IF 6.4 1区生物学

eLife Pub Date : 2025-07-09 DOI: 10.7554/eLife.100947

Rubén Mollá-Albaladejo, Manuel Jiménez-Caballero, Juan Antonio Sanchez-Alcaniz

{"title":"Molecular characterization of gustatory second-order neurons reveals integrative mechanisms of gustatory and metabolic information.","authors":"Rubén Mollá-Albaladejo, Manuel Jiménez-Caballero, Juan Antonio Sanchez-Alcaniz","doi":"10.7554/eLife.100947","DOIUrl":"10.7554/eLife.100947","url":null,"abstract":"Animals must balance the urgent need to find food during starvation with the critical necessity to avoid toxic substances to ensure their survival. In Drosophila, specialized Gustatory Receptors (GRs) expressed in Gustatory Receptor Neurons (GRNs) are critical for distinguishing between nutritious and potentially toxic food. GRNs project their axons from taste organs to the Subesophageal Zone (SEZ) in the Central Brain (CB) of Drosophila, where gustatory information is processed. Although the roles of GRs and GRNs are well-documented, the processing of gustatory information in the SEZ remains unclear. To better understand gustatory sensory processing and feeding decision-making, we molecularly characterized the first layer of gustatory interneurons, referred to as Gustatory Second-Order Neurons (G2Ns), which receive direct input from GRNs. Using trans-synaptic tracing with trans-Tango, cell sorting, and bulk RNAseq under fed and starved conditions, we discovered that G2Ns vary based on gustatory input and that their molecular profile changes with the fly's metabolic state. Further data analysis has revealed that a pair of neurons in the SEZ, expressing the neuropeptide Leucokinin (SELK neurons), receive simultaneous input from GRNs sensing bitter (potentially toxic) and sweet (nutritious) information. Additionally, these neurons also receive inputs regarding the starvation levels of the fly. These results highlight a novel mechanism of feeding regulation and metabolic integration.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590715","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

CRISPR-edited DPSCs constitutively expressing BDNF enhance dentin regeneration in injured teeth. crispr编辑的组成性表达BDNF的DPSCs促进损伤牙齿的牙本质再生。

IF 6.4 1区生物学

eLife Pub Date : 2025-07-09 DOI: 10.7554/eLife.105153

Ji Hyun Kim, Muhammad Irfan, Sreelekshmi Sreekumar, Atsawasuwan Phimon, Stephanie Kim, Seung Chung

{"title":"CRISPR-edited DPSCs constitutively expressing BDNF enhance dentin regeneration in injured teeth.","authors":"Ji Hyun Kim, Muhammad Irfan, Sreelekshmi Sreekumar, Atsawasuwan Phimon, Stephanie Kim, Seung Chung","doi":"10.7554/eLife.105153","DOIUrl":"10.7554/eLife.105153","url":null,"abstract":"Dental caries, a prevalent global health issue, results from complex bacterial interactions. In response to harmful stimuli, a desirable outcome for the tooth is the formation of tertiary dentin, a protective reparative process that generates new hard tissue. This reparative dentinogenesis is associated with significant inflammation, which triggers the recruitment and differentiation of dental pulp stem cells (DPSCs). Previously, we have demonstrated that brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB), key mediators of neural functions, are activated during the DPSC-mediated dentin regeneration process. In this study, we further define the role of inflammation in this process and apply stem cell engineering to enhance dentin regeneration in injured teeth. Our data show that TrkB expression and activation in DPSCs rapidly increase during odontogenic differentiation, further amplified by inflammatory inducers and mediators such as tumor necrosis factor alpha (TNFα), lymphotoxin-alpha, and lipopolysaccharide. An in vivo dentin formation assessment was conducted using a mouse pulp-capping/caries model, where Clustered Regularly Interspaced Short Palindromic Repeats-engineered DPSCs overexpressing BDNF were transplanted into inflamed pulp tissue. This transplantation significantly enhanced dentin regeneration in injured teeth. To further explore potential downstream pathways, we conducted transcriptomic profiling of TNFα-treated DPSCs, both with and without TrkB antagonist cyclotraxin-B. The results revealed significant changes in gene expression related to immune response, cytokine signaling, and extracellular matrix interactions. Taken together, our study advances our understanding of the role of BDNF in dental tissue engineering using DPSCs and identifies potential therapeutic avenues for improving dental tissue repair and regeneration strategies.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590720","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 temporally restricted function of the dopamine receptor Dop1R2 during memory formation. 多巴胺受体Dop1R2在记忆形成过程中的暂时受限功能。

