Featured
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Article
| Open AccessMucosal-associated invariant T cells contribute to suppression of inflammatory myeloid cells in immune-mediated kidney disease
Mucosal associated invariant T (MAIT) cells reside in barrier organs, but their contribution to inflammatory processes in the kidneys is not fully known. Here authors find by single cell RNA sequencing that among the different MAIT cell subtypes found at steady state, a population with MAIT17 signature is expanded in both human crescentic glomerulonephritis and its mouse model, and these cells may play protective role in the disease.
- Ann-Christin Gnirck
- , Marie-Sophie Philipp
- & Jan-Eric Turner
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Article
| Open AccessDimension-agnostic and granularity-based spatially variable gene identification using BSP
Identifying spatially variable genes (SVGs) is essential for linking molecular cell functions with tissue phenotypes. Here, authors introduce a non-parametric model that detects SVGs from two or three-dimensional spatial transcriptomics data by comparing gene expression patterns at granularities.
- Juexin Wang
- , Jinpu Li
- & Dong Xu
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Article
| Open AccessImaging cellular forces with photonic crystals
Current techniques for visualizing cell generated forces suffer from throughput limitations. Here, Gu et al. introduced photonic crystal cellular force microscopy, inspired by chameleons, enabling visualization and quantification of vertically directed cell forces, well-suited for drug screening.
- Qiwei Li
- , Zaozao Chen
- & Zhongze Gu
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Article
| Open AccessCryo-EM structures of the plant anion channel SLAC1 from Arabidopsis thaliana suggest a combined activation model
Phosphorylation-mediated activation of SLAC1 anion channel is crucial in plant responses for abiotic stresses including drought. Here, authors determine the open and closed structures of SLAC1, revealing how phosphorylation can activate SLAC1.
- Yeongmok Lee
- , Hyeon Seong Jeong
- & Sangho Lee
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Article
| Open AccessCHEX-seq detects single-cell genomic single-stranded DNA with catalytical potential
The in situ single-stranded open chromatin landscape is dynamically regulated in single cells. In their efforts to understand brain cells’ functional dynamics and to complement the other single-cell chromatin approaches, the authors present a method named CHEX-seq (CHromatin EXposed).
- Youtao Lu
- , Jaehee Lee
- & James Eberwine
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Article
| Open AccessLong-term cargo tracking reveals intricate trafficking through active cytoskeletal networks in the crowded cellular environment
Leveraging a label-free interferometric scattering microscope, scientists tracked numerous cargos within a crowded cellular environment. Intriguingly, cells employ effective strategies echoing human transportation systems to manage such transportation hurdles.
- Jin-Sung Park
- , Il-Buem Lee
- & Minhaeng Cho
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Article
| Open AccessCLOOME: contrastive learning unlocks bioimaging databases for queries with chemical structures
Artificial intelligence can assist in obtaining knowledge from bioimaging data, but need human annotation. Here the authors use multimodal contrastive learning to link chemical structures and cell phenotypes, which can lead to foundation models for microscopy images.
- Ana Sanchez-Fernandez
- , Elisabeth Rumetshofer
- & Günter Klambauer
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Article
| Open AccessCombinatorial quantification of distinct neural projections from retrograde tracing
Comprehensive quantification of neural architectures underlying brain circuitry remains challenging. Here, the authors present a practical method to quantitatively identify nerve cells with specific axonal projections from retrograde anatomical injections.
- Siva Venkadesh
- , Anthony Santarelli
- & Giorgio A. Ascoli
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Article
| Open AccessSpatial-linked alignment tool (SLAT) for aligning heterogenous slices
Spatial omics technologies reveal the organisation of cells in various biological systems. Here, authors propose SLAT, a graph-based algorithm for aligning heterogenous data across technologies, modalities and timepoints, enabling spatiotemporal reconstruction of complex developmental processes.
- Chen-Rui Xia
- , Zhi-Jie Cao
- & Ge Gao
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Article
| Open AccessCamoTSS: analysis of alternative transcription start sites for cellular phenotypes and regulatory patterns from 5' scRNA-seq data
Five-prime single-cell RNA-seq, especially the read 1, has precise capture of transcription start sites (TSS), but such information is often overlooked. Here, authors present a computational method suite, CamoTSS, to precisely identify TSS and quantify its expression, enabling effective detection of alternative TSS usage in different biological processes.
