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MIA40 suppresses cell death induced by apoptosis-inducing factor 1. MIA40抑制凋亡诱导因子1诱导的细胞死亡。
IF 6.5 1区 生物学
EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-07 DOI: 10.1038/s44319-025-00406-8
Ben Hur Marins Mussulini, Klaudia K Maruszczak, Piotr Draczkowski, Mayra A Borrero-Landazabal, Selvaraj Ayyamperumal, Artur Wnorowski, Michal Wasilewski, Agnieszka Chacinska
{"title":"MIA40 suppresses cell death induced by apoptosis-inducing factor 1.","authors":"Ben Hur Marins Mussulini, Klaudia K Maruszczak, Piotr Draczkowski, Mayra A Borrero-Landazabal, Selvaraj Ayyamperumal, Artur Wnorowski, Michal Wasilewski, Agnieszka Chacinska","doi":"10.1038/s44319-025-00406-8","DOIUrl":"10.1038/s44319-025-00406-8","url":null,"abstract":"<p><p>Mitochondria harbor respiratory complexes that perform oxidative phosphorylation. Complex I is the first enzyme of the respiratory chain that oxidizes NADH. A dysfunction in complex I can result in higher cellular levels of NADH, which in turn strengthens the interaction between apoptosis-inducing factor 1 (AIFM1) and Mitochondrial intermembrane space import and assembly protein 40 (MIA40) in the mitochondrial intermembrane space. We investigated whether MIA40 modulates the activity of AIFM1 upon increased NADH/NAD+ balance. We found that in model cells characterized by an increase in NADH the AIFM1-MIA40 interaction is strengthened and these cells demonstrate resistance to AIFM1-induced cell death. Either silencing of MIA40, rescue of complex I, or depletion of NADH through the expression of yeast NADH-ubiquinone oxidoreductase-2 sensitized NDUFA13-KO cells to AIFM1-induced cell death. These findings indicate that the complex of MIA40 and AIFM1 suppresses AIFM1-induced cell death in a NADH-dependent manner. This study identifies an effector complex involved in regulating the programmed cell death that accommodates the metabolic changes in the cell and provides a molecular explanation for AIFM1-mediated chemoresistance of cancer cells.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1835-1862"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Autocrine Wingless constricts the Drosophila embryonic gut by Ca+2-mediated repolarisation of mesoderm cells. 自分泌无翅通过Ca+2介导的中胚层细胞重极化收缩果蝇胚胎肠。
IF 6.5 1区 生物学
EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-07 DOI: 10.1038/s44319-025-00411-x
Delia Ricolo, Francesca Tamba, Jordi Casanova
{"title":"Autocrine Wingless constricts the Drosophila embryonic gut by Ca<sup>+2</sup>-mediated repolarisation of mesoderm cells.","authors":"Delia Ricolo, Francesca Tamba, Jordi Casanova","doi":"10.1038/s44319-025-00411-x","DOIUrl":"10.1038/s44319-025-00411-x","url":null,"abstract":"<p><p>Wg/Wnt signalling-a highly conserved transduction pathway-has most commonly been found to be involved in patterning, cell fate, or cell proliferation, but less so in shaping organs or body parts. A remarkable case of the latter is the role of Wg signalling in the midgut of the Drosophila embryo. The Drosophila embryonic midgut is divided into four chambers that arise by the formation of three constrictions at distinct sites along the midgut. In particular, Wg is responsible for the middle constriction, a role first described more than 30 years ago. However, while some partial data have been obtained regarding the formation of this gut constriction, an overall picture of the process is lacking. Here we unveil that Wg signalling leads to this constriction by inducing ClC-a transcription in a subset of mesodermal cells. ClC-a, encodes a chloride channel, which in turn prompts a Ca<sup>+2</sup> pulse in these cells. Consequently, the mesoderm cells, which already showed some polarity, repolarise and in so doing so they reshape the microtubule organisation, therefore inducing the constriction of the cells.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1737-1748"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cytosolic CRISPR RNAs for efficient application of RNA-targeting CRISPR-Cas systems. 有效应用 RNA 靶向 CRISPR-Cas 系统的细胞膜 CRISPR RNA。
IF 6.5 1区 生物学
EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-02-26 DOI: 10.1038/s44319-025-00399-4
Ezra C K Cheng, Joe K C Lam, S Chul Kwon