IF 6.4 1区生物学

eLife Pub Date : 2025-07-09 DOI: 10.7554/eLife.99368

Jenifer C Kaldun, Emanuele Calia, Ganesh Chinmai Bangalore Mukunda, Cornelia Fritsch, Nikita Komarov, Simon G Sprecher

{"title":"A temporally restricted function of the dopamine receptor Dop1R2 during memory formation.","authors":"Jenifer C Kaldun, Emanuele Calia, Ganesh Chinmai Bangalore Mukunda, Cornelia Fritsch, Nikita Komarov, Simon G Sprecher","doi":"10.7554/eLife.99368","DOIUrl":"10.7554/eLife.99368","url":null,"abstract":"Dopamine is a crucial neuromodulator involved in many brain processes, including learning and the formation of memories. Dopamine acts through multiple receptors and controls an intricate signaling network to regulate different tasks. While the diverse functions of dopamine are intensely studied, the interplay and role of the distinct dopamine receptors to regulate different processes is less well understood. An interesting candidate is the dopamine receptor Dop1R2 (also known as Damb), as it could connect to different downstream pathways. Dop1R2 is reported to be involved in forgetting and memory maintenance; however, the circuits requiring the receptors are unknown. To study Dop1R2 and its role in specific spatial and temporal contexts, we generated a conditional knockout line using the CRISPR-Cas9 technique. Two FRT sites were inserted, allowing flippase-mediated excision of the dopamine receptor in neurons of interest. To study the function of Dop1R2, we knocked it out conditionally in the mushroom body of Drosophila melanogaster, a well-studied brain region for memory formation. We show that Dop1R2 is required for later memory forms but not for short-term aversive or appetitive memories. Moreover, Dop1R2 is specifically required in the α/β-lobe and the α'/β'-lobe but not in the γ-lobe of the mushroom body. Our findings show a spatially and temporally restricted role of Dop1R2 in the process of memory formation, highlighting the differential requirement of receptors during distinct phases of learning.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590712","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

Prebiotic gas flow environment enables isothermal nucleic acid replication. 益生元气体流动环境使核酸等温复制成为可能。

IF 6.4 1区生物学

eLife Pub Date : 2025-07-09 DOI: 10.7554/eLife.100152

Philipp Schwintek, Emre Eren, Christof Bernhard Mast, Dieter Braun

{"title":"Prebiotic gas flow environment enables isothermal nucleic acid replication.","authors":"Philipp Schwintek, Emre Eren, Christof Bernhard Mast, Dieter Braun","doi":"10.7554/eLife.100152","DOIUrl":"10.7554/eLife.100152","url":null,"abstract":"Nucleic acid replication is a central process at the origin of life. On early Earth, replication is challenged by the dilution of molecular building blocks and the difficulty of separating daughter from parent strands, a necessity for exponential replication. While thermal gradient systems have been shown to address these problems, elevated temperatures lead to degradation. Also, compared to constant temperature environments, such systems are rare. The isothermal system studied here models an abundant geological environment of the prebiotic Earth, in which water is continuously evaporated at the point of contact with the gas flows, inducing up-concentration and circular flow patterns at the gas-water interface through momentum transfer. We show experimentally that this setting drives a 30-fold accumulation of nucleic acids and their periodic separation by a threefold reduction in salt and product concentration. Fluid dynamic simulations agree with observations from tracking fluorescent beads. In this isothermal system, we were able to drive exponential DNA replication with Taq polymerase. The results provide a model for a ubiquitous non-equilibrium system to host early Darwinian molecular evolution at constant temperature.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590716","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

Fast evolution of SOS-independent multi-drug resistance in bacteria. 细菌不依赖于sos的多药耐药性的快速进化。

IF 6.4 1区生物学

eLife Pub Date : 2025-07-09 DOI: 10.7554/eLife.95058

Le Zhang, Yunpeng Guan, YuenYee Cheng, Nural N Cokcetin, Amy L Bottomley, Andrew Robinson, Elizabeth J Harry, Antoine M van Oijen, Qian Peter Su, Dayong Jin

