| Table of Contents |
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| Activation-induced cytidine deaminase: The missing piece of many puzzles |
| Thiago Carvalho, Sidonia Fagarasan, Masamichi Muramatsu |
| Twenty-five years ago, two Cell papers reported the key missing functional piece in three molecular puzzles. The genetic swapping of immunoglobulin constant regions, the mutational fine-tuning of antibody specificity, and a baffling human immunodeficiency were traced to the action of one enzyme: activation-induced cytidine deaminase (AID). |
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| Turning up the volume: BNST couples internal state to consumption |
| J. Nicholas Betley |
| In this issue of Cell, Canovas and colleagues identify a consummatory dial in the brain that controls ingestion levels in a state-dependent manner. By continuing to trace the flow of sweet taste information, the authors identify a generalized intensity dial that broadly modulates consumption. |
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| A systematic approach to tuberculosis vaccine development |
| Chetan Seshadri |
| M. tuberculosis is once again the leading infectious cause of death worldwide despite the existence of a licensed vaccine (BCG). In this issue of Cell, Vidal et al. systematically evaluate 42 candidate antigens and develop a trivalent mRNA vaccine that demonstrates effective and durable protection from tuberculosis in several mouse models. This vaccine also enhances protection conferred by BCG. |
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| Feeding from the sun—Successes and prospects in bioengineering photosynthesis for food security |
| Stephen P. Long, Yu Wang, Elizabete Carmo-Silva, Amanda P. Cavanagh, Martin C. Jonikas, Johannes Kromdijk, Benedict M. Long, Amy Marshall-Colón, Diwakar Shukla, Robert H. Wilson, Xin-Guang Zhu, Elizabeth A. Ainsworth |
| This review explores how recent advances in bioengineering photosynthesis can enhance crop productivity and address global food security challenges. |
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| CRATER tumor niches facilitate CD8+ T cell engagement and correspond with immunotherapy success |
| Aya Ludin, Georgia L. Stirtz, Asaf Tal, Ajit J. Nirmal, Kathleen L. Pfaff, Michael Manos, Naomi Besson, Nebiyat Eskndir, Billie Porter, Stephanie M. Jones, Hannah M. Faulkner, Qiyu Gong, Sophia Liu, Irving Barrera, Lijian Wu, Cecilia Pessoa Rodrigues, Aditi Sahu, Elizabeth Jerison, Joao V. Alessi, Biagio Ricciuti, Douglas S. Richardson, Jodi D. Weiss, Hadley M. Moreau, Meredith E. Stanhope, Alexander B. Afeyan, James Sefton, Wyatt D. McCall, Emily Formato, Song Yang, Yi Zhou, David P. Hoytema van Konijnenburg, Hannah L. Cole, Miguel Cordova, Liang Deng, Milind Rajadhyaksha, Stephen R. Quake, Mark M. Awad, Fei Chen, Kai W. Wucherpfennig, Peter K. Sorger, F. Stephen Hodi, Scott J. Rodig, George F. Murphy, Leonard I. Zon |
| Open Access |
| CD8+ T cells preferentially engage tumor cells in pockets termed CRATERs, which are rich with antigen presentation molecules and breach into the tumor mass from the stromal compartment. CRATERs expand and become the major site of tumor killing during immune-stimulatory treatment, and their expansion parallels clinical benefit in patients undergoing immunotherapy. |
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| Safe immunosuppression-resistant pan-cancer immunotherapeutics by velcro-like density-dependent targeting of tumor-associated carbohydrate antigens |
| Raymond W. Zhou, Paresh Kumar Purohit, Jai Hyun Kim, Sung-Uk Lee, Nicole Burshteyn, Delia Tifrea, Andres Cordon, Ani Grigorian, Barbara L. Newton, Robert A. Edwards, Michael Demetriou |
