Pub Date : 2024-10-30DOI: 10.1038/s42003-024-07117-1
Chuankai Zhang, Qi Wu, Hongwei Yang, Hui Zhang, Changqing Liu, Bo Yang, Qingsong Hu
Epidermal growth factor receptor wild type lung adenocarcinoma (EGFRWT LUAD) still has limited treatment options and unsatisfactory clinical outcomes. Ferroptosis, as a form of cell death, has been reported to play a dual role in regulating tumor cell survival. In this study, we constructed a 3-ferroptosis-gene signature, FeSig, and verified its accuracy and efficacy in predicting EGFRWT LUAD prognosis at both the RNA and protein levels. Patients with higher FeSig scores were found to have worse clinical outcomes. Additionally, we explored the relationship between FeSig and tumor microenvironment, revealing that enhanced interactions between fibroblasts and tumor cells in FeSighigh patients causing tumor resistance to ferroptosis. To address this challenge, we screened potential drugs from NCI-60 (The US National Cancer Institute 60 human tumour cell line anticancer drug screen) and Connectivity map database, ultimately identifying 6-mercatopurine (6-MP) as a promising candidate. Both in vitro and in vivo experiments demonstrated its efficacy in treating FeSighigh EGFRWT LUAD tumor models. In summary, we develop a novel FeSig for predicting prognosis and guiding drug application. A ferroptosis signature predicts clinical prognosis and identifies 6-Mercaptopurine as a promising drug for patients with EGFR wild type lung adenocarcinoma.
{"title":"Ferroptosis-related gene signature for predicting prognosis and identifying potential therapeutic drug in EGFR wild-type lung adenocarcinoma","authors":"Chuankai Zhang, Qi Wu, Hongwei Yang, Hui Zhang, Changqing Liu, Bo Yang, Qingsong Hu","doi":"10.1038/s42003-024-07117-1","DOIUrl":"10.1038/s42003-024-07117-1","url":null,"abstract":"Epidermal growth factor receptor wild type lung adenocarcinoma (EGFRWT LUAD) still has limited treatment options and unsatisfactory clinical outcomes. Ferroptosis, as a form of cell death, has been reported to play a dual role in regulating tumor cell survival. In this study, we constructed a 3-ferroptosis-gene signature, FeSig, and verified its accuracy and efficacy in predicting EGFRWT LUAD prognosis at both the RNA and protein levels. Patients with higher FeSig scores were found to have worse clinical outcomes. Additionally, we explored the relationship between FeSig and tumor microenvironment, revealing that enhanced interactions between fibroblasts and tumor cells in FeSighigh patients causing tumor resistance to ferroptosis. To address this challenge, we screened potential drugs from NCI-60 (The US National Cancer Institute 60 human tumour cell line anticancer drug screen) and Connectivity map database, ultimately identifying 6-mercatopurine (6-MP) as a promising candidate. Both in vitro and in vivo experiments demonstrated its efficacy in treating FeSighigh EGFRWT LUAD tumor models. In summary, we develop a novel FeSig for predicting prognosis and guiding drug application. A ferroptosis signature predicts clinical prognosis and identifies 6-Mercaptopurine as a promising drug for patients with EGFR wild type lung adenocarcinoma.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07117-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544179","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 expansion of VapBC TA systems in M. tuberculosis has been linked with its fitness and survival upon exposure to stress conditions. Here, we have functionally characterized VapBC13 and VapBC26 TA modules of M. tuberculosis. We report that overexpression of VapC13 and VapC26 toxins in M. tuberculosis results in growth inhibition and transcriptional reprogramming. We have also identified various regulatory proteins as hub nodes in the top response network of VapC13 and VapC26 overexpression strains. Further, analysis of RNA protection ratios revealed potential tRNA targets for VapC13 and VapC26. Using in vitro ribonuclease assays, we demonstrate that VapC13 and VapC26 degrade serT and leuW tRNA, respectively. However, no significant changes in rRNA cleavage profiles were observed upon overexpression of VapC13 and VapC26 in M. tuberculosis. In order to delineate the role of these TA systems in M. tuberculosis physiology, various mutant strains were constructed. We show that in comparison to the parental strain, ΔvapBC13 and ΔvapBC26 strains were mildly susceptible to oxidative stress. Surprisingly, the growth patterns of parental and mutant strains were comparable in aerosol-infected guinea pigs. These observations imply that significant functional redundancy exists for some TA systems from M. tuberculosis. The ectopic expression of VapC13 and VapC26 results in transcriptional reprogramming of M. tuberculosis. Both, VapBC13 and VapBC26 TA systems are dispensable for infection in guinea pigs, suggesting a degree of functional redundancy in M. tuberculosis.