{"title":"Fast evolution of SOS-independent multi-drug resistance in bacteria.","authors":"Le Zhang, Yunpeng Guan, YuenYee Cheng, Nural N Cokcetin, Amy L Bottomley, Andrew Robinson, Elizabeth J Harry, Antoine M van Oijen, Qian Peter Su, Dayong Jin","doi":"10.7554/eLife.95058","DOIUrl":"10.7554/eLife.95058","url":null,"abstract":"The killing mechanism of many antibiotics involves the induction of DNA damage, either directly or indirectly, which activates the SOS response. RecA, the master regulator of the SOS response, has been shown to play a central role in the evolution of resistance to fluoroquinolones, even after short-term exposure. While this paradigm is well established for DNA-damaging antibiotics, it remains unclear whether β-lactams elicit similar resistance dynamics or depend on RecA and SOS-mediated mechanisms. In this study, we observed a rapid and stable evolution of β-lactam resistance (20-fold MIC increase within 8 hr) in Escherichia coli lacking RecA after a single exposure to ampicillin. Contrary to expectation, this resistance emerged through an SOS-independent mechanism involving two distinct evolutionary forces: increased mutational supply and antibiotic-driven selection. Specifically, we found that RecA deletion impaired DNA repair and downregulated base excision repair pathways, while concurrently repressing the transcription of antioxidative defence genes. This dual impairment led to excessive accumulation of reactive oxygen species (ROS), which in turn promoted the emergence of resistance-conferring mutations. While ampicillin treatment did not alter survival, it selectively enriched for rare mutants arising in the RecA-deficient and ROS-elevated background. Collectively, our findings demonstrate that this oxidative environment, together with compromised DNA repair capacity, increases genetic instability and creates a selective landscape favouring the expansion of resistant clones. These results highlight the repair-redox axis as a key determinant of bacterial evolvability under antimicrobial stress.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590713","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

Returning aging cells to productivity. 使老化细胞恢复生产力。

IF 6.4 1区生物学

eLife Pub Date : 2025-07-08 DOI: 10.7554/eLife.107777

Rachana S Vaidya, Simon Y Tang

引用次数: 0

Humans adapt rationally to approximate estimates of uncertainty. 人类理性地适应对不确定性的近似估计。

IF 6.4 1区生物学

eLife Pub Date : 2025-07-08 DOI: 10.7554/eLife.103734

Erdem Pulcu, Michael Browning

引用次数: 0

Epithelial cell chirality emerges through the dynamic concentric pattern of actomyosin cytoskeleton. 上皮细胞手性是通过肌动球蛋白细胞骨架的动态同心模式产生的。

IF 6.4 1区生物学

eLife Pub Date : 2025-07-08 DOI: 10.7554/eLife.102296

Takaki Yamamoto, Tomoki Ishibashi, Yuko Mimori-Kiyosue, Sylvain Hiver, Naoko Tokushige, Mitsusuke Tarama, Masatoshi Takeichi, Tatsuo Shibata

{"title":"Epithelial cell chirality emerges through the dynamic concentric pattern of actomyosin cytoskeleton.","authors":"Takaki Yamamoto, Tomoki Ishibashi, Yuko Mimori-Kiyosue, Sylvain Hiver, Naoko Tokushige, Mitsusuke Tarama, Masatoshi Takeichi, Tatsuo Shibata","doi":"10.7554/eLife.102296","DOIUrl":"https://doi.org/10.7554/eLife.102296","url":null,"abstract":"The chirality of tissues and organs is essential for their proper function and development. Tissue-level chirality derives from the chirality of individual cells that comprise the tissue, and cellular chirality is considered to emerge through the organization of chiral molecules within the cell. However, the principle of how molecular chirality leads to cellular chirality remains unresolved. To address this fundamental question, we experimentally studied the chiral behaviors of isolated epithelial cells derived from a carcinoma line and developed a theoretical understanding of how their behaviors arise from molecular-level chirality. We first found that the nucleus undergoes clockwise rotation, accompanied by robust cytoplasmic circulation in the same direction. During the rotation, actin and Myosin IIA assemble into the stress fibers with a vortex-like chiral orientation at the ventral side of the cell periphery, concurrently forming a concentric pattern at the dorsal side. Further analysis revealed that the intracellular rotation is driven by the concentric actomyosin filaments located dorsally, not by the ventral vortex-like chiral stress fibers. To elucidate how these concentric actomyosin filaments induce chiral rotation, we analyzed a theoretical model developed based on the theory of active chiral fluid. This model demonstrated that the observed cell-scale unidirectional rotation is driven by the molecular-scale chirality of actomyosin filaments even in the absence of cell-scale chiral orientational order. Our study thus provides novel mechanistic insights into how the molecular chirality is organized into the cellular chirality, representing an important step towards understanding left-right symmetry breaking in tissues and organs.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583418","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