{"title":"Cytosolic CRISPR RNAs for efficient application of RNA-targeting CRISPR-Cas systems.","authors":"Ezra C K Cheng, Joe K C Lam, S Chul Kwon","doi":"10.1038/s44319-025-00399-4","DOIUrl":"10.1038/s44319-025-00399-4","url":null,"abstract":"<p><p>Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) technologies have evolved rapidly over the past decade with the continuous discovery of new Cas systems. In particular, RNA-targeting CRISPR-Cas13 proteins are promising single-effector systems to regulate target mRNAs without altering genomic DNA, yet the current Cas13 systems are restrained by suboptimal efficiencies. Here, we show that U1 promoter-driven CRISPR RNAs (crRNAs) increase the efficiency of various applications, including RNA knockdown and editing, without modifying the Cas13 protein effector. We confirm that U1-driven crRNAs are exported into the cytoplasm, while conventional U6 promoter-driven crRNAs are mostly confined to the nucleus. Furthermore, we reveal that the end positions of crRNAs expressed by the U1 promoter are consistent regardless of guide sequences and lengths. We also demonstrate that U1-driven crRNAs, but not U6-driven crRNAs, can efficiently repress the translation of target genes in combination with catalytically inactive Cas13 proteins. Finally, we show that U1-driven crRNAs can counteract the inhibitory effect of miRNAs. Our simple and effective engineering enables unprecedented cytosolic RNA-targeting applications.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1891-1912"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of cable bacteria genera reveals details of their conduction machinery. 电缆细菌属的比较揭示了它们的传导机制的细节。
IF 6.5 1区 生物学
EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-02-17 DOI: 10.1038/s44319-025-00387-8
Leonid Digel, Mads L Justesen, Nikoline S Madsen, Nico Fransaert, Koen Wouters, Robin Bonné, Lea E Plum-Jensen, Ian P G Marshall, Pia B Jensen, Louison Nicolas-Asselineau, Taner Drace, Andreas Bøggild, John L Hansen, Andreas Schramm, Espen D Bøjesen, Lars Peter Nielsen, Jean V Manca, Thomas Boesen
{"title":"Comparison of cable bacteria genera reveals details of their conduction machinery.","authors":"Leonid Digel, Mads L Justesen, Nikoline S Madsen, Nico Fransaert, Koen Wouters, Robin Bonné, Lea E Plum-Jensen, Ian P G Marshall, Pia B Jensen, Louison Nicolas-Asselineau, Taner Drace, Andreas Bøggild, John L Hansen, Andreas Schramm, Espen D Bøjesen, Lars Peter Nielsen, Jean V Manca, Thomas Boesen","doi":"10.1038/s44319-025-00387-8","DOIUrl":"10.1038/s44319-025-00387-8","url":null,"abstract":"<p><p>Cable bacteria are centimeter-long multicellular bacteria conducting electricity through periplasmic conductive fibers (PCFs). Using single-strain enrichments of the genera Electrothrix and Electronema we systematically investigate variations and similarities in morphology and electrical properties across both genera. Electrical conductivity of different PCFs spans three orders of magnitude warranting further investigations of the plasticity of their conduction machinery. Using electron microscopy and elemental analyses, we show that the two cable bacteria genera have similar cell envelopes and cell-cell junction ultrastructures. Iron, sulfur, and nickel signals are co-localized with the PCFs, indicating key functional roles of these elements. The PCFs are organized as stranded rope-like structures composed of multiple strands. Furthermore, we report lamellae-like structures formed at the cell-cell junctions with a core layer connecting to the PCFs, and intriguing vesicle-like inner membrane invaginations below the PCFs. Finally, using bioinformatic tools, we identify a cytochrome family with predicted structural homology to known multi-heme nanowire proteins from other electroactive microorganisms and suggest that these cytochromes can play a role in the extra- or intercellular electron conduction of cable bacteria.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1749-1767"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Auditory fear memory retrieval requires BLA-LS and LS-VMH circuitries via GABAergic and dopaminergic neurons. 听觉恐惧记忆提取需要通过gaba能和多巴胺能神经元的BLA-LS和LS-VMH回路。
IF 6.5 1区 生物学
EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-07 DOI: 10.1038/s44319-025-00403-x
