eLife最新文献

{"title":"Regulative synthesis of capsular polysaccharides in the pathogenesis of <i>Streptococcus suis</i>.","authors":"Xingye Wang, Jie Wang, Ning Li, Xin Fan, Beinan Wang","doi":"10.7554/eLife.101760","DOIUrl":"https://doi.org/10.7554/eLife.101760","url":null,"abstract":"<p><p><i>Streptococcus suis</i> (<i>S. suis</i>) is an important zoonotic pathogen causing substantial economic losses in the swine industry. <i>S. suis</i> serotype 2 (SS2) is often isolated from the diseased. <i>S. suis</i> expresses capsular polysaccharide (CPS), a virulence factor crucial for their survival in the blood. However, the role of CPS in the pathogenesis of <i>S. suis</i> is incomplete. Here, we showed that thin CPS or no CPS was associated with efficient binding of an SS2 strain, 05ZYH33, to respiratory epithelial cells, while thick CPS increased resistance of 05ZYH33 to blood clearance. In a mouse infection model, 05ZYH33 was detected in the nasal-associated lymphoid tissue (NALT) and cerebrospinal fluid (CSF) as early as 30 min after intranasal inoculation without bacteremia. Histological analysis revealed that 05ZYH33 in the nasal cavity invaded the olfactory epithelium, resulting in early brain inflammation. Transmission electron microscopy showed that 05ZYH33 isolated from NALT and CSF at early infection time had a thin layer of CPS, and those detected in the blood 5 hr post-inoculation showed a much thicker CPS. In addition, adoptive transfer of anti-CPS restricted 05ZYH33 in the blood but not in NALT or CSF. However, an antiserum directed to multiple non-CPS virulence factors (anti-V5) efficiently inhibited 05ZYH33 in NALT, CSF, and blood. Thus, 05ZYH33 colonizes NALT more efficiently without CPS and subsequently invades the meninges through the olfactory nerve system. These findings provide valuable information for the treatment of <i>S. suis</i> infection and the development of vaccines across serotypes of <i>S. suis</i> by targeting CPS-independent immunity.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474276","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}

{"title":"Cognitive control of behavior and hippocampal information processing without medial prefrontal cortex.","authors":"Eun Hye Park, Kally C O'Reilly Sparks, Griffin Grubbs, David Taborga, Kyndall Nicholas, Armaan S Ahmed, Natalie Ruiz-Péreza, Natalie Kim, Simon Segura-Carrillo, André A Fenton","doi":"10.7554/eLife.104475","DOIUrl":"https://doi.org/10.7554/eLife.104475","url":null,"abstract":"<p><p>Cognitive control tasks require using one class of information while ignoring competing classes of information. The central role of the medial prefrontal cortex (mPFC) in cognitive control is well established in the primate literature and largely accepted in the rodent literature because mPFC damage causes deficits in tasks that may require cognitive control, as inferred, typically from the task design. In prior work, we used an active place avoidance task where a rat or mouse on a rotating arena is required to avoid the stationary task-relevant locations of a mild shock and ignore the rotating task-irrelevant locations of those shocks. The task is impaired by hippocampal manipulations, and the discharge of hippocampal place cell populations judiciously alternates between representing stationary locations near the shock zone and rotating locations far from the shock zone, demonstrating cognitive control concurrently in behavior and the hippocampal representation of spatial information. Here, we test whether rat mPFC lesion impairs the active place avoidance task to evaluate two competing hypotheses, a 'central-computation' hypothesis that the mPFC is essential for the computations required for cognitive control and an alternative 'local-computation' hypothesis that other brain areas can perform the computations required for cognitive control, independent of mPFC. Ibotenic acid lesion of the mPFC was effective, damaging the cingulate, prelimbic, and infralimbic cortices. The lesion also altered the normal coordination of metabolic activity across remaining structures. The lesion did not impair learning to avoid the initial location of shock or long-term place avoidance memory, but impaired avoidance after the shock was relocated. The lesion also did not impair the alternation between task-relevant and task-irrelevant hippocampal representations of place information. These findings support the local-computation hypothesis that computations required for cognitive control can occur locally in brain networks independently of the mPFC.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474261","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}