结核杆菌中 VapBC TA 系统的扩展与其暴露于压力条件下的适应性和存活率有关。在这里，我们对结核杆菌的 VapBC13 和 VapBC26 TA 模块进行了功能鉴定。我们报告说，在结核杆菌中过表达 VapC13 和 VapC26 毒素会导致生长抑制和转录重编程。我们还在 VapC13 和 VapC26 过表达菌株的顶部反应网络中发现了各种调控蛋白作为枢纽节点。此外，对 RNA 保护率的分析揭示了 VapC13 和 VapC26 的潜在 tRNA 靶标。通过体外核糖核酸酶测定，我们证明 VapC13 和 VapC26 可分别降解 serT 和 leuW tRNA。然而，在结核杆菌中过表达 VapC13 和 VapC26 后，并没有观察到 rRNA 裂解曲线的明显变化。为了明确这些 TA 系统在结核杆菌生理过程中的作用，我们构建了各种突变株。我们发现，与亲本菌株相比，ΔvapBC13 和 ΔvapBC26 菌株对氧化应激有轻微的敏感性。令人惊讶的是，亲本菌株和突变菌株在气溶胶感染豚鼠体内的生长模式相当。这些观察结果表明，结核杆菌的某些 TA 系统存在明显的功能冗余。
{"title":"Deciphering the role of VapBC13 and VapBC26 toxin antitoxin systems in the pathophysiology of Mycobacterium tuberculosis","authors":"Arun Sharma, Neelam Singh, Munmun Bhasin, Prabhakar Tiwari, Pankaj Chopra, Raghavan Varadarajan, Ramandeep Singh","doi":"10.1038/s42003-024-06998-6","DOIUrl":"10.1038/s42003-024-06998-6","url":null,"abstract":"The expansion of VapBC TA systems in M. tuberculosis has been linked with its fitness and survival upon exposure to stress conditions. Here, we have functionally characterized VapBC13 and VapBC26 TA modules of M. tuberculosis. We report that overexpression of VapC13 and VapC26 toxins in M. tuberculosis results in growth inhibition and transcriptional reprogramming. We have also identified various regulatory proteins as hub nodes in the top response network of VapC13 and VapC26 overexpression strains. Further, analysis of RNA protection ratios revealed potential tRNA targets for VapC13 and VapC26. Using in vitro ribonuclease assays, we demonstrate that VapC13 and VapC26 degrade serT and leuW tRNA, respectively. However, no significant changes in rRNA cleavage profiles were observed upon overexpression of VapC13 and VapC26 in M. tuberculosis. In order to delineate the role of these TA systems in M. tuberculosis physiology, various mutant strains were constructed. We show that in comparison to the parental strain, ΔvapBC13 and ΔvapBC26 strains were mildly susceptible to oxidative stress. Surprisingly, the growth patterns of parental and mutant strains were comparable in aerosol-infected guinea pigs. These observations imply that significant functional redundancy exists for some TA systems from M. tuberculosis. The ectopic expression of VapC13 and VapC26 results in transcriptional reprogramming of M. tuberculosis. Both, VapBC13 and VapBC26 TA systems are dispensable for infection in guinea pigs, suggesting a degree of functional redundancy in M. tuberculosis.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-06998-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544177","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 : 2024-10-30DOI: 10.1038/s42003-024-06979-9
Orhan Efe Yavuz, Gregorio Oxilia, Sara Silvestrini, Laura Tassoni, Ella Reiter, Dorothée G. Drucker, Sahra Talamo, Federica Fontana, Stefano Benazzi, Cosimo Posth
The Epigravettian human remains from Riparo Tagliente in northern Italy represent some of the earliest evidence of human occupation in the southern Alpine slopes after the Last Glacial Maximum. Genomic analyses of the 17,000-year-old Tagliente 2 mandible revealed the oldest presence of a genetic profile with affinities to the Near East in the Italian peninsula, which later became the most widespread hunter-gatherer ancestry across Europe. However, a comparable biomolecular characterization of the Tagliente 1 burial remains unavailable, preventing us from defining its biological relationships with Tagliente 2. Here, we apply paleogenomic, isotopic, and radiocarbon dating analyses on a femur fragment of Tagliente 1 and compare the reconstructed data with previously reported results from Tagliente 2. Despite their different isotopic signatures and non-overlapping radiocarbon dates, we reveal that the two human remains belong to the same male individual. We determine that the distinct isotopic values can be explained by different dietary practices during lifetime, whereas the non-overlapping radiocarbon dates can be caused by minimal radiocarbon contamination, possibly deriving from chemical treatments for conservation purposes. These findings highlight the importance of interdisciplinary biomolecular studies in offering new perspectives on the Palaeolithic fossil record and addressing long-standing bioarchaeological questions. Biomolecular investigation of Epigravettian human remains from Riparo Tagliente in northern Italy using paleogenetics, stable isotopes and radiocarbon dating.