- Ruiyan Hou
- , Chung-Chau Hon
- & Yuanhua Huang
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Article
| Open AccessProgesterone activation of β1-containing BK channels involves two binding sites
Progesterone is used in recovery of cerebral ischemia however the mechanism of action is unknown. Authors report here that micromolar progesterone activates mouse cerebrovascular myocyte BK channels, involving two steroid binding sites.
- Kelsey C. North
- , Andrew A. Shaw
- & Alex M. Dopico
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Article
| Open AccesstrRosettaRNA: automated prediction of RNA 3D structure with transformer network
Here, authors develop trRosettaRNA, a deep learning-based approach for predicting RNA 3D structures. Blind tests demonstrate that the automated predictions compete effectively with top human predictions on natural RNAs.
- Wenkai Wang
- , Chenjie Feng
- & Jianyi Yang
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Article
| Open AccessreplicAnt: a pipeline for generating annotated images of animals in complex environments using Unreal Engine
Deep learning-based computer vision tools are transforming animal behavioural research; however, many challenges remain. Here, Plum et al. present replicAnt, a novel tool for generating synthetic data to train computer vision models for animal behaviour studies, reducing the need for manual annotation.
- Fabian Plum
- , René Bulla
- & David Labonte
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Article
| Open AccessMePMe-seq: antibody-free simultaneous m6A and m5C mapping in mRNA by metabolic propargyl labeling and sequencing
Methylation is the dominant modification in mRNA and occurs at a variety of sites. Here, Hartstock et al. show that a clickable analogue of the key cosubstrate S-adenosyl-L-methionine (SAM) can be produced in cells, allowing for identification and mapping of different methylated nucleosides in mRNA.
- Katja Hartstock
- , Nadine A. Kueck
- & Andrea Rentmeister
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Article
| Open AccessNIPMAP: niche-phenotype mapping of multiplex histology data by community ecology
Multiplex histology faces the challenge of integrating tissue architecture with the identification of relevant spatial cellular phenotypes. Using community ecology principles, the authors propose NIPMAP, a tool for niche-phenotype mapping of multiplex histology data.
- Anissa El Marrahi
- , Fabio Lipreri
- & Jean Hausser
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Article
| Open AccessStructural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans
In this work, the authors combine cryo-electron tomography of vitrified virions, mass spectrometry, modeling, molecular dynamics and infectivity assay and report that a hinge glycan on viral spike protein influences virus infection and immune evasion.
- David Chmielewski
- , Eric A. Wilson
- & Wah Chiu
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Article
| Open AccessLensAge index as a deep learning-based biological age for self-monitoring the risks of age-related diseases and mortality
Age is closely related to health, but chronologically defined age often disagrees with biological age. Here, the authors develop an indicator of biological age - LensAge index - to reveal individuals’ aging level, and it can be implemented with smartphones, showing potential for self-monitoring of aging.
- Ruiyang Li
- , Wenben Chen
- & Haotian Lin
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Article
| Open AccessIL-21R-STAT3 signalling initiates a differentiation program in uterine tissue-resident NK cells to support pregnancy
Uterine natural killer (NK) cells support tissue homeostasis in the uterus during pregnancy, but it is not fully known how they differentiate into potentially cytotoxic effector cells while avoiding tissue damage. Here authors show that Il21 receptor signalling via STAT3 activation governs their differentiation, while an apoptotic cell death program ensures that harm is limited.
- Mengwei Han
- , Luni Hu
- & Chao Zhong
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Article
| Open AccessLipofuscin-like autofluorescence within microglia and its impact on studying microglial engulfment
Microglia are brain macrophages that engulf and clear cellular material and protein aggregates. Here, the authors show that lipofuscin-like autofluorescence can confound microglial engulfment analyses, which they can resolve with a photobleaching protocol.
- Jacob M. Stillman
- , Francisco Mendes Lopes
- & Dorothy P. Schafer
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Article
| Open AccessPRO-IP-seq tracks molecular modifications of engaged Pol II complexes at nucleotide resolution
Tracking molecular modifications of engaged Pol II complexes is important for studying transcriptional regulation. Here, the authors combine run-on sequencing (PRO-seq) and immunoprecipitation, revealing dynamics of Pol II CTD phosphorylation at nucleotide-resolution.
