Featured
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Article
| Open AccessSelf-rechargeable cardiac pacemaker system with triboelectric nanogenerators
Self-powered implantable devices have the potential to extend device operation, though current energy harvesters are both insufficient and inconvenient. Here the authors report on a commercial coin battery-sized high-performance inertia-driven triboelectric nanogenerator based on body motion and gravity that can be used to charge a lithium-ion battery and integrated into a cardiac pacemaker.
- Hanjun Ryu
- , Hyun-moon Park
- & Sang-Woo Kim
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Article
| Open AccessIon mobility-based sterolomics reveals spatially and temporally distinctive sterol lipids in the mouse brain
Sterol lipids are crucial for maintaining proper brain function. Here, the authors combine ion mobility-mass spectrometry and machine learning to assemble a sterol lipid library and characterize differences in sterol lipids across ten brain regions and two age groups in mice.
- Tongzhou Li
- , Yandong Yin
- & Zheng-Jiang Zhu
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Article
| Open AccessReprogrammed CRISPR-Cas13b suppresses SARS-CoV-2 replication and circumvents its mutational escape through mismatch tolerance
Cas13b can be harnessed to target and degrade RNA transcripts inside a cellular environment. Here the authors reprogram Cas13b to target SARSCoV-2 transcripts in infected mammalian cells and reveal its resilience to variants thanks to single mismatch tolerance.
- Mohamed Fareh
- , Wei Zhao
- & Joseph A. Trapani
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Article
| Open AccessSensing leg movement enhances wearable monitoring of energy expenditure
Current methods to estimate energy expenditure are either infeasible for everyday use or associated with significant errors. Here the authors present a Wearable System using inertial measurement units worn on the shank and thigh that estimates metabolic energy expenditure in real-time during common steady-state and time-varying activities.
- Patrick Slade
- , Mykel J. Kochenderfer
- & Steven H. Collins
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Article
| Open AccessData storage using peptide sequences
Finding durable, high-density media for data storage is necessary to support the ever-expanding generation of digital data. Here, the authors use peptide sequences to store digital data and retrieve them using tandem mass spectrometry, proving that peptides can be used as a storage medium.
- Cheuk Chi A. Ng
- , Wai Man Tam
- & Zhong-Ping Yao
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Article
| Open AccessSingle-nucleus RNA-seq2 reveals functional crosstalk between liver zonation and ploidy
Single-cell RNA-seq reveals the cellular heterogeneity in development and disease. Here the authors present a single-nucleus RNA-seq2 that allows deep characterization of nuclei isolated from frozen archived tissues, apply it for transcriptional profiling of individual hepatocytes, and determine a functional crosstalk between liver zonation and ploidy.
- M. L. Richter
- , I. K. Deligiannis
- & C. P. Martinez-Jimenez
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Article
| Open AccessImproved CRISPR genome editing using small highly active and specific engineered RNA-guided nucleases
Small CRISPR Cas9 proteins have potential in gene therapies but generally have poor editing efficiency or specificity and often recognize sub-optimal PAM sequences. Here the authors characterise four small nucleases and use protein engineering to create effective in vivo editors.
- Moritz J. Schmidt
- , Ashish Gupta
- & Wayne M. Coco
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Article
| Open AccessGapClust is a light-weight approach distinguishing rare cells from voluminous single cell expression profiles
While rare cell type identification is indispensable in single cell studies, powerful tools with high detection accuracy and computational efficiency are still lacking. Here, the authors propose a light-weight algorithm which can distinguish rare cell types from voluminous single cell expression profiles.
- Botao Fa
- , Ting Wei
- & Zhangsheng Yu
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Article
| Open AccessLure-and-kill macrophage nanoparticles alleviate the severity of experimental acute pancreatitis
Phospholipase A2 (PLA2) inhibitors have been shown to be able to treat acute pancreatitis, but are toxic with systemic application. Here the authors design a nanoparticle with macrophage membrane components to carry PLA2 inhibitor to macrophages and treat pancreatitis in mice, with no evidence of toxicity.
- Qiangzhe Zhang
- , Julia Zhou
- & Liangfang Zhang
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Article
| Open Access4D polycarbonates via stereolithography as scaffolds for soft tissue repair
Shape memory scaffolds are needed for minimally invasive tissue repair and void filling. Here the authors report on the development of 4D printed polycarbonate-based scaffolds with surface degradation properties which fill voids without deforming tissue and allow for tissue ingrowth with reduced immune response.
