eLife最新文献_第2页

The cow udder as an influenza mixing ground. 奶牛的乳房是流感的温床。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-15 DOI: 10.7554/eLife.113101

Silke Rimaux, Robert P de Vries

引用次数: 0

The 42 problem in AI-assisted research. 人工智能辅助研究中的第42个问题。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-14 DOI: 10.7554/eLife.113137

Giovanni Spitale, Federico Germani

引用次数: 0

Salmonids elicit an acute behavioral response to heterothermal environments. 鲑鱼引起急性行为反应，以异温环境。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-14 DOI: 10.7554/eLife.99126

Robert Naudascher, Stefano Brizzolara, Jonasz Slomka, Robert M Boes, Markus Holzner, Luiz G M Silva, Roman Stocker

{"title":"Salmonids elicit an acute behavioral response to heterothermal environments.","authors":"Robert Naudascher, Stefano Brizzolara, Jonasz Slomka, Robert M Boes, Markus Holzner, Luiz G M Silva, Roman Stocker","doi":"10.7554/eLife.99126","DOIUrl":"10.7554/eLife.99126","url":null,"abstract":"Most fish species are ectothermic and rely on behavioral strategies to control their body temperature in heterothermal environments. Both thermotaxis and thermokinesis have been suggested as important underlying mechanisms. However, to what extent these behaviors allow fish to respond to rapid (timescales of minutes) and strong thermal disturbances, like those caused by anthropogenic water releases into natural freshwater systems, is poorly understood. Here, we quantify this response for a salmonid species with a novel laboratory approach coupled with image-based tracking. We exposed brown trout parr (Salmo trutta), acclimated to 12 °C, to rapidly forming cold- and warm-water interfaces with temperatures ranging from 4 to 20 °C. We found that fish actively avoided colder water (≤8 °C) through a rapid response that combined thermotaxis and thermokinesis. In contrast, fish did not avoid warmer water and frequently crossed interfaces having temperature contrasts of up to 8 °C. This study shows that brown trout parr swiftly deploy multiple behavioral strategies to minimize exposure to cold water and take advantage of warm water, illustrating their capability to cope with rapidly occurring thermal alterations.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180075","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

Correction: A Ctnnb1 enhancer transcriptionally regulates Wnt signaling dosage to balance homeostasis and tumorigenesis of intestinal epithelia. 更正：Ctnnb1增强子通过转录调节Wnt信号剂量来平衡肠道上皮的稳态和肿瘤发生。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-14 DOI: 10.7554/eLife.113472

Xiaojiao Hua, Chen Zhao, Jianbo Tian, Junbao Wang, Xiaoping Miao, Gen Zheng, Min Wu, Mei Ye, Ying Liu, Yan Zhou

引用次数: 0

Allosteric disulfide control of ligand binding and endocytosis of KIR2DL4, the natural killer cell receptor for HLA-G. HLA-G的自然杀伤细胞受体KIR2DL4的配体结合和内吞的变构二硫控制。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-13 DOI: 10.7554/eLife.111018

Sumati Rajagopalan, Joyce Chiu, Priyanka Chaurasia, Jinghua Lu, George M Mastorakos, Saurav Majumder, Kristof T Nolan, Jan Petersen, Erin J Adams, Peter D Sun, Jamie Rossjohn, Philip J Hogg, Eric O Long