{"title":"Biomolecular analysis of the Epigravettian human remains from Riparo Tagliente in northern Italy","authors":"Orhan Efe Yavuz, Gregorio Oxilia, Sara Silvestrini, Laura Tassoni, Ella Reiter, Dorothée G. Drucker, Sahra Talamo, Federica Fontana, Stefano Benazzi, Cosimo Posth","doi":"10.1038/s42003-024-06979-9","DOIUrl":"10.1038/s42003-024-06979-9","url":null,"abstract":"The Epigravettian human remains from Riparo Tagliente in northern Italy represent some of the earliest evidence of human occupation in the southern Alpine slopes after the Last Glacial Maximum. Genomic analyses of the 17,000-year-old Tagliente 2 mandible revealed the oldest presence of a genetic profile with affinities to the Near East in the Italian peninsula, which later became the most widespread hunter-gatherer ancestry across Europe. However, a comparable biomolecular characterization of the Tagliente 1 burial remains unavailable, preventing us from defining its biological relationships with Tagliente 2. Here, we apply paleogenomic, isotopic, and radiocarbon dating analyses on a femur fragment of Tagliente 1 and compare the reconstructed data with previously reported results from Tagliente 2. Despite their different isotopic signatures and non-overlapping radiocarbon dates, we reveal that the two human remains belong to the same male individual. We determine that the distinct isotopic values can be explained by different dietary practices during lifetime, whereas the non-overlapping radiocarbon dates can be caused by minimal radiocarbon contamination, possibly deriving from chemical treatments for conservation purposes. These findings highlight the importance of interdisciplinary biomolecular studies in offering new perspectives on the Palaeolithic fossil record and addressing long-standing bioarchaeological questions. Biomolecular investigation of Epigravettian human remains from Riparo Tagliente in northern Italy using paleogenetics, stable isotopes and radiocarbon dating.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-06979-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544175","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 : 2024-10-30DOI: 10.1038/s42003-024-06281-8
Harsimran Kaur, Cody N. Heiser, Eliot T. McKinley, Lissa Ventura-Antunes, Coleman R. Harris, Joseph T. Roland, Melissa A. Farrow, Hilary J. Selden, Ellie L. Pingry, John F. Moore, Lauren I. R. Ehrlich, Martha J. Shrubsole, Jeffrey M. Spraggins, Robert J. Coffey, Ken S. Lau, Simon N. Vandekar
Spatially resolved molecular assays provide high dimensional genetic, transcriptomic, proteomic, and epigenetic information in situ and at various resolutions. Pairing these data across modalities with histological features enables powerful studies of tissue pathology in the context of an intact microenvironment and tissue structure. Increasing dimensions across molecular analytes and samples require new data science approaches to functionally annotate spatially resolved molecular data. A specific challenge is data-driven cross-sample domain detection that allows for analysis within and between consensus tissue compartments across high volumes of multiplex datasets stemming from tissue atlasing efforts. Here, we present MILWRM (multiplex image labeling with regional morphology)—a Python package for rapid, multi-scale tissue domain detection and annotation at the image- or spot-level. We demonstrate MILWRM’s utility in identifying histologically distinct compartments in human colonic polyps, lymph nodes, mouse kidney, and mouse brain slices through spatially-informed clustering in two different spatial data modalities from different platforms. We used tissue domains detected in human colonic polyps to elucidate the molecular distinction between polyp subtypes, and explored the ability of MILWRM to identify anatomical regions of the brain tissue and their respective distinct molecular profiles. MILWRM is a Python package that can perform tissue domain detection on spatial transcriptomics (ST) and multiplex immunofluorescence (mIF) data across multiple specimens.