| Open Access |
| Targeting tumor-associated carbohydrate antigens, the most abundant and widespread cancer antigens known, via “velcro-like” binding of lectins allows immunosuppression-resistant pan-cancer killing while ignoring normal tissues. |
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| Cancer cells co-opt an inter-organ neuroimmune circuit to escape immune surveillance |
| Yu Zhang, Yibo Guo, Zheqi Liu, Yiting Sun, Xi Yang, Mingtao Chen, Guanying Feng, Chengzhong Lin, Yang Wang, Zhen Zhang, Yun Zhu, Jinhai Ye, Jiajia Liu, Jun Shi, Xiaomeng Zhou, Qingjian Han, Yu Liu, Qian Jiang, Youcheng Yu, Xu Wang, Chenping Zhang, Yunfan Sun, Jian Zhou, Jia Fan, Tong Ji |
| Cancer cells exploit distant tissues and organs to escape immune surveillance by activating nociceptive neurons, which remodel tumor-draining lymph nodes into an immune-suppressed state. Blocking this inter-organ neuroimmune crosstalk reduces tumor growth, alleviates cancer-induced pain, and enhances the efficacy of immune checkpoint blockade therapy. |
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| Mucosal viral infection elicits long-lived IgA responses via type 1 follicular helper T cells |
| Kei Haniuda, Natalie M. Edner, Yuko Makita, Sandhya Appiah, Tania H. Watts, Gregory F. Wu, Thamotharampillai Dileepan, Jennifer L. Gommerman |
| Long-lived plasma cells that secrete virus-specific IgA at the mucosae are a key determinant in preventing viral infection. Generation of this response is dependent on a unique subset of follicular helper T cells with a type 1 signature—the helper T cells are generated through unconventional priming by B cells and promote the migration of virus-specific IgA+ plasma cells to mucosal effector sites. |
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| Mining the CD4 antigen repertoire for next-generation tuberculosis vaccines |
| Samuel J. Vidal, Ninaad Lasrado, Lisa H. Tostanoski, Jayeshbhai Chaudhari, Esther R. Mbiwan, Ganad D. Neka, Ellis A. Strutton, Alejandro A. Espinosa Perez, Daniel Sellers, Julia Barrett, Michelle Lifton, Shoko Wakabayashi, Behnaz Eshaghi, Erica N. Borducchi, Malika Aid, Wenjun Li, Thomas J. Scriba, Ana Jaklenec, Robert Langer, Dan H. Barouch |
| Open Access |
| Systematic antigen selection is an enduring challenge in tuberculosis (TB) vaccine development. An antigen screen ranks protective CD4 T cell antigens and yields a novel trivalent mRNA vaccine that protects against TB challenges in mice. |
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| Intrinsic heterogeneity of primary cilia revealed through spatial proteomics |
| Jan N. Hansen, Huangqingbo Sun, Konstantin Kahnert, Eini Westenius, Alexandra Johannesson, Carmela Villegas, Trang Le, Kalliopi Tzavlaki, Casper Winsnes, Emmie Pohjanen, Anna Mäkiniemi, Jenny Fall, Frederic Ballllosera Navarro, Anna Bäckström, Cecilia Lindskog, Fredric Johansson, Kalle von Feilitzen, Angelica M. Delgado-Vega, Anna Martinez Casals, Diana Mahdessian, Mathias Uhlén, Shu-Hsien Sheu, Anna Lindstrand, Ulrika Axelsson, Emma Lundberg |
| Open Access |
| An antibody-based spatial proteomics screen on human primary cilia explores 715 proteins across single cilia of different cell types and reveals extensive cell-type specificity, single-cilium heterogeneity, ciliary microdomains, CFAP300 as a new cilium marker protein, 91 novel proteins including CREB3, and a CREB3 variant associated to ciliopathy phenotypes. |
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| Pan-modification profiling facilitates a cross-evolutionary dissection of the thermoregulated ribosomal epitranscriptome |
