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Antipsychotic-induced epigenomic reorganization in frontal cortex of individuals with schizophrenia eLife (IF 7.7) Pub Date : 2024-04-22 Bohan Zhu, Richard I Ainsworth, Zengmiao Wang, Zhengzhi Liu, Salvador Sierra, Chengyu Deng, Luis F Callado, J Javier Meana, Wei Wang, Chang Lu, Javier González-Maeso
Genome-wide association studies have revealed >270 loci associated with schizophrenia risk, yet these genetic factors do not seem to be sufficient to fully explain the molecular determinants behind this psychiatric condition. Epigenetic marks such as post-translational histone modifications remain largely plastic during development and adulthood, allowing a dynamic impact of environmental factors,
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Membrane-bound O-acyltransferase 7 (MBOAT7) shapes lysosomal lipid homeostasis and function to control alcohol-associated liver injury eLife (IF 7.7) Pub Date : 2024-04-22 Venkateshwari Varadharajan, Iyappan Ramachandiran, William J Massey, Raghav Jain, Rakhee Banerjee, Anthony J Horak, Megan R McMullen, Emily Huang, Annette Bellar, Shuhui W Lorkowski, Kailash Gulshan, Robert N Helsley, Isabella James, Vai Pathak, Jaividhya Dasarathy, Nicole Welch, Srinivasan Dasarathy, David Streem, Ofer Reizes, Daniela S Allende, Jonathan D Smith, Judith Simcox, Laura E Nagy, J Mark
Recent genome-wide association studies (GWAS) have identified a link between single-nucleotide polymorphisms (SNPs) near the MBOAT7 gene and advanced liver diseases. Specifically, the common MBOAT7 variant (rs641738) associated with reduced MBOAT7 expression is implicated in non-alcoholic fatty liver disease (NAFLD), alcohol-associated liver disease (ALD), and liver fibrosis. However, the precise mechanism
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LRMP inhibits cAMP potentiation of HCN4 channels by disrupting intramolecular signal transduction eLife (IF 7.7) Pub Date : 2024-04-23 Colin H Peters, Rohit K Singh, Avery A Langley, William G Nichols, Hannah R Ferris, Danielle A Jeffrey, Catherine Proenza, John R Bankston
Lymphoid restricted membrane protein (LRMP) is a specific regulator of the hyperpolarization-activated cyclic nucleotide-sensitive isoform 4 (HCN4) channel. LRMP prevents cAMP-dependent potentiation of HCN4, but the interaction domains, mechanisms of action, and basis for isoform-specificity remain unknown. Here, we identify the domains of LRMP essential for this regulation, show that LRMP acts by
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Endogenous tagging using split mNeonGreen in human iPSCs for live imaging studies eLife (IF 7.7) Pub Date : 2024-04-23 Mathieu C Husser, Nhat P Pham, Chris Law, Flavia RB Araujo, Vincent JJ Martin, Alisa Piekny
Endogenous tags have become invaluable tools to visualize and study native proteins in live cells. However, generating human cell lines carrying endogenous tags is difficult due to the low efficiency of homology-directed repair. Recently, an engineered split mNeonGreen protein was used to generate a large-scale endogenous tag library in HEK293 cells. Using split mNeonGreen for large-scale endogenous
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Inhibitory G proteins play multiple roles to polarize sensory hair cell morphogenesis eLife (IF 7.7) Pub Date : 2024-04-23 Amandine Jarysta, Abigail LD Tadenev, Matthew Day, Barry Krawchuk, Benjamin E Low, Michael V Wiles, Basile Tarchini
Inhibitory G alpha (GNAI or Gαi) proteins are critical for the polarized morphogenesis of sensory hair cells and for hearing. The extent and nature of their actual contributions remains unclear, however, as previous studies did not investigate all GNAI proteins and included non-physiological approaches. Pertussis toxin can downregulate functionally redundant GNAI1, GNAI2, GNAI3, and GNAO proteins,
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A multi-hierarchical approach reveals d-serine as a hidden substrate of sodium-coupled monocarboxylate transporters eLife (IF 7.7) Pub Date : 2024-04-23 Pattama Wiriyasermkul, Satomi Moriyama, Masataka Suzuki, Pornparn Kongpracha, Nodoka Nakamae, Saki Takeshita, Yoko Tanaka, Akina Matsuda, Masaki Miyasaka, Kenji Hamase, Tomonori Kimura, Masashi Mita, Jumpei Sasabe, Shushi Nagamori
Transporter research primarily relies on the canonical substrates of well-established transporters. This approach has limitations when studying transporters for the low-abundant micromolecules, such as micronutrients, and may not reveal physiological functions of the transporters. While d-serine, a trace enantiomer of serine in the circulation, was discovered as an emerging biomarker of kidney function
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Recording and classifying MET receptor mutations in cancers eLife (IF 7.7) Pub Date : 2024-04-23 Célia Guérin, David Tulasne
Tyrosine kinase inhibitors (TKI) directed against MET have been recently approved to treat advanced non-small cell lung cancer (NSCLC) harbouring activating MET mutations. This success is the consequence of a long characterization of MET mutations in cancers, which we propose to outline in this review. MET, a receptor tyrosine kinase (RTK), displays in a broad panel of cancers many deregulations liable
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A logic-incorporated gene regulatory network deciphers principles in cell fate decisions eLife (IF 7.7) Pub Date : 2024-04-23 Gang Xue, Xiaoyi Zhang, Wanqi Li, Lu Zhang, Zongxu Zhang, Xiaolin Zhou, Di Zhang, Lei Zhang, Zhiyuan Li
Organisms utilize gene regulatory networks (GRN) to make fate decisions, but the regulatory mechanisms of transcription factors (TF) in GRNs are exceedingly intricate. A longstanding question in this field is how these tangled interactions synergistically contribute to decision-making procedures. To comprehensively understand the role of regulatory logic in cell fate decisions, we constructed a logic-incorporated
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Five interdisciplinary tensions and opportunities in neurodiversity research eLife (IF 7.7) Pub Date : 2024-04-23 Olujolagbe Layinka, Luca D Hargitai, Punit Shah, Lucy H Waldren, Florence YN Leung
Improving our understanding of autism, ADHD, dyslexia and other neurodevelopmental conditions requires collaborations between genetics, psychiatry, the social sciences and other fields of research.