Miao Chen, Jun Li, Weiran Shan, Jianjun Yang, Zhiyi Zuo
{"title":"Auditory fear memory retrieval requires BLA-LS and LS-VMH circuitries via GABAergic and dopaminergic neurons.","authors":"Miao Chen, Jun Li, Weiran Shan, Jianjun Yang, Zhiyi Zuo","doi":"10.1038/s44319-025-00403-x","DOIUrl":"10.1038/s44319-025-00403-x","url":null,"abstract":"<p><p>Fear and associated learning and memory are critical for developing defensive behavior. Excessive fear and anxiety are important components of post-traumatic stress disorder. However, the neurobiology of fear conditioning, especially tone-related fear memory retrieval, has not been clearly defined, which limits specific intervention development for patients with excessive fear and anxiety. Here, we show that auditory fear memory retrieval stimuli activate multiple brain regions including the lateral septum (LS). Inhibition of the LS and the connection between basolateral amygdala (BLA) and LS or between LS and ventromedial nucleus of the hypothalamus (VMH) attenuates tone-related fear conditioning and memory retrieval. Inhibiting GABAergic neurons or dopaminergic neurons in the LS also attenuates tone-related fear conditioning. Our data further show that fear conditioning is inhibited by blocking orexin B signaling in the LS. Our results indicate that the neural circuitries BLA-LS and LS-VMH are critical for tone-related fear conditioning and memory retrieval, and that GABAergic neurons, dopaminergic neurons and orexin signaling in the LS participate in this auditory fear conditioning.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1816-1834"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regulating stem cell-based embryo model research in Japan : Proposals, debates, and future directions. 调控日本干细胞胚胎模型研究:建议、争论和未来方向。
IF 6.5 1区 生物学
EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-14 DOI: 10.1038/s44319-025-00409-5
Tsutomu Sawai, Shu Ishida, Chie Kobayashi, Yasuna Murase, Gyo Nakao, Tomonori Nakamura, Julian Savulescu
{"title":"Regulating stem cell-based embryo model research in Japan : Proposals, debates, and future directions.","authors":"Tsutomu Sawai, Shu Ishida, Chie Kobayashi, Yasuna Murase, Gyo Nakao, Tomonori Nakamura, Julian Savulescu","doi":"10.1038/s44319-025-00409-5","DOIUrl":"10.1038/s44319-025-00409-5","url":null,"abstract":"","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1682-1687"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Caspase cleavage of influenza A virus M2 disrupts M2-LC3 interaction and regulates virion production. 甲型流感病毒M2的Caspase切割破坏了M2- lc3相互作用并调节病毒粒子的产生。
IF 6.5 1区 生物学
EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-03 DOI: 10.1038/s44319-025-00388-7
Carmen Figueras-Novoa, Masato Akutsu, Daichi Murata, Anne Weston, Ming Jiang, Beatriz Montaner, Christelle Dubois, Avinash Shenoy, Rupert Beale
{"title":"Caspase cleavage of influenza A virus M2 disrupts M2-LC3 interaction and regulates virion production.","authors":"Carmen Figueras-Novoa, Masato Akutsu, Daichi Murata, Anne Weston, Ming Jiang, Beatriz Montaner, Christelle Dubois, Avinash Shenoy, Rupert Beale","doi":"10.1038/s44319-025-00388-7","DOIUrl":"10.1038/s44319-025-00388-7","url":null,"abstract":"<p><p>Influenza A virus (IAV) Matrix 2 protein (M2) is an ion channel, required for efficient viral entry and egress. M2 interacts with the small ubiquitin-like LC3 protein through a cytoplasmic C-terminal LC3-interacting region (LIR). Here, we report that M2 is cleaved by caspases, abolishing the M2-LC3 interaction. A crystal structure of the M2 LIR in complex with LC3 indicates the caspase cleavage tetrapeptide motif (<sub>82</sub>SAVD<sub>85</sub>) is an unstructured linear motif that does not overlap with the LIR. IAV mutant expressing a permanently truncated M2, mimicking caspase cleavage, exhibit defects in M2 plasma membrane transport, viral filament formation, and virion production. Our results reveal a dynamic regulation of the M2-LC3 interaction by caspases. This highlights the role of host proteases in regulating IAV exit, relating virion production with host cell state.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1768-1791"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pumilio differentially binds to mRNA 3' UTR isoforms to regulate localization of synaptic proteins. Pumilio与mRNA 3' UTR异构体的差异结合调节突触蛋白的定位。
