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Article
| Open AccessIn situ assembly of bioresorbable organic bioelectronics in the brain
Temporary bioelectronics can complement classical therapies in non-chronic treatments. Here, the authors describe the minimally invasive implantation of bioresorbable electrodes in the brain that form in situ from water-dispersed nanoparticles and show no tissue damage after bioresorption.
- Martin Hjort
- , Abdelrazek H. Mousa
- & Roger Olsson
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Article
| Open AccessTwo point mutations in protocadherin-1 disrupt hantavirus recognition and afford protection against lethal infection
Protocadherin-1 (PCDH1) is a critical host factor for hantaviruses that can cause severe cardiopulmonary syndrome. Here, the authors map the binding site of the viral glycoprotein complex within PCDH1 and show that mutations engineered at this site can protect Syrian hamsters from viral challenge.
- Megan M. Slough
- , Rong Li
- & Kartik Chandran
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Article
| Open AccessEngineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine
Although diagnosis of urinary tract infections has improved through the use of point-of-care molecular technologies, they are however limited by poor specificity and / or sensitivity, and requirement of laboratory resources. In this work, the authors develop a bacteriophage-based diagnostic assay for the detection of prevalent uropathogens.
- Susanne Meile
- , Jiemin Du
- & Samuel Kilcher
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Article
| Open AccessDual-color DNA-PAINT single-particle tracking enables extended studies of membrane protein interactions
Single-particle tracking (SPT) has revolutionised studies of protein interactions but is often limited by photobleaching. Here, the authors evolve DNA-PAINT-SPT to enable simultaneous dual-colour detection for the quantification of protein dimerization and live cell membrane protein tracking.
- Christian Niederauer
- , Chikim Nguyen
- & Kristina A. Ganzinger
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Article
| Open AccessHighly specific and non-invasive imaging of Piezo1-dependent activity across scales using GenEPi
Stretch-activated ion channel Piezo1 contribures to mechanotransduction in many tissues, but its output is mostly measured indirectly. Here, the authors introduce GenEPi, a fluorescent reporter for directly visualizing Piezo1 activation-dependent calcium influx.
- Sine Yaganoglu
- , Konstantinos Kalyviotis
- & Periklis Pantazis
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Article
| Open AccessPrecise in-field molecular diagnostics of crop diseases by smartphone-based mutation-resolved pathogenic RNA analysis
On-site crop disease diagnostics is critical for precise application of pesticides. Here, the authors report an in-field molecular diagnostic tool for wheat pathogens using a nucleic acid amplification-free, gene mutation-resolved and smartphone-integrated genetic assay.
- Ting Zhang
- , Qingdong Zeng
- & Ruijie Deng
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Article
| Open AccessBiodegradable polyphosphoester micelles act as both background-free 31P magnetic resonance imaging agents and drug nanocarriers
MRI agents can result in environmental pollution and organ accumulation. Here, the authors show that modifying the molecular structure of biodegradable polyphosphoesters and tailoring the polymers’ microstructure to adjust MRI relaxation times can overcome challenges in 31P MR imaging.
- Olga Koshkina
- , Timo Rheinberger
- & Frederik R. Wurm
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Article
| Open AccessSpatially controlled construction of assembloids using bioprinting
Bioprinting has potential in the biofabrication of three dimensional tissues, but is poorly suited to the manipulation of neural organoids. Here, the authors develop a bioprinting platform to allow the arrangement of organoids to form assembloids.
- Julien G. Roth
- , Lucia G. Brunel
- & Sarah C. Heilshorn
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Article
| Open AccessConformational restriction shapes the inhibition of a multidrug efflux adaptor protein
Multidrug efflux protein pumps are key players in bacterial antimicrobial resistance. Here, the authors show how dynamics of a periplasmic pump component can be targeted for efflux inhibition.
- Benjamin Russell Lewis
- , Muhammad R. Uddin
- & Eamonn Reading
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Article
| Open AccessNext generation pan-cancer blood proteome profiling using proximity extension assay
Comprehensive and scalable proteomic profiling of plasma samples can improve the screening and diagnosis of cancer patients. Here, the authors use the Olink Proximity Extension Assay technology to characterise the plasma proteomes of 1477 patients across twelve cancer types, and use machine learning to obtain a protein panel for cancer classification.