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Experience transforms crossmodal object representations in the anterior temporal lobes eLife (IF 7.7) Pub Date : 2024-04-22 Aedan Yue Li, Natalia Ladyka-Wojcik, Heba Qazilbash, Ali Golestani, Dirk Bernhardt-Walther, Chris B Martin, Morgan Barense
Combining information from multiple senses is essential to object recognition, core to the ability to learn concepts, make new inferences, and generalize across distinct entities. Yet how the mind combines sensory input into coherent crossmodal representations - the crossmodal binding problem - remains poorly understood. Here, we applied multi-echo fMRI across a four-day paradigm, in which participants
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Warming and altered precipitation independently and interactively suppress alpine soil microbial growth in a decadal-long experiment eLife (IF 7.7) Pub Date : 2024-04-22 Yang Ruan, Ning Ling, Shengjing Jiang, Xin Jing, Jin-Sheng He, Qirong Shen, Zhibiao Nan
Warming and precipitation anomalies affect terrestrial carbon balance partly through altering microbial eco-physiological processes (e.g., growth and death) in soil. However, little is known about how such processes responds to simultaneous regime shifts in temperature and precipitation. We used the 18O-water quantitative stable isotope probing approach to estimate bacterial growth in alpine meadow
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Convergent epigenetic evolution drives relapse in acute myeloid leukemia eLife (IF 7.7) Pub Date : 2024-04-22 Kevin Nuno, Armon Azizi, Thomas Koehnke, Caleb Lareau, Asiri Ediriwickrema, M Ryan Corces, Ansuman T Satpathy, Ravindra Majeti
Relapse of acute myeloid leukemia (AML) is highly aggressive and often treatment refractory. We analyzed previously published AML relapse cohorts and found that 40% of relapses occur without changes in driver mutations, suggesting that non-genetic mechanisms drive relapse in a large proportion of cases. We therefore characterized epigenetic patterns of AML relapse using 26 matched diagnosis-relapse
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X-ray structure and enzymatic study of a bacterial NADPH oxidase highlight the activation mechanism of eukaryotic NOX eLife (IF 7.7) Pub Date : 2024-04-19 Isabelle Petit-Hartlein, Annelise Vermot, Michel Thepaut, Anne-Sophie Humm, Florine Dupeux, Jerome Dupuy, Vincent Chaptal, Jose Antonio Marquez, Susan ME Smith, Franck Fieschi
NADPH oxidases (NOX) are transmembrane proteins, widely spread in eukaryotes and prokaryotes, that produce reactive oxygen species (ROS). Eukaryotes use the ROS products for innate immune defense and signaling in critical (patho)physiological processes. Despite the recent structures of human NOX isoforms, the activation of electron transfer remains incompletely understood. SpNOX, a homolog from Streptococcus
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Lesions in a songbird vocal circuit increase variability in song syntax eLife (IF 7.7) Pub Date : 2024-04-18 Avani Koparkar, Timothy L Warren, Jonathan D Charlesworth, Sooyoon Shin, Michael S Brainard, Lena Veit
Complex skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for the syntactic ordering of actions is poorly understood. Birdsong is a learned vocal behavior composed of syntactically ordered syllables, controlled in part by the songbird premotor nucleus HVC (proper name). Here, we test whether one of HVC’s recurrent inputs, mMAN (medial magnocellular
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Species -shared and -unique gyral peaks on human and macaque brains eLife (IF 7.7) Pub Date : 2024-04-18 Songyao Zhang, Tuo Zhang, Guannan Cao, Jingchao Zhou, Zhibin He, Xiao Li, Yudan Ren, Tao Liu, Xi Jiang, Lei Guo, Junwei Han, Tianming Liu
Cortical folding is an important feature of primate brains that plays a crucial role in various cognitive and behavioral processes. Extensive research has revealed both similarities and differences in folding morphology and brain function among primates including macaque and human. The folding morphology is the basis of brain function, making cross-species studies on folding morphology important for
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Transposable elements regulate thymus development and function eLife (IF 7.7) Pub Date : 2024-04-18 Jean-David Larouche, Céline M Laumont, Assya Trofimov, Krystel Vincent, Leslie Hesnard, Sylvie Brochu, Caroline Côté, Juliette F Humeau, Éric Bonneil, Joel Lanoix, Chantal Durette, Patrick Gendron, Jean-Philippe Laverdure, Ellen R Richie, Sébastien Lemieux, Pierre Thibault, Claude Perreault
Transposable elements (TEs) are repetitive sequences representing ~45% of the human and mouse genomes and are highly expressed by medullary thymic epithelial cells (mTECs). In this study, we investigated the role of TEs on T-cell development in the thymus. We performed multiomic analyses of TEs in human and mouse thymic cells to elucidate their role in T-cell development. We report that TE expression