- Anniina Vihervaara
- , Philip Versluis
- & John T. Lis
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Article
| Open AccessEfficient optical plasmonic tweezer-controlled single-molecule SERS characterization of pH-dependent amylin species in aqueous milieus
Studying rare species in mixtures is challenging. Here, authors utilize on-and-off optical plasmonic trapping to control SERS-active nanocavity to analyse pH-dependent amylin species at single-molecule level, unveiling amyloid aggregation mechanisms.
- Wenhao Fu
- , Huanyu Chi
- & Jinqing Huang
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Article
| Open AccessIn situ quantification of osmotic pressure within living embryonic tissues
Osmotic pressure is thought to play a key role in many cellular and developmental processes, but remains challenging to measure it in cells and tissues. Here, the authors present a sensor based on double emulsion droplets that allows quantification of osmotic pressure in situ and in vivo.
- Antoine Vian
- , Marie Pochitaloff
- & Otger Campàs
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Article
| Open AccessDefining neutralization and allostery by antibodies against COVID-19 variants
Here, Tulsian et al. identified the effect of biologically relevant full-length IgG binding on the Spike protein from different SARS-CoV-2 variants to comprehensively understand the mechanisms of antibody evasion, towards the development of better antiviral strategies.
- Nikhil Kumar Tulsian
- , Raghuvamsi Venkata Palur
- & Paul Anthony MacAry
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Article
| Open AccessContinually recruited naïve T cells contribute to the follicular helper and regulatory T cell pools in germinal centers
B cell clonal expansion and affinity maturation takes place in germinal centers (GC) and is orchestrated by follicular T cells. Here authors show that naïve conventional T cells are continuously recruited to the GCs during the GC reaction and develop into follicular helper and regulatory T cells, thus quantitatively contribute to remodelling the GC overtime.
- Julia Merkenschlager
- , Riza-Maria Berz
- & Michel C. Nussenzweig
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Article
| Open AccessOptogenetic control of YAP reveals a dynamic communication code for stem cell fate and proliferation
The transcriptional regulator YAP controls cellular decisions such as proliferation, differentiation, and pluripotency. Here, the authors show a concentration-dependent and temporal communication code for YAP that enables cells to choose between these programs.
- Kirstin Meyer
- , Nicholas C. Lammers
- & Orion D. Weiner
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Article
| Open AccessNear-infrared-II photoacoustic imaging and photo-triggered synergistic treatment of thrombosis via fibrin-specific homopolymer nanoparticles
The near-infrared-II (NIR-II) window has shown great promise for in vivo imaging and therapy. Here, the authors integrate a homopolymer and thermo-sensitive nitric oxide prodrug into nanoparticles for long-wavelength NIR-II photoacoustic imaging and synergistic treatment in preclinical thrombosis models.
- Jianwen Song
- , Xiaoying Kang
- & Ji Qi
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Article
| Open AccessLactate biosensors for spectrally and spatially multiplexed fluorescence imaging
l-Lactate is increasingly recognized as a key metabolite and signalling molecule in mammals, but the methods to investigate it in vivo have been limited. Here, authors report a pair of improved biosensors—one green and one red—for visualizing l-lactate both inside and outside of cells.
- Yusuke Nasu
- , Abhi Aggarwal
- & Robert E. Campbell
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Article
| Open AccessAntibody-directed extracellular proximity biotinylation reveals that Contactin-1 regulates axo-axonic innervation of axon initial segments
Few resident cell surface proteins have been identified at the axon initial segment. Here, Ogawa and colleagues use proximity labeling and proteomics to identify Contactin-1 as a transmembrane axon initial segment protein that regulates brain wiring.
- Yuki Ogawa
- , Brian C. Lim
- & Matthew N. Rasband
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Article
| Open AccessFHL1 promotes chikungunya and o’nyong-nyong virus infection and pathogenesis with implications for alphavirus vaccine design
FHL1A is a crucial host factor for alphavirus infection but its impact on pathogenesis is unclear. Here, the authors use a FHL1−/− knockout mouse model to show that the FHL1 splice variant impacts arthritis and myositis after chikungunya or o’nyong-nyong infections but not Ross River or mayaro virus infection.
