eLife最新文献_第6页

fmo-4 promotes longevity and stress resistance via ER to mitochondria calcium regulation in C. elegans.

IF 6.4 1区生物学

eLife Pub Date : 2025-02-14 DOI: 10.7554/eLife.99971

Angela M Tuckowski, Safa Beydoun, Elizabeth S Kitto, Ajay Bhat, Marshall B Howington, Aditya Sridhar, Mira Bhandari, Kelly Chambers, Scott F Leiser

{"title":"fmo-4 promotes longevity and stress resistance via ER to mitochondria calcium regulation in C. elegans.","authors":"Angela M Tuckowski, Safa Beydoun, Elizabeth S Kitto, Ajay Bhat, Marshall B Howington, Aditya Sridhar, Mira Bhandari, Kelly Chambers, Scott F Leiser","doi":"10.7554/eLife.99971","DOIUrl":"10.7554/eLife.99971","url":null,"abstract":"Flavin-containing monooxygenases (FMOs) are a conserved family of xenobiotic enzymes upregulated in multiple longevity interventions, including nematode and mouse models. Previous work supports that C. elegans fmo-2 promotes longevity, stress resistance, and healthspan by rewiring endogenous metabolism. However, there are five C. elegans FMOs and five mammalian FMOs, and it is not known whether promoting longevity and health benefits is a conserved role of this gene family. Here, we report that expression of C. elegans fmo-4 promotes lifespan extension and paraquat stress resistance downstream of both dietary restriction and inhibition of mTOR. We find that overexpression of fmo-4 in just the hypodermis is sufficient for these benefits, and that this expression significantly modifies the transcriptome. By analyzing changes in gene expression, we find that genes related to calcium signaling are significantly altered downstream of fmo-4 expression. Highlighting the importance of calcium homeostasis in this pathway, fmo-4 overexpressing animals are sensitive to thapsigargin, an ER stressor that inhibits calcium flux from the cytosol to the ER lumen. This calcium/fmo-4 interaction is solidified by data showing that modulating intracellular calcium with either small molecules or genetics can change expression of fmo-4 and/or interact with fmo-4 to affect lifespan and stress resistance. Further analysis supports a pathway where fmo-4 modulates calcium homeostasis downstream of activating transcription factor-6 (atf-6), whose knockdown induces and requires fmo-4 expression. Together, our data identify fmo-4 as a longevity-promoting gene whose actions interact with known longevity pathways and calcium homeostasis.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413681","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 within-host infection model to explore tolerance and resistance.

IF 6.4 1区生物学

eLife Pub Date : 2025-02-13 DOI: 10.7554/eLife.104052

David Duneau, Pierre D M Lafont, Christine Lauzeral, Nathalie Parthuisot, Christian Faucher, Xuerong Jin, Nicolas Buchon, Jean-Baptiste Ferdy

{"title":"A within-host infection model to explore tolerance and resistance.","authors":"David Duneau, Pierre D M Lafont, Christine Lauzeral, Nathalie Parthuisot, Christian Faucher, Xuerong Jin, Nicolas Buchon, Jean-Baptiste Ferdy","doi":"10.7554/eLife.104052","DOIUrl":"https://doi.org/10.7554/eLife.104052","url":null,"abstract":"How are some individuals surviving infections while others die? The answer lies in how infected individuals invest into controlling pathogen proliferation and mitigating damage, two strategies respectively called resistance and disease tolerance. Pathogen within-host dynamics (WHD), influenced by resistance, and its connection to host survival, determined by tolerance, decide the infection outcome. To grasp these intricate effects of resistance and tolerance, we used a deterministic theoretical model where pathogens interact with the immune system of a host. The model describes the positive and negative regulation of the immune response, consider the way damage accumulate during the infection and predicts WHD. When chronic, infections stabilize at a Set-Point Pathogen Load (SPPL). Our model predicts that this situation can be transient, the SPPL being then a predictor of life span which depends on initial condition (e.g. inoculum). When stable, the SPPL is rather diagnostic of non lethal chronic infections. In lethal infections, hosts die at a Pathogen Load Upon Death (PLUD) which is almost independent from the initial conditions. As the SPPL, the PLUD is affected by both resistance and tolerance but we demonstrate that it can be used in conjunction with mortality measurement to distinguish the effect of disease tolerance from that of resistance. We validate empirically this new approach, using Drosophila melanogaster and the pathogen Providencia rettgeri. We found that, as predicted by the model, hosts that were wounded or deficient of key antimicrobial peptides had a higher PLUD, while Catalase mutant hosts, likely to have a default in disease tolerance, had a lower PLUD.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406250","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

