Pub Date : 2024-10-22eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002841
Meiyu Ruan, Fan Xu, Na Li, Jing Yu, Fukang Teng, Jiawei Tang, Cheng Huang, Huanhu Zhu
Postembryonic development of animals has long been considered an internally predetermined program, while macronutrients were believed to be essential solely for providing biomatters and energy to support this process. However, in this study, by using a nematode Caenorhabditis elegans (abbreviated as C. elegans hereafter) model, we surprisingly discovered that dietary supplementation of palmitic acid alone, rather than other abundant essential nutrients such as glucose or amino acid mixture, was sufficient to initiate early postembryonic development even under complete macronutrient deprivation. Such a development was evidenced by changes in morphology, cellular markers in multiple tissues, behaviors, and the global transcription pattern and it occurred earlier than the well-known early L1 nutrient checkpoint. Mechanistically, palmitic acid did not function as a biomatter/energy provider, but rather as a ligand to activate the nuclear hormone receptor NHR-49/80, leading to the production of an unknown peroxisome-derived secretive hormone in the intestine. This hormonal signal was received by chemosensory neurons in the head, regulating the insulin-like neuropeptide secretion and its downstream nuclear receptor to orchestrate global development. Additionally, the nutrient-sensing hub mTORC1 played a negative role in this process. In conclusion, our data indicate that free fatty acids act as a primary nutrient signal to launch the early development in C. elegans, which suggests that specific nutrients, rather than the internal genetic program, serve as the first impetus for postembryonic development.
{"title":"Free long-chain fatty acids trigger early postembryonic development in starved Caenorhabditis elegans by suppressing mTORC1.","authors":"Meiyu Ruan, Fan Xu, Na Li, Jing Yu, Fukang Teng, Jiawei Tang, Cheng Huang, Huanhu Zhu","doi":"10.1371/journal.pbio.3002841","DOIUrl":"10.1371/journal.pbio.3002841","url":null,"abstract":"<p><p>Postembryonic development of animals has long been considered an internally predetermined program, while macronutrients were believed to be essential solely for providing biomatters and energy to support this process. However, in this study, by using a nematode Caenorhabditis elegans (abbreviated as C. elegans hereafter) model, we surprisingly discovered that dietary supplementation of palmitic acid alone, rather than other abundant essential nutrients such as glucose or amino acid mixture, was sufficient to initiate early postembryonic development even under complete macronutrient deprivation. Such a development was evidenced by changes in morphology, cellular markers in multiple tissues, behaviors, and the global transcription pattern and it occurred earlier than the well-known early L1 nutrient checkpoint. Mechanistically, palmitic acid did not function as a biomatter/energy provider, but rather as a ligand to activate the nuclear hormone receptor NHR-49/80, leading to the production of an unknown peroxisome-derived secretive hormone in the intestine. This hormonal signal was received by chemosensory neurons in the head, regulating the insulin-like neuropeptide secretion and its downstream nuclear receptor to orchestrate global development. Additionally, the nutrient-sensing hub mTORC1 played a negative role in this process. In conclusion, our data indicate that free fatty acids act as a primary nutrient signal to launch the early development in C. elegans, which suggests that specific nutrients, rather than the internal genetic program, serve as the first impetus for postembryonic development.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511126","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 : 2024-10-21eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002858
David R Quiroga-Martinez, Gemma Fernández Rubio, Leonardo Bonetti, Kriti G Achyutuni, Athina Tzovara, Robert T Knight, Peter Vuust
Vividly imagining a song or a melody is a skill that many people accomplish with relatively little effort. However, we are only beginning to understand how the brain represents, holds, and manipulates these musical "thoughts." Here, we decoded perceived and imagined melodies from magnetoencephalography (MEG) brain data (N = 71) to characterize their neural representation. We found that, during perception, auditory regions represent the sensory properties of individual sounds. In contrast, a widespread network including fronto-parietal cortex, hippocampus, basal nuclei, and sensorimotor regions hold the melody as an abstract unit during both perception and imagination. Furthermore, the mental manipulation of a melody systematically changes its neural representation, reflecting volitional control of auditory images. Our work sheds light on the nature and dynamics of auditory representations, informing future research on neural decoding of auditory imagination.
