Communications Biology最新文献_第7页

Deletion of ESX-3 and ESX-4 secretion systems in Mycobacterium abscessus results in highly impaired pathogenicity.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-03 DOI: 10.1038/s42003-025-07572-4

Wassim Daher, Vincent Le Moigne, Yara Tasrini, Shweta Parmar, Danielle L Sexton, John Jairo Aguilera-Correa, Valentin Berdal, Elitza I Tocheva, Jean-Louis Herrmann, Laurent Kremer

{"title":"Deletion of ESX-3 and ESX-4 secretion systems in Mycobacterium abscessus results in highly impaired pathogenicity.","authors":"Wassim Daher, Vincent Le Moigne, Yara Tasrini, Shweta Parmar, Danielle L Sexton, John Jairo Aguilera-Correa, Valentin Berdal, Elitza I Tocheva, Jean-Louis Herrmann, Laurent Kremer","doi":"10.1038/s42003-025-07572-4","DOIUrl":"10.1038/s42003-025-07572-4","url":null,"abstract":"Type VII secretion systems participate in protein export, virulence, conjugation, and metabolic regulation. Five subtypes (ESX-1 to ESX-5) exist, each with specific roles and well-characterized secretion profiles in various mycobacterial species. Mycobacterium abscessus, encodes only ESX-3 and ESX-4. Here, single and double M. abscessus mutants lacking the main ATPases EccC3 and EccC4 were used to define ESX-3 and ESX-4 contributions to substrate secretion and virulence. Our results demonstrate that EsxG/H secretion depends entirely on ESX-3, whereas both ESX-3 and ESX-4 secrete EsxU/T. Furthermore, two newly identified PE/PPE substrates (MAB_0046/MAB_0047) require ESX-3 for secretion. Functional complementation restored secretion and revealed subpolar localization of these systems. Macrophage infections showed that ESX-3 and ESX-4 contribute to bacterial internalization, phagosomal escape, and intracellular survival. In mice, infections with eccC3- and/or eccC4-deletion mutants resulted in complete survival and reduced bacterial loads in the lungs. These findings demonstrate that both ESX systems drive M. abscessus pathogenicity.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"166"},"PeriodicalIF":5.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122258","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}

引用次数: 0

Mapping and modeling age-related changes in intrinsic neural timescales.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-03 DOI: 10.1038/s42003-025-07517-x

Kaichao Wu, Leonardo L Gollo

{"title":"Mapping and modeling age-related changes in intrinsic neural timescales.","authors":"Kaichao Wu, Leonardo L Gollo","doi":"10.1038/s42003-025-07517-x","DOIUrl":"10.1038/s42003-025-07517-x","url":null,"abstract":"Intrinsic timescales of brain regions exhibit heterogeneity, escalating with hierarchical levels, and are crucial for the temporal integration of external stimuli. Aging, often associated with cognitive decline, involves progressive neuronal and synaptic loss, reshaping brain structure and dynamics. However, the impact of these structural changes on temporal coding in the aging brain remains unclear. We mapped intrinsic timescales and gray matter volume (GMV) using magnetic resonance imaging (MRI) in young and elderly adults. We found shorter intrinsic timescales across multiple large-scale functional networks in the elderly cohort, and a significant positive association between intrinsic timescales and GMV. Additionally, age-related decline in performance on visual discrimination tasks was linked to a reduction in intrinsic timescales in the cuneus. To explain these age-related shifts, we developed an age-dependent spiking neuron network model. In younger subjects, brain regions were near a critical branching regime, while regions in elderly subjects had fewer neurons and synapses, pushing the dynamics toward a subcritical regime. The model accurately reproduced the empirical results, showing longer intrinsic timescales in young adults due to critical slowing down. Our findings reveal how age-related structural brain changes may drive alterations in brain dynamics, offering testable predictions and informing possible interventions targeting cognitive decline.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"167"},"PeriodicalIF":5.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122260","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}

引用次数: 0

A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-03 DOI: 10.1038/s42003-025-07600-3

Man Lu, Zhiqiang Cao, Luoan Xiong, Hongying Deng, Kangkang Ma, Ning Liu, Yanding Qin, Shen-Bo Chen, Jun-Hu Chen, Yao Li, Yijin Liu, Zhongbo Yu