Mechanism of dimer selectivity and binding cooperativity of BRAF inhibitors.

IF 6.4 1区生物学

eLife Pub Date : 2025-02-13 DOI: 10.7554/eLife.95334

Joseph Clayton, Aarion Romany, Evangelia Matenoglou, Evripidis Gavathiotis, Poulikos I Poulikakos, Jana Shen

{"title":"Mechanism of dimer selectivity and binding cooperativity of BRAF inhibitors.","authors":"Joseph Clayton, Aarion Romany, Evangelia Matenoglou, Evripidis Gavathiotis, Poulikos I Poulikakos, Jana Shen","doi":"10.7554/eLife.95334","DOIUrl":"10.7554/eLife.95334","url":null,"abstract":"Aberrant signaling of BRAFV600E is a major cancer driver. Current FDA-approved RAF inhibitors selectively inhibit the monomeric BRAFV600E and suffer from tumor resistance. Recently, dimer-selective and equipotent RAF inhibitors have been developed; however, the mechanism of dimer selectivity is poorly understood. Here, we report extensive molecular dynamics (MD) simulations of the monomeric and dimeric BRAFV600E in the apo form or in complex with one or two dimer-selective (PHI1) or equipotent (LY3009120) inhibitor(s). The simulations uncovered the unprecedented details of the remarkable allostery in BRAFV600E dimerization and inhibitor binding. Specifically, dimerization retrains and shifts the αC helix inward and increases the flexibility of the DFG motif; dimer compatibility is due to the promotion of the αC-in conformation, which is stabilized by a hydrogen bond formation between the inhibitor and the αC Glu501. A more stable hydrogen bond further restrains and shifts the αC helix inward, which incurs a larger entropic penalty that disfavors monomer binding. This mechanism led us to propose an empirical way based on the co-crystal structure to assess the dimer selectivity of a BRAFV600E inhibitor. Simulations also revealed that the positive cooperativity of PHI1 is due to its ability to preorganize the αC and DFG conformation in the opposite protomer, priming it for binding the second inhibitor. The atomically detailed view of the interplay between BRAF dimerization and inhibitor allostery as well as cooperativity has implications for understanding kinase signaling and contributes to the design of protomer selective RAF inhibitors.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405585","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

Quantification of Salmonella enterica serovar Typhimurium population dynamics in murine infection using a highly diverse barcoded library.

IF 6.4 1区生物学

eLife Pub Date : 2025-02-13 DOI: 10.7554/eLife.101388

Julia A Hotinger, Ian W Campbell, Karthik Hullahalli, Akina Osaki, Matthew K Waldor