{"title":"Consensus tissue domain detection in spatial omics data using multiplex image labeling with regional morphology (MILWRM)","authors":"Harsimran Kaur, Cody N. Heiser, Eliot T. McKinley, Lissa Ventura-Antunes, Coleman R. Harris, Joseph T. Roland, Melissa A. Farrow, Hilary J. Selden, Ellie L. Pingry, John F. Moore, Lauren I. R. Ehrlich, Martha J. Shrubsole, Jeffrey M. Spraggins, Robert J. Coffey, Ken S. Lau, Simon N. Vandekar","doi":"10.1038/s42003-024-06281-8","DOIUrl":"10.1038/s42003-024-06281-8","url":null,"abstract":"Spatially resolved molecular assays provide high dimensional genetic, transcriptomic, proteomic, and epigenetic information in situ and at various resolutions. Pairing these data across modalities with histological features enables powerful studies of tissue pathology in the context of an intact microenvironment and tissue structure. Increasing dimensions across molecular analytes and samples require new data science approaches to functionally annotate spatially resolved molecular data. A specific challenge is data-driven cross-sample domain detection that allows for analysis within and between consensus tissue compartments across high volumes of multiplex datasets stemming from tissue atlasing efforts. Here, we present MILWRM (multiplex image labeling with regional morphology)—a Python package for rapid, multi-scale tissue domain detection and annotation at the image- or spot-level. We demonstrate MILWRM’s utility in identifying histologically distinct compartments in human colonic polyps, lymph nodes, mouse kidney, and mouse brain slices through spatially-informed clustering in two different spatial data modalities from different platforms. We used tissue domains detected in human colonic polyps to elucidate the molecular distinction between polyp subtypes, and explored the ability of MILWRM to identify anatomical regions of the brain tissue and their respective distinct molecular profiles. MILWRM is a Python package that can perform tissue domain detection on spatial transcriptomics (ST) and multiplex immunofluorescence (mIF) data across multiple specimens.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-06281-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544176","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 : 2024-10-29DOI: 10.1038/s42003-024-07112-6
Yu Fu, Jiajia Li, Jin Wang, Erkang Wang, Xiaona Fang
Recent advancements in bacterial two-component systems (TCS) have spurred research into TCS-based biosensors, notably for their signal amplification and broad input responsiveness. The CusRS system in Escherichia coli (E. coli), comprising cusS and cusR genes, is a copper-sensing module in E. coli. However, due to insufficient sensing performance, CusRS-based biosensors often cannot meet practical requirements. To address this issue, we made improvements and innovation from several aspects. CusR and CusS expression were adjusted to enhance the Cu(II) biosensor’s performance. A copy-number inducible plasmid was used for signal amplification, while removing copper detox genes cueO and cusCFBA improved sensitivity and lowered detection limits. Ultimately, in the optimized biosensor of Cu26, the fold-change (I/I0) increased from 1.5-fold to 18-fold at 1 μM, rising to 100-fold after optimizing the cell culture procedure. The biosensor’s high fluorescence enabled rapid, instrument-free detection and an improved analysis strategy reduced the detection limit to 0.01 μM, surpassing traditional methods. Optimizing the CusRS copper-sensing system in E.coli by adjusting CusR/CusS expression and deleting detox genes, achieving a 100-fold signal increase and a detection limit of 0.01 μM, enabling rapid, instrument-free detection.