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Staphylococcus aureus FtsZ and PBP4 bind to the conformationally dynamic N-terminal domain of GpsB eLife (IF 7.7) Pub Date : 2024-04-19 Michael D Sacco, Lauren R Hammond, Radwan E Noor, Dipanwita Bhattacharya, Lily J McKnight, Jesper J Madsen, Xiujun Zhang, Shane G Butler, M Trent Kemp, Aiden C Jaskolka-Brown, Sebastian J Khan, Ioannis Gelis, Prahathees Eswara, Yu Chen
In the Firmicutes phylum, GpsB is a membrane associated protein that coordinates peptidoglycan synthesis with cell growth and division. Although GpsB has been studied in several bacteria, the structure, function, and interactome of Staphylococcus aureus GpsB is largely uncharacterized. To address this knowledge gap, we solved the crystal structure of the N-terminal domain of S. aureus GpsB, which adopts
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MEMO1 binds iron and modulates iron homeostasis in cancer cells eLife (IF 7.7) Pub Date : 2024-04-19 Natalia Dolgova, Eva-Maria E Uhlemann, Michal T Boniecki, Frederick S Vizeacoumar, Anjuman Ara, Paria Nouri, Martina Ralle, Marco Tonelli, Syed A Abbas, Jaala Patry, Hussain Elhasasna, Andrew Freywald, Franco Vizeacoumar, Oleg Y Dmitriev
Mediator of ERBB2-driven Cell Motility 1 (MEMO1) is an evolutionary conserved protein implicated in many biological processes; however, its primary molecular function remains unknown. Importantly, MEMO1 is overexpressed in many types of cancer and was shown to modulate breast cancer metastasis through altered cell motility. To better understand the function of MEMO1 in cancer cells, we analyzed genetic
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A modified BCG with depletion of enzymes associated with peptidoglycan amidation induces enhanced protection against tuberculosis in mice eLife (IF 7.7) Pub Date : 2024-04-19 Moagi Tube Shaku, Peter K Um, Karl L Ocius, Alexis J Apostolos, Marcos M Pires, William R Bishai, Bavesh D Kana
Mechanisms by which Mycobacterium tuberculosis (Mtb) evades pathogen recognition receptor activation during infection may offer insights for the development of improved tuberculosis (TB) vaccines. Whilst Mtb elicits NOD-2 activation through host recognition of its peptidoglycan-derived muramyl dipeptide (MDP), it masks the endogenous NOD-1 ligand through amidation of glutamate at the second position
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Haplotype function score improves biological interpretation and cross-ancestry polygenic prediction of human complex traits eLife (IF 7.7) Pub Date : 2024-04-19 Weichen Song, Yongyong Shi, Guan ning Lin
We propose a new framework for human genetic association studies: at each locus, a deep learning model (in this study, Sei) is used to calculate the functional genomic activity score for two haplotypes per individual. This score, defined as the Haplotype Function Score (HFS), replaces the original genotype in association studies. Applying the HFS framework to 14 complex traits in the UK Biobank, we
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The rapidly evolving X-linked MIR-506 family fine-tunes spermatogenesis to enhance sperm competition eLife (IF 7.7) Pub Date : 2024-04-19 Zhuqing Wang, Yue Wang, Tong Zhou, Sheng Chen, Dayton Morris, Rubens Daniel Miserani Magalhães, Musheng Li, Shawn Wang, Hetan Wang, Yeming Xie, Hayden McSwiggin, Daniel Oliver, Shuiqiao Yuan, Huili Zheng, Jaaved Mohammed, Eric C Lai, John R McCarrey, Wei Yan
Despite rapid evolution across eutherian mammals, the X-linked MIR-506 family miRNAs are located in a region flanked by two highly conserved protein-coding genes (SLITRK2 and FMR1) on the X chromosome. Intriguingly, these miRNAs are predominantly expressed in the testis, suggesting a potential role in spermatogenesis and male fertility. Here, we report that the X-linked MIR-506 family miRNAs were derived
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The CD4 transmembrane GGXXG and juxtamembrane (C/F)CV+C motifs mediate pMHCII-specific signaling independently of CD4-LCK interactions eLife (IF 7.7) Pub Date : 2024-04-19 Mark S Lee, Peter J Tuohy, Caleb Y Kim, Philip P Yost, Katrina Lichauco, Heather L Parrish, Koenraad Van Doorslaer, Michael S Kuhns
CD4+ T cell activation is driven by five-module receptor complexes. The T cell receptor (TCR) is the receptor module that binds composite surfaces of peptide antigens embedded within MHCII molecules (pMHCII). It associates with three signaling modules (CD3γε, CD3δε, and CD3ζζ) to form TCR-CD3 complexes. CD4 is the coreceptor module. It reciprocally associates with TCR-CD3-pMHCII assemblies on the outside
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Genome-scale annotation of protein binding sites via language model and geometric deep learning eLife (IF 7.7) Pub Date : 2024-04-17 Qianmu Yuan, Chong Tian, Yuedong Yang