{"title":"Decoding reveals the neural representation of perceived and imagined musical sounds.","authors":"David R Quiroga-Martinez, Gemma Fernández Rubio, Leonardo Bonetti, Kriti G Achyutuni, Athina Tzovara, Robert T Knight, Peter Vuust","doi":"10.1371/journal.pbio.3002858","DOIUrl":"10.1371/journal.pbio.3002858","url":null,"abstract":"<p><p>Vividly imagining a song or a melody is a skill that many people accomplish with relatively little effort. However, we are only beginning to understand how the brain represents, holds, and manipulates these musical \"thoughts.\" Here, we decoded perceived and imagined melodies from magnetoencephalography (MEG) brain data (N = 71) to characterize their neural representation. We found that, during perception, auditory regions represent the sensory properties of individual sounds. In contrast, a widespread network including fronto-parietal cortex, hippocampus, basal nuclei, and sensorimotor regions hold the melody as an abstract unit during both perception and imagination. Furthermore, the mental manipulation of a melody systematically changes its neural representation, reflecting volitional control of auditory images. Our work sheds light on the nature and dynamics of auditory representations, informing future research on neural decoding of auditory imagination.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478509","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 : 2024-10-18eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002868
Muniyandi Selvaraj, AmirAli Toghani, Hsuan Pai, Yu Sugihara, Jiorgos Kourelis, Enoch Lok Him Yuen, Tarhan Ibrahim, He Zhao, Rongrong Xie, Abbas Maqbool, Juan Carlos De la Concepcion, Mark J Banfield, Lida Derevnina, Benjamin Petre, David M Lawson, Tolga O Bozkurt, Chih-Hang Wu, Sophien Kamoun, Mauricio P Contreras
Nucleotide-binding domain and leucine-rich repeat (NLR) proteins can engage in complex interactions to detect pathogens and execute a robust immune response via downstream helper NLRs. However, the biochemical mechanisms of helper NLR activation by upstream sensor NLRs remain poorly understood. Here, we show that the coiled-coil helper NLR NRC2 from Nicotiana benthamiana accumulates in vivo as a homodimer that converts into a higher-order oligomer upon activation by its upstream virus disease resistance protein Rx. The cryo-EM structure of NbNRC2 in its resting state revealed intermolecular interactions that mediate homodimer formation and contribute to immune receptor autoinhibition. These dimerization interfaces have diverged between paralogous NRC proteins to insulate critical network nodes and enable redundant immune pathways, possibly to minimise undesired cross-activation and evade pathogen suppression of immunity. Our results expand the molecular mechanisms of NLR activation pointing to transition from homodimers to higher-order oligomeric resistosomes.
