Featured
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Technology Feature |
Eavesdropping on extracellular vesicles
A rapidly evolving toolbox is helping researchers to get a handle on the biological and functional diversity of these ubiquitous — but still somewhat enigmatic — cell-secreted nanoparticles
- Michael Eisenstein
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Brief Communication |
An improved imaging system that corrects MS2-induced RNA destabilization
An improved version of the MS2-MCP system for imaging RNA dynamics involves tethering translation termination factors to tagged mRNAs to bypass destabilization caused by NMD machinery.
- Weihan Li
- , Anna Maekiniemi
- & Robert H. Singer
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Article |
Capturing the start point of the virus–cell interaction with high-speed 3D single-virus tracking
3D-TrIm combines real-time, high-speed, single-virion tracking with volumetric imaging of cellular microenvironments.
- Courtney Johnson
- , Jack Exell
- & Kevin D. Welsher
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Editorial |
The beauty of imaging
This month we continue our yearly celebration of the beauty of imaging.
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Research Highlight |
Imaging-based spatial transcriptomics goes electric
Researchers use electric fields to transfer RNA from a tissue sample onto a surface for subsequent fluorescence in situ hybridization-based profiling of transcriptomes at the single-cell level.
- Rita Strack
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Article |
Unsupervised discovery of tissue architecture in multiplexed imaging
Unsupervised discovery of tissue architecture with graphs (UTAG) combines information on cellular morphology and protein expression with the physical proximity of cells to identify architectural domains from highly multiplexed imaging data.
- Junbum Kim
- , Samir Rustam
- & Olivier Elemento
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Article
| Open AccessIncorporating the image formation process into deep learning improves network performance
Richardson–Lucy Network (RLN) combines the traditional Richardson–Lucy iteration with deep learning for improved deconvolution. RLN is more generalizable, offers fewer artifacts and requires less computing time than alternative approaches.
- Yue Li
- , Yijun Su
- & Hari Shroff
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Article |
Annotation of spatially resolved single-cell data with STELLAR
STELLAR (spatial cell learning) is a geometric deep learning model that works with spatially resolved single-cell datasets to both assign cell types in unannotated datasets based on a reference dataset and discover new cell types.
- Maria Brbić
- , Kaidi Cao
- & Jure Leskovec
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Article |
CODA: quantitative 3D reconstruction of large tissues at cellular resolution
CODA: a method for 3D reconstruction of large serially sectioned tissues.
- Ashley L. Kiemen
- , Alicia M. Braxton
- & Pei-Hsun Wu
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Correspondence |
ShareLoc — an open platform for sharing localization microscopy data
- Wei Ouyang
- , Jiachuan Bai
- & Christophe Zimmer
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Perspective |
Practical considerations for quantitative light sheet fluorescence microscopy
This Perspective describes common pitfalls that can occur when using light sheet microscopy and offers guidance for improved quantitative imaging with these instruments.
- Chad M. Hobson
- , Min Guo
- & Teng-Leong Chew
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Research Briefing |
Light-Seq: from microscopy to transcriptomics and back
Light-Seq combines high resolution imaging with next generation sequencing of selected cell populations in fixed biological samples. Specifically, microscopically analyzed cells can be subjected to RNA expression profiling while keeping the sample intact for further assays, enabling cellular phenotypes and states to be assessed in the context of the original tissue.
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Article
| Open AccessOmnipose: a high-precision morphology-independent solution for bacterial cell segmentation
Omnipose is a deep neural network algorithm for image segmentation that improves upon existing approaches by solving the challenging problem of accurately segmenting morphologically diverse cells from images acquired with any modality.
- Kevin J. Cutler
- , Carsen Stringer
- & Joseph D. Mougous
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Article
| Open AccessLight-Seq: light-directed in situ barcoding of biomolecules in fixed cells and tissues for spatially indexed sequencing
Light-Seq uses light-directed DNA barcoding in fixed cells and tissues for multiplexed spatial indexing and subsequent next generation sequencing. This approach blends spatial and omics information to enable analysis of rare cell types in complex tissues.
- Jocelyn Y. Kishi
- , Ninning Liu
- & Peng Yin
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News & Views |
The data science future of neuroscience theory
An approach for integrating the wealth of heterogeneous brain data — from gene expression and neurotransmitter receptor density to structure and function — allows neuroscientists to easily place their data within the broader neuroscientific context.
- Bradley Voytek
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Research Highlight |
A closer look at FluoroCubes
Researchers explore the unique and puzzling photostability of DNA FluoroCubes. Moreover, they improve the probes’ performance and highlight their diverse applicability.
- Rita Strack
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News & Views |
Microscopes are coming for your job
Advances in microscopy, computer vision and open source software are converging to usher in a new era of microscopes that control themselves.
- Henry Pinkard
- & Laura Waller
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Article
| Open AccessAntibody stabilization for thermally accelerated deep immunostaining
Thermostable antibodies called SPEARs enable rapid immunostaining with improved tissue penetration.