{"title":"A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA.","authors":"Man Lu, Zhiqiang Cao, Luoan Xiong, Hongying Deng, Kangkang Ma, Ning Liu, Yanding Qin, Shen-Bo Chen, Jun-Hu Chen, Yao Li, Yijin Liu, Zhongbo Yu","doi":"10.1038/s42003-025-07600-3","DOIUrl":"10.1038/s42003-025-07600-3","url":null,"abstract":"Ribozymes, widely found in prokaryotes and eukaryotes, target nucleic acids and can be engineered as biotechnical tools or for gene regulation or immune therapy. Among them, hammerhead is the smallest and best characterized ribozyme. However, the structure and biochemical data of ribozymes have been disagreed on, making the understanding of its catalysis mechanism a longstanding issue. Particularly, the role of conformational dynamics in ribozyme catalysis remains elusive. Here, we use single-molecule magnetic tweezers to reveal a concerted catalysis mechanism of mechanical conformational selection for a mini hammerhead ribozyme against a viral RNA sequence from the SARS-CoV-2. We identify a conformational set containing five mechanical conformers of the mini ribozyme, where magnesium ions select the active one. Our results are supported by molecular dynamics simulations. Our understanding of the RNA catalytic mechanism will be beneficial for ribozyme's biotechnological applications and as potential therapeutics against RNA viruses.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"165"},"PeriodicalIF":5.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122345","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}

引用次数: 0

Cryo-EM structure of Sudan ebolavirus glycoprotein complexed with its human endosomal receptor NPC1.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-02 DOI: 10.1038/s42003-025-07613-y

Fan Bu, Gang Ye, Hailey Turner-Hubbard, Morgan Herbst, Bin Liu, Fang Li

{"title":"Cryo-EM structure of Sudan ebolavirus glycoprotein complexed with its human endosomal receptor NPC1.","authors":"Fan Bu, Gang Ye, Hailey Turner-Hubbard, Morgan Herbst, Bin Liu, Fang Li","doi":"10.1038/s42003-025-07613-y","DOIUrl":"10.1038/s42003-025-07613-y","url":null,"abstract":"Sudan ebolavirus (SUDV), like Ebola ebolavirus (EBOV), poses a significant threat to global health and security due to its high lethality. However, unlike EBOV, there are no approved vaccines or treatments for SUDV, and its structural interaction with the endosomal receptor NPC1 remains unclear. This study compares the glycoproteins of SUDV and EBOV (in their proteolytically primed forms) and their binding to human NPC1 (hNPC1). The findings reveal that the SUDV glycoprotein binds significantly more strongly to hNPC1 than the EBOV glycoprotein. Using cryo-EM, we determined the structure of the SUDV glycoprotein/hNPC1 complex, identifying four key residues in the SUDV glycoprotein that differ from those in the EBOV glycoprotein and influence hNPC1 binding: Ile79, Ala141, and Pro148 enhance binding, while Gln142 reduces it. Collectively, these residue differences account for SUDV's stronger binding affinity for hNPC1. This study provides critical insights into receptor recognition across all viruses in the ebolavirus genus, including their interactions with receptors in bats, their suspected reservoir hosts. These findings advance our understanding of ebolavirus cell entry, tissue tropism, and host range.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"156"},"PeriodicalIF":5.2,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078823","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}

引用次数: 0

Author Correction: Comparative genomics reveal a novel phylotaxonomic order in the genus Fusobacterium.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-01 DOI: 10.1038/s42003-025-07578-y

Cristian Molteni, Diego Forni, Rachele Cagliani, Manuela Sironi

引用次数: 0

Evidence from a mouse model supports repurposing an anti-asthmatic drug, bambuterol, against Alzheimer's disease by administration through an intranasal route.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-01 DOI: 10.1038/s42003-025-07599-7

Anne-Claire Groo, Thomas Curel, Aurélie Malzert-Fréon, Line Séguy, Ophélie Bento, Sophie Corvaisier, Thomas Culerier, Romain Legrand, Noëlle Callizot, Alexandre Henriques, Georgia Culley, Sylvie Claeysen, Christophe Rochais, Patrick Dallemagne