{"title":"Development of a two component system based biosensor with high sensitivity for the detection of copper ions","authors":"Yu Fu, Jiajia Li, Jin Wang, Erkang Wang, Xiaona Fang","doi":"10.1038/s42003-024-07112-6","DOIUrl":"10.1038/s42003-024-07112-6","url":null,"abstract":"Recent advancements in bacterial two-component systems (TCS) have spurred research into TCS-based biosensors, notably for their signal amplification and broad input responsiveness. The CusRS system in Escherichia coli (E. coli), comprising cusS and cusR genes, is a copper-sensing module in E. coli. However, due to insufficient sensing performance, CusRS-based biosensors often cannot meet practical requirements. To address this issue, we made improvements and innovation from several aspects. CusR and CusS expression were adjusted to enhance the Cu(II) biosensor’s performance. A copy-number inducible plasmid was used for signal amplification, while removing copper detox genes cueO and cusCFBA improved sensitivity and lowered detection limits. Ultimately, in the optimized biosensor of Cu26, the fold-change (I/I0) increased from 1.5-fold to 18-fold at 1 μM, rising to 100-fold after optimizing the cell culture procedure. The biosensor’s high fluorescence enabled rapid, instrument-free detection and an improved analysis strategy reduced the detection limit to 0.01 μM, surpassing traditional methods. Optimizing the CusRS copper-sensing system in E.coli by adjusting CusR/CusS expression and deleting detox genes, achieving a 100-fold signal increase and a detection limit of 0.01 μM, enabling rapid, instrument-free detection.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07112-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142525720","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 : 2024-10-29DOI: 10.1038/s42003-024-07075-8
Rossella Delle Donne, Rosa Iannucci, Laura Rinaldi, Luca Roberto, Maria A. Oliva, Emanuela Senatore, Domenica Borzacchiello, Luca Lignitto, Giorgio Giurato, Francesca Rizzo, Assunta Sellitto, Francesco Chiuso, Salvatore Castaldo, Giovanni Scala, Virginia Campani, Valeria Nele, Giuseppe De Rosa, Chiara D’Ambrosio, Corrado Garbi, Andrea Scaloni, Alessandro Weisz, Concetta Ambrosino, Antonella Arcella, Antonio Feliciello
{"title":"Author Correction: Targeted inhibition of ubiquitin signaling reverses metabolic reprogramming and suppresses glioblastoma growth","authors":"Rossella Delle Donne, Rosa Iannucci, Laura Rinaldi, Luca Roberto, Maria A. Oliva, Emanuela Senatore, Domenica Borzacchiello, Luca Lignitto, Giorgio Giurato, Francesca Rizzo, Assunta Sellitto, Francesco Chiuso, Salvatore Castaldo, Giovanni Scala, Virginia Campani, Valeria Nele, Giuseppe De Rosa, Chiara D’Ambrosio, Corrado Garbi, Andrea Scaloni, Alessandro Weisz, Concetta Ambrosino, Antonella Arcella, Antonio Feliciello","doi":"10.1038/s42003-024-07075-8","DOIUrl":"10.1038/s42003-024-07075-8","url":null,"abstract":"","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07075-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544174","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 : 2024-10-29DOI: 10.1038/s42003-024-07029-0
Michelle R. Shero, Daniel P. Costa, Jennifer M. Burns, Kimberly T. Goetz
Air-breathing vertebrates must balance their response to diel shifts in prey accessibility with physiological thresholds and the need to surface after each dive. Weddell seal (Leptonychotes weddellii) dive behaviors were tracked across the year under rapidly-changing light regimes in the Ross Sea, Antarctica ( ~ 75-77°S). This provides a ‘natural experiment’ with free-living seals experiencing 24-hrs of light (Polar Day), light/dark cycling, and continuous darkness (Polar Night). The Weddell seal’s temporal niche switches from nocturnal diving in the summer to diurnality for the remainder of the year. Rhythmicity in dive efforts (depth, duration, post-dive surface recuperation, bottom time, and exceeding physiologic thresholds) is stronger and more closely circadian during times of the year with light/dark cycling compared with Polar Day or Night. With light/dark cycling, animals also make the most extreme dives (those that far exceed the calculated aerobic dive limit, cADL) significantly earlier than solar noon. Offsetting the longest dives that require longer surface recuperation times from mid-day allows animals to maximize total dive time under high-light conditions conducive for visual hunting. We identify an optimal foraging strategy to exploit a diel preyscape in a highly-seasonal environment, while balancing tradeoffs imposed by physiological thresholds in a diving mammal. Antarctic Weddell seals may strategically time their most extreme dives. Seals preferentially did not make their longest dives that push physiological limits at mid-day. This minimized surface time and maximized foraging time during daylight hours.