- Andrew C. Weems
- , Maria C. Arno
- & Andrew P. Dove
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Article
| Open AccessPost-capillary venules are the key locus for transcytosis-mediated brain delivery of therapeutic nanoparticles
Limited understanding of the interactions between nanoparticle drug carriers and the blood-brain barrier underlies many translational failures in treatments of brain disorders. Here the authors use two-photon microscopy in mice to characterize the receptor-mediated transcytosis of nanoparticles at all steps of delivery from the blood to the brain in vivo.
- Krzysztof Kucharz
- , Kasper Kristensen
- & Martin Johannes Lauritzen
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Article
| Open AccessEnhanced regulation of prokaryotic gene expression by a eukaryotic transcriptional activator
Expanded toolkits for prokaryotic synthetic biology can enhance the dynamic range of gene expression. Here the authors move the eukaryotic transcription factor QF into E. coli and integrate it into genetic devices.
- I. Cody MacDonald
- , Travis R. Seamons
- & Tara L. Deans
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Article
| Open AccessSurfactant-guided spatial assembly of nano-architectures for molecular profiling of extracellular vesicles
Current methods for controlled assembly of nanomaterials into desired architectures often lack the precision and versatility to develop complex architectures. Here the authors report STAR, surfactant tunable spatial architecture, to guide nanomaterial integration in metal-organic frameworks.
- Zhigang Wang
- , Haitao Zhao
- & Huilin Shao
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Article
| Open AccessRAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site
Oncogenic RAS mutants remain difficult to target with small molecules. Here, the authors show that RAS-binding Affimer proteins inhibit RAS signaling while binding diverse regions on the RAS surface, suggesting the potential to use Affimers as tools to identify new binding pockets and pharmacophores.
- Katarzyna Z. Haza
- , Heather L. Martin
- & Darren C. Tomlinson
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Article
| Open AccessA genetically encoded anti-CRISPR protein constrains gene drive spread and prevents population suppression
Technologies that can halt the spread of gene drives would be highly useful in controlling or reverting their effect. Here the authors use the anti-CRISPR protein AcrIIA4 to inactivate drives in A. gambiae.
- Chrysanthi Taxiarchi
- , Andrea Beaghton
- & Andrea Crisanti
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Article
| Open AccessImproved pyrrolysine biosynthesis through phage assisted non-continuous directed evolution of the complete pathway
Pyrrolysine (Pyl) exists in nature as the 22nd proteinogenic amino acid, but studies of Pyl have been hindered by the difficulty and inefficiency of both its chemical and biological syntheses. Here, the authors developed an improved PANCE approach to evolve the pylBCD pathway for increased production of Pyl proteins in E. coli.
- Joanne M. L. Ho
- , Corwin A. Miller
- & Matthew R. Bennett
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Article
| Open AccessSingle-component near-infrared optogenetic systems for gene transcription regulation
Current near-IR optogenetic systems to regulate transcription consist of a number of large protein components. Here the authors report a smaller single-component near-IR system, iLight, developed from a bacterial phytochrome that they use to control gene transcription in bacterial and mammalian cells.
- Andrii A. Kaberniuk
- , Mikhail Baloban
- & Vladislav V. Verkhusha
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Article
| Open AccessAnalysis of gene network bifurcation during optic cup morphogenesis in zebrafish
The gene regulatory network controlling the bifurcation of common progenitors into the neural retina and retinal-pigmented epithelium programs remains poorly understood. Here the authors study transcriptome dynamics and chromatin accessibility during this process in zebrafish, revealing network redundancy, as well as context-dependent and sequential transcription factor activity.
- Lorena Buono
- , Jorge Corbacho
- & Juan-Ramón Martínez-Morales
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Article
| Open AccessAsCas12a ultra nuclease facilitates the rapid generation of therapeutic cell medicines
The utility of AsCas12a can be limited to poor editing efficiency. Here the authors identify a variant, “AsCas12a Ultra”, that has high on-target specificity demonstrated through editing of clinically relevant T cell genes.