- Wern Hann Ng
- , Xiang Liu
- & Suresh Mahalingam
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Article
| Open AccessEnzymatic synthesis and nanopore sequencing of 12-letter supernumerary DNA
Unnatural base pairing xenonucleic acids (XNAs) can be used to expand life’s alphabet beyond ATGC. Here, authors show strategies for enzymatic synthesis and next-generation nanopore sequencing of XNA base pairs for reading and writing 12-letter DNA (ATGCBSPZXKJV).
- Hinako Kawabe
- , Christopher A. Thomas
- & Jorge A. Marchand
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Article
| Open AccessSialic acid O-acetylation patterns and glycosidic linkage type determination by ion mobility-mass spectrometry
O-acetylation is a common modification of sialic acids. Here, a library of synthetic O-acetylated sialosides made it possible to develop an ion mobility mass spectrometry (IM-MS) approach that can elucidate exact O-acetylation patterns and glycosidic linkage types of sialosides isolated from biological samples.
- Gaёl M. Vos
- , Kevin C. Hooijschuur
- & Geert-Jan Boons
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Article
| Open AccessIDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma
The role of human glioma IDH1 mutations in regulation of antiviral response is unclear. Here, the authors show that D2HG produced by mutant IDH1 inhibits IFN antiviral responses in glioma cells, which confers sensitivity to oncolytic virotherapy.
- Xueqin Chen
- , Jun Liu
- & Haipeng Zhang
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Article
| Open AccessVisualization of accessible cholesterol using a GRAM domain-based biosensor
Regulated cholesterol transport is essential for the maintenance of cellular cholesterol distribution and homeostasis, but tools to monitor this process are limited. Here, the authors develop a genetically encoded cholesterol biosensor and demonstrate its use for visualising cellular cholesterol distribution in various live cells in real time.
- Dylan Hong Zheng Koh
- , Tomoki Naito
- & Yasunori Saheki
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Article
| Open AccessAn interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models
Here, the authors report the generation of a live but defective SARS-CoV-2 virus that is envelope-deficient and expresses human interferon beta. They show that nasal vaccination enhances mucosal and lung T cell response and provides pan-sarbecovirus protection in small animals.
- Chun-Kit Yuen
- , Wan-Man Wong
- & Kin-Hang Kok
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Article
| Open AccessHierarchical organization and assembly of the archaeal cell sheath from an amyloid-like protein
Cellular cryoET reveals how an amyloid-like protein of the prototypical archaeon, Methanospirillum hungatei, oligomerizes into a ring containing a giant 2700-strand β sheet, and how rings stack into hoops and into the cylindrical sheath of the cell.
- Hui Wang
- , Jiayan Zhang
- & Z. Hong Zhou
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Article
| Open AccessMass production of lumenogenic human embryoid bodies and functional cardiospheres using in-air-generated microcapsules
Current methods to generate spheroids are associated with low production throughputs, limiting clinical and industrial translation. Here the authors present a clean ultra-high-throughput in-air microfluidic platform for mass production of lumenogenic embryoid bodies and functional cardiospheres.
- Bas van Loo
- , Simone A. ten Den
- & Jeroen Leijten
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Article
| Open AccessRepurposing conformational changes in ANL superfamily enzymes to rapidly generate biosensors for organic and amino acids
Biosensors have a wide number of potential applications, but rapidly constructing genetically encoded biosensors remains challenging. Here, authors report a method for rapidly converting ANL superfamily enzymes into biosensors for organic acids, based on their conformational changes upon binding.
- Jin Wang
- , Ning Xue
- & Meng Wang
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Article
| Open AccessSingle virus fingerprinting by widefield interferometric defocus-enhanced mid-infrared photothermal microscopy
The study of viruses relies on the detection of viral proteins or viral nucleic acids. Here, the authors present a widefield interferometric defocus-enhanced mid-infrared photothermal (WIDE-MIP) microscope for high-throughput fingerprinting of single viruses.
- Qing Xia
- , Zhongyue Guo
- & Ji-Xin Cheng
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Article
| Open AccessDeveloping mitochondrial base editors with diverse context compatibility and high fidelity via saturated spacer library
Ddd-Aderived cytosine base editors (DdCBEs) are important for research of mitochondrial DNA mutation diseases. Here the authors report a strategy for screening and characterising dsDNA cytidine deaminases, and identify 7 DddA homologs which they optimise to minimise nuclear and mitochondrial off-target editing.