- María Bueno Álvez
- , Fredrik Edfors
- & Mathias Uhlén
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Article
| Open AccessPhase intensity nanoscope (PINE) opens long-time investigation windows of living matter
The authors present phase intensity nanoscope (PINE), which uses an integrated phase-intensity multilayer thin film to localize randomly distributed nanoprobes and resolve sub-10 nm cellular architectures. They demonstrate dynamic imaging of nanoscopic reorganization over 250 h and find that nanoscale rearrangements emerging into macroscale rearrangements are synchronized.
- Guangjie Cui
- , Yunbo Liu
- & Somin Eunice Lee
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Article
| Open AccessImmunogenicity and efficacy of vaccine boosters against SARS-CoV-2 Omicron subvariant BA.5 in male Syrian hamsters
Long-term BA.5-specific efficiency of booster vaccination is incompletely understood. Here, analyzing immunity to and efficacy of various COVID-19 vaccination regimens in Syrian hamster, the authors found that heterologous boosting provides more durable immunity and that NVX-CoV2373 provides the strongest boosting effect.
- Rafael R. G. Machado
- , Jordyn L. Walker
- & Scott C. Weaver
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Article
| Open AccessA polycistronic system for multiplexed and precalibrated expression of multigene pathways in fungi
Unlike prokaryotic hosts, most genes in eukaryotes are transcribed to monocistronic mRNA for single protein translation. Here, the authors develop a polycistronic system for multiplexed and precalibrated expression of multiple genes, and show its application in constructing yeast cell factories for terpenoids production.
- Qun Yue
- , Jie Meng
- & Shuobo Shi
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Article
| Open AccessAtlas-scale single-cell multi-sample multi-condition data integration using scMerge2
Recent advances in multi-condition single-cell multi-cohort studies enable exploration of diverse cell states. Here, authors present scMerge2, an algorithm that allows integration of a large COVID-19 data collection with over five million cells to uncover distinct signatures of disease progression.
- Yingxin Lin
- , Yue Cao
- & Jean Y. H. Yang
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Article
| Open AccessMass spectrometry imaging for biosolids characterization to assess ecological or health risks before reuse
Mass spectrometry imaging is a suitable tool for the analysis of non-cohesive materials. Here, authors show that it can be used to detect persistent organic pollutants (POPs) and heavy metals (HMs) in biosolids using small amounts of material with speed and safety.
- Claire Villette
- , Loïc Maurer
- & Dimitri Heintz
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Article
| Open AccessA seven-transmembrane methyltransferase catalysing N-terminal histidine methylation of lytic polysaccharide monooxygenases
N-terminal histidine methylation modification has only been observed on certain fungal proteins. Here, the authors identify and validate the methyltransferase responsible for this modification through the combination of mass spectrometry-based proteomics and CRISPR/Cas9.
- Tanveer S. Batth
- , Jonas L. Simonsen
- & Jesper V. Olsen
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Article
| Open AccessSpatial and functional arrangement of Ebola virus polymerase inside phase-separated viral factories
Here, the authors characterized the phase separation properties and internal structures of intracellular viral factories induced by Ebola virus and correlated these properties to important steps of viral biogenesis.
- Jingru Fang
- , Guillaume Castillon
- & Erica Ollmann Saphire
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Article
| Open AccessLabel-free adaptive optics single-molecule localization microscopy for whole zebrafish
Specimen-induced aberration can limit the imaging depth in single-molecule localization microscopy (SMLM). Here, the authors apply label-free wavefront sensing adaptive optics to SMLM for deep-tissue super-resolution imaging.
- Sanghyeon Park
- , Yonghyeon Jo
- & Wonshik Choi
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Article
| Open AccessMulti-batch single-cell comparative atlas construction by deep learning disentanglement
Comparing single-cell RNA-seq and ATAC-seq data from multiple batches is challenging due to technical artifacts. Here, the authors propose a method that disentangles technical and biological effects, facilitating batch-confounded chromatin and gene expression state discovery and enhancing the analysis of perturbation effects on cell populations.