Revealing protein binding sites with other molecules, such as nucleic acids, peptides, or small ligands, sheds light on disease mechanism elucidation and novel drug design. With the explosive growth of proteins in sequence databases, how to accurately and efficiently identify these binding sites from sequences becomes essential. However, current methods mostly rely on expensive multiple sequence alignments
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Inhibition of the serine protease HtrA1 by SerpinE2 suggests an extracellular proteolytic pathway in the control of neural crest migration eLife (IF 7.7) Pub Date : 2024-04-18 Edgar M Pera, Josefine Nilsson-De Moura, Yuriy Pomeshchik, Laurent Roybon, Ivana Milas
We previously showed that SerpinE2 and the serine protease HtrA1 modulate fibroblast growth factor (FGF) signaling in germ layer specification and head-to-tail development of Xenopus embryos. Here, we present an extracellular proteolytic mechanism involving this serpin-protease system in the developing neural crest (NC). Knockdown of SerpinE2 by injected antisense morpholino oligonucleotides did not
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Somatotopic organization among parallel sensory pathways that promote a grooming sequence in Drosophila eLife (IF 7.7) Pub Date : 2024-04-18 Katharina Eichler, Stefanie Hampel, Adrián Alejandro-García, Steven A Calle-Schuler, Alexis Santana-Cruz, Lucia Kmecova, Jonathan M Blagburn, Eric D Hoopfer, Andrew M Seeds
Mechanosensory neurons located across the body surface respond to tactile stimuli and elicit diverse behavioral responses, from relatively simple stimulus location-aimed movements to complex movement sequences. How mechanosensory neurons and their postsynaptic circuits influence such diverse behaviors remains unclear. We previously discovered that Drosophila perform a body location-prioritized grooming
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Tools and methods for high-throughput single-cell imaging with the mother machine eLife (IF 7.7) Pub Date : 2024-04-18 Ryan Thiermann, Michael Sandler, Gursharan Ahir, John T Sauls, Jeremy Schroeder, Steven Brown, Guillaume Le Treut, Fangwei Si, Dongyang Li, Jue D Wang, Suckjoon Jun
Despite much progress, image processing remains a significant bottleneck for high-throughput analysis of microscopy data. One popular platform for single-cell time-lapse imaging is the mother machine, which enables long-term tracking of microbial cells under precisely controlled growth conditions. While several mother machine image analysis pipelines have been developed in the past several years, adoption
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Making progress eLife (IF 7.7) Pub Date : 2024-04-17 Jurgen Denecke
Mapping proteins in and associated with the Golgi apparatus reveals how this cellular compartment emerges in budding yeast and progresses over time.
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High-altitude hypoxia exposure inhibits erythrophagocytosis by inducing macrophage ferroptosis in the spleen eLife (IF 7.7) Pub Date : 2024-04-17 Wan-ping Yang, Mei-qi Li, Jie Ding, Jia-yan Li, Gang Wu, Bao Liu, Yu-qi Gao, Guo-hua Wang, Qian-qian Luo
High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic conditions. The exact mechanisms behind HAPC are not fully understood. We utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis
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Plastic vasomotion entrainment eLife (IF 7.7) Pub Date : 2024-04-17 Daichi Sasaki, Ken Imai, Yoko Ikoma, Ko Matsui
The presence of global synchronization of vasomotion induced by oscillating visual stimuli was identified in the mouse brain. Endogenous autofluorescence was used and the vessel ‘shadow’ was quantified to evaluate the magnitude of the frequency-locked vasomotion. This method allows vasomotion to be easily quantified in non-transgenic wild-type mice using either the wide-field macro-zoom microscopy
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Heat stress impairs centromere structure and segregation of meiotic chromosomes in Arabidopsis eLife (IF 7.7) Pub Date : 2024-04-17 Lucie Crhak Khaitova, Pavlina Mikulkova, Jana Pecinkova, Manikandan Kalidass, Stefan Heckmann, Inna Lermontova, Karel Riha
Heat stress is a major threat to global crop production, and understanding its impact on plant fertility is crucial for developing climate-resilient crops. Despite the known negative effects of heat stress on plant reproduction, the underlying molecular mechanisms remain poorly understood. Here, we investigated the impact of elevated temperature on centromere structure and chromosome segregation during