{"title":"Breath-hold capacities and circadian dive rhythmicity shape optimal foraging strategies in a polar marine mammal, the Weddell seal (Leptonychotes weddellii)","authors":"Michelle R. Shero, Daniel P. Costa, Jennifer M. Burns, Kimberly T. Goetz","doi":"10.1038/s42003-024-07029-0","DOIUrl":"10.1038/s42003-024-07029-0","url":null,"abstract":"Air-breathing vertebrates must balance their response to diel shifts in prey accessibility with physiological thresholds and the need to surface after each dive. Weddell seal (Leptonychotes weddellii) dive behaviors were tracked across the year under rapidly-changing light regimes in the Ross Sea, Antarctica ( ~ 75-77°S). This provides a ‘natural experiment’ with free-living seals experiencing 24-hrs of light (Polar Day), light/dark cycling, and continuous darkness (Polar Night). The Weddell seal’s temporal niche switches from nocturnal diving in the summer to diurnality for the remainder of the year. Rhythmicity in dive efforts (depth, duration, post-dive surface recuperation, bottom time, and exceeding physiologic thresholds) is stronger and more closely circadian during times of the year with light/dark cycling compared with Polar Day or Night. With light/dark cycling, animals also make the most extreme dives (those that far exceed the calculated aerobic dive limit, cADL) significantly earlier than solar noon. Offsetting the longest dives that require longer surface recuperation times from mid-day allows animals to maximize total dive time under high-light conditions conducive for visual hunting. We identify an optimal foraging strategy to exploit a diel preyscape in a highly-seasonal environment, while balancing tradeoffs imposed by physiological thresholds in a diving mammal. Antarctic Weddell seals may strategically time their most extreme dives. Seals preferentially did not make their longest dives that push physiological limits at mid-day. This minimized surface time and maximized foraging time during daylight hours.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07029-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142525712","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 : 2024-10-29DOI: 10.1038/s42003-024-07101-9
Alessandro Agostini, David Bína, Dovilė Barcytė, Marco Bortolus, Marek Eliáš, Donatella Carbonera, Radek Litvín
Photosynthetic organisms harvest light for energy. Some eukaryotic algae have specialized in harvesting far-red light by tuning chlorophyll a absorption through a mechanism still to be elucidated. Here, we combined optically detected magnetic resonance and pulsed electron paramagnetic resonance measurements on red-adapted light-harvesting complexes, rVCP, isolated from the freshwater eustigmatophyte alga Trachydiscus minutus to identify the location of the pigments responsible for this remarkable adaptation. The pigments have been found to belong to an excitonic cluster of chlorophylls a at the core of the complex, close to the central carotenoids in L1/L2 sites. A pair of structural features of the Chl a403/a603 binding site, namely the histidine-to-asparagine substitution in the magnesium-ligation residue and the small size of the amino acid at the i-4 position, resulting in a [A/G]xxxN motif, are proposed to be the origin of this trait. Phylogenetic analysis of various eukaryotic red antennae identified several potential LHCs that could share this tuning mechanism. This knowledge of the red light acclimation mechanism in algae is a step towards rational design of algal strains in order to enhance light capture and efficiency in large-scale biotechnology applications. A histidine-to-asparagine exchange and a small-sidechain residue at the i-4 position of the chlorophyll a403/a603 binding sites are responsible for the red-shifted light adaption of the light harvesting complexes from Trachydiscus minutus and other eukaryotic algae.
光合生物利用光获取能量。一些真核藻类专门通过调整叶绿素 a 的吸收来获取远红光，其机制仍有待阐明。在这里，我们结合光学检测磁共振和脉冲电子顺磁共振测量，对从淡水尾柱藻中分离出来的红色适应光收集复合物（rVCP）进行了研究，以确定负责这种显著适应的色素的位置。研究发现，这些色素属于叶绿素 a 的激发簇，位于复合体的核心，靠近 L1/L2 位点的类胡萝卜素中心。Chl a403/a603 结合位点的一对结构特征，即镁连接残基中组氨酸对天冬酰胺的取代和 i-4 位氨基酸的小尺寸，导致了[A/G]xxxN 主题，被认为是这一特征的起源。对各种真核生物红触角的系统发育分析发现，有几种潜在的 LHC 可能共享这种调谐机制。对藻类红光适应机制的了解有助于合理设计藻类品系，从而提高大规模生物技术应用中的光捕获能力和效率。组氨酸到天冬酰胺的交换以及叶绿素 a403/a603 结合位点 i-4 位上的小侧链残基是小栉水母和其他真核藻类采光复合物红移光适应性的原因。