IF 6.5 1区 生物学
EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-02-21 DOI: 10.1038/s44319-025-00401-z
Dominika Grzejda, Anton Hess, Andrew Rezansoff, Sakshi Gorey, Judit Carrasco, Carlos Alfonso-Gonzalez, Stylianos Tsagkris, Lena Neuhaus, Mengjin Shi, Hasan Can Ozbulut, Friederike-Nora Vögtle, Andreas Vlachos, Valérie Hilgers
{"title":"Pumilio differentially binds to mRNA 3' UTR isoforms to regulate localization of synaptic proteins.","authors":"Dominika Grzejda, Anton Hess, Andrew Rezansoff, Sakshi Gorey, Judit Carrasco, Carlos Alfonso-Gonzalez, Stylianos Tsagkris, Lena Neuhaus, Mengjin Shi, Hasan Can Ozbulut, Friederike-Nora Vögtle, Andreas Vlachos, Valérie Hilgers","doi":"10.1038/s44319-025-00401-z","DOIUrl":"10.1038/s44319-025-00401-z","url":null,"abstract":"<p><p>In neuronal cells, the regulation of RNA is crucial for the spatiotemporal control of gene expression, but how the correct localization, levels, and function of synaptic proteins are achieved is not well understood. In this study, we globally investigate the role of alternative 3' UTRs in regulating RNA localization in the synaptic regions of the Drosophila brain. We identify direct mRNA targets of the translational repressor Pumilio, finding that mRNAs bound by Pumilio encode proteins enriched in synaptosomes. Pumilio differentially binds to RNA isoforms of the same gene, favoring long, neuronal 3' UTRs. These longer 3' UTRs tend to remain in the neuronal soma, whereas shorter UTR isoforms localize to the synapse. In cultured pumilio mutant neurons, axon outgrowth defects are accompanied by mRNA isoform mislocalization, and proteins encoded by these Pumilio target mRNAs display excessive abundance at synaptic boutons. Our study identifies an important mechanism for the spatiotemporal regulation of protein function in neurons.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1792-1815"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Under pressure. 在压力下。
IF 6.5 1区 生物学
EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-18 DOI: 10.1038/s44319-025-00419-3
Bernd Pulverer
{"title":"Under pressure.","authors":"Bernd Pulverer","doi":"10.1038/s44319-025-00419-3","DOIUrl":"10.1038/s44319-025-00419-3","url":null,"abstract":"","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1673-1675"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The NLRP1 inflammasome is an essential and selective mediator of axon pruning in neurons. NLRP1炎性体是神经元轴突修剪的一个重要和选择性介质。
IF 6.5 1区 生物学
EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-02-26 DOI: 10.1038/s44319-025-00402-y
Selena E Romero, Matthew J Geden, Richa Basundra, Kiran Kelly-Rajan, Edward A Miao, Mohanish Deshmukh
{"title":"The NLRP1 inflammasome is an essential and selective mediator of axon pruning in neurons.","authors":"Selena E Romero, Matthew J Geden, Richa Basundra, Kiran Kelly-Rajan, Edward A Miao, Mohanish Deshmukh","doi":"10.1038/s44319-025-00402-y","DOIUrl":"10.1038/s44319-025-00402-y","url":null,"abstract":"<p><p>Axon pruning is a unique process neurons utilize to selectively degenerate axon branches while keeping the neuronal cell body intact. The mechanisms of axon pruning have much in common with those of apoptosis. Both axon pruning and apoptosis pathways require key apoptotic proteins (Bax, Caspase-9, Caspase-3). Interestingly, axon pruning does not require Apaf-1, a key member of the apoptosome complex. As such, exactly how caspases are activated in an apoptosome-independent manner during axon pruning is unknown. Here we show that neurons utilize the NLRP1 inflammasome, an innate immune sensor of pathogens, specifically for axon pruning. Strikingly, NLRP1b-deficient neurons were unable to prune axons both in vitro and in vivo, but fully capable of degenerating during apoptosis. Our results reveal NLRP1 as an immune molecule engaged by neurons for an unexpected physiological function independent of its pathogen-induced proinflammatory role.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"1724-1736"},"PeriodicalIF":6.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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