| Miguel A. Garcia-Campos, Joe Georgeson, Ronit Nir, Robert Reichelt, Kristin A. Fluke, Donna Matzov, Vinithra Iyer, Brett W. Burkhart, Lauren Lui, Anatoly Kustanovich, Felix Grünberger, Supuni Thalalla-Gamage, Shereen A. Howpay-Manage, Milan Gerovac, Nicolas Alexandre, Yuko Nobe, Jakub S. Nowak, Manoj Perera, Alexander Apostle, Shiyue Fang, Sebastian Glatt, Ghil Jona, Sébastien Ferreira-Cerca, Jörg Vogel, Masato Taoka, Jordan L. Meier, Eric Westhof, Thomas J. Santangelo, Dina Grohmann, Moran Shalev-Benami, Schraga Schwartz |
| Pan-Mod-seq enables systematic, multi-modification mapping of rRNA across life. Applying it to diverse organisms reveals that hyperthermophiles dynamically install stabilizing modifications to support ribosome function at extreme temperatures. |
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| Choreography of rapid actin filament disassembly by coronin, cofilin, and AIP1 |
| Wout Oosterheert, Micaela Boiero Sanders, Oliver Hofnagel, Peter Bieling, Stefan Raunser |
| Open Access |
| The rapid turnover of actin filament networks drives eukaryotic cell migration and morphogenesis. Single-particle cryo-EM structures reveal how the conserved actin-binding proteins coronin, cofilin, and AIP1 act in synergy to rapidly disassemble these actin filament networks. |
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| Unveiling conformation-selective regulation of the norepinephrine transporter |
| Heng Zhang, Tianwei Zhang, Dingyan Wang, Antao Dai, Jianhang Mao, Qihui Chen, Tianyuan Du, Xue Lu, Yongxin Hao, Chao Zhang, Yu-Ling Yin, Wen Hu, Benxun Pan, Sanshan Jin, Mengting Jiang, Yuan Si, Qingning Yuan, Ming-Wei Wang, Mingyue Zheng, Zhen Wang, Dehua Yang, H. Eric Xu, Yi Jiang |
| The inward-open-state-specific allosteric site in NET was structurally characterized, enabling the rational discovery of conformation-selective inhibitors. |
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| Distinct circuit motifs evaluate opposing innate values of odors |
| Makoto Someya, Ka-Yuet Liu, Kazumi Ohta, Hokto Kazama |
| Open Access |
| Innate hedonic values of odors are computed in the Drosophila higher olfactory area, the lateral horn, where distinct neurons represent opposing values in a graded manner. Representations of negative values emerge through convergent feedforward excitation, whereas those of positive values emerge through additional local inhibition implementing gain control and thresholding. |
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| A brain center that controls consummatory responses |
| Jose A. Canovas, Li Wang, Ahmed A.M. Mohamed, Larry F. Abbott, Charles S. Zuker |
| Open Access |
| The BNST brain region integrates a broad range of external and internal signals to flexibly regulate consumption, revealing a unified control over consummatory responses. |
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| Time-resolved reprogramming of single somatic cells into totipotent states during plant regeneration |
| Li Ping Tang, Li Ming Zhai, Jiming Li, Yue Gao, Qiu Li Ma, Rui Li, Qing Fei Liu, Wen Jie Zhang, Wang Jinsong Yao, Bangbang Mu, Chao Qin, Xin Tian, Rahul Shaw, Keke Xia, Jian Xu, Ying Hua Su, Xian Sheng Zhang |
| Open Access |
| In Arabidopsis, transcriptional factors LEC2 and SPCH enhance local auxin biosynthesis, establishing a transcriptional framework that enables differentiated single somatic epidermal cells to regain totipotency and uncovering the molecular basis of cellular plasticity and reprogramming. |
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| Reference genome choice compromises population genetic analyses |
| Maria Akopyan, Matthew Genchev, Ellie E. Armstrong, Jazlyn A. Mooney |