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A retrospective cohort study of Paxlovid efficacy depending on treatment time in hospitalized COVID-19 patients eLife (IF 7.7) Pub Date : 2024-04-16 Zhanwei Du, Lin Wang, Yuan Bai, Yunhu Liu, Eric HY Lau, Alison P Galvani, Robert M Krug, Benjamin John Cowling, Lauren A Meyers
Paxlovid, a SARS-CoV-2 antiviral, not only prevents severe illness but also curtails viral shedding, lowering transmission risks from treated patients. By fitting a mathematical model of within-host Omicron viral dynamics to electronic health records data from 208 hospitalized patients in Hong Kong, we estimate that Paxlovid can inhibit over 90% of viral replication. However, its effectiveness critically
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High-risk Escherichia coli clones that cause neonatal meningitis and association with recrudescent infection eLife (IF 7.7) Pub Date : 2024-04-16 Nguyen Thi Khanh Nhu, Minh-Duy Phan, Steven J Hancock, Kate M Peters, Laura Alvarez-Fraga, Brian M Forde, Stacey B Andersen, Thyl Miliya, Patrick NA Harris, Scott A Beatson, Sanmarie Schlebusch, Haakon Bergh, Paul Turner, Annelie Brauner, Benita Westerlund-Wikström, Adam D Irwin, Mark A Schembri
Neonatal meningitis is a devastating disease associated with high mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis in full-term infants (herein NMEC) and the most common cause of meningitis in preterm neonates. Here, we investigated the genomic relatedness of a collection of 58 NMEC isolates spanning 1974–2020 and isolated from seven different
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Early recovery of proteasome activity in cells pulse-treated with proteasome inhibitors is independent of DDI2 eLife (IF 7.7) Pub Date : 2024-04-15 Ibtisam Ibtisam, Alexei F Kisselev
Rapid recovery of proteasome activity may contribute to intrinsic and acquired resistance to FDA-approved proteasome inhibitors. Previous studies have demonstrated that the expression of proteasome genes in cells treated with sub-lethal concentrations of proteasome inhibitors is upregulated by the transcription factor Nrf1 (NFE2L1), which is activated by a DDI2 protease. Here, we demonstrate that the
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Enhancing fear extinction eLife (IF 7.7) Pub Date : 2024-04-15 Sydney Trask, Nicole C Ferrara
Gradually reducing a source of fear during extinction treatments may weaken negative memories in the long term.
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Tissue-specific O-GlcNAcylation profiling identifies substrates in translational machinery in Drosophila mushroom body contributing to olfactory learning eLife (IF 7.7) Pub Date : 2024-04-15 Haibin Yu, Dandan Liu, Yaowen Zhang, Ruijun Tang, Xunan Fan, Song Mao, Lu Lv, Fang Chen, Hongtao Qin, Zhuohua Zhang, Daan MF van Alten, Bing Yang, Kai Yuan
O-GlcNAcylation is a dynamic post-translational modification that diversifies the proteome. Its dysregulation is associated with neurological disorders that impair cognitive function, and yet identification of phenotype-relevant candidate substrates in a brain-region specific manner remains unfeasible. By combining an O-GlcNAc binding activity derived from Clostridium perfringens OGA (CpOGA) with TurboID
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Continuous endosomes form functional subdomains and orchestrate rapid membrane trafficking in trypanosomes eLife (IF 7.7) Pub Date : 2024-04-15 Fabian Link, Alyssa Borges, Oliver Karo, Marvin Jungblut, Thomas Müller, Elisabeth Meyer-Natus, Timothy Krüger, Stefan Sachs, Nicola G Jones, Mary Morphew, Markus Sauer, Christian Stigloher, J Richard McIntosh, Markus Engstler
Endocytosis is a common process observed in most eukaryotic cells, although its complexity varies among different organisms. In Trypanosoma brucei, the endocytic machinery is under special selective pressure because rapid membrane recycling is essential for immune evasion. This unicellular parasite effectively removes host antibodies from its cell surface through hydrodynamic drag and fast endocytic
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A remarkable genetic shift in a transmitted/founder virus broadens antibody responses against HIV-1 eLife (IF 7.7) Pub Date : 2024-04-15 Swati Jain, Gherman Uritskiy, Marthandan Mahalingam, Himanshu Batra, Subhash Chand, Hung V Trinh, Charles Beck, Woong-Hee Shin, Wadad Alsalmi, Gustavo Kijak, Leigh A Eller, Jerome Kim, Daisuke Kihara, Sodsai Tovanabutra, Guido Ferrari, Merlin L Robb, Mangala Rao, Venigalla B Rao
A productive HIV-1 infection in humans is often established by transmission and propagation of a single transmitted/founder (T/F) virus, which then evolves into a complex mixture of variants during the lifetime of infection. An effective HIV-1 vaccine should elicit broad immune responses in order to block the entry of diverse T/F viruses. Currently, no such vaccine exists. An in-depth study of escape
