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| CRISPR meets AI-based robotics: Advancing sustainable agriculture |
| Fabienne Gehrke, Holger Puchta |
| Advances in genome editing, artificial intelligence, and robotics are transforming approaches to crop improvement by linking genetic design with cultivation practices. In this issue of Cell, Xu and colleagues develop a genome editing-artificial intelligence-robotics (GEAIR) system in tomato, using CRISPR-based multiplexing to convert recessed stigmas into exserted, male-sterile floral morphologies that enable efficient robotic pollination and accelerated hybrid seed production. Combined with speed breeding and de novo domestication, GEAIR generates parental lines with improved stress tolerance, flavor, and yield, and its transferability to soybean demonstrates applicability across plant families. By demonstrating how targeted editing can reconfigure reproductive traits for compatibility with automation, GEAIR establishes a platform that integrates genome editing with artificial intelligence and robotics. Such strategies should enable systems-level crop design that can expand agricultural diversity, enhance resilience, and contribute to sustainable food production. |
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| Don’t forget to floss! An innovative approach for vaccine delivery |
| Heather D. Hickman, Niki M. Moutsopoulos |
| In a recent issue of Nature Biomedical Engineering, Ingrole et al. explore a new approach for needle-free vaccine delivery through the mouth. They devise and test a dental-floss-based flu vaccine as an alternative mode of mucosal vaccination. |
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| Exploring Latin America one cell at a time |
| Patricia A. Possik, David J. Adams, Flavia C. Aguiar, Tamires Caixeta Alves, Fabíola S. Alves-Hanna, Carlos Mario Restrepo Arboleda, Erick Armingol, Liã Bárbara Arruda, Yesid Cuesta Astroz, Jacqueline M. Boccacino, Danielle C. Bonfim, Juan F. Calderon, Alexis Germán Murillo Carrasco, Danielle G. Carvalho, Benilton S. Carvalho, Paulo Vinícius Sanches Daltro de Carvalho, Alex Castro, Lia Chappell, Ricardo Chinchilla-Monge, Daniela Di Bella, Sandra Martha Gomes Dias, Rafaela Fagundes, Marina L. Fernández, Bianca Braga Frade, Federico J. Garde, Hugo Gonzalez, Gabriela Rapozo Guimarães, Lucas Inchausti, Edith Kordon, Laura Leaden, Rafael S. Lima, Alvaro Lladser, Julieth López-Castiblanco, Isabela Malta, Vinicius Maracaja-Coutinho, Domenica Marchese, Alice Matimba, Andres Moreno-Estrada, Marcelo A. Mori, Helder Nakaya, Silvana Pereyra, Yulye Jessica Romo Ramos, Natalia Rego, Carla Daniela Robles-Espinoza, Adolfo Rojas-Hidalgo, Maria Natalia Rubinsztain, Leandro Santos, Anita Scoones, Patricia Severino, Annie Cristhine M. Sousa-Squiavinato, Lucia Spangenberg, Ana Victoria Suescún, Nayara Gusmão Tessarollo, Martha Estefania Vázquez-Cruz, Ma’n H. Zawati, Joao P.B. Viola, Mariana Boroni |
| Single-cell and spatial transcriptomics are revolutionizing science. Latin America’s unique genetic diversity, environment, and endemic infectious diseases offer exceptional opportunities to deploy these technologies for societal and scientific impact. We highlight regional challenges and opportunities, offering recommendations to boost capacity, foster collaboration, and promote research equity. |
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| A mechano-resistance mechanism in skin adapts to terrestrial locomotion |
| Ruonan Di, Qianqian Du, Yuhua Xie, Yanhua Lu, Wenxuan Gao, Lei Zhang, Xiaoli Qi, Yanyan Fan, Jiao Li, Fengchao Wang, She Chen, Ting Chen |
| An evolutionarily emerged ER-based mechano-resistance mechanism supports epidermal function under mechanical pressure. SLURP1, an ER membrane protein, preserves SERCA2b activity and calcium homeostasis, preventing pPERK-NRF2 activation to maintain epidermal homeostasis. |
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| Engineering crop flower morphology facilitates robotization of cross-pollination and speed breeding |
| Yue Xie, Tinghao Zhang, Minghao Yang, Hongchang Lyu, Yupan Zou, Yangchang Sun, Jun Xiao, Wenzhao Lian, Jianhua Tao, Hua Han, Cao Xu |