- Haifeng Sun
- , Zhaojun Wang
- & Bin Shen
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Article
| Open AccessSonogenetic control of multiplexed genome regulation and base editing
Exogenous control of genes in vivo is important. Here the authors report a system that can be inducibly activated through thermal energy produced by ultrasound absorption and use this to control induction of gene activation and base editing: they apply this in cell lines and in a mouse model.
- Pei Liu
- , Josquin Foiret
- & Lei S. Qi
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Article
| Open AccessA spatial sequencing atlas of age-induced changes in the lung during influenza infection
Ageing is known to impair the immune response against infectious pathogens. Here, Kasmani et al. present a spatial and transcriptomic atlas of immune changes in the lungs of young and aged mice in response to influenza virus infection.
- Moujtaba Y. Kasmani
- , Paytsar Topchyan
- & Weiguo Cui
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Article
| Open AccessDirect regulation of the voltage sensor of HCN channels by membrane lipid compartmentalization
Voltage sensing of ion channels relies on charged transmembrane helices. Here authors use live-cell FLIM-FRET and nonsense suppression-mediated fluorescence labeling to reveal that voltage sensors undergo direct modulation by compartmentalized membrane domains.
- Lucas J. Handlin
- & Gucan Dai
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Article
| Open AccessIdentification of errors in draft genome assemblies at single-nucleotide resolution for quality assessment and improvement
A high-quality genome assembly is essential for various genomic studies in life sciences. Here the authors develop CRAQ, a reference-free method that facilitates the evaluation and improvement of any de novo genome assembly with single nucleotide resolution.
- Kunpeng Li
- , Peng Xu
- & Yuannian Jiao
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Article
| Open AccessDeep-LASI: deep-learning assisted, single-molecule imaging analysis of multi-color DNA origami structures
Analysis of single-molecule experiments remains time-consuming and prone to human bias. Here, the authors propose Deep-Learning Assisted Single-molecule Imaging analysis, a tool to rapidly analyse single-, two- and three-color single-molecule FRET data.
- Simon Wanninger
- , Pooyeh Asadiatouei
- & Don C. Lamb
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Article
| Open AccessAn automated single-molecule FRET platform for high-content, multiwell plate screening of biomolecular conformations and dynamics
Single-molecule FRET (smFRET) studies often struggle with large parameter spaces. Here, the authors introduce an automated smFRET platform for multiwell plate screening of biomolecular conformations and dynamics.
- Andreas Hartmann
- , Koushik Sreenivasa
- & Michael Schlierf
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Article
| Open AccessA human lung alveolus-on-a-chip model of acute radiation-induced lung injury
Acute exposure to radiation can lead to acute pneumonitis, fibrosis or death. Here the authors develop an alveolus-on chip model to study the molecular characteristics of radiation induced lung injury, better understand radiation induced lung disease and facilitate drug screening.
- Queeny Dasgupta
- , Amanda Jiang
- & Donald E. Ingber
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Article
| Open AccessMolecular landscape and functional characterization of centrosome amplification in ovarian cancer
The prevalence of centrosome amplification (CA) and the genomic landscape of chromosomal instability in high-grade serous ovarian carcinoma (HGSOC) remain to be explored. Here the authors suggest CA as a potential driver of tumour evolution and a biomarker for treatment response in HGSOC.
- Carolin M. Sauer
- , James A. Hall
- & James D. Brenton
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Article
| Open AccessAutomated imaging and identification of proteoforms directly from ovarian cancer tissue
Identification of tissue proteoforms by top-down mass spectrometry remains challenging. Here, the authors present AutoPiMS, a semi-automated multiplexed tandem mass spectrometry workflow for proteoform identification directly from tissue contexts.
- John P. McGee
- , Pei Su
- & Neil L. Kelleher
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Article
| Open AccessMitigating a TDP-43 proteinopathy by targeting ataxin-2 using RNA-targeting CRISPR effector proteins
TDP43 proteinopathies are a devastating group of neurodegenerative disorders. Here the authors show that RNA-targeting CRISPR effector proteins can be used to mitigate TDP-43 pathology when targeting ataxin-2, a modifier of TDP-43-associated toxicity, and apply this to a mouse model.
- M. Alejandra Zeballos C.
- , Hayden J. Moore
- & Thomas Gaj
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