{"title":"Activation of plant immunity through conversion of a helper NLR homodimer into a resistosome.","authors":"Muniyandi Selvaraj, AmirAli Toghani, Hsuan Pai, Yu Sugihara, Jiorgos Kourelis, Enoch Lok Him Yuen, Tarhan Ibrahim, He Zhao, Rongrong Xie, Abbas Maqbool, Juan Carlos De la Concepcion, Mark J Banfield, Lida Derevnina, Benjamin Petre, David M Lawson, Tolga O Bozkurt, Chih-Hang Wu, Sophien Kamoun, Mauricio P Contreras","doi":"10.1371/journal.pbio.3002868","DOIUrl":"10.1371/journal.pbio.3002868","url":null,"abstract":"<p><p>Nucleotide-binding domain and leucine-rich repeat (NLR) proteins can engage in complex interactions to detect pathogens and execute a robust immune response via downstream helper NLRs. However, the biochemical mechanisms of helper NLR activation by upstream sensor NLRs remain poorly understood. Here, we show that the coiled-coil helper NLR NRC2 from Nicotiana benthamiana accumulates in vivo as a homodimer that converts into a higher-order oligomer upon activation by its upstream virus disease resistance protein Rx. The cryo-EM structure of NbNRC2 in its resting state revealed intermolecular interactions that mediate homodimer formation and contribute to immune receptor autoinhibition. These dimerization interfaces have diverged between paralogous NRC proteins to insulate critical network nodes and enable redundant immune pathways, possibly to minimise undesired cross-activation and evade pathogen suppression of immunity. Our results expand the molecular mechanisms of NLR activation pointing to transition from homodimers to higher-order oligomeric resistosomes.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478607","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 : 2024-10-18eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002874
Rakesh Maharjan, Zhemin Zhang, Philip A Klenotic, William D Gregor, Marios L Tringides, Meng Cui, Georgiana E Purdy, Edward W Yu
The Mycobacterium tuberculosis (Mtb) pathogen, the causative agent of the airborne infection tuberculosis (TB), harbors a number of mycobacterial membrane protein large (MmpL) transporters. These membrane proteins can be separated into 2 distinct subclasses, where they perform important functional roles, and thus, are considered potential drug targets to combat TB. Previously, we reported both X-ray and cryo-EM structures of the MmpL3 transporter, providing high-resolution structural information for this subclass of the MmpL proteins. Currently, there is no structural information available for the subclass associated with MmpL4 and MmpL5, transporters that play a critical role in iron homeostasis of the bacterium. Here, we report cryo-EM structures of the M. smegmatis MmpL4 and MmpL5 transporters to resolutions of 2.95 Å and 3.00 Å, respectively. These structures allow us to propose a plausible pathway for siderophore translocation via these 2 transporters, an essential step for iron acquisition that enables the survival and replication of the mycobacterium.
结核分枝杆菌(Mtb)病原体是通过空气传播的结核病(TB)的致病菌,它携带有许多分枝杆菌膜蛋白大(MmpL)转运体。这些膜蛋白可分为两个不同的亚类,它们在其中发挥着重要的功能作用,因此被认为是抗击结核病的潜在药物靶标。此前,我们报道了 MmpL3 转运体的 X 射线和低温电子显微镜结构,为该亚类 MmpL 蛋白提供了高分辨率的结构信息。目前,还没有与 MmpL4 和 MmpL5 相关的亚类的结构信息,这些转运体在细菌的铁平衡中发挥着关键作用。在此,我们报告了 M. smegmatis MmpL4 和 MmpL5 转运体的低温电子显微镜结构,其分辨率分别为 2.95 Å 和 3.00 Å。通过这些结构,我们提出了通过这两个转运体进行苷酸转运的合理途径,而苷酸转运是获得铁的一个重要步骤,可使分枝杆菌得以生存和复制。
{"title":"Structures of the mycobacterial MmpL4 and MmpL5 transporters provide insights into their role in siderophore export and iron acquisition.","authors":"Rakesh Maharjan, Zhemin Zhang, Philip A Klenotic, William D Gregor, Marios L Tringides, Meng Cui, Georgiana E Purdy, Edward W Yu","doi":"10.1371/journal.pbio.3002874","DOIUrl":"10.1371/journal.pbio.3002874","url":null,"abstract":"<p><p>The Mycobacterium tuberculosis (Mtb) pathogen, the causative agent of the airborne infection tuberculosis (TB), harbors a number of mycobacterial membrane protein large (MmpL) transporters. These membrane proteins can be separated into 2 distinct subclasses, where they perform important functional roles, and thus, are considered potential drug targets to combat TB. Previously, we reported both X-ray and cryo-EM structures of the MmpL3 transporter, providing high-resolution structural information for this subclass of the MmpL proteins. Currently, there is no structural information available for the subclass associated with MmpL4 and MmpL5, transporters that play a critical role in iron homeostasis of the bacterium. Here, we report cryo-EM structures of the M. smegmatis MmpL4 and MmpL5 transporters to resolutions of 2.95 Å and 3.00 Å, respectively. These structures allow us to propose a plausible pathway for siderophore translocation via these 2 transporters, an essential step for iron acquisition that enables the survival and replication of the mycobacterium.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478513","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 : 2024-10-17eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002786
