Featured
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Article
| Open AccessA molecular toolkit for heterologous protein secretion across Bacteroides species
Bacteroides species are a promising chassis for developing living therapeutics, but this application is challenged by their poorly understood protein secretion abilities. Here, the authors report the discovery, characterization, and implementation of a molecular toolkit that enables efficient protein secretion in Bacteroides species.
- Yu-Hsuan Yeh
- , Vince W. Kelly
- & Shannon J. Sirk
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Article
| Open AccessMultiplexed expansion revealing for imaging multiprotein nanostructures in healthy and diseased brain
Mapping the nature of multiprotein nanostructures in cellular contexts remains challenging. Here, Kang and Schroeder et al. report multiplexed expansion revealing, a technique which expands proteins away from each other, for nanoscale localisation and antibody visualisation of >20 proteins in the same specimen.
- Jinyoung Kang
- , Margaret E. Schroeder
- & Edward S. Boyden
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Article
| Open AccessThe genetic mechanism of B chromosome drive in rye illuminated by chromosome-scale assembly
Drive mechanisms in B chromosome systems remain unclear. Here, the authors assemble the rye B chromosome pseudomolecule, identify candidate trans-acting, drive-controlling factors of the B chromosomal drive, and show a microtubule-associated protein could derive from a functional A chromosomal ancestor.
- Jianyong Chen
- , Jan Bartoš
- & Andreas Houben
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Article
| Open AccessThe massed-spaced learning effect in non-neural human cells
When learning is spaced in time, memory is enhanced, but so far this was only observed in neural systems. Here, the authors show that non-neural cells, including kidney cells, also show a spaced effect in terms of transcriptional responses.
- N. V. Kukushkin
- , R. E. Carney
- & T. J. Carew
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Article
| Open AccessIdentifying the bioimaging features of Alzheimer’s disease based on pupillary light response-driven brain-wide fMRI in awake mice
This work applies high-resolution fMRI with real-time pupillometry in 5xFAD transgenic mice to verify pupillary biomarkers of Alzheimer’s disease (AD). In particular, the pupil-driven fMRI maps identify dysfunction of neuromodulatory pathways affected by AD degeneration.
- Xiaochen Liu
- , David Hike
- & Xin Yu
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Article
| Open AccessHuD impairs neuromuscular junctions and induces apoptosis in human iPSC and Drosophila ALS models
Impairment at the neuromuscular junction (NMJ) is an early sign of ALS. Here, the authors show that the RNA-binding protein HuD causes NMJ and apoptosis phenotypes in human iPSC and Drosophila ALS models, highlighting a possible role in disease onset.
- Beatrice Silvestri
- , Michela Mochi
- & Alessandro Rosa
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Article
| Open AccessPredicting synthetic mRNA stability using massively parallel kinetic measurements, biophysical modeling, and machine learning
The authors carried out massively parallel mRNA decay measurements on over 50,000 mRNAs, revealing the interactions controlling mRNA stability in bacteria. Biophysical modeling and machine learning were combined to predict mRNA decay rates from mRNA sequences.
- Daniel P. Cetnar
- , Ayaan Hossain
- & Howard M. Salis
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Article
| Open AccessReplication stress induces POLQ-mediated structural variant formation throughout common fragile sites after entry into mitosis
The mechanisms of nonrecurrent structural variant (SV) formation are poorly understood. Here, the authors sequenced thousands of SV junctions as they formed at common fragile sites in human cell lines to reveal a primary role for DNA polymerase theta-mediated end joining activated during mitosis.
- Thomas E. Wilson
- , Samreen Ahmed
- & Thomas W. Glover
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Article
| Open AccessFast and light-efficient remote focusing for volumetric voltage imaging
The authors develop a high-speed remote focusing method for volumetric voltage imaging enabling imaging at 500 volumes/s. This is combined with light sheet microscopy to record data from >100 spontaneously active neurons in parallel.
- Urs L. Böhm
- & Benjamin Judkewitz
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Article
| Open AccessAn ultrasensitive multimodal intracranial pressure biotelemetric system enabled by exceptional point and iontronics
The monitoring of vital physiological parameters exemplified by intracranial pressure is of paramount importance. Here, the authors propose an ultrasensitive multimodal biotelemetric system to monitor ICP, respiratory, and heart rate.