{"title":"Eustigmatophyte model of red-shifted chlorophyll a absorption in light-harvesting complexes","authors":"Alessandro Agostini, David Bína, Dovilė Barcytė, Marco Bortolus, Marek Eliáš, Donatella Carbonera, Radek Litvín","doi":"10.1038/s42003-024-07101-9","DOIUrl":"10.1038/s42003-024-07101-9","url":null,"abstract":"Photosynthetic organisms harvest light for energy. Some eukaryotic algae have specialized in harvesting far-red light by tuning chlorophyll a absorption through a mechanism still to be elucidated. Here, we combined optically detected magnetic resonance and pulsed electron paramagnetic resonance measurements on red-adapted light-harvesting complexes, rVCP, isolated from the freshwater eustigmatophyte alga Trachydiscus minutus to identify the location of the pigments responsible for this remarkable adaptation. The pigments have been found to belong to an excitonic cluster of chlorophylls a at the core of the complex, close to the central carotenoids in L1/L2 sites. A pair of structural features of the Chl a403/a603 binding site, namely the histidine-to-asparagine substitution in the magnesium-ligation residue and the small size of the amino acid at the i-4 position, resulting in a [A/G]xxxN motif, are proposed to be the origin of this trait. Phylogenetic analysis of various eukaryotic red antennae identified several potential LHCs that could share this tuning mechanism. This knowledge of the red light acclimation mechanism in algae is a step towards rational design of algal strains in order to enhance light capture and efficiency in large-scale biotechnology applications. A histidine-to-asparagine exchange and a small-sidechain residue at the i-4 position of the chlorophyll a403/a603 binding sites are responsible for the red-shifted light adaption of the light harvesting complexes from Trachydiscus minutus and other eukaryotic algae.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07101-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142525725","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}
Zoospores of the filamentous actinomycete Actinoplanes missouriensis swim vigorously using flagella and stop swimming to initiate germination in response to nutrient exposure. However, the molecular mechanisms underlying swimming cessation remain unknown. A protein (FtgA) of unknown function encoded by a chemotaxis gene cluster (che cluster-1) was found to be required for flagellar rotation arrest; the zoospores of ftgA-knockout mutants kept swimming awkwardly after germination. An ftgA-overexpressing strain exhibited a non-flagellated phenotype. Isolation of a suppressor strain from this strain and further in vivo experiments revealed that the extended N-terminal region of FliN, a component of the C-ring of the flagellar basal body, was involved in the function of FtgA; FliN-P101S canceled the flagellar rotation arrest by FtgA, as well as the negative effect of ftgA-overexpression on flagellation. Furthermore, bacterial two-hybrid assays suggested that FtgA interacted not only with the C-terminal core region of FliN but also with chemotaxis regulatory proteins CheA1 and CheW1-2, which are encoded by che cluster-1. We propose the following working model of motility regulation in A. missouriensis zoospores: the chemotaxis sensory complex initially captures FtgA to allow zoospores to swim and then releases FtgA to stop flagellar rotation (i.e., swimming) in response to external nutrient signals. The actinomycete Actinoplanes missouriensis produces flagellated zoospores that stop swimming before germination. A genetic study has revealed that a hypothetical protein encoded by a chemotaxis gene cluster is required for flagellar rotation arrest.
丝状放线菌放线菌（Actinoplanes missouriensis）的卵孢子利用鞭毛剧烈游动，并在接触营养物质后停止游动以开始发芽。然而，停止游动的分子机制仍然未知。研究发现，由趋化基因簇（che cluster-1）编码的一种功能不明的蛋白质（FtgA）是鞭毛旋转停止所必需的；ftgA基因敲除突变体的动物孢子在萌发后继续笨拙地游动。ftgA过表达菌株表现出无鞭毛表型。从该菌株中分离出的抑制菌株和进一步的体内实验发现，鞭毛基体 C 环的一个组成部分 FliN 的 N 端延长区参与了 FtgA 的功能；FliN-P101S 取消了 FtgA 对鞭毛旋转的抑制作用，以及 ftgA 高表达对鞭毛的负面影响。此外，细菌双杂交实验表明，FtgA不仅与FliN的C端核心区相互作用，还与che cluster-1编码的趋化调控蛋白CheA1和CheW1-2相互作用。我们提出了以下关于 A. missouriensis 动物孢子运动调控的工作模型：趋化感官复合体最初捕获 FtgA 以允许动物孢子游动，然后释放 FtgA 以停止鞭毛旋转（即游动），以响应外部营养信号。放线菌 Actinoplanes missouriensis 产生的鞭毛状动物孢子在发芽前停止游动。一项遗传学研究发现，一个趋化基因簇编码的假定蛋白是鞭毛旋转停止所必需的。
{"title":"Molecular mechanism of flagellar motor rotation arrest in bacterial zoospores of Actinoplanes missouriensis before germination","authors":"Hiromu Kato, Hiroki Tanemura, Tomohiro Kimura, Yohei Katsuyama, Takeaki Tezuka, Yasuo Ohnishi","doi":"10.1038/s42003-024-07104-6","DOIUrl":"10.1038/s42003-024-07104-6","url":null,"abstract":"Zoospores of the filamentous actinomycete Actinoplanes missouriensis swim vigorously using flagella and stop swimming to initiate germination in response to nutrient exposure. However, the molecular mechanisms underlying swimming cessation remain unknown. A protein (FtgA) of unknown function encoded by a chemotaxis gene cluster (che cluster-1) was found to be required for flagellar rotation arrest; the zoospores of ftgA-knockout mutants kept swimming awkwardly after germination. An ftgA-overexpressing strain exhibited a non-flagellated phenotype. Isolation of a suppressor strain from this strain and further in vivo experiments revealed that the extended N-terminal region of FliN, a component of the C-ring of the flagellar basal body, was