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Convergent insulin and TGF-β signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model EMBO Rep. (IF 7.7) Pub Date : 2023-11-28 Daniel Bakopoulos, Sofya Golenkina, Callum Dark, Elizabeth L Christie, Besaiz J Sánchez-Sánchez, Brian M Stramer, Louise Y Cheng
In this study, we found that in the adipose tissue of wildtype animals, insulin and TGF-β signalling converge via a BMP antagonist short gastrulation (sog) to regulate ECM remodelling. In tumour bearing animals, Sog also modulates TGF-β signalling to regulate ECM accumulation in the fat body. TGF-β signalling causes ECM retention in the fat body and subsequently depletes muscles of fat body-derived
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A YTHDF–PABP interaction is required for m6A-mediated organogenesis in plants EMBO Rep. (IF 7.7) Pub Date : 2023-11-27 Mathias Due Tankmar, Marlene Reichel, Laura Arribas-Hernández, Peter Brodersen
N6-methyladenosine (m6A) in mRNA is key to eukaryotic gene regulation. Many m6A functions involve RNA-binding proteins that recognize m6A via a YT521-B Homology (YTH) domain. YTH domain proteins contain long intrinsically disordered regions (IDRs) that may mediate phase separation and interaction with protein partners, but whose precise biochemical functions remain largely unknown. The Arabidopsis
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The 5:2 diet does not increase adult hippocampal neurogenesis or enhance spatial memory in mice EMBO Rep. (IF 7.7) Pub Date : 2023-11-21 Luke D Roberts, Amanda KE Hornsby, Alanna Thomas, Martina Sassi, Aimee Kinzett, Nathan Hsiao, Bethan R David, Mark Good, Timothy Wells, Jeffrey S Davies
New neurones are generated throughout life in the mammalian brain in a process known as adult hippocampal neurogenesis (AHN). Since this phenomenon grants a high degree of neuroplasticity influencing learning and memory, identifying factors that regulate AHN may be important for ameliorating age-related cognitive decline. Calorie restriction (CR) has been shown to enhance AHN and improve memory, mediated
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Structural study of UFL1-UFC1 interaction uncovers the role of UFL1 N-terminal helix in ufmylation EMBO Rep. (IF 7.7) Pub Date : 2023-11-21 Sayanika Banerjee, Julia K Varga, Manoj Kumar, Guy Zoltsman, Shahar Rotem-Bamberger, Einav Cohen-Kfir, Michail N Isupov, Rina Rosenzweig, Ora Schueler-Furman, Reuven Wiener
Ufmylation plays a crucial role in various cellular processes including DNA damage response, protein translation, and ER homeostasis. To date, little is known about how the enzymes responsible for ufmylation coordinate their action. Here, we study the details of UFL1 (E3) activity, its binding to UFC1 (E2), and its relation to UBA5 (E1), using a combination of structural modeling, X-ray crystallography
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Genome-wide association and environmental suppression of the mortal germline phenotype of wild C. elegans EMBO Rep. (IF 7.7) Pub Date : 2023-11-20 Lise Frézal, Marie Saglio, Gaotian Zhang, Luke Noble, Aurélien Richaud, Marie-Anne Félix
The animal germline lineage needs to be maintained along generations. However, some Caenorhabditis elegans wild isolates display a mortal germline phenotype, leading to sterility after several generations at 25°C. Using a genome-wide association approach, we detect a significant peak on chromosome III around 5 Mb, confirmed by introgressions. Thus, a seemingly deleterious genotype is maintained at
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Molecular view of ER membrane remodeling by the Sec61/TRAP translocon EMBO Rep. (IF 7.7) Pub Date : 2023-11-20 Sudeep Karki, Matti Javanainen, Shahid Rehan, Dale Tranter, Juho Kellosalo, Juha Huiskonen, Lotta Happonen, Ville Paavilainen
Protein translocation across the endoplasmic reticulum (ER) membrane is an essential step during protein entry into the secretory pathway. The conserved Sec61 protein-conducting channel facilitates polypeptide translocation and coordinates cotranslational polypeptide-processing events. In cells, the majority of Sec61 is stably associated with a heterotetrameric membrane protein complex, the translocon-associated
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Microautophagy regulated by STK38 and GABARAPs is essential to repair lysosomes and prevent aging EMBO Rep. (IF 7.7) Pub Date : 2023-11-21 Monami Ogura, Tatsuya Kaminishi, Takayuki Shima, Miku Torigata, Nao Bekku, Keisuke Tabata, Satoshi Minami, Kohei Nishino, Akiko Nezu, Maho Hamasaki, Hidetaka Kosako, Tamotsu Yoshimori, Shuhei Nakamura
Lysosomes are degradative organelles and signaling hubs that maintain cell and tissue homeostasis, and lysosomal dysfunction is implicated in aging and reduced longevity. Lysosomes are frequently damaged, but their repair mechanisms remain unclear. Here, we demonstrate that damaged lysosomal membranes are repaired by microautophagy (a process termed “microlysophagy”) and identify key regulators of
