Highlights | | | | | | | | Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization | | Xuefeng Zhu, Xie Xie, Hrishikesh Das, Benedict G. Tan, Yonghong Shi, Ali Al-Behadili, Bradley Peter, Elisa Motori, Sebastian Valenzuela, Viktor Posse, Claes M. Gustafsson, B. Martin Hällberg, Maria Falkenberg | |
| | Mobilization-based chemotherapy-free engraftment of gene-edited human hematopoietic stem cells | | Attya Omer-Javed, Gabriele Pedrazzani, Luisa Albano, Sherash Ghaus, Claire Latroche, Maura Manzi, Samuele Ferrari, Martina Fiumara, Aurelien Jacob, Valentina Vavassori, Alessandro Nonis, Daniele Canarutto, Luigi Naldini | |
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Table of Contents | | | | | APOE told me put my fat in the bag and nobody gets hurt | | Garam Kim, Aaron D. Gitler | The ε4 variant in the APOE gene is the strongest genetic risk factor for Alzheimer’s disease. How does this gene impact different cell types in the brain to increase disease risk? In this issue of Cell, TCW and colleagues report APOE-driven cell-type-specific changes that may contribute to Alzheimer’s disease risk. | |
| | BacPROTACs to basics: Targeted protein degradation in bacteria | | George M. Burslem | Targeted protein degradation has emerged as a powerful tool for therapeutic development and biological exploration. In this issue of Cell, Morreale et al. report the development of the BacPROTAC technology to enable targeted protein degradation in Gram-positive bacteria and mycobacteria via reprogramming of Clp proteases. | |
| | Shigella “Osp”pression of innate immunity | | Skylar S. Wright, Sivapriya Kailasan Vanaja | Interferons are potent antimicrobial effectors and thus an attractive target for pathogen interference. In this issue of Cell, Alphonse et al. reveal that the Shigella effectors OspC1 and OspC3 employ a surprising mechanism to block interferon signaling and attenuate antibacterial responses, thus securing their replicative niche. | |
| | TIR domains as two-tiered enzymes to activate plant immunity | | Lei Tian, Xin Li | Plant immune receptors often contain TIR domains, which can oligomerize to form active enzyme complexes in response to pathogen infections. In this issue of Cell, Yu and colleagues discover that some plant TIR domains possess a novel 2′,3′-cAMP/cGMP synthetase activity that cleaves double-stranded RNA/DNA, triggering cell death during plant immune responses. | |
| | New antivirals exploit viral feedback tricks for a cure without resistance | | Gábor Balázsi | Many approved drugs, including antivirals, are small-molecule inhibitors of disease-causing proteins. Such inhibitors often elicit resistance during treatment. Chaturvedi et al. propose new, feedback-disruptor (FD) antivirals that efficiently cure infected cells from viruses and minimize the chance of resistance, providing a new paradigm to treat viral infections and possibly other diseases. | |
| | | Cholesterol and matrisome pathways dysregulated in astrocytes and microglia | | Julia TCW, Lu Qian, Nina H. Pipalia, Michael J. Chao, Shuang A. Liang, Yang Shi, Bharat R. Jain, Sarah E. Bertelsen, Manav Kapoor, Edoardo Marcora, Elizabeth Sikora, Elizabeth J. Andrews, Alessandra C. Martini, Celeste M. Karch, Elizabeth Head, David M. Holtzman, Bin Zhang, Minghui Wang, Frederick R. Maxfield, Wayne W. Poon, Alison M. Goate | Global transcriptomic analyses reveal human-specific, APOE4-driven lipid metabolic dysregulation in astrocytes and microglia that may contribute to increased Alzheimer’s disease risk. | |