{"title":"Allosteric disulfide control of ligand binding and endocytosis of KIR2DL4, the natural killer cell receptor for HLA-G.","authors":"Sumati Rajagopalan, Joyce Chiu, Priyanka Chaurasia, Jinghua Lu, George M Mastorakos, Saurav Majumder, Kristof T Nolan, Jan Petersen, Erin J Adams, Peter D Sun, Jamie Rossjohn, Philip J Hogg, Eric O Long","doi":"10.7554/eLife.111018","DOIUrl":"https://doi.org/10.7554/eLife.111018","url":null,"abstract":"Human Leukocyte Antigen (HLA)-G is selectively expressed by fetal trophoblast cells that encounter maternal natural killer (NK) cells early in pregnancy. In response to HLA-G, the endosomal NK cell receptor KIR2DL4 induces a transcriptional program to support placental development. Structural features of KIR2DL4 that control HLA-G binding and endocytosis are unclear. Random mutagenesis revealed that three cysteines in the first immunoglobulin domain of KIR2DL4 regulate endocytosis and uptake of HLA-G. The atypical Cys10-Cys28 disulfide bond in the KIR2DL4 structure is an allosteric disulfide with potential to switch to a conventional Cys28-Cys74 bond. KIR2DL4 in human cells exists in both disulfide-bonded states, as shown by mass spectrometry analysis. The Cys10-Cys28 bond in a Cys74Ser KIR2DL4 mutant was reduced by protein disulfide isomerase (PDI) in vitro. Inhibition of PDI prevented HLA-G uptake by KIR2DL4 in NK cells. Mutants in the Cys10-Cys28 configuration endocytosed spontaneously but did not bind HLA-G. Conversely, KIR2DL4 with a Cys28-Cys74 bond was detectable at the plasma membrane and internalized soluble HLA-G. A purified Cys10Leu KIR2DL4 mutant bound HLA-G with micromolar affinity in a peptide-dependent manner. Thus, allosteric disulfide-mediated conversion from an inactive to an HLA-G binding form regulates KIR2DL4 trafficking and a functional response that promotes fetal development.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180060","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

Designing optimal perturbation inputs for system identification in neuroscience. 设计神经科学系统辨识的最佳摄动输入。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-13 DOI: 10.7554/eLife.110030

Mikito Ogino, Daiki Sekizawa, Jun Kitazono, Masafumi Oizumi

{"title":"Designing optimal perturbation inputs for system identification in neuroscience.","authors":"Mikito Ogino, Daiki Sekizawa, Jun Kitazono, Masafumi Oizumi","doi":"10.7554/eLife.110030","DOIUrl":"https://doi.org/10.7554/eLife.110030","url":null,"abstract":"Investigating the dynamics of neural networks, which are governed by connectivity between neurons, is a fundamental challenge in neuroscience. Because passive (spontaneous) activity provides only limited information for estimating connectivity, perturbation-based approaches are widely applied in neuroscience as they can evoke underlying hidden dynamics. However, the characteristics of such perturbations have typically been designed based on empirical or biological intuition. To enable more accurate estimation of connectivity, we propose a data-driven and theoretically grounded framework for optimally designing perturbation inputs, based on formulating the neural model as a control system. The core theoretical insight underlying our approach is that neural signals observed in the passive state lack sufficient latent information, which leads to failures in the system identification. Perturbations reveal these hidden dynamics and lead to improved estimation. Guided by these insights, we derive a theoretical basis for optimizing perturbation inputs that minimize estimation errors in neural system identification. Building upon this, we further explore the relationship of this theory with stimulation patterns commonly used in neuroscience, such as frequency, impulse, and step inputs. We demonstrate the effectiveness of this framework for neuroscience through simulations grounded in experimental paradigms, such as neural state classification and optimal control of neural states. Our theoretical analysis, together with multiple simulations, consistently shows that perturbations designed according to our framework achieve substantially more accurate system identification compared to the conventional, intuition-based inputs. This study provides a theoretical foundation for designing perturbation inputs to achieve accurate estimation of neural dynamics. This, in turn, enables reliable discrimination of neural states such as levels of consciousness and pathological conditions, and facilitates precise control of their transitions toward recovery from abnormal states.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180096","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

Reduced dorsal CA1 activity limits retention of the temporal component of declarative memory in the Cntnap2 knockout mouse model of autism. 在Cntnap2基因敲除的自闭症小鼠模型中，背侧CA1活性的降低限制了陈述性记忆的时间成分的保留。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-13 DOI: 10.7554/eLife.111851

Elise Caitlin Rawlinson, Michael Hugh McCullough, Azza Sellami, Aline Marighetto, Alice Shaam Al-Abed, Nathalie Dehorter