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Adult neural stem cells and neurogenesis are resilient to intermittent fasting EMBO Rep. (IF 7.7) Pub Date : 2023-11-21 Rut Gabarró-Solanas, Amarbayasgalan Davaatseren, Justus Kleifeld, Tatjana Kepčija, Thomas Köcher, Albert Giralt, Iván Crespo-Enríquez, Noelia Urbán
Intermittent fasting (IF) is a promising strategy to counteract ageing shown to increase the number of adult-born neurons in the dentate gyrus of mice. However, it is unclear which steps of the adult neurogenesis process are regulated by IF. The number of adult neural stem cells (NSCs) decreases with age in an activation-dependent manner and, to counteract this loss, adult NSCs are found in a quiescent
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Natural probiotics improve heritable sterility EMBO Rep. (IF 7.7) Pub Date : 2023-11-20 Chee Kiang Ewe, Oded Rechavi
Disrupting the small RNA pathway and chromatin-modifying enzymes in C. elegans often leads to a mortal germline (Mrt) phenotype, characterized by progressive sterility observed over multiple generations at elevated temperature. This phenotype arises from the inheritance of aberrant epigenetic memory across generations. In this issue of EMBO Reports, Frézal and colleagues reported that, while in standard
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Recognition of centromere-specific histone Cse4 by the inner kinetochore Okp1-Ame1 complex EMBO Rep. (IF 7.7) Pub Date : 2023-11-20 Sunbin Deng, Jiaxi Cai, Stephen C Harrison, Huilin Zhou, Stephen M Hinshaw
Successful mitosis depends on the timely establishment of correct chromosomal attachments to microtubules. The kinetochore, a modular multiprotein complex, mediates this connection by recognizing specialized chromatin containing a histone H3 variant called Cse4 in budding yeast and CENP-A in vertebrates. Structural features of the kinetochore that enable discrimination between Cse4/CENP-A and H3 have
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Protein phosphatase 1 regulates core PCP signaling EMBO Rep. (IF 7.7) Pub Date : 2023-11-17 Song Song, Bomsoo Cho, Alexis T Weiner, Silas Boye Nissen, Irene Ojeda Naharros, Pablo Sanchez Bosch, Kaye Suyama, Yanhui Hu, Li He, Tanya Svinkina, Namrata D Udeshi, Steven A Carr, Norbert Perrimon, Jeffrey D Axelrod
Planar cell polarity (PCP) signaling polarizes epithelial cells within the plane of an epithelium. Core PCP signaling components adopt asymmetric subcellular localizations within cells to both polarize and coordinate polarity between cells. Achieving subcellular asymmetry requires additional effectors, including some mediating post-translational modifications of core components. Identification of such
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Blood flow diverts extracellular vesicles from endothelial degradative compartments to promote angiogenesis EMBO Rep. (IF 7.7) Pub Date : 2023-11-16 Benjamin Mary, Nandini Asokan, Katerina Jerabkova-Roda, Annabel Larnicol, Ignacio Busnelli, Tristan Stemmelen, Angélique Pichot, Anne Molitor, Raphaël Carapito, Olivier Lefebvre, Jacky G Goetz, Vincent Hyenne
Extracellular vesicles released by tumors (tEVs) disseminate via circulatory networks and promote microenvironmental changes in distant organs favoring metastatic seeding. Despite their abundance in the bloodstream, how hemodynamics affect the function of circulating tEVs remains unsolved. We demonstrated that efficient uptake of tEVs occurs in venous endothelial cells that are subjected to hemodynamics
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Circadian oscillation in primary cilium length by clock genes regulates fibroblast cell migration EMBO Rep. (IF 7.7) Pub Date : 2023-11-16 Ryota Nakazato, Yuki Matsuda, Faryal Ijaz, Koji Ikegami
Various mammalian cells have autonomous cellular clocks that are produced by the transcriptional cycle of clock genes. Cellular clocks provide circadian rhythms for cellular functions via transcriptional and cytoskeletal regulation. The vast majority of mammalian cells possess a primary cilium, an organelle protruding from the cell surface. Here, we investigated the little-known relationship between
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MAPL loss dysregulates bile and liver metabolism in mice EMBO Rep. (IF 7.7) Pub Date : 2023-11-14 Vanessa Goyon, Aurèle Besse-Patin, Rodolfo Zunino, Olesia Ignatenko, Mai Nguyen, Étienne Coyaud, Jonathan M Lee, Bich N Nguyen, Brian Raught, Heidi M McBride
Mitochondrial and peroxisomal anchored protein ligase (MAPL) is a dual ubiquitin and small ubiquitin-like modifier (SUMO) ligase with roles in mitochondrial quality control, cell death and inflammation in cultured cells. Here, we show that MAPL function in the organismal context converges on metabolic control, as knockout mice are viable, insulin-sensitive, and protected from diet-induced obesity.