- Jie Li
- , Fan Zhang
- & Jikui Luo
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Article
| Open AccessCytosine base editors with increased PAM and deaminase motif flexibility for gene editing in zebrafish
Cytosine base editing is crucial for modeling human diseases in zebrafish. Here, the authors present zevoCDA1 and zevoCDA1-198, optimized editors that improve editing efficiency and precision, allowing zebrafish modeling for disease-related mutations which were previously limited by DNA sequence contexts.
- Yu Zhang
- , Yang Liu
- & Yanmei Liu
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Article
| Open AccessTalin and vinculin combine their activities to trigger actin assembly
In cells, focal adhesions (FAs) strengthen their connection with the actin cytoskeleton to resist force. By combining biochemistry and cell biology, the authors show that the proteins talin and vinculin control actin assembly, thus reinforcing the anchoring of actin to FAs.
- Hong Wang
- , Rayan Said
- & Christophe Le Clainche
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Article
| Open AccessHierarchical regulation of functionally antagonistic neuropeptides expressed in a single neuron pair
Whether and how different neuropeptides in the same neuron might be differentially regulated are not fully understood. This study in C. elegans demonstrates that the signaling of two neuropeptides, expressed in the same neuron, interacts through autocrine feedback. Their antagonistic functions fine-tune behavior in response to different stimuli.
- Ichiro Aoki
- , Luca Golinelli
- & Alexander Gottschalk
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Article
| Open AccessHiDDEN: a machine learning method for detection of disease-relevant populations in case-control single-cell transcriptomics data
Many perturbations affect only a subset of cells, while the rest remain largely unaffected. Existing single-cell analysis methods may fail to isolate the affected cells and their markers. Here, authors introduce HiDDEN, a machine learning method that reveals the perturbation status of individual cells.
- Aleksandrina Goeva
- , Michael-John Dolan
- & Evan Macosko
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Article
| Open AccessSingle-molecule imaging and molecular dynamics simulations reveal early activation of the MET receptor in cells
The hepatocyte growth factor receptor MET is a receptor tyrosine kinase involved in cellular processes such as proliferation, migration, and survival. Here the authors combine molecular dynamics simulations and smFRET in cells, to investigate the early stages of MET activation.
- Yunqing Li
- , Serena M. Arghittu
- & Mike Heilemann
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Article
| Open AccessLive imaging of airway epithelium reveals that mucociliary clearance modulates SARS-CoV-2 spread
Becker et al. use live imaging of SARS-CoV-2 infected airway epithelium cultures to demonstrate a dual role for mucociliary clearance in viral spread. Initially, virus goes with the mucus flow, facilitating local spread; later, increased mucus secretion and ciliary motion defects limit spread.
- Mark E. Becker
- , Laura Martin-Sancho
- & Thomas J. Hope
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Article
| Open AccessNOVAsort for error-free droplet microfluidics
Droplet microfluidic tools with single-cell resolution and high-throughput screening capacities remain scarce. Here, the authors propose NOVAsort, a next-generation droplet sorter that can discern droplets based on both size and fluorescence, which can overcome common problems with conventional sorters.
- Han Zhang
- , Rohit Gupte
- & Arum Han
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Article
| Open AccessTransfer of mitochondrial DNA into the nuclear genome during induced DNA breaks
Emerging genome editing tools have been reported to possess threats to genome stability, while their impact on mitochondrial DNA (mtDNA) remains unknown. Here, authors report that genome editing of both nuclear and mitochondrial genome triggers transfer of mtDNA fragments into the nuclear genome.
- Jinchun Wu
- , Yang Liu
- & Jiazhi Hu
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Article
| Open AccessChromaFold predicts the 3D contact map from single-cell chromatin accessibility
Obtaining a high-resolution contact map using current 3D genomics technologies can be challenging with small input cell numbers. Here, the authors develop ChromaFold, a deep learning model that predicts cell-type-specific 3D contact maps from single-cell chromatin accessibility data alone.