Ruth M Williams, Guneş Taylor, Irving T C Ling, Ivan Candido-Ferreira, Daniel M Fountain, Sarah Mayes, Perihan Seda Ateş-Kalkan, Julianna O Haug, Andrew J Price, Sean A McKinney, Yavor K Bozhilovh, Richard C V Tyser, Shankar Srinivas, Jim R Hughes, Tatjana Sauka-Spengler
Neurocristopathies such as CHARGE syndrome result from aberrant neural crest development. A large proportion of CHARGE cases are attributed to pathogenic variants in the gene encoding CHD7, chromodomain helicase DNA binding protein 7, which remodels chromatin. While the role for CHD7 in neural crest development is well documented, how this factor is specifically up-regulated in neural crest cells is not understood. Here, we use epigenomic profiling of chick and human neural crest to identify a cohort of enhancers regulating Chd7 expression in neural crest cells and other tissues. We functionally validate upstream transcription factor binding at candidate enhancers, revealing novel epistatic relationships between neural crest master regulators and Chd7, showing tissue-specific regulation of a globally acting chromatin remodeller. Furthermore, we find conserved enhancer features in human embryonic epigenomic data and validate the activity of the human equivalent CHD7 enhancers in the chick embryo. Our findings embed Chd7 in the neural crest gene regulatory network and offer potentially clinically relevant elements for interpreting CHARGE syndrome cases without causative allocation.
{"title":"Chromatin remodeller Chd7 is developmentally regulated in the neural crest by tissue-specific transcription factors.","authors":"Ruth M Williams, Guneş Taylor, Irving T C Ling, Ivan Candido-Ferreira, Daniel M Fountain, Sarah Mayes, Perihan Seda Ateş-Kalkan, Julianna O Haug, Andrew J Price, Sean A McKinney, Yavor K Bozhilovh, Richard C V Tyser, Shankar Srinivas, Jim R Hughes, Tatjana Sauka-Spengler","doi":"10.1371/journal.pbio.3002786","DOIUrl":"10.1371/journal.pbio.3002786","url":null,"abstract":"<p><p>Neurocristopathies such as CHARGE syndrome result from aberrant neural crest development. A large proportion of CHARGE cases are attributed to pathogenic variants in the gene encoding CHD7, chromodomain helicase DNA binding protein 7, which remodels chromatin. While the role for CHD7 in neural crest development is well documented, how this factor is specifically up-regulated in neural crest cells is not understood. Here, we use epigenomic profiling of chick and human neural crest to identify a cohort of enhancers regulating Chd7 expression in neural crest cells and other tissues. We functionally validate upstream transcription factor binding at candidate enhancers, revealing novel epistatic relationships between neural crest master regulators and Chd7, showing tissue-specific regulation of a globally acting chromatin remodeller. Furthermore, we find conserved enhancer features in human embryonic epigenomic data and validate the activity of the human equivalent CHD7 enhancers in the chick embryo. Our findings embed Chd7 in the neural crest gene regulatory network and offer potentially clinically relevant elements for interpreting CHARGE syndrome cases without causative allocation.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478508","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 : 2024-10-15eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002496
Rachel S Clein, Megan R Warren, Joshua P Neunuebel
Intraspecies aggression has profound ecological and evolutionary consequences, as recipients can suffer injuries, decreases in fitness, and become outcasts from social groups. Although animals implement diverse strategies to avoid hostile confrontations, the extent to which social influences affect escape tactics is unclear. Here, we used computational and machine-learning approaches to analyze complex behavioral interactions as mixed-sex groups of mice, Mus musculus, freely interacted. Mice displayed a rich repertoire of behaviors marked by changes in behavioral state, aggressive encounters, and mixed-sex interactions. A distinctive behavioral sequence consistently occurred after aggressive encounters, where males in submissive states quickly approached and transiently interacted with females immediately before the aggressor engaged with the same female. The behavioral sequences were also associated with substantially fewer physical altercations. Furthermore, the male's behavioral state could be predicted by distinct features of the behavioral sequence, such as kinematics and the latency to and duration of male-female interactions. More broadly, our work revealed an ethologically relevant escape strategy influenced by the presence of females that may serve as a mechanism for de-escalating social conflict and preventing consequential reductions in fitness.