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USP3 plays a critical role in the induction of innate immune tolerance EMBO Rep. (IF 7.7) Pub Date : 2023-11-16 Tianhao Duan, Yanchun Feng, Yang Du, Changsheng Xing, Junjun Chu, Jiayu Ou, Xin Liu, Motao Zhu, Chen Qian, Bingnan Yin, Helen Y Wang, Jun Cui, Rong-Fu Wang
Microbial products, such as lipopolysaccharide (LPS), can elicit efficient innate immune responses against invading pathogens. However, priming with LPS can induce a form of innate immune memory, termed innate immune “tolerance”, which blunts subsequent NF-κB signaling. Although epigenetic and transcriptional reprogramming has been shown to play a role in innate immune memory, the involvement of post-translational
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The nucleolar protein GNL3 prevents resection of stalled replication forks EMBO Rep. (IF 7.7) Pub Date : 2023-11-15 Rana Lebdy, Marine Canut, Julie Patouillard, Jean-Charles Cadoret, Anne Letessier, Josiane Ammar, Jihane Basbous, Serge Urbach, Benoit Miotto, Angelos Constantinou, Raghida Abou Merhi, Cyril Ribeyre
Faithful DNA replication requires specific proteins that protect replication forks and so prevent the formation of DNA lesions that may damage the genome. Identification of new proteins involved in this process is essential to understand how DNA lesions accumulate in cancer cells and how they tolerate them. Here, we show that human GNL3/nucleostemin, a GTP-binding protein localized mostly in the nucleolus
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A plea for the ultimate optimism: Cognitive biology as a foundation for a worldview. EMBO Rep. (IF 7.7) Pub Date : 2023-11-15 Ladislav Kováč
Homo sapiens' cultural evolution has far outpaced its biological evolution and led us into an impasse.
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Trained immunity induced by high-salt diet impedes stroke recovery EMBO Rep. (IF 7.7) Pub Date : 2023-11-15 Tze-Yen Lin, Danye Jiang, Wan-Ru Chen, Jhih Syuan Lin, Xin-Yu Zhang, Chih-Hung Chen, Chia-Lang Hsu, Liang-Chuan Lai, Ping-Hung Chen, Kai-Chien Yang, Lauren H Sansing, Che-Feng Chang
A high-salt diet (HSD) elicits sustained sterile inflammation and worsens tissue injury. However, how this occurs after stroke, a leading cause of morbidity and mortality, remains unknown. Here, we report that HSD impairs long-term brain recovery after intracerebral hemorrhage, a severe form of stroke, despite salt withdrawal prior to the injury. Mechanistically, HSD induces innate immune priming and
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Excessive apoptosis of Rip1-deficient T cells leads to premature aging EMBO Rep. (IF 7.7) Pub Date : 2023-11-15 Lingxia Wang, Xixi Zhang, Haiwei Zhang, Kaili Lu, Ming Li, Xiaoming Li, Yangjing Ou, Xiaoming Zhao, Xiaoxia Wu, Xuanhui Wu, Jianling Liu, Mingyan Xing, Han Liu, Yue Zhang, Yongchang Tan, Fang Li, Xiaoxue Deng, Jiangshan Deng, Xiaojie Zhang, Jinbao Li, Yuwu Zhao, Qiurong Ding, Haikun Wang, Xiuzhe Wang, Yan Luo, Ben Zhou, Haibing Zhang
In mammals, the most remarkable T cell variations with aging are the shrinking of the naïve T cell pool and the enlargement of the memory T cell pool, which are partially caused by thymic involution. However, the mechanism underlying the relationship between T-cell changes and aging remains unclear. In this study, we find that T-cell-specific Rip1 KO mice show similar age-related T cell changes and
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(Free) Creative Commons content on the internet is not so free after all: The pitfalls and details of copyright laws and licenses. EMBO Rep. (IF 7.7) Pub Date : 2023-11-14 Verena Roder-Hießerich
A short guide on how copyright law affects using content from the internet for academic publications and presentations.
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RNF144A promotes antiviral responses by modulating STING ubiquitination EMBO Rep. (IF 7.7) Pub Date : 2023-11-13 Bo Yang, Jinyong Pei, Chen Lu, Yi Wang, Mengyang Shen, Xiao Qin, Yulu Huang, Xi Yang, Xin Zhao, Shujun Ma, Zhishan Song, Yinming Liang, Hui Wang, Jie Wang
Stimulator of interferon (IFN) genes (STING, also named MITA, ERIS, MPYS, or TMEM173) plays an essential role in DNA virus- or cytosolic DNA-triggered innate immune responses. Here, we demonstrate that the RING-in-between RING (RBR) E3 ubiquitin ligase family member RING-finger protein (RNF) 144A interacts with STING and promotes its K6-linked ubiquitination at K236, thereby enhancing STING translocation
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Androgen signaling stabilizes genomes to counteract senescence by promoting XRCC4 transcription EMBO Rep. (IF 7.7) Pub Date : 2023-11-13 Yu Chen, Zhengyi Zhen, Lingjiang Chen, Hao Wang, Xuhui Wang, Xiaoxiang Sun, Zhiwei Song, Haiyan Wang, Yizi Lin, Wenjun Zhang, Guizhu Wu, Ying Jiang, Zhiyong Mao
Aging is accompanied by a decreased DNA repair capacity, which might contribute to age-associated functional decline in multiple tissues. Disruption in hormone signaling, associated with reproductive organ dysfunction, is an early event of age-related tissue degeneration, but whether it impacts DNA repair in nonreproductive organs remains elusive. Using skin fibroblasts derived from healthy donors
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Exogenous L-Alanine promotes phagocytosis of multidrug-resistant bacterial pathogens EMBO Rep. (IF 7.7) Pub Date : 2023-11-09 Ming Jiang, Xin-Hai Chen, Hui Li, Xuan-Xian Peng, Bo Peng
