with a reduction in neuroinflammation. We have previously shown that the benefits of astrocytic IFNγ arise from a variety of mechanisms; however, downstream effectors responsible for regulating this protection are unknown. We address this by identifying a specific transcription factor that may play a key role in modulating the consequences of IFNγ signaling. RNA-sequencing of primary human astrocytes treated with IFNγ revealed basic leucine zipper ATF-like transcription factor (BATF)2 as a highly expressed interferon-specific gene. Primarily studied in the periphery, BATF2 has been shown to exert both inflammatory and protective functions; however, its function in the central nervous system (CNS) is unknown. Here, we demonstrate that human spinal cord astrocytes upregulate BATF2 transcript and protein in an IFNγ-specific manner. Additionally, we found that BATF2 prevents overexpression of interferon regulatory factor (IRF)1 and IRF1 targets such as Caspase-1, which are known downstream pro-inflammatory mediators. We also show that Batf2−/− mice exhibit exacerbated clinical disease severity in a murine model of CNS autoimmunity, characterized by an increase in both CNS immune cell infiltration and demyelination. Batf2−/− mice also exhibit increased astrocyte-specific expression of IRF1 and Caspase-1, suggesting an amplified interferon response in vivo. Further, we demonstrate that BATF2 is expressed primarily in astrocytes in MS lesions and that this expression is co-localized with IRF1. Collectively, our results further support a protective role for IFNγ and implicate BATF2 as a key suppressor of overactive immune signaling in astrocytes during neuroinflammation.
{"title":"BATF2 is a regulator of interferon-γ signaling in astrocytes during neuroinflammation","authors":"Rachel A. Tinkey, Brandon C. Smith, Maria L. Habean, Jessica L. Williams","doi":"10.1101/2024.07.10.602938","DOIUrl":"https://doi.org/10.1101/2024.07.10.602938","url":null,"abstract":"Astrocytic interferon (IFN)γ signaling is associated with a reduction in neuroinflammation. We have previously shown that the benefits of astrocytic IFNγ arise from a variety of mechanisms; however, downstream effectors responsible for regulating this protection are unknown. We address this by identifying a specific transcription factor that may play a key role in modulating the consequences of IFNγ signaling. RNA-sequencing of primary human astrocytes treated with IFNγ revealed basic leucine zipper ATF-like transcription factor (BATF)2 as a highly expressed interferon-specific gene. Primarily studied in the periphery, BATF2 has been shown to exert both inflammatory and protective functions; however, its function in the central nervous system (CNS) is unknown. Here, we demonstrate that human spinal cord astrocytes upregulate BATF2 transcript and protein in an IFNγ-specific manner. Additionally, we found that BATF2 prevents overexpression of interferon regulatory factor (IRF)1 and IRF1 targets such as Caspase-1, which are known downstream pro-inflammatory mediators. We also show that Batf2−/− mice exhibit exacerbated clinical disease severity in a murine model of CNS autoimmunity, characterized by an increase in both CNS immune cell infiltration and demyelination. Batf2−/− mice also exhibit increased astrocyte-specific expression of IRF1 and Caspase-1, suggesting an amplified interferon response in vivo. Further, we demonstrate that BATF2 is expressed primarily in astrocytes in MS lesions and that this expression is co-localized with IRF1. Collectively, our results further support a protective role for IFNγ and implicate BATF2 as a key suppressor of overactive immune signaling in astrocytes during neuroinflammation.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"1 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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