- Liyang Zhang
- , John A. Zuris
- & Christopher A. Vakulskas
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Article
| Open AccessRETRACTED ARTICLE: Selective inheritance of target genes from only one parent of sexually reproduced F1 progeny in Arabidopsis
Unlike insects and mice, CRISPR/Cas9-based gene drives have not been achieved in plants. Here, the authors demonstrate homozygous F1 Arabidopsis plants can be obtained through zygotic conversion using CRISPR/Cas9-mediated homology-directed repair.
- Tao Zhang
- , Michael Mudgett
- & Yunde Zhao
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Article
| Open AccessRepurposing tRNAs for nonsense suppression
Here, the authors report de novo design, optimization and characterization of tRNAs that decode UGA stop codons in E. coli. The structure of the ribosome in a complex with the designed tRNA bound to a UGA stop codon suggests that distinct A-site ligands (tRNAs versus release factors) induce distinct conformation of the stop codon within the mRNA in the decoding center.
- Suki Albers
- , Bertrand Beckert
- & Zoya Ignatova
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Article
| Open AccessHigh-throughput screening and rational design of biofunctionalized surfaces with optimized biocompatibility and antimicrobial activity
Optimizing the concentration of different functional peptides on a surface can be a complex process. Here, the authors report on the use of a click immobilization strategy to create gradients of two different functional peptides on a surface to screen different density functions for rapid optimization.
- Zhou Fang
- , Junjian Chen
- & Chuanbin Mao
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Article
| Open AccessIonic contrast across a lipid membrane for Debye length extension: towards an ultimate bioelectronic transducer
The design of bioelectronic devices that enables accurate detection of biomolecules in ionic solutions at physiologically-relevant concentrations remains a challenge. Here, the authors report a ion-impermeable supported lipid bilayer-assisted field-effect transistor platform for biomolecule detection.
- Donggeun Lee
- , Woo Hyuk Jung
- & Chulki Kim
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Article
| Open AccessPreventing post-surgical cardiac adhesions with a catechol-functionalized oxime hydrogel
Postsurgical adhesions are a problem during routine cardiothoracic procedures. Here, the authors report on a catechol functionalised hydrogel as an anti-adhesion material with improved retention on the heart which is biocompatible and biodegradable with minimal swelling, demonstrating application in vivo.
- Masaki Fujita
- , Gina M. Policastro
- & Karen L. Christman
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Article
| Open AccessEfficient precise in vivo base editing in adult dystrophic mice
Base editing is one approach used to correct mutations causing cause Duchenne muscular dystrophy (DMD), but limitations are in the requirement for a specific PAM motif and the large size beyond the packaging capacity of adeno-associated virus (AAV). Here, the authors modify the NG-targeting adenine base editor to recognize a broader PAM, devise an intein split strategy to package the otherwise oversized adenine base editor into AAV, and show it efficiently restores dystrophin expression in muscle and heart when systemically injected in a mouse model of DMD
- Li Xu
- , Chen Zhang
- & Renzhi Han
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Article
| Open AccessSingle-cell RNA-seq reveals fibroblast heterogeneity and increased mesenchymal fibroblasts in human fibrotic skin diseases
Fibroblasts are found to be heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. Here the authors employ scRNA-seq to explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases.
- Cheng-Cheng Deng
- , Yong-Fei Hu
- & Bin Yang
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Article
| Open AccessUnravelling cytosolic delivery of cell penetrating peptides with a quantitative endosomal escape assay
Our understanding of cytosolic delivery is hindered by existing methods for quantification which suffer from being indirect and showing low sensitivity. Here the authors report a SLEEQ (Split Luciferase Endosomal Escape Quantification) assay to assess cytosolic delivery of cell-penetrating peptides.
- Serena L. Y. Teo
- , Joshua J. Rennick
- & Colin W. Pouton
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Article
| Open AccessModel-based prediction of spatial gene expression via generative linear mapping
Single cell RNA-seq loses spatial information of gene expression in multicellular systems because tissue must be dissociated. Here, the authors show the spatial gene expression profiles can be both accurately and robustly reconstructed by a new computational method using a generative linear mapping, Perler.
- Yasushi Okochi
- , Shunta Sakaguchi
- & Honda Naoki
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Article
| Open AccessMultivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers
Here, the authors combine three different antibody specificities and an Fc domain on a single multivalent molecule, resulting in high neutralization activity despite viral sequence variability.