Multidrug-resistant bacteria present a major threat to public health that urgently requires new drugs or treatment approaches. Here, we conduct integrated proteomic and metabolomics analyses to screen for molecular candidates improving survival of mice infected with Vibrio parahaemolyticus, which indicate that L-Alanine metabolism and phagocytosis are strongly correlated with mouse survival. We also
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Combining organotypic tissue culture with light-sheet microscopy (OTCxLSFM) to study glioma invasion EMBO Rep. (IF 7.7) Pub Date : 2023-11-08 Alicia Haydo, Andrej Wehle, Christel Herold-Mende, Donat Kögel, Francesco Pampaloni, Benedikt Linder
Glioblastoma is a very aggressive tumor and represents the most common primary brain malignancy. Key characteristics include its high resistance against conventional treatments, such as radio- and chemotherapy and its diffuse tissue infiltration, preventing complete surgical resection. The analysis of migration and invasion processes in a physiological microenvironment allows for enhanced understanding
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Lipin-2 regulates the antiviral and anti-inflammatory responses to interferon EMBO Rep. (IF 7.7) Pub Date : 2023-11-06 Nagore de Pablo, Clara Meana, Javier Martínez-García, Pablo Martínez-Vicente, Manuel Albert, Susana Guerra, Ana Angulo, Jesús Balsinde, María A Balboa
Interferons (IFN) are crucial antiviral and immunomodulatory cytokines that exert their function through the regulation of a myriad of genes, many of which are not yet characterized. Here, we reveal that lipin-2, a phosphatidic acid phosphatase whose mutations produce an autoinflammatory syndrome known as Majeed syndrome in humans, is regulated by IFN in a STAT-1-dependent manner. Lipin-2 inhibits
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Breast adipose tissue-derived extracellular vesicles from obese women alter tumor cell metabolism EMBO Rep. (IF 7.7) Pub Date : 2023-11-06 Shuchen Liu, Alberto Benito-Martin, Fanny A Pelissier Vatter, Sarah Z Hanif, Catherine Liu, Priya Bhardwaj, Praveen Sethupathy, Alaa R Farghli, Phoebe Piloco, Paul Paik, Malik Mushannen, Xue Dong, David M Otterburn, Leslie Cohen, Rohan Bareja, Jan Krumsiek, Leona Cohen-Gould, Samuel Calto, Jason A Spector, Olivier Elemento, David C Lyden, Kristy A Brown
Breast adipose tissue is an important contributor to the obesity–breast cancer link. Extracellular vesicles (EVs) are nanosized particles containing selective cargo, such as miRNAs, that act locally or circulate to distant sites to modulate target cell functions. Here, we find that long-term education of breast cancer cells with EVs obtained from breast adipose tissue of women who are overweight or
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MARCH5 promotes STING pathway activation by suppressing polymer formation of oxidized STING EMBO Rep. (IF 7.7) Pub Date : 2023-11-02 Kyungpyo Son, Seokhwan Jeong, Eunchong Eom, Dohyeong Kwon, Suk-Jo Kang
Stimulator of interferon genes (STING) is a core DNA sensing adaptor in innate immune signaling. STING activity is regulated by a variety of post-translational modifications (PTMs), including phosphorylation, ubiquitination, sumoylation, palmitoylation, and oxidation, as well as the balance between active and inactive polymer formation. It remains unclear, though, how different PTMs and higher order
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Forceful patterning: theoretical principles of mechanochemical pattern formation EMBO Rep. (IF 7.7) Pub Date : 2023-11-02 Jan Rombouts, Jenna Elliott, Anna Erzberger
Biological pattern formation is essential for generating and maintaining spatial structures from the scale of a single cell to tissues and even collections of organisms. Besides biochemical interactions, there is an important role for mechanical and geometrical features in the generation of patterns. We review the theoretical principles underlying different types of mechanochemical pattern formation
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Structural insights into coordinating 5S RNP rotation with ITS2 pre-RNA processing during ribosome formation EMBO Rep. (IF 7.7) Pub Date : 2023-11-03 Matthias Thoms, Benjamin Lau, Jingdong Cheng, Lisa Fromm, Timo Denk, Nikola Kellner, Dirk Flemming, Paulina Fischer, Laurent Falquet, Otto Berninghausen, Roland Beckmann, Ed Hurt
The rixosome defined in Schizosaccharomyces pombe and humans performs diverse roles in pre-ribosomal RNA processing and gene silencing. Here, we isolate and describe the conserved rixosome from Chaetomium thermophilum, which consists of two sub-modules, the sphere-like Rix1-Ipi3-Ipi1 and the butterfly-like Las1-Grc3 complex, connected by a flexible linker. The Rix1 complex of the rixosome utilizes
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Antibody-mediated SARS-CoV-2 entry in cultured cells EMBO Rep. (IF 7.7) Pub Date : 2023-11-02 Md Golam Kibria, Christy L Lavine, Weichun Tang, Shaowei Wang, Hailong Gao, Wei Shi, Haisun Zhu, Jewel Voyer, Sophia Rits-Volloch, Keerti, Caihong Bi, Hanqin Peng, Duane R Wesemann, Jianming Lu, Hang Xie, Michael S Seaman, Bing Chen
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells by first engaging its cellular receptor angiotensin converting enzyme 2 (ACE2) to induce conformational changes in the virus-encoded spike protein and fusion between the viral and target cell membranes. Here, we report that certain monoclonal neutralizing antibodies against distinct epitopic regions of the receptor-binding