{"title":"Mice employ a bait-and-switch escape mechanism to de-escalate social conflict.","authors":"Rachel S Clein, Megan R Warren, Joshua P Neunuebel","doi":"10.1371/journal.pbio.3002496","DOIUrl":"10.1371/journal.pbio.3002496","url":null,"abstract":"<p><p>Intraspecies aggression has profound ecological and evolutionary consequences, as recipients can suffer injuries, decreases in fitness, and become outcasts from social groups. Although animals implement diverse strategies to avoid hostile confrontations, the extent to which social influences affect escape tactics is unclear. Here, we used computational and machine-learning approaches to analyze complex behavioral interactions as mixed-sex groups of mice, Mus musculus, freely interacted. Mice displayed a rich repertoire of behaviors marked by changes in behavioral state, aggressive encounters, and mixed-sex interactions. A distinctive behavioral sequence consistently occurred after aggressive encounters, where males in submissive states quickly approached and transiently interacted with females immediately before the aggressor engaged with the same female. The behavioral sequences were also associated with substantially fewer physical altercations. Furthermore, the male's behavioral state could be predicted by distinct features of the behavioral sequence, such as kinematics and the latency to and duration of male-female interactions. More broadly, our work revealed an ethologically relevant escape strategy influenced by the presence of females that may serve as a mechanism for de-escalating social conflict and preventing consequential reductions in fitness.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478512","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 : 2024-10-14eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002849
Frans Nordén, Behzad Iravani, Martin Schaefer, Anja L Winter, Mikael Lundqvist, Artin Arshamian, Johan N Lundström
A core function of the olfactory system is to determine the valence of odors. In humans, central processing of odor valence perception has been shown to take form already within the olfactory bulb (OB), but the neural mechanisms by which this important information is communicated to, and from, the olfactory cortex (piriform cortex, PC) are not known. To assess communication between the 2 nodes, we simultaneously measured odor-dependent neural activity in the OB and PC from human participants while obtaining trial-by-trial valence ratings. By doing so, we could determine when subjective valence information was communicated, what kind of information was transferred, and how the information was transferred (i.e., in which frequency band). Support vector machine (SVM) learning was used on the coherence spectrum and frequency-resolved Granger causality to identify valence-dependent differences in functional and effective connectivity between the OB and PC. We found that the OB communicates subjective odor valence to the PC in the gamma band shortly after odor onset, while the PC subsequently feeds broader valence-related information back to the OB in the beta band. Decoding accuracy was better for negative than positive valence, suggesting a focus on negative valence. Critically, we replicated these findings in an independent data set using additional odors across a larger perceived valence range. Combined, these results demonstrate that the OB and PC communicate levels of subjective odor pleasantness across multiple frequencies, at specific time points, in a direction-dependent pattern in accordance with a two-stage model of odor processing.