{"title":"Evidence from a mouse model supports repurposing an anti-asthmatic drug, bambuterol, against Alzheimer's disease by administration through an intranasal route.","authors":"Anne-Claire Groo, Thomas Curel, Aurélie Malzert-Fréon, Line Séguy, Ophélie Bento, Sophie Corvaisier, Thomas Culerier, Romain Legrand, Noëlle Callizot, Alexandre Henriques, Georgia Culley, Sylvie Claeysen, Christophe Rochais, Patrick Dallemagne","doi":"10.1038/s42003-025-07599-7","DOIUrl":"10.1038/s42003-025-07599-7","url":null,"abstract":"Bambuterol is a long-acting anti-asthmatic prodrug which releases terbutaline. Terbutaline is an agonist of the β2-adrenergic receptors which is formed by decarbamoylation of bambuterol by butyrylcholinesterase. Inhibition of the latter, as well as activation of β2-AR, are of interest for the treatment of Alzheimer's disease (AD). Combining these two activities, bambuterol could express a good clinical efficacy against AD. The present work firstly confirmed the capacity of bambuterol to display in cellulo neuroprotective activities, reduction of Tau hyperphosphorylation and preservation of synapses in rat hippocampal neuronal cultures intoxicated with Aβ peptides. Further, bambuterol, in the form of a liposomal gel, showed a good bioavailability in CNS after intranasal administration, which should reduce any side effects linked to peripheral terbutaline release. Indeed, even if the latter is more selective than other β2-mimetics towards bronchial β2-AR, cardiovascular effects (tachycardia, arrhythmias…) could occur upon cardiac β1-AR activation. Finally, intranasal administration of low doses of bambuterol gel in mice intoxicated with Aβ peptides, prevented long-term spatial memory impairment and showed beneficial effects on the survival of neurons and on synapse preservation.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"155"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074085","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}

引用次数: 0

Selective inhibition of TGF-β-induced epithelial-mesenchymal transition overcomes chemotherapy resistance in high-risk lung squamous cell carcinoma.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-01 DOI: 10.1038/s42003-025-07595-x

Liangdong Sun, Jue Wang, Huansha Yu, Xinsheng Zhu, Jing Zhang, Junjie Hu, Yilv Yan, Xun Zhang, Yuming Zhu, Gening Jiang, Ming Ding, Peng Zhang, Lele Zhang

{"title":"Selective inhibition of TGF-β-induced epithelial-mesenchymal transition overcomes chemotherapy resistance in high-risk lung squamous cell carcinoma.","authors":"Liangdong Sun, Jue Wang, Huansha Yu, Xinsheng Zhu, Jing Zhang, Junjie Hu, Yilv Yan, Xun Zhang, Yuming Zhu, Gening Jiang, Ming Ding, Peng Zhang, Lele Zhang","doi":"10.1038/s42003-025-07595-x","DOIUrl":"10.1038/s42003-025-07595-x","url":null,"abstract":"Lung squamous cell carcinoma (LUSC) represents a major subtype of lung cancer, and it demonstrates limited treatment options and worse survival. Identifications of a prognostic model and chemoresistance mechanism can be helpful for improving stratification and guiding therapy decisions. The integrative development of machine learning-based models reveals a random survival forest (RSF) prognostic model for LUSC. The 12-gene RSF model exhibits high prognostic power in more than 1,000 LUSC patients. High-risk LUSC patients are associated with worse survival and the activation of the epithelial-mesenchymal transition pathway. Additionally, high-risk LUSC patients are resistant to docetaxel or vinorelbine treatment. In vitro and in vivo drug sensitivity experiments indicates that high-risk HCC15/H226 tumour cells and cell line-derived xenograft models are more resistant to vinorelbine treatment. Furthermore, the combination of chemotherapy with transforming growth factor-β inhibition augments antitumour responses in LUSC tumours. Our study provides valuable insights into prognosis stratification and the development of therapeutic strategies for LUSC.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"152"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074100","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}

引用次数: 0

Cholecystokinin facilitates the formation of long-term heterosynaptic plasticity in the distal subiculum.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-02-01 DOI: 10.1038/s42003-025-07597-9