- Allen W. Lynch
- , Myles Brown
- & Clifford A. Meyer
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Article
| Open AccessThree-dimensional images reveal the impact of the endosymbiont Midichloria mitochondrii on the host mitochondria
The mitochondrial symbiont, Candidatus Midichloria mitochondrii, exists in the hard tick Ixodus ricinus, the main vector for Lyme disease. Here, the authors use FIB-SEM to characterise mitochondrial morphology and bacterial interactions in the context of oocyte maturation and endosymbiosis.
- Zerrin Uzum
- , Dmitry Ershov
- & Fabrizia Stavru
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Article
| Open AccessLarge depth-of-field ultra-compact microscope by progressive optimization and deep learning
Traditional optical microscope, while bulky, often fails to deliver optimal performance. Here, the authors have engineered an integrated microscope of 0.15 cm3 in volume and a weight of 0.5 g, which outperforms a commercial microscope and can be seamlessly integrated with a smartphone.
- Yuanlong Zhang
- , Xiaofei Song
- & Qionghai Dai
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Article
| Open AccessEstablishing mammalian GLUT kinetics and lipid composition influences in a reconstituted-liposome system
Transport assays using purified glucose transporters (GLUTs) have proven to be difficult to implement, hampering deeper mechanistic insights. Here the authors have optimized a transport assay in liposomes that will provide insight to study other membrane transport proteins.
- Albert Suades
- , Aziz Qureshi
- & David Drew
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Article
| Open AccessIndividual bat virome analysis reveals co-infection and spillover among bats and virus zoonotic potential
Viral diversity and abundance in bats are incompletely understood. Here, analyzing individual bat viromes, the authors observe a high frequency of co-infection and spillover among the animals and identify viruses with the potential to infect humans or livestock.
- Jing Wang
- , Yuan-fei Pan
- & Mang Shi
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Article
| Open AccessnnSVG for the scalable identification of spatially variable genes using nearest-neighbor Gaussian processes
The identification of top spatially variable genes is a key step in the analysis of spatially-resolved transcriptomics data. Here, the authors develop a scalable method based on nearest-neighbor Gaussian processes and evaluate performance compared to existing and baseline methods.
- Lukas M. Weber
- , Arkajyoti Saha
- & Stephanie C. Hicks
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Article
| Open AccessRoving methyltransferases generate a mosaic epigenetic landscape and influence evolution in Bacteroides fragilis group
Here, Tisza, Dekker, and colleagues perform large scale analysis of genome methylation in the gut commensal and pathogen, Bacteroides fragilis group, revealing immense methyl motif diversity and evidence of widespread methyltransferase exchange among phages.
- Michael J. Tisza
- , Derek D. N. Smith
- & John P. Dekker
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Article
| Open AccessReal-time environmental surveillance of SARS-CoV-2 aerosols
Rapid detection of respiratory pathogens circulating in indoor environments could facilitate improved infection prevention responses. In this proof-of-concept study, the authors develop a pathogen air quality monitor for real-time direct detection of SARS-CoV-2 aerosols and demonstrate its application in rooms of people with SARS-CoV-2 infections.
- Joseph V. Puthussery
- , Dishit P. Ghumra
- & Rajan K. Chakrabarty
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Article
| Open AccessExpanded vacuum-stable gels for multiplexed high-resolution spatial histopathology
Emerging high-plex imaging technologies are limited in resolving subcellular biomolecular features. Here, the authors propose a spatial histopathology tool that allows for high-plex protein staining and physical expansion, while retaining the lateral tissue expansion.
- Yunhao Bai
- , Bokai Zhu
- & Sizun Jiang
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Article
| Open AccessMapping mechanical stress in curved epithelia of designed size and shape
Marin-Llaurado and colleagues engineer curved epithelial monolayers of controlled geometry and develop a new technique to map their state of stress. They show that pronounced stress anisotropies influence cell alignment.
- Ariadna Marín-Llauradó
- , Sohan Kale
- & Xavier Trepat
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Article
| Open AccessMultiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function
ApoE is known to be important for lipid nanoparticle function. Here, the authors shows that efficacious coronal ApoE originates from high-density lipoprotein (HDL) particles and, enhances hepatic delivery, making HDL a superior biomarker for lipid nanoparticle potency.