| A genome editing and AI-driven robotic system that overcomes floral barriers to facilitate automated hybrid breeding in tomato and soybean. |
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| AI-generated MLH1 small binder improves prime editing efficiency |
| Ju-Chan Park, Heesoo Uhm, Yong-Woo Kim, Ye Eun Oh, Jang Hyeon Lee, Jiyun Yang, Kyoungmi Kim, Sangsu Bae |
| Open Access |
| A compact, AI-generated suppressor of DNA mismatch repair can enhance prime editing in vivo and in vitro and can be integrated into a variety of prime editing architectures. |
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| Kiwa is a membrane-embedded defense supercomplex activated at phage attachment sites |
| Zhiying Zhang, Thomas C. Todeschini, Yi Wu, Roman Kogay, Ameena Naji, Joaquin Cardenas Rodriguez, Rupavidhya Mondi, Daniel Kaganovich, David W. Taylor, Jack P.K. Bravo, Marianna Teplova, Triana Amen, Eugene V. Koonin, Dinshaw J. Patel, Franklin L. Nobrega |
| Open Access |
| Zhang, Todeschini, and Wu et al. show that the bacterial defense system Kiwa senses phage attachment at the membrane and assembles a transmembrane complex that halts infection by blocking phage DNA replication and late transcription. The activity of Kiwa is safeguarded against phage-encoded inhibitors by cooperation with the RecBCD system. |
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| Prevalent mesenchymal drift in aging and disease is reversed by partial reprogramming |
| Jinlong Y. Lu, William B. Tu, Ronghui Li, Mingxi Weng, Bhargav D. Sanketi, Baolei Yuan, Pradeep Reddy, Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte |
| Loss of cellular identity across aging and disease is linked to a widespread “mesenchymal drift,” characterized by upregulation of mesenchymal genes and altered stromal cell composition across tissues. Mesenchymal drift correlates with worse clinical outcomes, whereas its suppression via Yamanaka factor-induced partial reprogramming restores youthful gene expression. |
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| A complete model of mouse embryogenesis through organogenesis enabled by chemically induced embryo founder cells |
| Huanhuan Li, Wei Guan, Jiahui Huang, Penglei Shen, Jinyi Wu, Haiping Luo, Yun Yang, Shaoqiang Ning, Litao Chang, Haiyong Zhao, Chuanxin Chen, Yake Gao, Yaoyu Chen, Xianfa Yang, Yael Costa, Chen-Leng Cai, Duanqing Pei, Guangdun Peng, Guangming Wu, Jiekai Chen, Jian Zhang, Naihe Jing, José C.R. Silva |
| Open Access |
| A small-molecule-only strategy enables reprogramming ESCs into embryo founder cells that give rise to a high-fidelity embryo model directly and efficiently. This embryo model replicates embryogenesis from initial cell fate specification through E8.5–E8.75-like organogenesis, capturing all key developmental features within a single system. |
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| The small GTPase Ran defines nuclear pore complex asymmetry |
| Jenny Sachweh, Mandy Börmel, Sven Klumpe, Anja Becker, Reiya Taniguchi, Marta Anna Kubańska, Verena Pintschovius, Eva Kaindl, Jürgen M. Plitzko, Florian Wilfling, Martin Beck, Bernhard Hampoelz |
| Open Access |
| Nuclear pore complexes at the nuclear envelope are asymmetric structures, whereas those in cytoplasmic or nuclear membranes are symmetric. The (a)symmetry of nuclear pore complexes and peripheral nucleoporin composition depend on the surrounding cellular milieu and the nucleotide state of the small GTPase Ran. |
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| The essential host genome for Cryptosporidium survival exposes metabolic dependencies that can be leveraged for treatment |
| N. Bishara Marzook, Ok-Ryul Song, Lotta Baumgärtel, Netanya Bernitz, Tapoka T. Mkandawire, Lucy C. Watson, Vanessa Nunes, Scott Warchal, James I. MacRae, Michael Howell, Adam Sateriale |
| Open Access |
| An arrayed microscopy-based CRISPR screen revealed host genes affecting multiple infection phenotypes of the intracellular parasite Cryptosporidium. Hits in the host cholesterol biosynthesis pathway affecting parasite growth and sexual development exposed a vulnerability that can be leveraged for treatment. |