involved in the function of FtgA; FliN-P101S canceled the flagellar rotation arrest by FtgA, as well as the negative effect of ftgA-overexpression on flagellation. Furthermore, bacterial two-hybrid assays suggested that FtgA interacted not only with the C-terminal core region of FliN but also with chemotaxis regulatory proteins CheA1 and CheW1-2, which are encoded by che cluster-1. We propose the following working model of motility regulation in A. missouriensis zoospores: the chemotaxis sensory complex initially captures FtgA to allow zoospores to swim and then releases FtgA to stop flagellar rotation (i.e., swimming) in response to external nutrient signals. The actinomycete Actinoplanes missouriensis produces flagellated zoospores that stop swimming before germination. A genetic study has revealed that a hypothetical protein encoded by a chemotaxis gene cluster is required for flagellar rotation arrest.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07104-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142525741","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}
Posttraumatic stress disorder (PTSD) is associated with glutamatergic neuron hyperactivation in the basolateral amygdala (BLA) brain area, while GABAergic interneurons in the BLA modulate glutamatergic neuron excitability. Studies have shown that propofol exerts its effects through potentiation of the inhibitory neurotransmitter γ-aminobutyric acid. The neuronal mechanism by which propofol anesthesia modulates fear memory is currently unknown. Here, we used optogenetics and chemogenetics to suppress glutamatergic neurons or activate GABAergic interneurons in the BLA to assess alterations in neuronal excitation-inhibition balance and investigate fear memory. The excitability of glutamatergic neurons in the BLA was significantly reduced by the suppression of glutamatergic neurons or activation of GABAergic interneurons, while propofol-mediated enhancement of fear memory was attenuated. We suggest that propofol anesthesia could reduce the excitability of GABAergic neurons through activation of GABAA receptors, subsequently increasing the excitability of glutamatergic neurons in the mice BLA; the effect of propofol on enhancing mice fear memory might be mediated by strengthening glutamatergic neuronal excitability and decreasing the excitability of GABAergic neurons in the BLA; neuronal excitation-inhibition imbalance in the BLA might be important in mediating the enhancement of fear memory induced by propofol. Propofol mediates enhancement of fear memory in mice by decreasing excitability of GABAergic neurons and enhancing excitability of glutamatergic neurons in BLA.
{"title":"Neuronal excitation-inhibition imbalance in the basolateral amygdala is involved in propofol-mediated enhancement of fear memory","authors":"Chen Chen, Shuai Li, Yue Zhou, Hui Huang, Jia-Tao Lin, Wei-Feng Wu, Yong-Kang Qiu, Wei Dong, Jie Wan, Qiang Liu, Hui Zheng, Yu-Qing Wu, Cheng-Hua Zhou","doi":"10.1038/s42003-024-07105-5","DOIUrl":"10.1038/s42003-024-07105-5","url":null,"abstract":"Posttraumatic stress disorder (PTSD) is associated with glutamatergic neuron hyperactivation in the basolateral amygdala (BLA) brain area, while GABAergic interneurons in the BLA modulate glutamatergic neuron excitability. Studies have shown that propofol exerts its effects through potentiation of the inhibitory neurotransmitter γ-aminobutyric acid. The neuronal mechanism by which propofol anesthesia modulates fear memory is currently unknown. Here, we used optogenetics and chemogenetics to suppress glutamatergic neurons or activate GABAergic interneurons in the BLA to assess alterations in neuronal excitation-inhibition balance and investigate fear memory. The excitability of glutamatergic neurons in the BLA was significantly reduced by the suppression of glutamatergic neurons or activation of GABAergic interneurons, while propofol-mediated enhancement of fear memory was attenuated. We suggest that propofol anesthesia could reduce the excitability of GABAergic neurons through activation of GABAA receptors, subsequently increasing the excitability of glutamatergic neurons in the mice BLA; the effect of propofol on enhancing mice fear memory might be mediated by strengthening glutamatergic neuronal excitability and decreasing the excitability of GABAergic neurons in the BLA; neuronal excitation-inhibition imbalance in the BLA might be important in mediating the enhancement of fear memory induced by propofol. Propofol mediates enhancement of fear memory in mice by decreasing excitability of GABAergic neurons and enhancing excitability of glutamatergic neurons in BLA.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07105-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142525677","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：