{"title":"Synaptic connectivity of sensorimotor circuits for vocal imitation in the songbird.","authors":"Massimo Trusel, Ziran Zhao, Danyal H Alam, Ethan S Marks, Maaya Z Ikeda, Todd F Roberts","doi":"10.7554/eLife.104609","DOIUrl":"10.7554/eLife.104609","url":null,"abstract":"<p><p>Sensorimotor computations for learning and behavior rely on precise patterns of synaptic connectivity. Yet, we typically lack the synaptic wiring diagrams for long-range connections between sensory and motor circuits in the brain. Here, we provide the synaptic wiring diagram for sensorimotor circuits involved in learning and production of male zebra finch song, a natural and ethologically relevant behavior. We examined the functional synaptic connectivity from the 4 main sensory afferent pathways onto the three known classes of projection neurons of the song premotor cortical region HVC. Recordings from hundreds of identified projection neurons reveal rules for monosynaptic connectivity and the existence of polysynaptic ensembles of excitatory and inhibitory neuronal populations in HVC. Circuit tracing further identifies novel connections between HVC's presynaptic partners. Our results indicate a modular organization of ensemble-like networks for integrating long-range input with local circuits, providing important context for information flow and computations for learned vocal behavior.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474282","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}

{"title":"Evidence from pupillometry, fMRI, and RNN modelling shows that gain neuromodulation mediates task-relevant perceptual switches.","authors":"Gabriel Wainstein, Christopher J Whyte, Kaylena A Ehgoetz Martens, Eli J Müller, Vicente Medel, Britt Anderson, Elisabeth Stöttinger, James Danckert, Brandon R Munn, James M Shine","doi":"10.7554/eLife.93191","DOIUrl":"10.7554/eLife.93191","url":null,"abstract":"<p><p>Perceptual updating has been hypothesised to rely on a network reset modulated by bursts of ascending neuromodulatory neurotransmitters, such as noradrenaline, abruptly altering the brain's susceptibility to changing sensory activity. To test this hypothesis at a large-scale, we analysed an ambiguous figures task using pupillometry and functional magnetic resonance imaging (fMRI). Behaviourally, qualitative shifts in the perceptual interpretation of an ambiguous image were associated with peaks in pupil diameter, an indirect readout of phasic bursts in neuromodulatory tone. We further hypothesised that stimulus ambiguity drives neuromodulatory tone, leading to heightened neural gain, hastening perceptual switches. To explore this hypothesis computationally, we trained a recurrent neural network (RNN) on an analogous perceptual categorisation task, allowing gain to change dynamically with classification uncertainty. As predicted, higher gain accelerated perceptual switching by transiently destabilising the network's dynamical regime in periods of maximal uncertainty. We leveraged a low-dimensional readout of the RNN dynamics to develop two novel macroscale predictions: perceptual switches should occur with peaks in low-dimensional brain state velocity and with a flattened egocentric energy landscape. Using fMRI, we confirmed these predictions, highlighting the role of the neuromodulatory system in the large-scale network reconfigurations mediating adaptive perceptual updates.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336325","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}

{"title":"Mapping HIV-1 RNA structure, homodimers, long-range interactions and persistent domains by HiCapR.","authors":"Yan Zhang, Jingwan Han, Xie Dejian, Wenlong Shen, Ping Li, Jian You Lau, Jingyun Li, Lin Li, Grzegorz Kudla, Zhihu Zhao","doi":"10.7554/eLife.102550","DOIUrl":"10.7554/eLife.102550","url":null,"abstract":"<p><p>Human Immunodeficiency Virus type 1 (HIV-1) RNA genome organization remains a critical knowledge gap in understanding its replication cycle. To address this, we developed HiCapR, a psoralen crosslinking-based RNA proximity ligation method coupled with post-library hybridization, enabling high-resolution mapping of RNA-RNA interactions across the HIV-1 genome. This approach confirmed canonical structural motifs, including stem-loop architectures in the 5'-untranslated region (5'-UTR) and Rev Response Element (RRE), as well as dimerization sites within the 5'-UTR critical for viral packaging. Notably, HiCapR identified novel homodimerization events distributed along the genome, suggesting an expanded regulatory role of RNA multimerization in splicing regulation and selective encapsidation. Intriguingly, while infected cells exhibited extensive long-range RNA interactions-particularly within the 5'-UTR-virion-packaged genomes displayed a marked reduction in such interactions, indicative of a structural transition from a loosely organized state to a condensed conformation. This spatial reorganization coincided with the preservation of stable genomic domains essential for dimerization, which persisted throughout virion assembly. These domains, enriched at homodimer interfaces, likely serve as structural scaffolds ensuring fidelity during genome packaging. This work establishes HiCapR as a robust tool for probing RNA interactomes and provides mechanistic insights into how HIV-1 exploits RNA topological heterogeneity to regulate its life cycle. The identification of conserved structural domains and transient interaction networks opens avenues for targeting RNA conformation in antiviral strategies.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332655","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}