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Tetraspanner-based nanodomains modulate BAR domain-induced membrane curvature EMBO Rep. (IF 7.7) Pub Date : 2023-10-30 Daniel Haase, Christiane Rasch, Ulrike Keller, Yaroslav Tsytsyura, Nataliya Glyvuk, Annegret Elting, Julia Wittmar, Annette Janning, Martin Kahms, Noah Wedlich, Christian Schuberth, Andreas Heuer, Jürgen Klingauf, Roland Wedlich-Söldner
The topography of biological membranes is critical for formation of protein and lipid microdomains. One prominent example in the yeast plasma membrane (PM) are BAR domain-induced PM furrows. Here we report a novel function for the Sur7 family of tetraspanner proteins in the regulation of local PM topography. Combining TIRF imaging, STED nanoscopy, freeze–fracture EM and membrane simulations we find
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Metabolic plasticity sustains the robustness of Caenorhabditis elegans embryogenesis EMBO Rep. (IF 7.7) Pub Date : 2023-10-27 Siyu Chen, Xing Su, Jinglin Zhu, Long Xiao, Yulin Cong, Leilei Yang, Zhuo Du, Xun Huang
Embryogenesis is highly dependent on maternally loaded materials, particularly those used for energy production. Different environmental conditions and genetic backgrounds shape embryogenesis. The robustness of embryogenesis in response to extrinsic and intrinsic changes remains incompletely understood. By analyzing the levels of two major nutrients, glycogen and neutral lipids, we discovered stage-dependent
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PLK1 promotes the mitotic surveillance pathway by controlling cytosolic 53BP1 availability EMBO Rep. (IF 7.7) Pub Date : 2023-10-27 Matteo Burigotto, Vincenza Vigorito, Colin Gliech, Alessia Mattivi, Sabrina Ghetti, Alessandra Bisio, Graziano Lolli, Andrew J Holland, Luca L Fava
53BP1 acts at the crossroads between DNA repair and p53-mediated stress response. With its interactors p53 and USP28, it is part of the mitotic surveillance (or mitotic stopwatch) pathway (MSP), a sensor that monitors the duration of cell division, promoting p53-dependent cell cycle arrest when a critical time threshold is surpassed. Here, we show that Polo-like kinase 1 (PLK1) activity is essential
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Mind the (CRISPR) gaps: The European Commission's proposal for the use of NGTs in the EU. EMBO Rep. (IF 7.7) Pub Date : 2023-10-26 German Vighi,Nico De Storme
The proposal by the European Commission to regulate New Genome Technique (NGT) plants is a leap forward, but it does not revise the current legislation on GMOs and includes many inconsistencies that may hinder the adoption of specific NGTs.
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From pollutant to powerhouse: The untapped potential of sewage sludge and wastewater. EMBO Rep. (IF 7.7) Pub Date : 2023-10-25 Rathika K,Sunil Kumar,Bholu Ram Yadav
Advances in science and technology that enable the recovery of energy and other valuable compounds from sewage sludge can play an important role in a global transition to renewable energy sources.
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Oxygen-regulated post-translation modifications as master signalling pathway in cells EMBO Rep. (IF 7.7) Pub Date : 2023-10-25 Michael Batie, Temitope Fasanya, Niall S Kenneth, Sonia Rocha
Oxygen is essential for viability in mammalian organisms. However, cells are often exposed to changes in oxygen availability, due to either increased demand or reduced oxygen supply, herein called hypoxia. To be able to survive and/or adapt to hypoxia, cells activate a variety of signalling cascades resulting in changes to chromatin, gene expression, metabolism and viability. Cellular signalling is
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Akkermansia muciniphila induces slow extramedullary hematopoiesis via cooperative IL-1R/TLR signals EMBO Rep. (IF 7.7) Pub Date : 2023-10-23 Yuxin Wang, Tatsuya Morishima, Maiko Sezaki, Ryo Sato, Gaku Nakato, Shinji Fukuda, Kouji Kobiyama, Ken J Ishii, Yuhua Li, Hitoshi Takizawa
Bacterial infections can activate and mobilize hematopoietic stem and progenitor cells (HSPCs) from the bone marrow (BM) to the spleen, a process termed extramedullary hematopoiesis (EMH). Recent studies suggest that commensal bacteria regulate not only the host immune system but also hematopoietic homeostasis. However, the impact of gut microbes on hematopoietic pathology remains unclear. Here, we
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Role and mechanism of PVN–sympathetic–adipose circuit in depression and insulin resistance induced by chronic stress EMBO Rep. (IF 7.7) Pub Date : 2023-10-23 Jing Wang, Linshan Sun, Jingjing You, Honghai Peng, Haijing Yan, Jiangong Wang, Fengjiao Sun, Minghu Cui, Sanwang Wang, Zheng Zhang, Xueli Fan, Dunjiang Liu, Cuilan Liu, Changyun Qiu, Chao Chen, Zhicheng Xu, Jinbo Chen, Wei Li, Bin Liu
Chronic stress induces depression and insulin resistance, between which there is a bidirectional relationship. However, the mechanisms underlying this comorbidity remain unclear. White adipose tissue (WAT), innervated by sympathetic nerves, serves as a central node in the interorgan crosstalk through adipokines. Abnormal secretion of adipokines is involved in mood disorders and metabolic morbidities