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Guanidine production by plant homoarginine-6-hydroxylases eLife (IF 7.7) Pub Date : 2024-04-15 Dietmar Funck, Malte Sinn, Giuseppe Forlani, Jörg S Hartig
Metabolism and biological functions of the nitrogen-rich compound guanidine have long been neglected. The discovery of four classes of guanidine-sensing riboswitches and two pathways for guanidine degradation in bacteria hint at widespread sources of unconjugated guanidine in nature. So far, only three enzymes from a narrow range of bacteria and fungi have been shown to produce guanidine, with the
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Hammerhead-type FXR agonists induce an enhancer RNA Fincor that ameliorates nonalcoholic steatohepatitis in mice eLife (IF 7.7) Pub Date : 2024-04-15 Jinjing Chen, Ruoyu Wang, Feng Xiong, Hao Sun, Byron Kemper, Wenbo Li, Jongsook Kemper
The nuclear receptor, farnesoid X receptor (FXR/NR1H4), is increasingly recognized as a promising drug target for metabolic diseases, including nonalcoholic steatohepatitis (NASH). Protein-coding genes regulated by FXR are well known, but whether FXR also acts through regulation of long non-coding RNAs (lncRNAs), which vastly outnumber protein-coding genes, remains unknown. Utilizing RNA-seq and global
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Deciphering molecular heterogeneity and dynamics of human hippocampal neural stem cells at different ages and injury states eLife (IF 7.7) Pub Date : 2024-04-12 Junjun Yao, Shaoxing Dai, Ran Zhu, Ju Tan, Qiancheng Zhao, Yu Yin, Jiansen Sun, Xuewei Du, Longjiao Ge, Jianhua Xu, Chunli Hou, Nan Li, Jun Li, Weizhi Ji, Chuhong Zhu, Runrui Zhang, Tianqing Li
While accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging, and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human
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Chemotherapy activates inflammasomes to cause inflammation-associated bone loss eLife (IF 7.7) Pub Date : 2024-04-11 Chun Wang, Khushpreet Kaur, Canxin Xu, Yousef Abu-Amer, Gabriel Mbalaviele
Chemotherapy is a widely used treatment for a variety of solid and hematological malignancies. Despite its success in improving the survival rate of cancer patients, chemotherapy causes significant toxicity to multiple organs, including the skeleton, but the underlying mechanisms have yet to be elucidated. Using tumor-free mouse models, which are commonly used to assess direct off-target effects of
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Exploratory mass cytometry analysis reveals immunophenotypes of cancer treatment-related pneumonitis eLife (IF 7.7) Pub Date : 2024-04-12 Toyoshi Yanagihara, Kentaro Hata, Keisuke Matsubara, Kazufumi Kunimura, Kunihiro Suzuki, Kazuya Tsubouchi, Satoshi Ikegame, Yoshihiro Baba, Yoshinori Fukui, Isamu Okamoto
Anticancer treatments can result in various adverse effects, including infections due to immune suppression/dysregulation and drug-induced toxicity in the lung. One of the major opportunistic infections is Pneumocystis jirovecii pneumonia (PCP), which can cause severe respiratory complications and high mortality rates. Cytotoxic drugs and immune-checkpoint inhibitors (ICIs) can induce interstitial
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The evolution of transposable elements in Brachypodium distachyon is governed by purifying selection, while neutral and adaptive processes play a minor role eLife (IF 7.7) Pub Date : 2024-04-12 Robert Horvath, Nikolaos Minadakis, Yann Bourgeois, Anne C Roulin
Understanding how plants adapt to changing environments and the potential contribution of transposable elements (TEs) to this process is a key question in evolutionary genomics. While TEs have recently been put forward as active players in the context of adaptation, few studies have thoroughly investigated their precise role in plant evolution. Here, we used the wild Mediterranean grass Brachypodium
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The Listeria monocytogenes persistence factor ClpL is a potent stand-alone disaggregase eLife (IF 7.7) Pub Date : 2024-04-10 Valentin Bohl, Nele Merret Hollmann, Tobias Melzer, Panagiotis Katikaridis, Lena Meins, Bernd Simon, Dirk Flemming, Irmgard Sinning, Janosch Hennig, Axel Mogk
Heat stress can cause cell death by triggering the aggregation of essential proteins. In bacteria, aggregated proteins are rescued by the canonical Hsp70/AAA+ (ClpB) bi-chaperone disaggregase. Man-made, severe stress conditions applied during, e.g., food processing represent a novel threat for bacteria by exceeding the capacity of the Hsp70/ClpB system. Here, we report on the potent autonomous AAA+
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Balancing metabolism and reproduction eLife (IF 7.7) Pub Date : 2024-04-11 Songdou Zhang, Shiheng An
The bacterium responsible for a disease that infects citrus plants across Asia facilitates its own proliferation by increasing the fecundity of its host insect.