- Hei Ming Lai
- , Yumi Tang
- & Ho Ko
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Comment |
Open microscopy in the life sciences: quo vadis?
Light microscopy enables researchers to observe cellular mechanisms with high spatial and temporal resolution. However, the increasing complexity of current imaging technologies, coupled with financial constraints of potential users, hampers the general accessibility and potential reach of cutting-edge microscopy. Open microscopy can address this issue by making well-designed and well-documented hardware and software solutions openly available to a broad audience. In this Comment, we provide a definition of open microscopy and present recent projects in the field. We discuss current and future challenges of open microscopy and their implications for funders, policymakers, researchers and scientists. We believe that open microscopy requires a holistic approach. Sample preparation, designing and building of hardware components, writing software, data acquisition and data interpretation must go hand in hand to enable interdisciplinary and reproducible science to the benefit of society.
- Johannes Hohlbein
- , Benedict Diederich
- & Kirti Prakash
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Article
| Open AccessFunctional ultrasound localization microscopy reveals brain-wide neurovascular activity on a microscopic scale
Functional ultrasound localization microscopy monitors cerebrovascular blood flow by detecting the flow of injected microbubbles, providing access to brain activity at high spatiotemporal resolution.
- Noémi Renaudin
- , Charlie Demené
- & Mickael Tanter
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News & Views |
Fluorophores’ talk turns them dark
Dipole–dipole crosstalk between fluorophores separated by a distance of less than 10 nm induces changes in their photophysics, which adds a challenge to localization microscopy in the sub-10-nm regime.
- Karim Almahayni
- , Malte Spiekermann
- & Leonhard Möckl
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Research Briefing |
Spectral phasor analysis enables multiplexed microscopy with bioluminescent probes
Bioluminescent phasor is a new technology for multiplexed, excitation-free imaging at the microscale using luciferase–luciferin pairs. This platform can readily unmix the broad, overlapping emission spectra of bioluminescent reporters, making possible the dynamic tracking of cellular and molecular features over prolonged time periods.
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Article |
Multiplexed bioluminescence microscopy via phasor analysis
The combination of engineered probes and spectral phasor analysis overcomes long-standing challenges associated with bioluminescence detection at the microscale, enabling multiplexed, real-time imaging of cellular features without the need for excitation light.
- Zi Yao
- , Caroline K. Brennan
- & Jennifer A. Prescher
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Article |
Automated high-speed 3D imaging of organoid cultures with multi-scale phenotypic quantification
A method for high-content 3D imaging of organoids.
- Anne Beghin
- , Gianluca Grenci
- & Virgile Viasnoff
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Research Highlight |
A fluorescent protein with staying power
A newly described fluorescent protein, StayGold, is bright and extremely photostable, enabling extended time-lapse imaging.
- Rita Strack
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Brief Communication |
ASLPrep: a platform for processing of arterial spin labeled MRI and quantification of regional brain perfusion
ASLPrep is a software suite for reproducible processing of arterial spin labeled magnetic resonance imaging data.
- Azeez Adebimpe
- , Maxwell Bertolero
- & Theodore D. Satterthwaite
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Article
| Open AccessLabel-free nanofluidic scattering microscopy of size and mass of single diffusing molecules and nanoparticles
Nanofluidic scattering microscopy enables label-free, quantitative measurements of the molecular weight and hydrodynamic radius of biological molecules and nanoparticles freely diffusing inside a nanofluidic channel.
- Barbora Špačková
- , Henrik Klein Moberg
- & Christoph Langhammer
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Article |
Single-domain near-infrared protein provides a scaffold for antigen-dependent fluorescent nanobodies
miRFP670nano3 offers improved near-infrared imaging and was used to develop fluorescent nanobodies whose stability and fluorescence strongly depend on antigen binding, with broad implications for detecting and manipulating cellular targets.
- Olena S. Oliinyk
- , Mikhail Baloban
- & Vladislav V. Verkhusha
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Article
| Open AccessOptimal precision and accuracy in 4Pi-STORM using dynamic spline PSF models
A dynamic model of the 4Pi point spread function enables localization microscopy with exceptional three-dimensional resolution and a simpler optical design. 4Pi-STORM images of neurons and mitochondria reveal new details of nanoscale protein and nucleic acid organization.
- Mark Bates
- , Jan Keller-Findeisen
- & Stefan W. Hell
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News & Views |
Imaging cleared tissues made easy
A flexible open-top light-sheet microscope has been developed that can perform deep three-dimensional imaging on all clearing protocols with low and high optical resolution.
- Shigeaki Kanatani
- & Per Uhlén
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Research Highlight |
Two-photon imaging in freely behaving mice
The MINI2P is a two-photon miniscope that enables robust calcium imaging during mouse behavior.