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Dynamic reversibility of α-synuclein serine-129 phosphorylation is impaired in synucleinopathy models EMBO Rep. (IF 7.7) Pub Date : 2023-10-23 Nagendran Ramalingam, Lisa Brontesi, Shan-Xue Jin, Dennis J Selkoe, Ulf Dettmer
α-Synuclein phosphorylation at serine-129 (pS129) is a widely used surrogate marker of pathology in Parkinson's disease and other synucleinopathies. However, we recently demonstrated that phosphorylation of S129 is also a physiological activator of synaptic transmission. In a feed-forward fashion, neuronal activity triggers reversible pS129. Here, we show that Parkinson's disease-linked missense mutations
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SIRT2 negatively regulates the cGAS-STING pathway by deacetylating G3BP1 EMBO Rep. (IF 7.7) Pub Date : 2023-10-23 Yutong Li, Juntao Bie, Chen Song, Yunfei Li, Tianzhuo Zhang, Haishuang Li, Long Zhao, Fuping You, Jianyuan Luo
SIRT2, a cytoplasmic member of the Sirtuin family, has important roles in immunity and inflammation. However, its function in regulating the response to DNA virus infection remains elusive. Here, we find that SIRT2 is a unique regulator among the Sirtuin family that negatively modulates the cGAS-STING-signaling pathway. SIRT2 is down-regulated after Herpes simplex virus-1 (HSV-1) infection, and SIRT2
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PARIS undergoes liquid–liquid phase separation and poly(ADP-ribose)-mediated solidification EMBO Rep. (IF 7.7) Pub Date : 2023-10-23 Hojin Kang, Soojeong Park, Areum Jo, Xiaobo Mao, Manoj Kumar, Chi-Hu Park, Jee-Yin Ahn, Yunjong Lee, Jeong-Yun Choi, Yun-Song Lee, Valina L Dawson, Ted M Dawson, Tae-In Kam, Joo-Ho Shin
ZNF746 was identified as parkin-interacting substrate (PARIS). Investigating its pathophysiological properties, we find that PARIS undergoes liquid–liquid phase separation (LLPS) and amorphous solid formation. The N-terminal low complexity domain 1 (LCD1) of PARIS is required for LLPS, whereas the C-terminal prion-like domain (PrLD) drives the transition from liquid to solid phase. In addition, we
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ORF3c is expressed in SARS-CoV-2-infected cells and inhibits innate sensing by targeting MAVS EMBO Rep. (IF 7.7) Pub Date : 2023-10-23 Martin Müller, Alexandra Herrmann, Shigeru Fujita, Keiya Uriu, Carolin Kruth, Adam Strange, Jan E Kolberg, Markus Schneider, Jumpei Ito, Marcel A Müller, Christian Drosten, Armin Ensser, , Kei Sato, Daniel Sauter
Most SARS-CoV-2 proteins are translated from subgenomic RNAs (sgRNAs). While the majority of these sgRNAs are monocistronic, some viral mRNAs encode more than one protein. One example is the ORF3a sgRNA that also encodes ORF3c, an enigmatic 41-amino-acid peptide. Here, we show that ORF3c is expressed in SARS-CoV-2-infected cells and suppresses RIG-I- and MDA5-mediated IFN-β induction. ORF3c interacts
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Tick-borne flavivirus NS5 antagonizes interferon signaling by inhibiting the catalytic activity of TYK2 EMBO Rep. (IF 7.7) Pub Date : 2023-10-20 Ségolène Gracias, Maxime Chazal, Alice Decombe, Yves Unterfinger, Adrià Sogues, Lauryne Pruvost, Valentine Robert, Sandrine A Lacour, Manon Lemasson, Marion Sourisseau, Zhi Li, Jennifer Richardson, Sandra Pellegrini, Etienne Decroly, Vincent Caval, Nolwenn Jouvenet
The mechanisms utilized by different flaviviruses to evade antiviral functions of interferons are varied and incompletely understood. Using virological approaches, biochemical assays, and mass spectrometry analyses, we report here that the NS5 protein of tick-borne encephalitis virus (TBEV) and Louping Ill virus (LIV), two related tick-borne flaviviruses, antagonize JAK–STAT signaling through interactions
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CCR4-NOT differentially controls host versus virus poly(a)-tail length and regulates HCMV infection EMBO Rep. (IF 7.7) Pub Date : 2023-10-17 Hannah M Burgess, Rebecca Grande, Sofia Riccio, Ikshitaa Dinesh, Gerlof Sebastiaan Winkler, Daniel P Depledge, Ian Mohr
Unlike most RNA and DNA viruses that broadly stimulate mRNA decay and interfere with host gene expression, human cytomegalovirus (HCMV) extensively remodels the host translatome without producing an mRNA decay enzyme. By performing a targeted loss-of-function screen in primary human fibroblasts, we here identify the host CCR4-NOT deadenylase complex members CNOT1 and CNOT3 as unexpected pro-viral host
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Cytotoxic T lymphocytes require transcription for infiltration but not target cell lysis EMBO Rep. (IF 7.7) Pub Date : 2023-10-20 Arianne C Richard, Claire Y Ma, John C Marioni, Gillian M Griffiths
Effector cytotoxic T lymphocytes (CTLs) are critical for ridding the body of infected or cancerous cells. CTL T cell receptor (TCR) ligation not only drives the delivery and release of cytolytic granules but also initiates a new wave of transcription. In order to address whether TCR-induced transcriptomic changes impact the ability of CTLs to kill, we asked which genes are expressed immediately after
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Getting the message right: An interview with mRNA vaccine pioneer Katalin Karikó. EMBO Rep. (IF 7.7) Pub Date : 2023-10-19 Adam Gristwood
An interview with Katalin Karikó who received the Nobel Prize in Physiology and Medicine for her groundbreaking work on mRNA modifications that enabled the development of mRNA vaccines.