{"title":"Quantification of Salmonella enterica serovar Typhimurium population dynamics in murine infection using a highly diverse barcoded library.","authors":"Julia A Hotinger, Ian W Campbell, Karthik Hullahalli, Akina Osaki, Matthew K Waldor","doi":"10.7554/eLife.101388","DOIUrl":"10.7554/eLife.101388","url":null,"abstract":"Murine models are often used to study the pathogenicity and dissemination of the enteric pathogen Salmonella enterica serovar Typhimurium. Here, we quantified S. Typhimurium population dynamics in mice using the STAMPR analytic pipeline and a highly diverse S. Typhimurium barcoded library containing ~55,000 unique strains distinguishable by genomic barcodes by enumerating S. Typhimurium founding populations and deciphering routes of spread in mice. We found that a severe bottleneck allowed only one in a million cells from an oral inoculum to establish a niche in the intestine. Furthermore, we observed compartmentalization of pathogen populations throughout the intestine, with few barcodes shared between intestinal segments and feces. This severe bottleneck widened and compartmentalization was reduced after streptomycin treatment, suggesting the microbiota plays a key role in restricting the pathogen's colonization and movement within the intestine. Additionally, there was minimal sharing between the intestine and extraintestinal organ populations, indicating dissemination to extraintestinal sites occurs rapidly, before substantial pathogen expansion in the intestine. Bypassing the intestinal bottleneck by inoculating mice via intravenous or intraperitoneal injection revealed that Salmonella re-enters the intestine after establishing niches in extraintestinal sites by at least two distinct pathways. One pathway results in a diverse intestinal population. The other re-seeding pathway is through the bile, where the pathogen is often clonal, leading to clonal intestinal populations and correlates with gallbladder pathology. Together, these findings deepen our understanding of Salmonella population dynamics.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406026","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

From histology to macroscale function in the human amygdala.

IF 6.4 1区生物学

eLife Pub Date : 2025-02-13 DOI: 10.7554/eLife.101950

Hans Auer, Donna Gift Cabalo, Raúl Rodríguez-Cruces, Oualid Benkarim, Casey Paquola, Jordan DeKraker, Yezhou Wang, Sofie Louise Valk, Boris C Bernhardt, Jessica Royer

{"title":"From histology to macroscale function in the human amygdala.","authors":"Hans Auer, Donna Gift Cabalo, Raúl Rodríguez-Cruces, Oualid Benkarim, Casey Paquola, Jordan DeKraker, Yezhou Wang, Sofie Louise Valk, Boris C Bernhardt, Jessica Royer","doi":"10.7554/eLife.101950","DOIUrl":"10.7554/eLife.101950","url":null,"abstract":"The amygdala is a subcortical region in the mesiotemporal lobe that plays a key role in emotional and sensory functions. Conventional neuroimaging experiments treat this structure as a single, uniform entity, but there is ample histological evidence for subregional heterogeneity in microstructure and function. The current study characterized subregional structure-function coupling in the human amygdala, integrating post-mortem histology and in vivo MRI at ultra-high fields. Core to our work was a novel neuroinformatics approach that leveraged multiscale texture analysis as well as non-linear dimensionality reduction techniques to identify salient dimensions of microstructural variation in a 3D post-mortem histological reconstruction of the human amygdala. We observed two axes of subregional variation in this region, describing inferior-superior as well as mediolateral trends in microstructural differentiation that in part recapitulated established atlases of amygdala subnuclei. Translating our approach to in vivo MRI data acquired at 7 Tesla, we could demonstrate the generalizability of these spatial trends across 10 healthy adults. We then cross-referenced microstructural axes with functional blood-oxygen-level dependent (BOLD) signal analysis obtained during task-free conditions, and revealed a close association of structural axes with macroscale functional network embedding, notably the temporo-limbic, default mode, and sensory-motor networks. Our novel multiscale approach consolidates descriptions of amygdala anatomy and function obtained from histological and in vivo imaging techniques.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406517","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

The population genetics of convergent adaptation in maize and teosinte is not locally restricted.

IF 6.4 1区生物学

eLife Pub Date : 2025-02-13 DOI: 10.7554/eLife.92405

Silas Tittes, Anne Lorant, Sean P McGinty, James B Holland, Jose de Jesus Sánchez-González, Arun Seetharam, Maud Tenaillon, Jeffrey Ross-Ibarra