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| A generative deep learning approach to de novo antibiotic design |
| Aarti Krishnan, Melis N. Anahtar, Jacqueline A. Valeri, Wengong Jin, Nina M. Donghia, Leif Sieben, Andreas Luttens, Yu Zhang, Seyed Majed Modaresi, Andrew Hennes, Jenna Fromer, Parijat Bandyopadhyay, Jonathan C. Chen, Danyal Rehman, Ronak Desai, Paige Edwards, Ryan S. Lach, Marie-Stéphanie Aschtgen, Margaux Gaborieau, Massimiliano Gaetani, Samantha G. Palace, Satotaka Omori, Lutete Khonde, Yurii S. Moroz, Bruce Blough, Chunyang Jin, Edmund Loh, Yonatan H. Grad, Amir Ata Saei, Connor W. Coley, Felix Wong, James J. Collins |
| A generative AI platform is developed for de novo antibiotic design, yielding lead compounds with selective antibacterial activity, distinct mechanisms of action, and in vivo efficacy against multidrug-resistant N. gonorrhoeae and S. aureus. |
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| Design of soluble Notch agonists that drive T cell development and boost immunity |
| Rubul Mout, Ran Jing, Mayuri Tanaka-Yano, Emily D. Egan, Helen Eisenach, Martin A. Kononov, Roland Windisch, Mohamad Ali Toufic Najia, Allison Tompkins, Luca Hensch, Trevor Bingham, Rajesh Gunage, Yunliang Zhao, Natasha I. Edman, Christopher Li, Dahai Wang, Thorsten M. Schlaeger, Leonard I. Zon, Trista E. North, Urban Lendahl, R. Grant Rowe, David Baker, Stephen C. Blacklow, George Q. Daley |
| Mout et al. report the development of soluble Notch agonists that can be used for T cell development in suspension cultures and 3D bioreactors and for enhancing immunity in vivo. |
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| A split-site E3 ligase mechanism enables ZNFX1 to ubiquitinate and cluster single-stranded RNA into ubiquitin-coated nucleoprotein particles |
| Daniel B. Grabarczyk, Eric J. Aird, Vanessa Reznikow, Paul C. Kirchgatterer, Julian F. Ehrmann, Robert Kurzbauer, Lillie E. Bell, Max J. Kellner, Ritika Aggarwal, Alexander Schleiffer, Victoria Faas, Luiza Deszcz, Anton Meinhart, Gijs A. Versteeg, Josef M. Penninger, Lukas S. Stelzl, Moritz M. Gaidt, Ingrid Tessmer, Jacob E. Corn, Tim Clausen |
| Open Access |
| Grabarczyk et al. show the structure and mechanism of a non-canonical ubiquitin ligase, which is activated through nucleic-acid-induced oligomerization and is critical for cell survival during immune responses. |
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| Identification of gut microbial bile acid metabolic enzymes via an AI-assisted pipeline |
| Yong Ding, Xi Luo, Jiasheng Guo, Baiying Xing, Haoyu Lin, Haohan Ma, Yicun Wang, Meng Li, Chuan Ye, Sen Yan, Kangjie Lin, Jinxin Zhang, Yingying Zhuo, Qixing Nie, Donghui Yang, Zhipeng Zhang, Yanli Pang, Kai Wang, Ming Ma, Luhua Lai, Changtao Jiang |
| Ding et al. report an AI-assisted workflow that enables top-down, cultivation-independent identification of human microbial bile acid metabolic enzymes. |
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| HT SpaceM: A high-throughput and reproducible method for small-molecule single-cell metabolomics |
| Jeany Delafiori, Mohammed Shahraz, Andreas Eisenbarth, Volker Hilsenstein, Bernhard Drotleff, Alberto Bailoni, Bishoy Wadie, Måns Ekelöf, Alexander Mattausch, Theodore Alexandrov |
| Open Access |
| Single-cell metabolomics (SCM) can probe metabolic heterogeneity but is hindered by low sensitivity for small molecules, limited scalability, and the lack of standardized frameworks for data analysis. HT SpaceM is a high-throughput MALDI-imaging-based SCM method to robustly detect small-molecule metabolites in single cells. Applied to over 140,000 cells across diverse conditions and cancer cell lines, HT SpaceM enabled reproducible metabolic profiling of over 100 small-molecule metabolites, identification of subpopulation-specific markers, and detection of heterogeneity and pathways coordination, thus facilitating scalable and reproducible SCM. |
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| Vagal blockade of the brain-liver axis deters cancer-associated cachexia |