- Vianne R. Gao
- , Rui Yang
- & Christina S. Leslie
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Article
| Open AccessOptogenetic patterning generates multi-strain biofilms with spatially distributed antibiotic resistance
In natural biofilm communities, bacterial spatial organization increases functional complexity. Here, authors present a synthetic biofilm toolkit that patterns distinct cell types with arbitrary spatial organization, and demonstrate how this organization can enable sharing of antibiotic protection.
- Xiaofan Jin
- & Ingmar H. Riedel-Kruse
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Article
| Open AccessIntravascular delivery of an ultraflexible neural electrode array for recordings of cortical spiking activity
Intravascular interfaces offer minimally invasive alternatives for intracranial neural recording and stimulation. Here, the authors introduce a novel intravascular implantation strategy using an ultraflexible microelectrode array, enabling multi-channel single-unit recording in large animals.
- Xingzhao Wang
- , Shun Wu
- & Zhengtuo Zhao
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Perspective
| Open AccessMapping bacterial extracellular vesicle research: insights, best practices and knowledge gaps
Bacterial extracellular vesicles are rapidly gaining attention in biomarker discovery and therapeutic innovation. Here, the authors map current BEV research practices, highlight knowledge gaps and best practices to ensure advances in BEV research and accelerate BEV applications.
- Nele De Langhe
- , Sofie Van Dorpe
- & An Hendrix
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Article
| Open AccessH2S scavenger as a broad-spectrum strategy to deplete bacteria-derived H2S for antibacterial sensitization
Bacteria-derived H2S functions as a universal defense against antibiotics challenge. Here, Ji et al developed a broad-spectrum H2S scavenger that efficiently removes endogenous H2S in several bacteria, disrupts biofilm formation and sensitizes persister cells to antibiotic-mediated killing in vitro and in vivo.
- Jiekai Sun
- , Xu Wang
- & Xingyue Ji
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Article
| Open AccessEncoding extracellular modification of artificial cell membranes using engineered self-translocating proteins
For artificial cells to mimic living cells and communicate with their environment, methods for the translocation of peptides and proteins are needed. Here the authors demonstrate that genetically encoded and engineered α-hemolysin pores can be used to translocate functional peptides across lipid membranes.
- Alexander Harjung
- , Alessandro Fracassi
- & Neal K. Devaraj
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Article
| Open AccessLineage tracing of nuclei in skeletal myofibers uncovers distinct transcripts and interplay between myonuclear populations
Skeletal muscle cells contain hundreds of nuclei, but can also add new nuclei in response to various stimuli. Here, the authors perform lineage tracing on the newly fused nuclei showing that these exhibit unique transcriptional states depending on the stimulus.
- Chengyi Sun
- , Casey O. Swoboda
- & Douglas P. Millay
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Article
| Open AccessStructural insights into epitope-paratope interactions of a monoclonal antibody targeting CEACAM5-expressing tumors
Cryo-electron microscopy was used to determine the high-resolution structure of the antigen-binding fragment of tusamitamab bound to the A3-B3 domains of CEACAM5. The conformational constraints discovered in this study may inform the rational design of new CEACAM5-targeting therapies.
- Anand Kumar
- , Francis Duffieux
- & Alexey Rak
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Article
| Open AccessSpatial proteomics of single cells and organelles on tissue slides using filter-aided expansion proteomics
Hydrogel-based tissue expansion proteomics represents an emerging spatial proteomics approach. Here, the authors develop the filter-aided expansion proteomics (FAXP) strategy, enabling proteomic analysis of single cells and nuclei in formalin-fixed paraffin-embedded (FFPE) tissue sections.
- Zhen Dong
- , Wenhao Jiang
- & Tiannan Guo
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Article
| Open AccessComposite Hedges Nanopores codec system for rapid and portable DNA data readout with high INDEL-Correction
DNA is a promising medium for data storage but requires efficient sequencing methods for real-time data retrieval. Here, authors introduce Composite Hedges Nanopores (CHN), a nanopore-based codec scheme that improves sequencing efficiency and data accuracy, supporting real-time data retrieval.
- Xuyang Zhao
- , Junyao Li
- & Yi Li
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Article
| Open AccessAutomated detection and de novo structure modeling of nucleic acids from cryo-EM maps
Modeling DNA/RNA from cryo-EM maps is challenging because they often have lower resolutions than proteins. Here, the authors propose a deep learning-based method for accurate detection and de novo structure determination of DNA/RNA from cryo-EM maps.