- Nina Vogt
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Article |
Correction of multiple-blinking artifacts in photoactivated localization microscopy
A model-based correction (MBC) algorithm offers fast and accurate correction of multiple-blinking artifacts in PALM data. MBC outperforms other algorithms in both speed and accuracy and improves quantitative downstream image analysis.
- Louis G. Jensen
- , Tjun Yee Hoh
- & Dylan M. Owen
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Article |
A hybrid open-top light-sheet microscope for versatile multi-scale imaging of cleared tissues
A ‘hybrid’ open-top light-sheet microscope is described, which can be used for broad multi-scale volumetric imaging of one or more large tissues, cleared with diverse protocols, and conveniently mounted on an array of sample holders.
- Adam K. Glaser
- , Kevin W. Bishop
- & Jonathan T. C. Liu
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Correspondence |
Best practices for reporting throughput in biomedical research
- Maik Herbig
- , Akihiro Isozaki
- & Keisuke Goda
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Brief Communication |
Fluorogenic DNA-PAINT for faster, low-background super-resolution imaging
Two-color fluorogenic DNA-PAINT introduces self-quenching, kinetics-optimized probe designs. This approach improves imaging speed 26-fold and eliminates the need for optical sectioning.
- Kenny K. H. Chung
- , Zhao Zhang
- & Joerg Bewersdorf
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Research Highlight |
Image in vivo, skip the lenses
A lensless microscope captures 3D fluorescence images of complex biological tissues.
- Rita Strack
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Article |
HYBRiD: hydrogel-reinforced DISCO for clearing mammalian bodies
HYBRiD is a tissue-clearing approach that combines elements of solvent-based and aqueous, hydrogel-based methods, thereby achieving high transparency while maintaining fluorescence.
- Victoria Nudell
- , Yu Wang
- & Li Ye
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Research Briefing |
DaXi: pushing the limits of single-objective light-sheet microscopy
A new single-objective light-sheet microscope has been developed that uses novel optics and imaging protocols to increase resolution without compromising imaging speed and volume.
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Research Highlight |
Unraveling immune cell behavior
Live imaging enables temporal tracking of immune cell behavior.
- Madhura Mukhopadhyay
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Editorial |
Catching up with multiplexed tissue imaging
Highly multiplexed tissue imaging continues to show its power for biomedical discovery. In this issue, we publish tools and guidance for implementing this class of methods and reporting subsequent results.
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Article |
Isotropic super-resolution light-sheet microscopy of dynamic intracellular structures at subsecond timescales
Combining a double-ring modulated SPIM with reduced side lobes and a sectionalized deep-learning based super-resolution algorithm enables fast, high-resolution, volumetric imaging of organelle interactions and dynamics in live cells.
- Yuxuan Zhao
- , Meng Zhang
- & Yu-Hui Zhang
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Research Highlight |
Tumor microenvironments in 3D
An imaging mass cytometry method reconstructs tissue microenvironments in 3D.
- Madhura Mukhopadhyay
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Research Highlight |
Three views are better than one
Researchers push the limits of confocal microscopy by combining multiple views, super-resolution and deep learning.
- Rita Strack
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Article |
A genetically encoded sensor for in vivo imaging of orexin neuropeptides
OxLight1 is a genetically encoded sensor for the orexin neuropeptides. It has been applied in fiber photometry recordings and two-photon imaging in mice during a variety of behaviors.
- Loïc Duffet
- , Seher Kosar
- & Tommaso Patriarchi
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Article |
VascuViz: a multimodality and multiscale imaging and visualization pipeline for vascular systems biology
VascuViz represents a versatile workflow for multimodal imaging of the vasculature in ex vivo tissue samples across length and resolution scales, paving the way for improved and novel image-based vascular systems biology applications.
- Akanksha Bhargava
- , Benjamin Monteagudo
- & Arvind P. Pathak
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Article
| Open AccessSquidpy: a scalable framework for spatial omics analysis
Squidpy enables comprehensive analysis and visualization of spatial omics data and image with high efficiency.
- Giovanni Palla
- , Hannah Spitzer
- & Fabian J. Theis
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News & Views |
Expansion microscopy opens the door to exploring more challenges
Cryofixation-based ultrastructure-expansion microscopy (cryo-ExM) bypasses artifacts caused by chemical fixation and establishes more-native preservation of biological samples.
- Mengfei Gao
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Article
| Open AccessVisualizing the native cellular organization by coupling cryofixation with expansion microscopy (Cryo-ExM)
Cryo-ExM combines the expansion microscopy for super-resolution imaging with cryofixation for ultrastructure preservation. Cryo-ExM outperforms established fixation methods on a range of sensitive subcellular structures.
- Marine H. Laporte
- , Nikolai Klena
- & Paul Guichard
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- Bioluminescence imaging
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- Positron-emission tomography
- Time-lapse imaging
- Ultrasound
- Viral tracing
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