Quantitative intra-Golgi transport and organization data suggest the stable compartment nature of the Golgi. 定量的高尔基体内部运输和组织数据表明高尔基体具有稳定的隔室性质。

IF 6.4 1区生物学

eLife Pub Date : 2025-07-08 DOI: 10.7554/eLife.98582

Hieng Chiong Tie, Haiyun Wang, Divyanshu Mahajan, Hilbert Yuen In Lam, Xiuping Sun, Bing Chen, Yuguang Mu, Lei Lu

{"title":"Quantitative intra-Golgi transport and organization data suggest the stable compartment nature of the Golgi.","authors":"Hieng Chiong Tie, Haiyun Wang, Divyanshu Mahajan, Hilbert Yuen In Lam, Xiuping Sun, Bing Chen, Yuguang Mu, Lei Lu","doi":"10.7554/eLife.98582","DOIUrl":"10.7554/eLife.98582","url":null,"abstract":"How the intra-Golgi secretory transport works remains a mystery. The cisternal progression and the stable compartment models have been proposed and are under debate. Classic cisternal progression model posits that both the intra-Golgi transport and Golgi exit of secretory cargos should occur at a constant velocity dictated by the cisternal progression; furthermore, COPI-mediated intra-Golgi retrograde transport is essential for maintaining the Golgi organization. Leveraging our recently developed Golgi imaging tools in nocodazole-induced Golgi ministacks, we found that the intra-Golgi transport velocity of a secretory cargo decreases during their transition from the cis to the trans-side of the Golgi, and different cargos exhibit distinct velocities even within the same cisternae. We observed a vast variation in the Golgi residence times of different cargos. Remarkably, truncation of the luminal domain causes the Golgi residence time of Tac - a standard transmembrane secretory cargo without intra-Golgi recycling signals - to extend from 16 min to a notable 3.4 hr. Additionally, when COPI-mediated intra-Golgi retrograde transport was inhibited by brefeldin A, we found that nocodazole-induced Golgi can remain stacked for over 30-60 min. Therefore, our findings challenge the classical cisternal progression model and suggest the stable compartment nature of the Golgi.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583415","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

Function and firing of the Streptomyces coelicolor contractile injection system requires the membrane protein CisA. 彩色链霉菌收缩注射系统的功能和激活需要膜蛋白CisA。

IF 6.4 1区生物学

eLife Pub Date : 2025-07-08 DOI: 10.7554/eLife.104064

Bastien Casu, Joseph W Sallmen, Peter E Haas, Govind Chandra, Pavel Afanasyev, Jingwei Xu, Martin Pilhofer, Susan Schlimpert

{"title":"Function and firing of the Streptomyces coelicolor contractile injection system requires the membrane protein CisA.","authors":"Bastien Casu, Joseph W Sallmen, Peter E Haas, Govind Chandra, Pavel Afanasyev, Jingwei Xu, Martin Pilhofer, Susan Schlimpert","doi":"10.7554/eLife.104064","DOIUrl":"10.7554/eLife.104064","url":null,"abstract":"Bacterial contractile injection systems (CIS) are phage tail-like macromolecular complexes that mediate cell-cell interactions by injecting effector proteins into target cells. CIS from Streptomyces coelicolor (CISSc) are localized in the cytoplasm. Under stress, they induce cell death and impact the Streptomyces life cycle. It remains unknown, however, whether CISSc require accessory proteins to directly interact with the cytoplasmic membrane to function. Here, we characterize the putative membrane adaptor CisA, a conserved factor in CIS gene clusters across Streptomyces species. We show by cryo-electron tomography imaging and in vivo assays that CISSc contraction and function depend on CisA. Using single-particle cryo-electron microscopy, we provide an atomic model of the extended CISSc apparatus; however, CisA is not part of the complex. Instead, our findings show that CisA is a membrane protein with a cytoplasmic N-terminus predicted to interact with CISSc components, thereby providing a possible mechanism for mediating CISSc recruitment to the membrane and subsequent firing. Our work shows that CIS function in multicellular bacteria is distinct from type VI secretion systems and extracellular CIS, and possibly evolved due to the role CISSc play in regulated cell death.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583419","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

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