{"title":"Efficacy and mechanism of action of cipargamin as an antibabesial drug candidate.","authors":"Hang Li, Shengwei Ji, Nanang R Ariefta, Eloiza May S Galon, Shimaa A E S El-Sayed, Thom Do, Lijun Jia, Miako Sakaguchi, Masahito Asada, Yoshifumi Nishikawa, Xin Qin, Mingming Liu, Xuenan Xuan","doi":"10.7554/eLife.101128","DOIUrl":"10.7554/eLife.101128","url":null,"abstract":"<p><p>Babesiosis is a disease brought on by intraerythrocytic parasites of the genus <i>Babesia</i>. Current chemotherapies are accompanied by side effects and parasite relapse. Therefore, it is crucial to develop highly effective drugs against <i>Babesia</i>. Cipargamin (CIP) has shown inhibition against apicomplexan parasites, mainly <i>Plasmodium</i> and <i>Toxoplasma</i>. This study evaluated the growth-inhibiting properties of CIP against <i>Babesia</i> spp. and investigated the mechanism of CIP on <i>B. gibsoni</i>. The half inhibitory concentration (IC₅₀) values of CIP against the in vitro growth of <i>B. bovis</i> and <i>B. gibsoni</i> were 20.2 ± 1.4 and 69.4 ± 2.2 nM, respectively. CIP significantly inhibited the growth of <i>B. microti</i> and <i>B. rodhaini</i> in vivo. Resistance was conferred by L921V and L921I mutations in BgATP4, which reduced the sensitivity to CIP by 6.1- and 12.8-fold. The inhibitory potency of CIP against BgATP4-associated ATPase activity was moderately reduced in mutant strains, with a 1.3- and 2.4-fold decrease in BgATP4^L921V and BgATP4^L921I, respectively, compared to that of BgATP4^WT. An in silico investigation revealed reductions in affinity for CIP binding to BgATP4^L921V and BgATP4^L921I compared to BgATP4^WT. Resistant strains showed no significant cross-resistance to atovaquone or tafenoquine succinate (TQ), with less than a onefold change in IC₅₀ values. Combining CIP with TQ effectively eliminated <i>B. microti</i> infection in SCID mice with no relapse, and parasite DNA was not detected by qPCR within 90 days post-infection. Our findings reveal the efficacy of CIP as an antibabesial agent, its limitations as a monotherapy due to resistance development, and the potential of combination therapy with TQ to overcome said resistance and achieve complete parasite clearance.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324808","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}

{"title":"<i>Salmonella</i> exploits host- and bacterial-derived β-alanine for replication inside host macrophages.","authors":"Shuai Ma, Bin Yang, Yuyang Sun, Xinyue Wang, Houliang Guo, Ruiying Liu, Ting Ye, Chenbo Kang, Jingnan Chen, Lingyan Jiang","doi":"10.7554/eLife.103714","DOIUrl":"10.7554/eLife.103714","url":null,"abstract":"<p><p><i>Salmonella</i> is a major foodborne pathogen that can effectively replicate inside host macrophages to establish life-threatening systemic infections. <i>Salmonella</i> must utilize diverse nutrients for growth in nutrient-poor macrophages, but which nutrients are required for intracellular <i>Salmonella</i> growth is largely unknown. Here, we found that either acquisition from the host or de novo synthesis of a nonprotein amino acid, β-alanine, is critical for <i>Salmonella</i> replication inside macrophages. The concentration of β-alanine is decreased in <i>Salmonella</i>-infected macrophages, while the addition of exogenous β-alanine enhances <i>Salmonella</i> replication in macrophages, suggesting that <i>Salmonella</i> can uptake host-derived β-alanine for intracellular growth. Moreover, the expression of <i>panD,</i> the rate-limiting gene required for β-alanine synthesis in <i>Salmonella,</i> is upregulated when <i>Salmonella</i> enters macrophages. Mutation of <i>panD</i> impaired <i>Salmonella</i> replication in macrophages and colonization in the mouse liver and spleen, indicating that de novo synthesis of β-alanine is essential for intracellular <i>Salmonella</i> growth and systemic infection. Additionally, we revealed that β-alanine influences <i>Salmonella</i> intracellular replication and in vivo virulence partially by increasing expression of the zinc transporter genes <i>znuABC</i>, which in turn facilitates the uptake of the essential micronutrient zinc by <i>Salmonella</i>. Taken together, these findings highlight the important role of β-alanine in the intracellular replication and virulence of <i>Salmonella</i>, and <i>panD</i> is a promising target for controlling systemic <i>Salmonella</i> infection.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324805","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}