{"title":"Reduced dorsal CA1 activity limits retention of the temporal component of declarative memory in the Cntnap2 knockout mouse model of autism.","authors":"Elise Caitlin Rawlinson, Michael Hugh McCullough, Azza Sellami, Aline Marighetto, Alice Shaam Al-Abed, Nathalie Dehorter","doi":"10.7554/eLife.111851","DOIUrl":"https://doi.org/10.7554/eLife.111851","url":null,"abstract":"Growing evidence implicates the hippocampus in the pathophysiology of autism spectrum disorder, particularly in the domains of social interactions and cognition. Yet, the mechanisms driving the hippocampal-dependent cognitive atypicalities in autism remain poorly defined. Here, we characterized how dysfunction of the CA1 subfield of the dorsal hippocampus drives abnormalities in critical components of declarative memory. Using trace fear conditioning in the Cntnap2 knockout mouse model of autism, we found that capabilities to retain the association of temporally distant stimuli (i.e. temporal binding) were reduced relative to wildtype mice. Fiber photometry and optogenetic experiments demonstrated that reduced CA1 activity during temporal gaps underlies this impairment, linking CA1 dysfunction to a deficit in long-term memory retention in autism. Using a relational/declarative memory task, we also revealed a deficit in flexible spatial memory, and a preferential use of egocentric learning strategy. This inflexible learning strategy resulted from an imbalance between memory system activity, promoting frontostriatal-dependent procedural learning instead of dorsal CA1/hippocampus-dependent relational/declarative memory. Overall, this study establishes dorsal CA1 dysfunction as a circuit-level mechanism underlying cognitive inflexibility in autism, providing a neurobiological framework for hippocampal-dependent memory deficits in the condition.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180070","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

Anatomy and mechanics of tsetse fly blood feeding. 采采蝇吸血的解剖学和力学。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-13 DOI: 10.7554/eLife.110151

Stephan Löwe, Laura Hauf, Elisabeth Meyer-Natus, Dianah Katiti, Dennis Petersen, Alexander Kovalev, Sebastian Büsse, Anna Steyer, Yoko Matsumura, Wolfgang Böhme, Daniel Masiga, Stanislav Gorb, Markus Engstler

{"title":"Anatomy and mechanics of tsetse fly blood feeding.","authors":"Stephan Löwe, Laura Hauf, Elisabeth Meyer-Natus, Dianah Katiti, Dennis Petersen, Alexander Kovalev, Sebastian Büsse, Anna Steyer, Yoko Matsumura, Wolfgang Böhme, Daniel Masiga, Stanislav Gorb, Markus Engstler","doi":"10.7554/eLife.110151","DOIUrl":"10.7554/eLife.110151","url":null,"abstract":"Human African trypanosomiasis (HAT) is a neglected tropical disease transmitted by infected tsetse flies (Glossina spp.) in sub-Saharan Africa. Infected tsetse flies can transmit trypanosomes, including Trypanosoma brucei subspecies that cause HAT in humans, as well as other trypanosome species that cause animal African trypanosomiasis in domestic animals and infect wildlife. Tsetse flies feed on a broad spectrum of hosts, including humans, elephants, buffaloes, rhinos, hippos, turtles, and monitor lizards. To understand how the insects can penetrate such diverse skin types, we detailed the anatomical structures involved in tsetse blood feeding, their mechanical properties, and the forces exerted by the fly during probing. We found that the tsetse fly's feeding apparatus does not rely on exceptionally unique structures or extraordinary forces. Instead, the tsetse fly has evolved subtle yet highly efficient adaptations, which include a labellum equipped with arrays of small teeth. When combined with a robust retraction movement of the proboscis, these structures create lesions on various types of skin, thus facilitating blood pool feeding on a broad host spectrum.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165344","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

JAK-STAT pathway heterogeneity governs immunotherapy response in breast cancer. JAK-STAT通路异质性决定乳腺癌免疫治疗反应。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-13 DOI: 10.7554/eLife.110635