- Tao Li
- , Hong Cao
- & Sheng-You Huang
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Article
| Open AccessHigh-parametric protein maps reveal the spatial organization in early-developing human lung
Understanding the development of the lung will inform treatments for congenital diseases and approaches for preterm infant care. Here they map human lung development using high-parametric imaging at the single-cell level to track abundance, proliferation, and spatial organization of key cell types during early gestation.
- Sanem Sariyar
- , Alexandros Sountoulidis
- & Burcu Ayoglu
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Article
| Open AccessSupercontinuum-tailoring multicolor imaging reveals spatiotemporal dynamics of heterogeneous tumor evolution
Studying tumour heterogeneity and tumour evolution remains a challenging task. Here, the authors propose a supercontinuum-tailoring two-photon microscope to enable the imaging of multiple fluorophores with a single light beam. They use this tool to monitor the dynamics of heterogeneous tumour evolution.
- Xiujuan Gao
- , Xinyuan Huang
- & Ling Fu
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Article
| Open AccessUsing in vivo intact structure for system-wide quantitative analysis of changes in proteins
This study introduces an in vivo protein footprinting method, revealing structural changes in proteome during progressing AD. It demonstrates these changes occur before expression alterations, advancing understanding of protein misfolding mechanisms.
- Ahrum Son
- , Hyunsoo Kim
- & John R. Yates
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Article
| Open AccessLignin valorization to bioplastics with an aromatic hub metabolite-based autoregulation system
One challenge in lignin valorization is that microorganisms possessing downstream metabolic advantages are unable to convert lignin. Here, the authors engineer the non-lignin-degrading bacterium Ralstonia eutropha to efficiently convert lignin into polyhydroxybutyrate using a self-enhanced autoregulation system.
- Yiquan Zhao
- , Le Xue
- & Shangxian Xie
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Article
| Open AccessImproving the suppressive power of homing gene drive by co-targeting a distant-site female fertility gene
Gene drive technology could be a valuable tool to control pest populations, but efficiency in many species is too low to achieve significant population suppression. Here, authors propose a two-target gene drive design to address this challenge, which they model and test in Drosophila melanogaster.
- Nicky R. Faber
- , Xuejiao Xu
- & Jackson Champer
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Article
| Open AccessOptogenetic dissection of transcriptional repression in a multicellular organism
Using optogenetics in the fly embryo, this study investigates how a transcriptional repressor drives switch-like, rapidly reversible repression by modulating transcriptional burst frequency, offering insights into gene regulation dynamics in development.
- Jiaxi Zhao
- , Nicholas C. Lammers
- & Hernan G. Garcia
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Article
| Open AccessNoninvasive in vivo photoacoustic detection of malaria with Cytophone in Cameroon
Improved diagnostics for malaria are desired. Here the authors present first-in-human data for a non-invasive device based on detection of hemozoin in malaria-infected red blood cells, and show that it is safe with comparable performance to current point-of-care diagnostics without the need for a blood sample.
- Aayire C. Yadem
- , Jillian N. Armstrong
- & Sunil Parikh
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Article
| Open AccessDeep-prior ODEs augment fluorescence imaging with chemical sensors
A key aspect of biosensor design is ensuring that fluorescent signals follow the concentration of the analytes as closely as possible, but binding kinetics are often overlooked. Here authors propose a method for reconstructing the spatiotemporal concentration of the underlying chemical messengers by considering the binding process.
- Thanh-an Pham
- , Aleix Boquet-Pujadas
- & George Barbastathis
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Article
| Open AccessSelective RNA pseudouridinylation in situ by circular gRNAs in designer organelles
Synthetic organelles enable the selective manipulation of cellular biochemistry. Here the authors focus on RNA modifications and use designer organelles in mammalian cells to selectively incorporate pseudouridine into mRNA using circular guide RNAs.
- Lukas Schartel
- , Cosimo Jann
- & Edward A. Lemke
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Review Article
| Open AccessThe role of polymers in enabling RNAi-based technology for sustainable pest management
Application of RNAi-based technology for crop pest control is hampered by the lacking of efficient system for the delivery of dsRNA molecules to pests or plants. Here, the authors review polymer systems for dsRNA delivery and provide perspectives on their application in sustainable agriculture production.