{"title":"The population genetics of convergent adaptation in maize and teosinte is not locally restricted.","authors":"Silas Tittes, Anne Lorant, Sean P McGinty, James B Holland, Jose de Jesus Sánchez-González, Arun Seetharam, Maud Tenaillon, Jeffrey Ross-Ibarra","doi":"10.7554/eLife.92405","DOIUrl":"10.7554/eLife.92405","url":null,"abstract":"What is the genetic architecture of local adaptation and what is the geographic scale over which it operates? We investigated patterns of local and convergent adaptation in five sympatric population pairs of traditionally cultivated maize and its wild relative teosinte (Zea mays subsp. parviglumis). We found that signatures of local adaptation based on the inference of adaptive fixations and selective sweeps are frequently exclusive to individual populations, more so in teosinte compared to maize. However, for both maize and teosinte, selective sweeps are also frequently shared by several populations, and often between subspecies. We were further able to infer that selective sweeps were shared among populations most often via migration, though sharing via standing variation was also common. Our analyses suggest that teosinte has been a continued source of beneficial alleles for maize, even after domestication, and that maize populations have facilitated adaptation in teosinte by moving beneficial alleles across the landscape. Taken together, our results suggest local adaptation in maize and teosinte has an intermediate geographic scale, one that is larger than individual populations but smaller than the species range.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"12 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406270","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

CryoEM structures of Kv1.2 potassium channels, conducting and non-conducting.

IF 6.4 1区生物学

eLife Pub Date : 2025-02-13 DOI: 10.7554/eLife.89459

Yangyu Wu, Yangyang Yan, Youshan Yang, Shumin Bian, Alberto Rivetta, Ken Allen, Fred J Sigworth

{"title":"CryoEM structures of Kv1.2 potassium channels, conducting and non-conducting.","authors":"Yangyu Wu, Yangyang Yan, Youshan Yang, Shumin Bian, Alberto Rivetta, Ken Allen, Fred J Sigworth","doi":"10.7554/eLife.89459","DOIUrl":"10.7554/eLife.89459","url":null,"abstract":"We present near-atomic-resolution cryoEM structures of the mammalian voltage-gated potassium channel Kv1.2 in open, C-type inactivated, toxin-blocked and sodium-bound states at 3.2 Å, 2.5 Å, 3.2 Å, and 2.9 Å. These structures, all obtained at nominally zero membrane potential in detergent micelles, reveal distinct ion-occupancy patterns in the selectivity filter. The first two structures are very similar to those reported in the related Shaker channel and the much-studied Kv1.2-2.1 chimeric channel. On the other hand, two new structures show unexpected patterns of ion occupancy. First, the toxin α-Dendrotoxin, like Charybdotoxin, is seen to attach to the negatively-charged channel outer mouth, and a lysine residue penetrates into the selectivity filter, with the terminal amine coordinated by carbonyls, partially disrupting the outermost ion-binding site. In the remainder of the filter two densities of bound ions are observed, rather than three as observed with other toxin-blocked Kv channels. Second, a structure of Kv1.2 in Na+ solution does not show collapse or destabilization of the selectivity filter, but instead shows an intact selectivity filter with ion density in each binding site. We also attempted to image the C-type inactivated Kv1.2 W366F channel in Na+ solution, but the protein conformation was seen to be highly variable and only a low-resolution structure could be obtained. These findings present new insights into the stability of the selectivity filter and the mechanism of toxin block of this intensively studied, voltage-gated potassium channel.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"12 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406257","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

Pharmacologic activation of integrated stress response kinases inhibits pathologic mitochondrial fragmentation. 药物激活综合应激反应激酶可抑制病理性线粒体破碎。

IF 6.4 1区生物学

eLife Pub Date : 2025-02-12 DOI: 10.7554/eLife.100541

Kelsey R Baron, Samantha Oviedo, Sophia Krasny, Mashiat Zaman, Rama Aldakhlallah, Prerona Bora, Prakhyat Mathur, Gerald Pfeffer, Michael J Bollong, Timothy E Shutt, Danielle A Grotjahn, R Luke Wiseman