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Things I wish I had done as a graduate student. EMBO Rep. (IF 7.7) Pub Date : 2023-10-19 David R Smith
Making the most of opportunities available during graduate school can pay dividends later on.
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A selective journal EMBO Rep. (IF 7.7) Pub Date : 2023-10-18 Bernd Pulverer
The stringent selection criteria applied at EMBO Reports result in the publication of around 16% of submitted papers. What do we select for and why is this a service to the scientific community? A counterpoint to EMBO Reports (2023) e58127.
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The four fronts of immunotherapy: The development of new immunotherapeutic approaches against a wide range of diseases. EMBO Rep. (IF 7.7) Pub Date : 2023-10-17 Philip Hunter
Research on harnessing the immune system to fight against diseases from cancer to allergies has been making progress but unintended side effects still pose challenges.
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An ULK1/2-PXN mechanotransduction pathway suppresses breast cancer cell migration EMBO Rep. (IF 7.7) Pub Date : 2023-10-17 Peigang Liang, Jiaqi Zhang, Yuchen Wu, Shanyuan Zheng, Zhaopeng Xu, Shuo Yang, Jinfang Wang, Suibin Ma, Li Xiao, Tianhui Hu, Wenxue Jiang, Chaoqun Huang, Qiong Xing, Mondira Kundu, Bo Wang
The remodeling and stiffening of the extracellular matrix (ECM) is a well-recognized modulator of breast cancer progression. How changes in the mechanical properties of the ECM are converted into biochemical signals that direct tumor cell migration and metastasis remain poorly characterized. Here, we describe a new role for the autophagy-inducing serine/threonine kinases ULK1 and ULK2 in mechanotransduction
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A1 is induced by pathogen ligands to limit myeloid cell death and NLRP3 inflammasome activation EMBO Rep. (IF 7.7) Pub Date : 2023-10-17 Mary Speir, Hazel Tye, Timothy A Gottschalk, Daniel S Simpson, Tirta M Djajawi, Pankaj Deo, Rebecca L Ambrose, Stephanie A Conos, Jack Emery, Gilu Abraham, Ashlyn Pascoe, Sebastian A Hughes, Ashley Weir, Edwin D Hawkins, Isabella Kong, Marco J Herold, Jaclyn S Pearson, Najoua Lalaoui, Thomas Naderer, James E Vince, Kate E Lawlor
Programmed cell death pathways play an important role in innate immune responses to infection. Activation of intrinsic apoptosis promotes infected cell clearance; however, comparatively little is known about how this mode of cell death is regulated during infections and whether it can induce inflammation. Here, we identify that the pro-survival BCL-2 family member, A1, controls activation of the essential
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The HACE1 E3 ligase mediates RAC1-dependent control of mTOR signaling complexes EMBO Rep. (IF 7.7) Pub Date : 2023-10-17 Busra Turgu, Amal El-Naggar, Melanie Kogler, Luigi Tortola, Hai-Feng Zhang, Mariam Hassan, Michael M Lizardo, Sonia HY Kung, Wan Lam, Josef M Penninger, Poul H Sorensen
HACE1 is a HECT family E3 ubiquitin–protein ligase with broad but incompletely understood tumor suppressor activity. Here, we report a previously unrecognized link between HACE1 and signaling complexes containing mammalian target of rapamycin (mTOR). HACE1 blocks mTORC1 and mTORC2 activities by reducing mTOR stability in an E3 ligase-dependent manner. Mechanistically, HACE1 binds to and ubiquitylates
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Cold-inducible lncRNA266 promotes browning and the thermogenic program in white adipose tissue EMBO Rep. (IF 7.7) Pub Date : 2023-10-12 Jinyu Ma, Yuting Wu, Lixue Cen, Zhe Wang, Ketao Jiang, Bolin Lian, Cheng Sun
Cold-induced nonshivering thermogenesis has contributed to the improvement of several metabolic syndromes caused by obesity. Several long noncoding RNAs (lncRNAs) have been shown to play a role in brown fat biogenesis and thermogenesis. Here we show that the lncRNA lnc266 is induced by cold exposure in inguinal white adipose tissue (iWAT). In vitro functional studies reveal that lnc266 promotes brown
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Nutritional and metabolic control of germ cell fate through O-GlcNAc regulation EMBO Rep. (IF 7.7) Pub Date : 2023-10-16 Yohei Hayashi, Yukiko Tando, Yumi Ito-Matsuoka, Kaho Ikuta, Asuka Takehara, Katsutaro Morino, Hiroshi Maegawa, Yasuhisa Matsui