- Kai Liu
- , Ralf Nilsson
- & Alan Sabirsh
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Article
| Open AccessSpatialDM for rapid identification of spatially co-expressed ligand–receptor and revealing cell–cell communication patterns
Spatial omics are increasingly being recognised to study cell-cell communications. Here, the authors present a bioinformatics toolbox for rapid identification of spatially co-expressed ligand-receptor and revealing cell-cell communication patterns.
- Zhuoxuan Li
- , Tianjie Wang
- & Yuanhua Huang
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Article
| Open AccessProfiling of basal and ligand-dependent GPCR activities by means of a polyvalent cell-based high-throughput platform
Interrogating the dynamic and functionally diverse signaling of GPCRs requires comprehensive cellular tools. Here Zeghal et al. develop Tango-Trio, a screening platform capable of profiling basal and drug-activated activities at hundreds of GPCRs.
- Manel Zeghal
- , Geneviève Laroche
- & Patrick M. Giguère
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Article
| Open AccessOzone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome
Fatty acids are fundamental biomolecular building blocks that are characterized by extraordinary structural diversity and present a formidable analytical challenge. Here the authors introduce a discovery workflow for de novo identification that adds more than 100 fatty acids to the human lipidome.
- Jan Philipp Menzel
- , Reuben S. E. Young
- & Stephen J. Blanksby
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Article
| Open AccessIn vitro and in vivo characterization of SARS-CoV-2 strains resistant to nirmatrelvir
Resistance to nirmatrelvir, an oral antiviral agent that targets SARS-CoV-2 and is clinically useful against infection with Omicron variants, is currently not well understood. In this study, the authors characterize mutant viruses with reduced sensitivity to nirmatrelvir in vitro and in vivo.
- Maki Kiso
- , Yuri Furusawa
- & Yoshihiro Kawaoka
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Article
| Open AccessCucurbit[8]uril-based water-dispersible assemblies with enhanced optoacoustic performance for multispectral optoacoustic imaging
The applications of organic small-molecule contrast agents for multispectral optoacoustic imaging have been restrained by several challenges including relatively low extinction coefficient, poor water solubility and weak optoacoustic performance. Here, the authors address these limitations by constructing water-dispersible supramolecular optoacoustic assemblies based on cucurbit[8]uril.
- Yinglong Wu
- , Lihe Sun
- & Yanli Zhao
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Article
| Open AccessA rapid cell-free expression and screening platform for antibody discovery
Antibody discovery is bottlenecked by the individual expression and evaluation of antigen specific hits. Here, the authors build an antibody screening workflow leveraging cell-free protein synthesis that enables expression and evaluation of hundreds of antibody fragments in less than 24 h.
- Andrew C. Hunt
- , Bastian Vögeli
- & Michael C. Jewett
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Article
| Open AccessSingle-cell profiling of lncRNA expression during Ebola virus infection in rhesus macaques
Long non-coding RNAs (lncRNAs) play key roles in the immune response but their properties at the single-cell level are less well understood. Here, the authors characterize differential features of lncRNAs and protein-coding genes upon Ebola infection in macaques at single-cell resolution.
- Luisa Santus
- , Maria Sopena-Rios
- & Marta Melé
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Article
| Open AccessFast-exchanging spirocyclic rhodamine probes for aptamer-based super-resolution RNA imaging
Live-cell RNA imaging with high spatial and temporal resolution remains a major challenge. Here the authors design spirocyclic rhodamine probes that enable a fluorescent light-up aptamer system suitable for visualizing RNAs in live or fixed cells with two different super-resolution microscopy modalities SMLM and STED.
- Daniel Englert
- , Eva-Maria Burger
- & Murat Sunbul
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Article
| Open AccessThe proteomic landscape of soft tissue sarcomas
Characterising the molecular profile of soft tissue sarcomas (STS) remains critical. Here, the authors analyse samples from 321 STS patients across 11 histological subtypes using proteomics and identify prognostic signatures that can be applied to multiple subtypes.
- Jessica Burns
- , Christopher P. Wilding
- & Paul H. Huang
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Article
| Open AccessAcute stress induces long-term metabolic, functional, and structural remodeling of the heart
Takotsubo disease, a stress induced cardiomyopathy mimicking acute coronary syndrome, increases the risk of heart failure and cardiac death. The authors show here that heart function and structure keep on deteriorating continuously after a single acute stress, this snowball effect being triggered by abnormalities incardiac metabolism.