{"title":"Pharmacologic activation of integrated stress response kinases inhibits pathologic mitochondrial fragmentation.","authors":"Kelsey R Baron, Samantha Oviedo, Sophia Krasny, Mashiat Zaman, Rama Aldakhlallah, Prerona Bora, Prakhyat Mathur, Gerald Pfeffer, Michael J Bollong, Timothy E Shutt, Danielle A Grotjahn, R Luke Wiseman","doi":"10.7554/eLife.100541","DOIUrl":"10.7554/eLife.100541","url":null,"abstract":"Excessive mitochondrial fragmentation is associated with the pathologic mitochondrial dysfunction implicated in the pathogenesis of etiologically diverse diseases, including many neurodegenerative disorders. The integrated stress response (ISR) - comprising the four eIF2α kinases PERK, GCN2, PKR, and HRI - is a prominent stress-responsive signaling pathway that regulates mitochondrial morphology and function in response to diverse types of pathologic insult. This suggests that pharmacologic activation of the ISR represents a potential strategy to mitigate pathologic mitochondrial fragmentation associated with human disease. Here, we show that pharmacologic activation of the ISR kinases HRI or GCN2 promotes adaptive mitochondrial elongation and prevents mitochondrial fragmentation induced by the calcium ionophore ionomycin. Further, we show that pharmacologic activation of the ISR reduces mitochondrial fragmentation and restores basal mitochondrial morphology in patient fibroblasts expressing the pathogenic D414V variant of the pro-fusion mitochondrial GTPase MFN2 associated with neurological dysfunctions, including ataxia, optic atrophy, and sensorineural hearing loss. These results identify pharmacologic activation of ISR kinases as a potential strategy to prevent pathologic mitochondrial fragmentation induced by disease-relevant chemical and genetic insults, further motivating the pursuit of highly selective ISR kinase-activating compounds as a therapeutic strategy to mitigate mitochondrial dysfunction implicated in diverse human diseases.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11820110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398656","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

Brain areas for reversible symbolic reference, a potential singularity of the human brain. 可逆符号参照的脑区，人脑的潜在奇异之处。

IF 6.4 1区生物学

eLife Pub Date : 2025-02-12 DOI: 10.7554/eLife.87380

Timo van Kerkoerle, Louise Pape, Milad Ekramnia, Xiaoxia Feng, Jordy Tasserie, Morgan Dupont, Xiaolian Li, Béchir Jarraya, Wim Vanduffel, Stanislas Dehaene, Ghislaine Dehaene-Lambertz

{"title":"Brain areas for reversible symbolic reference, a potential singularity of the human brain.","authors":"Timo van Kerkoerle, Louise Pape, Milad Ekramnia, Xiaoxia Feng, Jordy Tasserie, Morgan Dupont, Xiaolian Li, Béchir Jarraya, Wim Vanduffel, Stanislas Dehaene, Ghislaine Dehaene-Lambertz","doi":"10.7554/eLife.87380","DOIUrl":"10.7554/eLife.87380","url":null,"abstract":"The emergence of symbolic thinking has been proposed as a dominant cognitive criterion to distinguish humans from other primates during hominisation. Although the proper definition of a symbol has been the subject of much debate, one of its simplest features is bidirectional attachment: the content is accessible from the symbol, and vice versa. Behavioural observations scattered over the past four decades suggest that this criterion might not be met in non-human primates, as they fail to generalise an association learned in one temporal order (A to B) to the reverse order (B to A). Here, we designed an implicit fMRI test to investigate the neural mechanisms of arbitrary audio-visual and visual-visual pairing in monkeys and humans and probe their spontaneous reversibility. After learning a unidirectional association, humans showed surprise signals when this learned association was violated. Crucially, this effect occurred spontaneously in both learned and reversed directions, within an extended network of high-level brain areas, including, but also going beyond, the language network. In monkeys, by contrast, violations of association effects occurred solely in the learned direction and were largely confined to sensory areas. We propose that a human-specific brain network may have evolved the capacity for reversible symbolic reference.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"12 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11820117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398675","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

Decoding phase separation of prion-like domains through data-driven scaling laws. 通过数据驱动的缩放规律解码朊病毒样域的相分离。

IF 6.4 1区生物学

eLife Pub Date : 2025-02-12 DOI: 10.7554/eLife.99068

M Julia Maristany, Anne Aguirre Gonzalez, Jorge R Espinosa, Jan Huertas, Rosana Collepardo-Guevara, Jerelle A Joseph

引用次数: 0