Fate determination of primordial germ cells (PGCs) is regulated in a multi-layered manner, involving signaling pathways, epigenetic mechanisms, and transcriptional control. Chemical modification of macromolecules, including epigenetics, is expected to be closely related with metabolic mechanisms but the detailed molecular machinery linking these two layers remains poorly understood. Here, we show that
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The functional significance of mitochondrial respiratory chain supercomplexes EMBO Rep. (IF 7.7) Pub Date : 2023-10-12 Andreas Kohler, Antoni Barrientos, Flavia Fontanesi, Martin Ott
The mitochondrial respiratory chain (MRC) is a key energy transducer in eukaryotic cells. Four respiratory chain complexes cooperate in the transfer of electrons derived from various metabolic pathways to molecular oxygen, thereby establishing an electrochemical gradient over the inner mitochondrial membrane that powers ATP synthesis. This electron transport relies on mobile electron carries that functionally
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Tetherin antagonism by SARS-CoV-2 ORF3a and spike protein enhances virus release EMBO Rep. (IF 7.7) Pub Date : 2023-10-11 Hazel Stewart, Roberta Palmulli, Kristoffer H Johansen, Naomi McGovern, Ola M Shehata, George W Carnell, Hannah K Jackson, Jin S Lee, Jonathan C Brown, Thomas Burgoyne, Jonathan L Heeney, Klaus Okkenhaug, Andrew E Firth, Andrew A Peden, James R Edgar
The antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including the Coronaviridae. Tetherin is an interferon-induced protein that forms parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrate that SARS-CoV-2 infection causes tetherin downregulation
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Immune–epithelial cell cross-talk enhances antiviral responsiveness to SARS-CoV-2 in children EMBO Rep. (IF 7.7) Pub Date : 2023-10-11 Vladimir G Magalhães, Sören Lukassen, Maike Drechsler, Jennifer Loske, Sandy S Burkart, Sandra Wüst, Eva-Maria Jacobsen, Jobst Röhmel, Marcus A Mall, Klaus-Michael Debatin, Roland Eils, Stella Autenrieth, Aleš Janda, Irina Lehmann, Marco Binder
The risk of developing severe COVID-19 rises dramatically with age. Schoolchildren are significantly less likely than older people to die from SARS-CoV-2 infection, but the molecular mechanisms underlying this age-dependence are unknown. In primary infections, innate immunity is critical due to the lack of immune memory. Children, in particular, have a significantly stronger interferon response due
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Break-induced RNA–DNA hybrids (BIRDHs) in homologous recombination: friend or foe? EMBO Rep. (IF 7.7) Pub Date : 2023-10-11 Belén Gómez-González, Andrés Aguilera
Double-strand breaks (DSBs) are the most harmful DNA lesions, with a strong impact on cell proliferation and genome integrity. Depending on cell cycle stage, DSBs are preferentially repaired by non-homologous end joining or homologous recombination (HR). In recent years, numerous reports have revealed that DSBs enhance DNA–RNA hybrid formation around the break site. We call these hybrids “break-induced
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Tetracyclines activate mitoribosome quality control and reduce ER stress to promote cell survival EMBO Rep. (IF 7.7) Pub Date : 2023-10-11 Conor T Ronayne, Thomas D Jackson, Christopher F Bennett, Elizabeth A Perry, Noa Kantorovic, Pere Puigserver
Mitochondrial diseases are a group of disorders defined by defects in oxidative phosphorylation caused by nuclear- or mitochondrial-encoded gene mutations. A main cellular phenotype of mitochondrial disease mutations is redox imbalances and inflammatory signaling underlying pathogenic signatures of these patients. One method to rescue this cell death vulnerability is the inhibition of mitochondrial
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UBR-1 ubiquitin ligase regulates the balance between GABAergic and glutamatergic signaling EMBO Rep. (IF 7.7) Pub Date : 2023-10-09 Yi Li, Jyothsna Chitturi, Bin Yu, Yongning Zhang, Jing Wu, Panpan Ti, Wesley Hung, Mei Zhen, Shangbang Gao
Excitation/inhibition (E/I) balance is carefully maintained by the nervous system. The neurotransmitter GABA has been reported to be co-released with its sole precursor, the neurotransmitter glutamate. The genetic and circuitry mechanisms to establish the balance between GABAergic and glutamatergic signaling have not been fully elucidated. Caenorhabditis elegans DVB is an excitatory GABAergic motoneuron