- Ana Isabel Quilez-Molina
- , Jonatan Niño Sanchez
- & Danila Merino
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Article
| Open AccessOverloading And unpacKing (OAK) - droplet-based combinatorial indexing for ultra-high throughput single-cell multiomic profiling
Single-cell sequencing approaches need to balance sensitivity, throughput and experimental complexity. Here the authors combine droplet-based microfluidics and combinatorial indexing to develop OAK, a versatile method for ultra-high throughput single-cell multiomic profiling.
- Bing Wu
- , Hayley M. Bennett
- & Spyros Darmanis
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Article
| Open AccessMETASPACE-ML: Context-specific metabolite annotation for imaging mass spectrometry using machine learning
Imaging mass spectrometry has revolutionised spatial metabolomics, but metabolites are annotated for only a fraction of the data. Here, authors show that METASPACE-ML enhances precision, increases throughput, and improves the identification of low-intensity and biologically relevant metabolites.
- Bishoy Wadie
- , Lachlan Stuart
- & Theodore Alexandrov
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Article
| Open AccessDarwinian Evolution of Self-Replicating DNA in a Synthetic Protocell
The construction of a synthetic cell will be contingent on the development of an evolvable genetic replicator. Here, authors create a Darwinian protocell that supports protein synthesis, DNA self-replication, and adaptive evolution.
- Zhanar Abil
- , Ana María Restrepo Sierra
- & Christophe Danelon
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Article
| Open AccessTranscription-dependent mobility of single genes and genome-wide motions in live human cells
The human genome is dynamic across all scales, from motions of single genes to the entire genome. Here, using live cell imaging, the authors study the connection between large-scale genomic motions and the transcriptional activity of single genes.
- Fang-Yi Chu
- , Alexis S. Clavijo
- & Alexandra Zidovska
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Article
| Open AccessData-driven fingerprint nanoelectromechanical mass spectrometry
The authors report a data-driven approach that enables mass spectrometry using any nanomechanical device without knowledge of its vibrational modes.
- John E. Sader
- , Alfredo Gomez
- & Michael L. Roukes
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Article
| Open AccessDevelopmental mouse brain common coordinate framework
3D brain atlases enable spatial data integration across studies. Here, the authors present the Developmental Mouse Brain Common Coordinate Framework, a 3D multimodal atlas from embryonic to adult ages for cell type mapping through brain development.
- Fae N. Kronman
- , Josephine K. Liwang
- & Yongsoo Kim
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Article
| Open AccessNon-averaged single-molecule tertiary structures reveal RNA self-folding through individual-particle cryo-electron tomography
Using cryogenic electron tomography (cryo-ET) and individual-particle cryo-electron tomography (IPET), non-averaged ternary structures of individual RNA origami 6HBC particles were determined, allowing observation of structural diversity and self-folding dynamics during the maturation process after transcription.
- Jianfang Liu
- , Ewan K. S. McRae
- & Gang Ren
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Article
| Open AccessSequencing-guided re-estimation and promotion of cultivability for environmental bacteria
The low cultivability of most environmental bacteria is well known, but previous estimates focused on the proportion of cultivable cells. Here, the authors use various techniques to show, for soil and activated sludge samples, that the proportion of cultivable taxa exceeds that of cultivable cells, and identify genetic and physiological traits associated with cultivability.
- Minjia Zheng
- , Linran Wen
- & Feng Guo
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Article
| Open AccessThe GIAB genomic stratifications resource for human reference genomes
The GIAB genomic stratification resource defines challenging regions in three commonly used human genome references, including the first complete human genome (CHM13). These help understand strengths and weaknesses of sequencing and analysis methods.
- Nathan Dwarshuis
- , Divya Kalra
- & Justin M. Zook
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Article
| Open AccessLigand-induced conformational changes in the β1-adrenergic receptor revealed by hydrogen-deuterium exchange mass spectrometry
GPCRs are vital drug targets. Here, authors use HDX-MS to gain insight into structural dynamics of β1AR upon ligand binding, revealing agonist-induced destabilisation and antagonist stabilisation of ICL1.
- Joanna Toporowska
- , Parth Kapoor
- & Argyris Politis
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