| | Bone marrow hematopoiesis drives multiple sclerosis progression | | Kaibin Shi, Handong Li, Ting Chang, Wenyan He, Ying Kong, Caiyun Qi, Ran Li, Huachen Huang, Zhibao Zhu, Pei Zheng, Zhe Ruan, Jie Zhou, Fu-Dong Shi, Qiang Liu | | Open Access | Autoreactive T cells migrate into the bone marrow and skew hematopoietic stem and progenitor cells toward myeloid lineages that augment inflammatory brain injury, suggesting the restriction of bone marrow myelopoiesis as a potential therapy for multiple sclerosis. | |
| | Mobilization-based chemotherapy-free engraftment of gene-edited human hematopoietic stem cells | | Attya Omer-Javed, Gabriele Pedrazzani, Luisa Albano, Sherash Ghaus, Claire Latroche, Maura Manzi, Samuele Ferrari, Martina Fiumara, Aurelien Jacob, Valentina Vavassori, Alessandro Nonis, Daniele Canarutto, Luigi Naldini | | Open Access | When transplanting engineered hematopoietic stem/progenitor cells, mobilizing the existing HSPCs out of the bone marrow can allow for the engraftment of new cells without the need to treat study animals with chemotherapy. This presents an opportunity to overcome the toxicity challenge that chemotherapy presents for HSPC transplantation in patients. | |
| | Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2 | | Kun Xu, Ping Gao, Sheng Liu, Shuaiyao Lu, Wenwen Lei, Tianyi Zheng, Xueyuan Liu, Yufeng Xie, Zhennan Zhao, Shuxin Guo, Cong Tang, Yun Yang, Wenhai Yu, Junbin Wang, Yanan Zhou, Qing Huang, Chuanyu Liu, Yaling An, Rong Zhang, Yuxuan Han, Minrun Duan, Shaofeng Wang, Chenxi Yang, Changwei Wu, Xiaoya Liu, Guangbiao She, Yan Liu, Xin Zhao, Ke Xu, Jianxun Qi, Guizhen Wu, Xiaozhong Peng, Lianpan Dai, Peiyi Wang, George F. Gao | | Open Access | Vaccine immunogens designed as chimeras of the spike protein receptor-binding domain of two distinct SARS-CoV-2 variants elicit broad serum neutralization and protection from infection by the Beta, Delta, and Omicron variants in mice and macaques. The chimeric approach is applicable for rapid updating of immunogens against both circulating and emerging variants. | |
| | Structure, receptor recognition, and antigenicity of the human coronavirus CCoV-HuPn-2018 spike glycoprotein | | M. Alejandra Tortorici, Alexandra C. Walls, Anshu Joshi, Young-Jun Park, Rachel T. Eguia, Marcos C. Miranda, Elizabeth Kepl, Annie Dosey, Terry Stevens-Ayers, Michael J. Boeckh, Amalio Telenti, Antonio Lanzavecchia, Neil P. King, Davide Corti, Jesse D. Bloom, David Veesler | Cryo-EM structures of the coronavirus CCoV-HuPn-2018 S reveal two conformations of domain 0, which recognize sialosides. Canine, feline, and porcine APNs and human N739 glycan knockin APN are entry receptors, suggesting that SNPs might account for CCoV-HuPn-2018 detection in patients. Human antibodies elicited by coronavirus 229E infection inhibit CCoV-HuPn-2018, highlighting ɑ-coronavirus cross-neutralizing activity. | |
| | Parkinson’s disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes | | Meiqin Hu, Ping Li, Ce Wang, Xinghua Feng, Qi Geng, Wei Chen, Matangi Marthi, Wenlong Zhang, Chenlang Gao, Whitney Reid, Joel Swanson, Wanlu Du, Richard I. Hume, Haoxing Xu | TMEM175 is a proton-activated proton channel under lysosomal physiological conditions, and it mediates lysosomal proton efflux to maintain a steady-state pH. | |
| | Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization | | Xuefeng Zhu, Xie Xie, Hrishikesh Das, Benedict G. Tan, Yonghong Shi, Ali Al-Behadili, Bradley Peter, Elisa Motori, Sebastian Valenzuela, Viktor Posse, Claes M. Gustafsson, B. Martin Hällberg, Maria Falkenberg | | Open Access | 7S RNA, a conserved non-coding transcript of human mitochondrial DNA, regulates mitochondrial transcription initiation by controlling mitochondrial RNA polymerase activity. | |
| | Structure and engineering of the type III-E CRISPR-Cas7-11 effector complex | | Kazuki Kato, Wenyuan Zhou, Sae Okazaki, Yukari Isayama, Tomohiro Nishizawa, Jonathan S. Gootenberg, Omar O. Abudayyeh, Hiroshi Nishimasu | Cryo-EM analysis of Cas7-11, the III-E CRISPR-Cas effector nuclease, provides mechanistic insights into the RNA-guided target RNA cleavage and enables rational designing of a compact variant capable of transcript knockdown in human cells. | |
| | BacPROTACs mediate targeted protein degradation in bacteria | | Francesca E. Morreale, Stefan Kleine, Julia Leodolter, Sabryna Junker, David M. Hoi, Stepan Ovchinnikov, Anastasia Okun, Juliane Kley, Robert Kurzbauer, Lukas Junk, Somraj Guha, David Podlesainski, Uli Kazmaier, Guido Boehmelt, Harald Weinstabl, Klaus Rumpel, Volker M. Schmiedel, Markus Hartl, David Haselbach, Anton Meinhart, Markus Kaiser, Tim Clausen | | Open Access | Small-molecule adaptors, BacPROTACs, redirect bacterial ClpCP protease to target neo-substrates in a highly specific manner and expand targeted protein degradation technology to bacteria. | |
| | A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling | | Noémie Alphonse, Joseph J. Wanford, Andrew A. Voak, Jack Gay, Shayla Venkhaya, Owen Burroughs, Sanjana Mathew, Truelian Lee, Sasha L. Evans, Weiting Zhao, Kyle Frowde, Abrar Alrehaili, Ruth E. Dickenson, Mads Munk, Svetlana Panina, Ishraque F. Mahmood, Miriam Llorian, Megan L. Stanifer, Steeve Boulant, Martin W. Berchtold, Julien R.C. Bergeron, Andreas Wack, Cammie F. Lesser, Charlotte Odendall | | Open Access | The OspC type-III-secreted effectors in Shigella bind calmodulin and block interferon signaling, independently of the cell-death-inhibitory activities of this family of proteins. Conservation of this function in homologs of other bacterial species suggests a common role for Ca2+ and interferon targeting in bacterial pathogenesis. | |
| | TIR domains of plant immune receptors are 2′,3′-cAMP/cGMP synthetases mediating cell death | | Dongli Yu, Wen Song, Eddie Yong Jun Tan, Li Liu, Yu Cao, Jan Jirschitzka, Ertong Li, Elke Logemann, Chenrui Xu, Shijia Huang, Aolin Jia, Xiaoyu Chang, Zhifu Han, Bin Wu, Paul Schulze-Lefert, Jijie Chai | Plant TIR domain-containing proteins are bifunctional enzymes with NADase and cyclic nucleotide monophosphate synthetase activity. Combinations of these activities may cooperate to control cell death and immune signaling processes in plants. | |
| | | Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation | | Tzu-Tang Wei, Mark Chandy, Masataka Nishiga, Angela Zhang, Kaavya Krishna Kumar, Dilip Thomas, Amit Manhas, Siyeon Rhee, Johanne Marie Justesen, Ian Y. Chen, Hung-Ta Wo, Saereh Khanamiri, Johnson Y. Yang, Frederick J. Seidl, Noah Z. Burns, Chun Liu, Nazish Sayed, Jiun-Jie Shie, Chih-Fan Yeh, Kai-Chien Yang, Edward Lau, Kara L. Lynch, Manuel Rivas, Brian K. Kobilka, Joseph C. Wu | | |
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