- Edurne Rujas
- , Iga Kucharska
- & Jean-Philippe Julien
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Article
| Open AccessUltra-strong bio-glue from genetically engineered polypeptides
Biomedical glues often face a challenge in providing strong adhesion and providing remodelling capabilities. Here the authors report on the development of a biocompatible and biodegradable protein-based coacervate adhesive and demonstrate application in haemostasis and wound healing using pig models.
- Chao Ma
- , Jing Sun
- & Andreas Herrmann
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Article
| Open AccessPromiscuous molecules for smarter file operations in DNA-based data storage
The molecular architecture of DNA data storage opens up interesting possibilities and functionalities. Here the authors leverage thermodynamics to control the access of different subsets of data in a file.
- Kyle J. Tomek
- , Kevin Volkel
- & Albert J. Keung
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Article
| Open AccessNucleoside-modified VEGFC mRNA induces organ-specific lymphatic growth and reverses experimental lymphedema
Dysfunction of the lymphatic system leads to secondary lymphedema and results in degradation of quality of life. Here, the authors show that delivery of nucleoside-modified Vascular Endothelial Growth Factor C (VEGFC) mRNA, encapsulated in lipid nanoparticles, induces organ-specific lymphatic growth and reverses experimental lymphedema.
- Dániel Szőke
- , Gábor Kovács
- & Zoltán Jakus
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Article
| Open AccessGeometrically encoded SERS nanobarcodes for the logical detection of nasopharyngeal carcinoma-related progression biomarkers
SERS assays have potential for multiplexed detection of biomarkers but differentiation of SERS tags remains a challenge. Here, the authors report the creation of 14 distinct geometrically controlled metal carbonyl tags and demonstrate multiplexed detection of nasopharyngeal carcinoma biomarkers from patient blood.
- Duo Lin
- , Chang-Lin Hsieh
- & Kien Voon Kong
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Article
| Open AccessLiving fabrication of functional semi-interpenetrating polymeric materials
Cell based materials production has potential for generating diverse materials with a range of functions. Here, the authors report development of living fabrication of biohybrid semi interpenetrating polymer networks by encapsulating protein producing bacteria within polymer microcapsules.
- Zhuojun Dai
- , Xiaoyu Yang
- & Lingchong You
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Article
| Open AccessCurvature in the reproductive tract alters sperm–surface interactions
The effect of fallopian tube’s curvature on sperm motion has not been studied in detail. Here, the authors use droplet microfluidics to create soft curved interfaces, revealing a dynamic switch in sperm motility from a progressive surface-aligned mode at low curvatures, to an aggressive surface-attacking mode at high curvatures.
- Mohammad Reza Raveshi
- , Melati S. Abdul Halim
- & Reza Nosrati
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Article
| Open AccessDesigning an irreversible metabolic switch for scalable induction of microbial chemical production
A promising strategy to increase product synthesis from bacteria uses inducible systems to switch metabolism to production. Here, the authors use models to show how engineering positive feedback loops into the genetic circuitry creates a switch that requires only temporary induction with a cheap nutrient to switch metabolism irreversibly, and so drastically reduce inducer use and cost.
- Ahmad A. Mannan
- & Declan G. Bates
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Article
| Open AccessVapor-phased fabrication and modulation of cell-laden scaffolding materials
Current methods for the modular assembly of biomaterials are associated with limitations. Here the authors implement vapor-phase deposition to fabricate 3D polymeric materials that permit biomolecule functionalization, tunable mass transport and mechanical properties, as well as control over boundaries between compartments, and analyze the behavior of 3D encapsulated cells.
- Chih-Yu Wu
- , Ting-Ying Wu
- & Hsien-Yeh Chen
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Perspective
| Open AccessTowards an engineering theory of evolution
Effective biological engineering requires the acknowledgement of evolution and its consideration during the design process. In this perspective, the authors present the concept of the evotype to reason about and shape the evolutionary potential of natural and engineered biosystems.
- Simeon D. Castle
- , Claire S. Grierson
- & Thomas E. Gorochowski
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Article
| Open AccessSpatio-temporal mRNA tracking in the early zebrafish embryo
Early stages of embryogenesis are known to depend on subcellular localization and transport of maternal mRNA, but systematic analyses have been hindered by a lack of methods for tracking of RNA. Here the authors combine spatially-resolved transcriptomics and single-cell RNA labeling to perform a spatio-temporal analysis of the transcriptome during early zebrafish development, revealing insights into this process.