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Statin-mediated reduction in mitochondrial cholesterol primes an anti-inflammatory response in macrophages by upregulating Jmjd3 eLife (IF 7.7) Pub Date : 2024-04-11 Zeina Salloum, Kristin Dauner, Yun-fang Li, Neha Verma, David Valdivieso-González, Víctor G Almendro-Vedia, John D Zhang, Kiran Nakka, Mei Xi Chen, Jeffrey G McDonald, Chase D Corley, Alexander Sorisky, Bao-Liang Song, Iván López-Montero, Jie Luo, Jeffrey F Dilworth, Xiaohui Zha
Stains are known to be anti-inflammatory, but the mechanism remains poorly understood. Here we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3, a H3K27me3 demethylase. We provide evidence that lowering cholesterol levels in macrophages suppresses the ATP synthase in the inner mitochondrial membrane
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Fetal influence on the human brain through the lifespan eLife (IF 7.7) Pub Date : 2024-04-11 Kristine B Walhovd, Stine K Krogsrud, Inge K Amlien, Øystein Sørensen, Yunpeng Wang, Anne Cecilie S Bråthen, Knut Overbye, Jonas Kransberg, Athanasia M Mowinckel, Fredrik Magnussen, Martine Herud, Asta K Håberg, Anders Martin Fjell, Didac Vidal-Pineiro
Human fetal development has been associated with brain health at later stages. It is unknown whether growth in utero, as indexed by birth weight (BW), relates consistently to lifespan brain characteristics and changes, and to what extent these influences are of a genetic or environmental nature. Here we show remarkably stable and lifelong positive associations between BW and cortical surface area and
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Rab7-dependent regulation of goblet cell protein CLCA1 modulates gastrointestinal homeostasis eLife (IF 7.7) Pub Date : 2024-04-09 Preksha Gaur, Yesheswini Rajendran, Bhagyashree Srivastava, Manasvini Markandey, Vered Fishbain-Yoskovitz, Gayatree Mohapatra, Aamir Suhail, Shikha Chaudhary, Shaifali Tyagi, Subhash Chandra Yadav, Amit Kumar Pandey, Yifat Merbl, Avinash Bajaj, Vineet Ahuja, Chittur Srikanth
Inflammation in ulcerative colitis is typically restricted to the mucosal layer of distal gut. Disrupted mucus barrier, coupled with microbial dysbiosis, has been reported to occur prior to the onset of inflammation. Here, we show the involvement of vesicular trafficking protein Rab7 in regulating the colonic mucus system. We identified a lowered Rab7 expression in goblet cells of colon during human
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Dysfunctional hippocampal-prefrontal network underlies a multidimensional neuropsychiatric phenotype following early-life seizure eLife (IF 7.7) Pub Date : 2024-04-09 Rafael Naime Ruggiero, Danilo Benette Marques, Matheus Teixeira Rossignoli, Jana Batista De Ross, Tamiris Prizon, Ikaro Jesus Silva Beraldo, Lezio Soares Bueno-Junior, Ludmyla Kandratavicius, Jose Eduardo Peixoto-Santos, Cleiton Lopes-Aguiar, Joao Pereira Leite
Brain disturbances during development can have a lasting impact on neural function and behavior. Seizures during this critical period are linked to significant long-term consequences such as neurodevelopmental disorders, cognitive impairments, and psychiatric symptoms, resulting in a complex spectrum of multimorbidity. The hippocampus-prefrontal cortex (HPC-PFC) circuit emerges as a potential common
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Structure-guided mutagenesis of OSCAs reveals differential activation to mechanical stimuli eLife (IF 7.7) Pub Date : 2024-04-09 Sebastian Jojoa-Cruz, Adrienne E Dubin, Wen-Hsin Lee, Andrew B Ward
The dimeric two-pore OSCA/TMEM63 family has recently been identified as mechanically activated ion channels. Previously, based on the unique features of the structure of OSCA1.2, we postulated the potential involvement of several structural elements in sensing membrane tension (Jojoa-Cruz et al., 2018). Interestingly, while OSCA1, 2, and 3 clades are activated by membrane stretch in cell-attached patches
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KIS counteracts PTBP2 and regulates alternative exon usage in neurons eLife (IF 7.7) Pub Date : 2024-04-10 Marcos Moreno-Aguilera, Alba M Neher, Mónica B Mendoza, Martin Dodel, Faraz K Mardakheh, Raúl Ortiz, Carme Gallego
Alternative RNA splicing is an essential and dynamic process in neuronal differentiation and synapse maturation, and dysregulation of this process has been associated with neurodegenerative diseases. Recent studies have revealed the importance of RNA-binding proteins in the regulation of neuronal splicing programs. However, the molecular mechanisms involved in the control of these splicing regulators
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ICAM-1 nanoclusters regulate hepatic epithelial cell polarity by leukocyte adhesion-independent control of apical actomyosin eLife (IF 7.7) Pub Date : 2024-04-10 Cristina Cacho-Navas, Carmen López-Pujante, Natalia Reglero-Real, Natalia Colás-Algora, Ana Cuervo, Jose Javier Conesa, Susana Barroso, Gema de Rivas, Sergio Ciordia, Alberto Paradela, Gianluca D'Agostino, Carlo Manzo, Jorge Feito, Germán Andrés, Francisca Molina-Jiménez, Pedro Majano, Isabel Correas, José-Maria Carazo, Sussan Nourshargh, Meritxell Huch, Jaime Millán
Epithelial intercellular adhesion molecule (ICAM)-1 is apically polarized, interacts with, and guides leukocytes across epithelial barriers. Polarized hepatic epithelia organize their apical membrane domain into bile canaliculi and ducts, which are not accessible to circulating immune cells but that nevertheless confine most of ICAM-1. Here, by analyzing ICAM-1_KO human hepatic cells, liver organoids