{"title":"A causal role of the NMDA receptor in recurrent processing during perceptual integration.","authors":"Samuel Noorman, Timo Stein, Jasper Zantvoord, Johannes Fahrenfort, Simon van Gaal","doi":"10.7554/eLife.100530","DOIUrl":"10.7554/eLife.100530","url":null,"abstract":"<p><p>Perceptual inference requires the integration of visual features through recurrent processing, the dynamic exchange of information between higher- and lower-level cortical regions. While animal research has demonstrated a crucial role of NMDA receptors in recurrent processing, establishing a causal link between NMDA receptors and recurrent processing in humans has remained challenging. Here, we report two pharmacological studies with randomized, double-blind, crossover designs in which we administered the NMDA antagonist memantine, while collecting human electroencephalography (EEG). We trained and tested EEG classifiers to reflect the processing of specific stimulus features with increasing levels of complexity, namely differences in stimulus contrast, collinearity between local line elements, and illusory surfaces of a Kanizsa triangle. In two experiments involving different participants and visual tasks, we found that memantine selectively improved decoding of the Kanizsa illusion, known to depend on recurrent processing, while leaving decoding of contrast and collinearity largely unaffected. Interestingly, the results from an attentional blink (experiment 1) and task-relevance manipulation (experiment 2) showed that memantine was only effective when the stimulus was attended and consciously accessed. These findings suggest that NMDA inhibition through memantine enhances recurrent processing, especially for attended objects, and thereby provide a crucial step toward bridging animal and human research, shedding light on the neural mechanisms underpinning perceptual inference and conscious perception.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324806","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}

{"title":"Retraction: Targeting posttranslational modifications of RIOK1 inhibits the progression of colorectal and gastric cancers.","authors":"Xuehui Hong, He Huang, Xingfeng Qiu, Zhijie Ding, Xing Feng, Yuekun Zhu, Huiqin Zhuo, Jingjing Hou, Jiabao Zhao, Wangyu Cai, Ruihua Sha, Xinya Hong, Yongxiang Li, Hongjiang Song, Zhiyong Zhang","doi":"10.7554/eLife.108007","DOIUrl":"10.7554/eLife.108007","url":null,"abstract":"<p><p></p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324812","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}

{"title":"A multi-gene predictive model for the radiation sensitivity of nasopharyngeal carcinoma based on machine learning.","authors":"Kailai Li, Junyi Liang, Nan Li, Jianbo Fang, Xinyi Zhou, Jian Zhang, Anqi Lin, Peng Luo, Hui Meng","doi":"10.7554/eLife.99849","DOIUrl":"10.7554/eLife.99849","url":null,"abstract":"<p><p>Radiotherapy resistance in nasopharyngeal carcinoma (NPC) is a major cause of recurrence and metastasis. Identifying radiotherapy-related biomarkers is crucial for improving patient survival outcomes. This study developed the nasopharyngeal carcinoma radiotherapy sensitivity score (NPC-RSS) to predict radiotherapy response. By evaluating 113 machine learning algorithm combinations, the glmBoost+NaiveBayes model was selected to construct the NPC-RSS based on 18 key genes, which demonstrated good predictive performance in both public and in-house datasets. The study found that NPC-RSS is closely associated with immune features, including chemokine factors and their receptor families and the major histocompatibility complex (MHC). Gene functional analysis revealed that NPC-RSS influences key signaling pathways such as Wnt/β-catenin, JAK-STAT, NF-κB, and T cell receptors. Cell line validation confirmed that SMARCA2 and CD9 gene expression is consistent with NPC-RSS. Single-cell analysis revealed that the radiotherapy-sensitive group exhibited richer immune infiltration and activation states. NPC-RSS can serve as a predictive tool for radiotherapy sensitivity in NPC, offering new insights for precise screening of patients who may benefit from radiotherapy.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324807","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}