- Karoline Holler
- , Anika Neuschulz
- & Jan Philipp Junker
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Article
| Open AccessRobust detection of translocations in lymphoma FFPE samples using targeted locus capture-based sequencing
Preservation of cancer biopsies by FFPE introduces DNA fragmentation, hindering analysis of rearrangements. Here the authors introduce FFPE Targeted Locus Capture for identification of translocations in preserved samples.
- Amin Allahyar
- , Mark Pieterse
- & Wouter de Laat
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Article
| Open AccessA recombined Sr26 and Sr61 disease resistance gene stack in wheat encodes unrelated NLR genes
The tall wheat grass-derived stem rust resistance genes Sr26 and Sr61 are among a few ones that are effective to all current dominant races of stem rust, including Ug99. Here, the authors show that the two genes are present in a small non-recombinogenic segment but encode two unrelated NLR proteins.
- Jianping Zhang
- , Timothy C. Hewitt
- & Evans S. Lagudah
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Article
| Open AccessA Bacillus thuringiensis Cry protein controls soybean cyst nematode in transgenic soybean plants
Genetic resistance to soybean cyst nematode (SCN) is beginning to decline. Here, the authors report that soybean lines expressing the Bacillus thuringiensis protein Cy14Ab have significant levels of protection from SCN in both greenhouse and field trials.
- Theodore W. Kahn
- , Nicholas B. Duck
- & Julia Daum
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Article
| Open AccessSynthetic extracellular matrices with tailored adhesiveness and degradability support lumen formation during angiogenic sprouting
Current tissue engineering strategies lack materials that promote angiogenesis. Here the authors develop a microfluidic in vitro model in which chemokine-guided endothelial cell sprouting into a tunable hydrogel is followed by the formation of perfusable lumens to determine the material properties that regulate angiogenesis.
- Jifeng Liu
- , Hongyan Long
- & Britta Trappmann
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Article
| Open AccessThe regulatory landscape of Arabidopsis thaliana roots at single-cell resolution
Existing studies of the chromatin accessibility, the primary mark of regulatory DNA, in Arabidopsis are based mainly on bulk samples. Here, the authors report the regulatory landscape of Arabidopsis thaliana roots at single-cell resolution.
- Michael W. Dorrity
- , Cristina M. Alexandre
- & Josh T. Cuperus
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Article
| Open AccessEstablishment of a fluorescent reporter of RNA-polymerase II activity to identify dormant cells
The identification and characterisation of dormant cells is currently difficult. Here the authors report Optical Stem Cell Activity Reporter (OSCAR) to assess RNA polymerase II activity and identify dormant cell populations in intestinal epithelial cells in vivo.
- Rasmus Freter
- , Paola Falletta
- & Francesco Neri
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Article
| Open AccessEngineered reproductively isolated species drive reversible population replacement
There exist only a handful of methods to engineer reproductive barriers in eukaryotes. Here the authors use CRISPR to engineer multiple barriers in D. melanogaster and model their spread.
- Anna Buchman
- , Isaiah Shriner
- & Omar S. Akbari
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Article
| Open AccessDevelopment of selective bispecific Wnt mimetics for bone loss and repair
Antibody-based Wnt agonists are able to phenocopy Wnt signaling in vivo resulting in increased bone density, repair, and strength. Here, the authors show that Wnt agonists can reverse bone loss associated with ovariectomy and build stronger bone when administered after fracture.
- Tristan W. Fowler
- , Troy L. Mitchell
- & Yang Li
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Article
| Open AccessMechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing
Macrophages perform diverse functions during immune responses, but the molecular mechanisms by which physical properties of the tissue regulate macrophage behavior remain unknown. Here the authors find that Piezo1 is a mechanosensor of stiffness, and that its activity modulates macrophage polarization responses.
- Hamza Atcha
- , Amit Jairaman
- & Wendy F. Liu
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Article
| Open AccessMitochondrial targeted meganuclease as a platform to eliminate mutant mtDNA in vivo
Heteroplasmic mitochondrial DNA mutations lack effective treatments. Here the authors adapt I-CreI meganuclease to target the mitochondria and specifically-eliminate mtDNA with a m.5024C>T mutation in the mttRNA Ala gene.
- Ugne Zekonyte
- , Sandra R. Bacman
- & Carlos T. Moraes
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