Fengwen Huang, Abdul Baset, Stephen Temitayo Bello, Xi Chen, Jufang He

{"title":"Cholecystokinin facilitates the formation of long-term heterosynaptic plasticity in the distal subiculum.","authors":"Fengwen Huang, Abdul Baset, Stephen Temitayo Bello, Xi Chen, Jufang He","doi":"10.1038/s42003-025-07597-9","DOIUrl":"10.1038/s42003-025-07597-9","url":null,"abstract":"It has been well established that Cornu Ammonis-(CA1) and subiculum (SUB) serve as the major output components of the entorhinal-hippocampal circuitry. Nevertheless, how the neuromodulators regulate the neurocircuitry in hippocampal formation has remained elusive. Cholecystokinin (CCK), is the most abundant neuropeptide in the central nervous system, which broadly regulates the animal's physiological status at multiple levels, including neuroplasticity and its behavioral consequences. Here, we uncover that exogenous CCK potentiates the excitatory synaptic transmission in the CA1-SUB projections via CCK-B receptor. Dual-color light theta burst stimulation elicits heterosynaptic long-term potentiation in distal SUB region. Light activation of medial entorhinal cortex (MEC) derived CCK-positive neurons triggers the CCK release in the SUB. Neuronal activities of SUB-projecting MECCCK neurons are necessary for conveying and processing of navigation-related information. In conclusion, our findings prove a crucial role of CCK in regulating neurobiological functions in the SUB region.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"153"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074081","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}

引用次数: 0

GABAergic neurons in basal forebrain exert frequency-specific modulation on auditory cortex and enhance attentional selection of auditory stimuli.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-01-31 DOI: 10.1038/s42003-024-07318-8

Kevin Thomas, Hamid Azimi, Davide Maggioni, Mark Sanders, Pilar Vaca Sánchez, Michael A Harvey, Gregor Rainer

{"title":"GABAergic neurons in basal forebrain exert frequency-specific modulation on auditory cortex and enhance attentional selection of auditory stimuli.","authors":"Kevin Thomas, Hamid Azimi, Davide Maggioni, Mark Sanders, Pilar Vaca Sánchez, Michael A Harvey, Gregor Rainer","doi":"10.1038/s42003-024-07318-8","DOIUrl":"10.1038/s42003-024-07318-8","url":null,"abstract":"The basal forebrain (BF), in particular its cholinergic projections to cortex, has been implicated in regulation of attention in sensory systems. Here, we examine the role of GABAergic projections of the posterior nucleus basalis (pNB) and globus pallidus (GP) in attentional regulation in the auditory system. We employed a detection task where rats detected a narrow band target embedded in broad band noise, while optogenetically modulating GABAergic BF activity. We found that GABAergic BF modulation impacted target detection specifically close to perceptual threshold, consistent with a role in attentional modulation. We also present evidence for target frequency specificity of this modulation, including frequency selectivity and tonotopic organization of pNB/GP, as well as frequency band specific effects of optogenetics on behavioural target detection and on neural activity in auditory cortex and thalamus. Our findings highlight an important role of BF GABAergic neurons in modulating attention in the auditory pathway.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"149"},"PeriodicalIF":5.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074087","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}

引用次数: 0

Selective activation of SIGMAR1 in anterior cingulate cortex glutamatergic neurons facilitates comorbid pain in depression in male mice.

IF 5.2 1区生物学

Communications Biology Pub Date : 2025-01-31 DOI: 10.1038/s42003-025-07590-2

Xianlei Wang, Shulin Wu, Junsheng Zuo, Keying Li, Yutong Chen, Zhijie Fan, Zhou Wu, Jun-Xia Yang, Weiyi Song, Jun-Li Cao, Mengqiao Cui

{"title":"Selective activation of SIGMAR1 in anterior cingulate cortex glutamatergic neurons facilitates comorbid pain in depression in male mice.","authors":"Xianlei Wang, Shulin Wu, Junsheng Zuo, Keying Li, Yutong Chen, Zhijie Fan, Zhou Wu, Jun-Xia Yang, Weiyi Song, Jun-Li Cao, Mengqiao Cui","doi":"10.1038/s42003-025-07590-2","DOIUrl":"10.1038/s42003-025-07590-2","url":null,"abstract":"Depression and comorbid pain are frequently encountered clinically, and the comorbidity complicates the overall medical management. However, the mechanism whereby depression triggers development of pain needs to be further elucidated. Here, by using the chronic restraint stress (CRS) mouse model of depression and comorbid pain, we showed that CRS hyperactivated the glutamatergic neurons in the anterior cingulate cortex (ACC), as well as increasing the dendrite complexity and number. Chemogenetic activation of these neurons can induce depression and pain, while chemogenetic blockade can reverse such depression-induced pain. Moreover, we utilized translating ribosome affinity purification (TRAP) in combination with c-Fos-tTA strategy and pharmacological approaches and identified SIGMAR1 as a potential therapeutic molecular target. These results revealed a previously unknown neural mechanism for depression and pain comorbidity and provided new mechanistic insights into the antidepressive and analgesic effects of the disease.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"8 1","pages":"150"},"PeriodicalIF":5.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074099","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}

引用次数: 0