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Bone canonical Wnt signaling is downregulated in type 2 diabetes and associates with higher advanced glycation end-products (AGEs) content and reduced bone strength eLife (IF 7.7) Pub Date : 2024-04-10 Giulia Leanza, Francesca Cannata, Malak Faraj, Claudio Pedone, Viola Viola, Flavia Tramontana, Niccolò Pellegrini, Gianluca Vadalà, Alessandra Piccoli, Rocky Strollo, Francesca Zalfa, Alec T Beeve, Erica L Scheller, Simon Y Tang, Roberto Civitelli, Mauro Maccarrone, Rocco Papalia, Nicola Napoli
Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (SOST and RUNX2) and advanced glycation end-products (AGEs) were impaired in T2D. We investigated Wnt signaling regulation and its association with AGEs accumulation and bone strength in T2D from bone tissue of 15 T2D and 21 non-diabetic postmenopausal women
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Evolution and diversity of biomineralized columnar architecture in early Cambrian phosphatic-shelled brachiopods eLife (IF 7.7) Pub Date : 2024-04-10 Zhiliang Zhang, Zhifei Zhang, Lars Holmer, Timothy P Topper, Bing Pan, Guoxiang Li
Biologically-controlled mineralization producing organic-inorganic composites (hard skeletons) by metazoan biomineralizers has been an evolutionary innovation since the earliest Cambrian. Among them, linguliform brachiopods are one of the key invertebrates that secrete calcium phosphate minerals to build their shells. One of the most distinct shell structures is the organo-phosphatic cylindrical column
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Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies eLife (IF 7.7) Pub Date : 2024-04-10 Thomas Grandits, Christoph M Augustin, Gundolf Haase, Norbert Jost, Gary R Mirams, Steven A Niederer, Gernot Plank, András Varró, László Virág, Alexander Jung
Computer models of the human ventricular cardiomyocyte action potential (AP) have reached a level of detail and maturity that has led to an increasing number of applications in the pharmaceutical sector. However, interfacing the models with experimental data can become a significant computational burden. To mitigate the computational burden, the present study introduces a neural network (NN) that emulates
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Substrate evaporation drives collective construction in termites eLife (IF 7.7) Pub Date : 2024-04-10 Giulio Facchini, Alann Rathery, Stéphane Douady, David Sillam-Dussès, Andrea Perna
Termites build complex nests which are an impressive example of self-organization. We know that the coordinated actions involved in the construction of these nests by multiple individuals are primarily mediated by signals and cues embedded in the structure of the nest itself. However, to date there is still no scientific consensus about the nature of the stimuli that guide termite construction, and
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Effect of α-tubulin acetylation on the doublet microtubule structure eLife (IF 7.7) Pub Date : 2024-04-10 Shun Kai Yang, Shintaroh Kubo, Corbin Steven Black, Katya Peri, Daniel Dai, Thibault Legal, Melissa Valente-Paterno, Jacek Gaertig, Khanh Huy Bui
Acetylation of α-tubulin at the lysine 40 residue (αK40) by αTAT1/MEC-17 acetyltransferase modulates microtubule properties and occurs in most eukaryotic cells. Previous literatures suggest that acetylated microtubules are more stable and damage resistant. αK40 acetylation is the only known microtubule luminal post-translational modification site. The luminal location suggests that the modification
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The molecular basis of Abelson kinase regulation by its αI-helix eLife (IF 7.7) Pub Date : 2024-04-08 Johannes Paladini, Annalena Maier, Judith Maria Habazettl, Ines Hertel, Rajesh Sonti, Stephan Grzesiek
Abelson tyrosine kinase (Abl) is regulated by the arrangement of its regulatory core, consisting sequentially of the SH3, SH2, and kinase (KD) domains, where an assembled or disassembled core corresponds to low or high kinase activity, respectively. It was recently established that binding of type II ATP site inhibitors, such as imatinib, generates a force from the KD N-lobe onto the SH3 domain and
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Transcriptomic atlas of midbrain dopamine neurons uncovers differential vulnerability in a Parkinsonism lesion model eLife (IF 7.7) Pub Date : 2024-04-08 Behzad Yaghmaeian Salmani, Laura Lahti, Linda Gillberg, Jesper Kjaer Jacobsen, Ioannis Mantas, Per Svenningsson, Thomas Perlmann
Midbrain dopamine (mDA) neurons comprise diverse cells with unique innervation targets and functions. This is illustrated by the selective sensitivity of mDA neurons of the substantia nigra compacta (SNc) in patients with Parkinson’s disease, while those in the ventral tegmental area (VTA) are relatively spared. Here, we used single nuclei RNA sequencing (snRNA-seq) of approximately 70,000 mouse midbrain
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N-cadherin directs the collective Schwann cell migration required for nerve regeneration through Slit2/3 mediated contact inhibition of locomotion eLife (IF 7.7) Pub Date : 2024-04-09 Julian J A Hoving, Elizabeth Harford-Wright, Patrick Wingfield-Digby, Anne-Laure Cattin, Mariana Campana, Alex Power, Toby Morgan, Erica Torchiaro, Victor Quereda, Alison C Lloyd
Collective cell migration is fundamental for the development of organisms and in the adult, for tissue regeneration and in pathological conditions such as cancer. Migration as a coherent group requires the maintenance of cell-cell interactions, while contact inhibition of locomotion (CIL), a local repulsive force, can propel the group forward. Here we show that the cell-cell interaction molecule, N-cadherin