Jianbo Zhou, Heng Zhang, Hailin Tang, Lei Yu, Fu Peng

{"title":"JAK-STAT pathway heterogeneity governs immunotherapy response in breast cancer.","authors":"Jianbo Zhou, Heng Zhang, Hailin Tang, Lei Yu, Fu Peng","doi":"10.7554/eLife.110635","DOIUrl":"10.7554/eLife.110635","url":null,"abstract":"The JAK-STAT pathway (JSP) is a well-known oncogenic cascade; however, recent clinical trials have detected JSP upregulation in breast cancer following anti-PD-1 immunotherapy. This paradoxical observation warrants further investigation into JSP's intercellular heterogeneity, tumor dynamics, molecular mechanisms, and clinical implications for immunotherapy. JSP expression showed dynamic shifts during breast cancer progression, with higher levels in T cells and paracancerous epithelial cells. In human breast cancer tumor cells, elevated JSP is highly correlated with malignant phenotypes. JSP-high tumor cells overexpressed oncogenic pathways, while exhibiting increased immunosuppressive signaling via the MIF-CD74 signaling axis. In T cells, higher JSP levels were associated with enhanced cytotoxic activity, improved differentiation, and reduced exhaustion, reflecting robust anti-tumor immunity. Analysis of immunotherapy datasets revealed that higher JSP levels were associated with improved responses toward PD-1 inhibitors, particularly in triple-negative breast cancer (TNBC) patients, with JSP serving as a predictive biomarker for immunotherapy sensitivity. As a key JSP component, STAT4 exerts dual roles in breast cancer: it drives tumorigenesis in malignant cells, sustains breast epithelial cell proliferation, and bolsters T-cell anti-tumor functionality, while also acting as a highly accurate biomarker for predicting immunotherapy response. This indicates that JSP targeting demands a nuanced approach: broad inhibition may impair anti-tumor immunity, and optimized therapeutic strategies paired with precise biomarkers are critical to maximize JSP's utility in breast cancer immunotherapy. Our findings highlight JSP's functional heterogeneity in epithelial, tumor, and T cells, with high JSP activity correlating with enhanced immunotherapy efficacy in breast cancer.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164456","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

Gluconeogenic compensation renders glycogen phosphorylase non-essential as an insecticidal target in Plutella xylostella. 糖异生补偿使得糖原磷酸化酶不需要作为小菜蛾的杀虫靶点。

IF 6.4 1区生物学

eLife Pub Date : 2026-10-13 DOI: 10.7554/eLife.111144

Yifei Zhou, Yanqi Kang, Yan Liu, Ruichi Li, Dongliang Wang, Chong Yi, Yifan Li, Yalin Zhang, Zhen Tian, Jiyuan Liu

{"title":"Gluconeogenic compensation renders glycogen phosphorylase non-essential as an insecticidal target in Plutella xylostella.","authors":"Yifei Zhou, Yanqi Kang, Yan Liu, Ruichi Li, Dongliang Wang, Chong Yi, Yifan Li, Yalin Zhang, Zhen Tian, Jiyuan Liu","doi":"10.7554/eLife.111144","DOIUrl":"https://doi.org/10.7554/eLife.111144","url":null,"abstract":"Glycogen phosphorylase (GP) catalyzes the rate-limiting step of glycogenolysis and supplies precursors for chitin biosynthesis in insects. Acyl urea compounds structurally related to benzoylphenylurea (BPU) insecticides are potent inhibitors of mammalian GP, raising the question of whether insect GP could serve as an independent insecticidal target. Here, we show that a mammalian GP inhibitor (GPI) potently inhibits recombinant Plutella xylostella GP (PxGP; IC50=2.96 nM), while the BPU insecticide diflubenzuron does not. Molecular docking and MM/GBSA analysis predict that this selectivity reflects differential side-chain engagement. Despite potent in vitro inhibition, GPI exhibits no insecticidal activity, and RNAi-mediated knockdown of PxGP does not impair development or survival. We provide evidence that insects compensate through upregulation of gluconeogenic enzymes (PEPCK, G-6-Pase) and protein catabolism, with enzyme activity measurements confirming ~29% reduction in GP-a activity following RNAi. Fitness assessment reveals transient larval weight loss with complete recovery of pupal weight, adult morphology, and fecundity. These findings demonstrate that GP is functionally non-essential under the tested conditions, likely through gluconeogenic compensation and alternative carbon sources, and highlight the importance of metabolic network redundancy in target-based insecticide design.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"15 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180085","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