| Using a species-specific reference genome significantly improves the accuracy of population genetic analyses, as exemplified by mapping gray fox sequence data to genomes of several canid species. Mapping to a conspecific genome provides more reliable estimates of genetic variation, diversity, and evolutionary history. |
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| Sequencing-free whole-genome spatial transcriptomics at single-molecule resolution |
| Yubao Cheng, Shengyuan Dang, Yuan Zhang, Yanbo Chen, Ruihuan Yu, Miao Liu, Shengyan Jin, Ailin Han, Samuel Katz, Siyuan Wang |
| Open Access |
| RAEFISH delivers whole-transcriptome (>20,000 genes) imaging at single-molecule resolution in cells and tissues and enables direct gRNA detection for high-content, image-based CRISPR screens. |
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| Nutrient competition predicts gut microbiome restructuring under drug perturbations |
| Handuo Shi, Daniel P. Newton, Taylor H. Nguyen, Sylvie Estrela, Juan Sanchez, Michael Tu, Po-Yi Ho, Qinglin Zeng, Brian C. DeFelice, Justin L. Sonnenburg, Kerwyn Casey Huang |
| Systematic profiling of 707 drugs on their impact on stool-derived microbial communities shows that nutrient competition explains and predicts species shifts under drug treatment and that post-drug recovery is driven by ecological interactions like extinction and strain swapping. |
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| Time-resolved fluorescent proteins expand fluorescent microscopy in temporal and spectral domains |
| Zizhu Tan, Chia-Heng Hsiung, Jiahui Feng, Yangye Zhang, Yihan Wan, Junlin Chen, Ke Sun, Peilong Lu, Jianyang Zang, Wenxing Yang, Ya Gao, Jiabin Yin, Tong Zhu, Yang Lu, Zijian Pan, Yilong Zou, Can Liao, Xiaosong Li, Yuxuan Ye, Yu Liu, Xin Zhang |
| A family of rationally designed time-resolved fluorescent proteins with controllable lifetimes across the visible spectrum enables simultaneous multiplexed live imaging, super-resolution microscopy, and protein stoichiometry quantification, offering a transformative toolset for advancing biological research with enhanced complexity and quantitative precision. |
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| Time-resolved fluorescent proteins expand fluorescent microscopy in temporal and spectral domains |
| Zizhu Tan, Chia-Heng Hsiung, Jiahui Feng, Yangye Zhang, Yihan Wan, Junlin Chen, Ke Sun, Peilong Lu, Jianyang Zang, Wenxing Yang, Ya Gao, Jiabin Yin, Tong Zhu, Yang Lu, Zijian Pan, Yilong Zou, Can Liao, Xiaosong Li, Yuxuan Ye, Yu Liu, Xin Zhang |
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| Time-resolved reprogramming of single somatic cells into totipotent states during plant regeneration |
| Li Ping Tang, Li Ming Zhai, Jiming Li, Yue Gao, Qiu Li Ma, Rui Li, Qing Fei Liu, Wen Jie Zhang, Wang Jinsong Yao, Bangbang Mu, Chao Qin, Xin Tian, Rahul Shaw, Keke Xia, Jian Xu, Ying Hua Su, Xian Sheng Zhang |
| Open Access |
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| Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer |
| Hui Zhang, Tao Liu, Zhen Zhang, Samuel H. Payne, Bai Zhang, Jason E. McDermott, Jian-Ying Zhou, Vladislav A. Petyuk, Li Chen, Debjit Ray, Shisheng Sun, Feng Yang, Lijun Chen, Jing Wang, Punit Shah, Seong Won Cha, Paul Aiyetan, Sunghee Woo, Yuan Tian, Marina A. Gritsenko, Therese R. Clauss, Caitlin Choi, Matthew E. Monroe, Stefani Thomas, Song Nie, Chaochao Wu, Ronald J. Moore, Kun-Hsing Yu, David L. Tabb, David Fenyö, Vineet Bafna, Yue Wang, Henry Rodriguez, Emily S. Boja, Tara Hiltke, Robert C. Rivers, Lori Sokoll, Heng Zhu, Ie-Ming Shih, Leslie Cope, Akhilesh Pandey, Bing Zhang, Michael P. Snyder, Douglas A. Levine, Richard D. Smith, Daniel W. Chan, Karin D. Rodland |
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