嗅觉系统的一个核心功能是确定气味的价值。在人类中,对气味价值感知的中枢处理已在嗅球(OB)中形成,但这一重要信息与嗅觉皮层(梨状皮层,PC)之间的神经机制尚不清楚。为了评估这两个节点之间的交流,我们同时测量了人类参与者嗅球和PC中依赖于气味的神经活动,同时获得了逐次试验的价值评级。通过这种方法,我们可以确定主观情绪信息何时被传递、传递了何种信息以及信息是如何传递的(即在哪个频段)。我们使用支持向量机(SVM)学习相干频谱和频率分辨格兰杰因果关系,以识别主观情感与主观情感之间的功能和有效连通性的差异。我们发现,在气味开始后不久,嗅觉器官就会在伽马波段将主观气味价值传递给个人计算机,而个人计算机随后会在β波段将与价值相关的信息反馈给嗅觉器官。对负面情绪的解码准确性要好于对正面情绪的解码准确性,这表明负面情绪是解码的重点。重要的是,我们在一个独立的数据集中使用了更多的气味,在更大的感知价位范围内重复了这些发现。综合上述结果,我们发现在特定的时间点,主观气味愉快度的水平会在多个频率上与 OB 和 PC 进行交流,这种交流模式与气味加工的两阶段模型相一致。
{"title":"The human olfactory bulb communicates perceived odor valence to the piriform cortex in the gamma band and receives a refined representation back in the beta band.","authors":"Frans Nordén, Behzad Iravani, Martin Schaefer, Anja L Winter, Mikael Lundqvist, Artin Arshamian, Johan N Lundström","doi":"10.1371/journal.pbio.3002849","DOIUrl":"10.1371/journal.pbio.3002849","url":null,"abstract":"<p><p>A core function of the olfactory system is to determine the valence of odors. In humans, central processing of odor valence perception has been shown to take form already within the olfactory bulb (OB), but the neural mechanisms by which this important information is communicated to, and from, the olfactory cortex (piriform cortex, PC) are not known. To assess communication between the 2 nodes, we simultaneously measured odor-dependent neural activity in the OB and PC from human participants while obtaining trial-by-trial valence ratings. By doing so, we could determine when subjective valence information was communicated, what kind of information was transferred, and how the information was transferred (i.e., in which frequency band). Support vector machine (SVM) learning was used on the coherence spectrum and frequency-resolved Granger causality to identify valence-dependent differences in functional and effective connectivity between the OB and PC. We found that the OB communicates subjective odor valence to the PC in the gamma band shortly after odor onset, while the PC subsequently feeds broader valence-related information back to the OB in the beta band. Decoding accuracy was better for negative than positive valence, suggesting a focus on negative valence. Critically, we replicated these findings in an independent data set using additional odors across a larger perceived valence range. Combined, these results demonstrate that the OB and PC communicate levels of subjective odor pleasantness across multiple frequencies, at specific time points, in a direction-dependent pattern in accordance with a two-stage model of odor processing.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11501019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478514","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 : 2024-10-14eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002823
Kevin Yuswan, Xiaofei Sun, Erina Kuranaga, Daiki Umetsu
Epithelial tissues undergo cell turnover both during development and for homeostatic maintenance. Removal of cells is coordinated with the increase in number of newly dividing cells to maintain barrier function of the tissue. In Drosophila metamorphosis, larval epidermal cells (LECs) are replaced by adult precursor cells called histoblasts. Removal of LECs must counterbalance the exponentially increasing adult histoblasts. Previous work showed that the LEC removal accelerates as endocytic activity decreases throughout all LECs. Here, we show that the acceleration is accompanied by a mode switching from isolated single-cell apoptosis to clustered ones induced by the endocytic activity reduction. We identify the epidermal growth factor receptor (EGFR) pathway via extracellular-signal regulated kinase (ERK) activity as the main components downstream of endocytic activity in LECs. The reduced ERK activity, caused by the decrease in endocytic activity, is responsible for the apoptotic mode switching. Initially, ERK is transiently activated in normal LECs surrounding a single apoptotic LEC in a ligand-dependent manner, preventing clustered cell death. Following the reduction of endocytic activity, LEC apoptosis events do not provoke these transient ERK up-regulations, resulting in the acceleration of the cell elimination rate by frequent clustered apoptosis. These findings contrasted with the common perspective that clustered apoptosis is disadvantageous. Instead, switching to clustered apoptosis is required to accommodate the growth of neighboring tissues.