| Aliesha Garrett, Naama Darzi, Ashlesha Deshmukh, Nataly Rosenfeld, Omer Goldman, Lital Adler, Elizabeta Bab-Dinitz, Oded Singer, Alireza Hassani Najafabadi, Chi Wut Wong, Shree Bose, Peggy M. Randon, Francisco Bustamante, Rene Larios, Alexander Brandis, Tevie Mehlman, Brandon Smaglo, Ping Chang, Jacqueline Oliva, Cara Haymaker, Laukik Nagawekar, Sophie R. Wu, Yixuan Huang, Aidan Shen, Ahana Vora, Jon Floyd Padilla, Alissa Pfeffer, Gary Sutherland, Mark Starr, Teresa Zimmers, Yangzhi Zhu, James Morizio, Ayelet Erez, Xiling Shen |
| Vagal dysfunction mediates the impact of tumor on liver metabolism, leading to cachexia. Blocking the right cervical vagus nerve with various invasive or non-invasive approaches alleviates cachexia, decoupling cachexia progression from tumor load, and synergizes with chemotherapy to improve overall health and survival in mice. |
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| Long shared haplotypes identify the southern Urals as a primary source for the 10th-century Hungarians |
| Balázs Gyuris, Leonid Vyazov, Attila Türk, Pavel Flegontov, Bea Szeifert, Péter Langó, Balázs Gusztáv Mende, Veronika Csáky, Andrey A. Chizhevskiy, Ilgizar R. Gazimzyanov, Aleksandr A. Khokhlov, Aleksandr G. Kolonskikh, Natalia P. Matveeva, Rida R. Ruslanova, Marina P. Rykun, Ayrat Sitdikov, Elizaveta V. Volkova, Sergei G. Botalov, Dmitriy G. Bugrov, Ivan V. Grudochko, Oleksii Komar, Alexander A. Krasnoperov, Olga E. Poshekhonova, Irina Chikunova, Flarit Sungatov, Dmitrii A. Stashenkov, Sergei Zubov, Alexander S. Zelenkov, Harald Ringbauer, Olivia Cheronet, Ron Pinhasi, Ali Akbari, Nadin Rohland, Swapan Mallick, David Reich, Anna Szécsényi-Nagy |
| Open Access |
| Genome-wide ancient DNA data from early medieval populations across the broader Ural region and adjacent areas identify the southern Urals as the primary ancestral source of 10th-century Hungarians. |
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| VIVIT: Resolving trans-scale volumetric biological architectures via ionic glassy tissue |
| Yixiao Gao, Fengyuan Xin, Tao Wang, Chengjun Shao, Ying Hu, Zhuoya Chen, Yiwei Wang, Fenghua Xie, Tianyu Li, Sijie Li, Liqun Ren, Caiqin Li, Xian Yang, Zhongjun Yang, Meijie Li, KaMun Tan, Tao Bai, Changwei Wei, Hanchuan Peng, Kun Li, Yichang Jia, Kexin Yuan |
| Leveraging the chemical properties of ionic liquids, VIVIT transforms biological tissue into a glassy state, addressing long-standing challenges in the optical clearing field. This enables precise and reliable mapping of trans-scale biostructures, facilitating the discovery of a link between the synaptic inputs and brain-wide outputs of higher-order auditory thalamic neurons and a distinct positioning pattern of parvalbumin+ synaptic terminals on human cortical pyramidal neurons. |
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| A Validated Regulatory Network for Th17 Cell Specification |
| Maria Ciofani, Aviv Madar, Carolina Galan, MacLean Sellars, Kieran Mace, Florencia Pauli, Ashish Agarwal, Wendy Huang, Christopher N. Parkurst, Michael Muratet, Kim M. Newberry, Sarah Meadows, Alex Greenfield, Yi Yang, Preti Jain, Francis K. Kirigin, Carmen Birchmeier, Erwin F. Wagner, Kenneth M. Murphy, Richard M. Myers, Richard Bonneau, Dan R. Littman |
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| The immunoproteasome disturbs neuronal metabolism and drives neurodegeneration in multiple sclerosis |
| Marcel S. Woo, Johannes Brand, Lukas C. Bal, Manuela Moritz, Mark Walkenhorst, Vanessa Vieira, Inbal Ipenberg, Nicola Rothammer, Man Wang, Batuhan Dogan, Desirée Loreth, Christina Mayer, Darwin Nagel, Ingrid Wagner, Lena Kristina Pfeffer, Peter Landgraf, Marco van Ham, Kuno M.-J. Mattern, Ingo Winschel, Noah Frantz, Jana K. Sonner, Henrike K. Grosshans, Albert Miguela, Simone Bauer, Nina Meurs, Anke Müller, Lars Binkle-Ladisch, Gabriela Salinas, Lothar Jänsch, Daniela C. Dieterich, Maria Riedner, Elke Krüger, Frank L. Heppner, Markus Glatzel, Victor G. Puelles, Jan Broder Engler, Jens Randel Nyengaard, Thomas Misgeld, Martin Kerschensteiner, Doron Merkler, Catherine Meyer-Schwesinger, Manuel A. Friese |
| Open Access |
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