- Thulaciga Yoganathan
- , Mailyn Perez-Liva
- & Bertrand Tavitian
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Article
| Open AccessStructure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red
The voltage-dependent CALHM1 channel is critical in neuromodulation and gustatory signaling. The authors present cryo-EM structures of human CALHM1 in apo- and blocked-states. They explore effects of lipid binding on channel structure and activity.
- Johanna L. Syrjänen
- , Max Epstein
- & Hiro Furukawa
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Article
| Open AccessMultidimensional characterization of inducible promoters and a highly light-sensitive LOV-transcription factor
The ability to independently control the expression of different genes is important for quantitative biology. Here, the authors report kinetic parameters, noise scaling, impact on growth, and the fundamental leakiness of a wide range of inducible transcriptional systems, including a new, highly light sensitive LOV-transcription factor.
- Vojislav Gligorovski
- , Ahmad Sadeghi
- & Sahand Jamal Rahi
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Article
| Open AccessAn optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells
Different activation patterns of Akt kinase direct downstream signaling outcomes. Here, the authors run phosphoproteomics on optogenetically-activated Akt1 to characterize the phosphorylation circuits induced by different intensities, durations, and patterns of stimulation.
- Wenping Zhou
- , Wenxue Li
- & Yansheng Liu
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Article
| Open AccessThe long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation
The transcription factor ΔNp63 is a master regulator of epithelial development and integrity of stratified epithelial tissues. Here, the authors unveiled the lncRNA NEAT1 as an additional player of the highly complex regulatory network by which ΔNp63 controls epidermal homeostasis.
- Claudia Fierro
- , Veronica Gatti
- & Angelo Peschiaroli
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Article
| Open AccessSystems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation
Epichaperomics allow the study of protein-protein interactions and their alterations, but probes have been limited to capturing HSP90 epichaperomes. Here, the authors introduce and validate a toolset of HSP70 epichaperome ligands, and use them in epichaperomics to identify a mechanism with which cancer cells can enhance the fitness of mitotic protein networks.
- Anna Rodina
- , Chao Xu
- & Gabriela Chiosis
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Article
| Open AccessA joint proteomic and genomic investigation provides insights into the mechanism of calcification in coccolithophores
Coccolithophorid algae are globally important for marine biogeochemical cycles, but the molecular basis of their biology is poorly understood. Using proteomics and a new genome, Skeffington et al. identify candidate proteins involved in calcification in Emiliania huxleyi.
- Alastair Skeffington
- , Axel Fischer
- & André Scheffel
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Article
| Open AccessMaternal NAT10 orchestrates oocyte meiotic cell-cycle progression and maturation in mice
Generation of mature oocytes requires tight regulation of a discontinuous meiotic cell cycle. Here they show that the acetyltransferase Nat10 mediates modification of RNAs targeted for degradation and find that this process is essential for female oocyte meiosis and maturation.
- Xue Jiang
- , Yu Cheng
- & Jianqiang Bao
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Article
| Open AccessStructural basis of protein condensation on microtubules underlying branching microtubule nucleation
TPX2 is a key factor stimulating branching microtubule (MT) nucleation. TPX2 forms condensates on MTs critical for branching. In this work, the authors report the atomic-level structure of TPX2 C-terminal minimal active domain on MT lattice and its binding interface, determined by magic-angle-spinning NMR.
- Changmiao Guo
- , Raymundo Alfaro-Aco
- & Tatyana Polenova
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Article
| Open AccessDynamic interplay between target search and recognition for a Type I CRISPR-Cas system
The details of CRISPR-Cas target search are unresolved. Here the authors analyse the target search process of the Type I CRISPR-Cas complex Cascade: they show that target search and target recognition are tightly linked, and DNA supercoiling and limited 1D diffusion play a role.
- Pierre Aldag
- , Marius Rutkauskas
- & Ralf Seidel
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Article
| Open AccessDeep optoacoustic localization microangiography of ischemic stroke in mice
Optoacoustic super-resolution at millimeter-scale depths has been impeded by the strong background absorption from blood cells. Here, the authors use dichloromethane microdroplets with high optical absorption and demonstrate 3D microangiography of the mouse brain via optoacoustic localization.
- Xosé Luís Deán-Ben
- , Justine Robin
- & Daniel Razansky
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