{"title":"Reduction of endocytosis and EGFR signaling is associated with the switch from isolated to clustered apoptosis during epithelial tissue remodeling in Drosophila.","authors":"Kevin Yuswan, Xiaofei Sun, Erina Kuranaga, Daiki Umetsu","doi":"10.1371/journal.pbio.3002823","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002823","url":null,"abstract":"<p><p>Epithelial tissues undergo cell turnover both during development and for homeostatic maintenance. Removal of cells is coordinated with the increase in number of newly dividing cells to maintain barrier function of the tissue. In Drosophila metamorphosis, larval epidermal cells (LECs) are replaced by adult precursor cells called histoblasts. Removal of LECs must counterbalance the exponentially increasing adult histoblasts. Previous work showed that the LEC removal accelerates as endocytic activity decreases throughout all LECs. Here, we show that the acceleration is accompanied by a mode switching from isolated single-cell apoptosis to clustered ones induced by the endocytic activity reduction. We identify the epidermal growth factor receptor (EGFR) pathway via extracellular-signal regulated kinase (ERK) activity as the main components downstream of endocytic activity in LECs. The reduced ERK activity, caused by the decrease in endocytic activity, is responsible for the apoptotic mode switching. Initially, ERK is transiently activated in normal LECs surrounding a single apoptotic LEC in a ligand-dependent manner, preventing clustered cell death. Following the reduction of endocytic activity, LEC apoptosis events do not provoke these transient ERK up-regulations, resulting in the acceleration of the cell elimination rate by frequent clustered apoptosis. These findings contrasted with the common perspective that clustered apoptosis is disadvantageous. Instead, switching to clustered apoptosis is required to accommodate the growth of neighboring tissues.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485879","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 : 2024-10-14eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002840
Mohammad Marhabaie, Tammy H Wharton, Sung Yun Kim, Robin P Wharton
The translational repressor Nanos (Nos) regulates a single target, maternal hunchback (hb) mRNA, to govern abdominal segmentation in the early Drosophila embryo. Nos is recruited to sites in the 3' UTR of hb mRNA in collaboration with the sequence-specific RNA-binding protein Pumilio (Pum); on its own, Nos has no binding specificity. Nos is expressed at other stages of development, but very few mRNA targets that might mediate its action at these stages have been described. Nor has it been clear whether Nos is targeted to other mRNAs in concert with Pum or via other mechanisms. In this report, we identify mRNAs targeted by Nos via 2 approaches. First, we identify mRNAs depleted upon expression of a chimera bearing Nos fused to the nonsense mediated decay (NMD) factor Upf1. We find that, in addition to hb, Upf1-Nos depletes approximately 2,600 mRNAs from the maternal transcriptome in early embryos. Virtually all of these appear to be targeted in a canonical, hb-like manner in concert with Pum. In a second, more conventional approach, we identify mRNAs that are stabilized during the maternal zygotic transition (MZT) in embryos from nos- females. Most (86%) of the 1,185 mRNAs regulated by Nos are also targeted by Upf1-Nos, validating use of the chimera. Previous work has shown that 60% of the maternal transcriptome is degraded in early embryos. We find that maternal mRNAs targeted by Upf1-Nos are hypoadenylated and inefficiently translated at the ovary-embryo transition; they are subsequently degraded in the early embryo, accounting for 59% of all destabilized maternal mRNAs. We suggest that the late ovarian burst of Nos represses a large fraction of the maternal transcriptome, priming it for later degradation by other factors in the embryo.
{"title":"Widespread regulation of the maternal transcriptome by Nanos in Drosophila.","authors":"Mohammad Marhabaie, Tammy H Wharton, Sung Yun Kim, Robin P Wharton","doi":"10.1371/journal.pbio.3002840","DOIUrl":"10.1371/journal.pbio.3002840","url":null,"abstract":"<p><p>The translational repressor Nanos (Nos) regulates a single target, maternal hunchback (hb) mRNA, to govern abdominal segmentation in the early Drosophila embryo. Nos is recruited to sites in the 3' UTR of hb mRNA in collaboration with the sequence-specific RNA-binding protein Pumilio (Pum); on its own, Nos has no binding specificity. Nos is expressed at other stages of development, but very few mRNA targets that might mediate its action at these stages have been described. Nor has it been clear whether Nos is targeted to other mRNAs in concert with Pum or via other mechanisms. In this report, we identify mRNAs targeted by Nos via 2 approaches. First, we identify mRNAs depleted upon expression of a chimera bearing Nos fused to the nonsense mediated decay (NMD) factor Upf1. We find that, in addition to hb, Upf1-Nos depletes approximately 2,600 mRNAs from the maternal transcriptome in early embryos. Virtually all of these appear to be targeted in a canonical, hb-like manner in concert with Pum. In a second, more conventional approach, we identify mRNAs that are stabilized during the maternal zygotic transition (MZT) in embryos from nos- females. Most (86%) of the 1,185 mRNAs regulated by Nos are also targeted by Upf1-Nos, validating use of the chimera. Previous work has shown that 60% of the maternal transcriptome is degraded in early embryos. We find that maternal mRNAs targeted by Upf1-Nos are hypoadenylated and inefficiently translated at the ovary-embryo transition; they are subsequently degraded in the early embryo, accounting for 59% of all destabilized maternal mRNAs. We suggest that the late ovarian burst of Nos represses a large fraction of the maternal transcriptome, priming it for later degradation by other factors in the embryo.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11501031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478515","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 : 2024-10-14eCollection Date: 2024-10-01DOI: 10.1371/journal.pbio.3002837
Marco Bocchio, Artem Vorobyev, Sadra Sadeh, Sophie Brustlein, Robin Dard, Susanne Reichinnek, Valentina Emiliani, Agnes Baude, Claudia Clopath, Rosa Cossart
Inhibitory interneurons are pivotal components of cortical circuits. Beyond providing inhibition, they have been proposed to coordinate the firing of excitatory neurons within cell assemblies. While the roles of specific interneuron subtypes have been extensively studied, their influence on pyramidal cell synchrony in vivo remains elusive. Employing an all-optical approach in mice, we simultaneously recorded hippocampal interneurons and pyramidal cells and probed the network influence of individual interneurons using optogenetics. We demonstrate that CA1 interneurons form a functionally interconnected network that promotes synchrony through disinhibition during awake immobility, while preserving endogenous cell assemblies. Our network model underscores the importance of both cell assemblies and dense, unspecific interneuron connectivity in explaining our experimental findings, suggesting that interneurons may operate not only via division of labor but also through concerted activity.
{"title":"Functional networks of inhibitory neurons orchestrate synchrony in the hippocampus.","authors":"Marco Bocchio, Artem Vorobyev, Sadra Sadeh, Sophie Brustlein, Robin Dard, Susanne Reichinnek, Valentina Emiliani, Agnes Baude, Claudia Clopath, Rosa Cossart","doi":"10.1371/journal.pbio.3002837","DOIUrl":"10.1371/journal.pbio.3002837","url":null,"abstract":"<p><p>Inhibitory interneurons are pivotal components of cortical circuits. Beyond providing inhibition, they have been proposed to coordinate the firing of excitatory neurons within cell assemblies. While the roles of specific interneuron subtypes have been extensively studied, their influence on pyramidal cell synchrony in vivo remains elusive. Employing an all-optical approach in mice, we simultaneously recorded hippocampal interneurons and pyramidal cells and probed the network influence of individual interneurons using optogenetics. We demonstrate that CA1 interneurons form a functionally interconnected network that promotes synchrony through disinhibition during awake immobility, while preserving endogenous cell assemblies. Our network model underscores the importance of both cell assemblies and dense, unspecific interneuron connectivity in explaining our experimental findings, suggesting that interneurons may operate not only via division of labor but also through concerted activity.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11501041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478510","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}