Featured
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| Open AccessMulti-molecular hyperspectral PRM-SRS microscopy
Spatial imaging methods in lipid research can disrupt tissue integrity and can have limited spatial and spectral resolution. Here, the authors present an SRS-based hyperspectral imaging platform to visualise lipids and lipoproteins in a variety of tissues and animal species.
- Wenxu Zhang
- , Yajuan Li
- & Lingyan Shi
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Article
| Open AccessAn ultrasensitive and broadband transparent ultrasound transducer for ultrasound and photoacoustic imaging in-vivo
Transparent ultrasound transducers suffer from practical limitations due to acoustic impedance mismatch. By using a transparent adhesive based on silicon dioxide epoxy, the authors demonstrate a broadband, ultrasensitive transparent ultrasound transducer, advancing the possibilities of sensor fusion.
- Seonghee Cho
- , Minsu Kim
- & Chulhong Kim
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Article
| Open AccessSingle-cell mapping of lipid metabolites using an infrared probe in human-derived model systems
Current metabolic imaging studies are limited by low resolution and low specificity. Here, the authors present a single-cell metabolic imaging platform to monitor lipid metabolism with high specificity in various human-derived 2D and 3D culture systems.
- Yeran Bai
- , Carolina M. Camargo
- & Kenneth S. Kosik
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Article
| Open AccessHigh resolution mapping of the tumor microenvironment using integrated single-cell, spatial and in situ analysis
The integration of single-cell and spatial data can provide a more comprehensive picture of the network of cells within the tumour microenvironment. Here the authors use a combination of single-cell and spatial technologies including 10x Xenium to characterise serial formalin-fixed, paraffin-embedded human breast cancer sections.
- Amanda Janesick
- , Robert Shelansky
- & Sarah E. B. Taylor
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Article
| Open AccessDeep learning-enabled realistic virtual histology with ultraviolet photoacoustic remote sensing microscopy
Oncologic tumour resection is not fully accurate. Here the authors report a label-free virtual histological imaging method based on a non-contact, reflection-mode ultraviolet photoacoustic remote sensing and scattering microscope, combined with unsupervised deep learning using a cycle-consistent GAN.
- Matthew T. Martell
- , Nathaniel J. M. Haven
- & Roger J. Zemp
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Article
| Open AccessSimultaneous magnetic resonance imaging of pH, perfusion and renal filtration using hyperpolarized 13C-labelled Z-OMPD
pH alterations are a hallmark of many pathologies including cancer and kidney disease. Here the authors describe [1,5- 13 C2]Z-OMPD as a probe for hyperpolarized 13C-MRI with good pH sensitivity and hyperpolarization properties which combined with tailored MRI protocols allow sub-minute imaging of pH, renal perfusion and filtration simultaneously.
- Martin Grashei
- , Pascal Wodtke
- & Franz Schilling
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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 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 AccessSpatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis
Spatial metabolomics are used to describe the location and chemistry of small molecules involved in metabolic phenotypes. Here, Conroy et al. present a bioinformatic pipeline to analyze MALDI data and show that it can be used to identify actionable targets such as glycogen in fibrotic lungs of both human and mice.
- Lindsey R. Conroy
- , Harrison A. Clarke
- & Ramon C. Sun
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Article
| Open AccessMolecular imaging of liver inflammation using an anti-VCAM-1 nanobody
Here, the authors present a noninvasive tool to detect liver inflammation using nuclear imaging, as an alternative to biopsy. The prove the diagnostic power of this tool to detect liver inflammation in preclinical models of chronic liver disease.
- Maxime Nachit
- , Christopher Montemagno
- & Pascale Perret
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Article
| Open AccessPrecisely translating computed tomography diagnosis accuracy into therapeutic intervention by a carbon-iodine conjugated polymer
Poly(diiododiacetylene)—PIDA—contains iodine atoms, which are commonly found in computed tomography contrast agents. Here, the authors find that PIDA can function as a contrast agent and can also be used as a visual marker to delineate tumour margins.
- Mingming Yin
- , Xiaoming Liu
- & Liang Luo
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Article
| Open AccessCarbonized paramagnetic complexes of Mn (II) as contrast agents for precise magnetic resonance imaging of sub-millimeter-sized orthotopic tumors
Improving the imaging of cancer may enhance the treatment of patients, Here, the authors develop a Mn(II) based nanoparticle contrast agent for MRI imaging and show that the nanoparticles can cross the brain barrier and image glioma cells.
- Ruixue Qin
- , Shi Li
- & Hongmin Chen
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Article
| Open AccessStructural library and visualization of endogenously oxidized phosphatidylcholines using mass spectrometry-based techniques
Oxidized phosphatidylcholines (oxPCs) are a structurally diverse class of lipids associated with various diseases. Here, the authors use mass spectrometry to construct a spectral library of 465 oxPCs and subsequently profile oxPCs formed during acetaminophen-induced acute liver failure in mice.
- Yuta Matsuoka
- , Masatomo Takahashi
- & Ken-ichi Yamada
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Article
| Open AccessClinically translatable quantitative molecular photoacoustic imaging with liposome-encapsulated ICG J-aggregates
Photoacoustic imaging is limited by a lack of contrast agents which can enable combined molecular and physiological imaging at depth. Here the authors address these limitations by developing and validating a contrast agent based on targeted liposomes loaded with J-aggregated indocyanine green dye.
- Cayla A. Wood
- , Sangheon Han
- & Richard R. Bouchard
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Article
| Open AccessSubcellular localization of biomolecules and drug distribution by high-definition ion beam imaging
Multiplexed ion beam imaging can provide subcellular localisation information but with limited resolution. Here the authors report an ion beam imaging method with nanoscale resolution which they use to assess the subcellular distribution of cisplatin.
- Xavier Rovira-Clavé
- , Sizun Jiang
- & Garry P. Nolan
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Article
| Open AccessKL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer’s disease
The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.
- Julia Neitzel
- , Nicolai Franzmeier
- & Michael Ewers
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Article
| Open AccessMultiplexed live-cell profiling with Raman probes
Currently relatively few functional probes for Raman-based live-cell profiling exist. Here the authors build on their previous ultra-bright Raman dots to devise a 14-plexed Raman probe panel to quantify cell surface proteins, endocytosis activities and metabolic dynamics of single live cells.
- Chen Chen
- , Zhilun Zhao
- & Wei Min
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Article
| Open AccessSwitchable stimulated Raman scattering microscopy with photochromic vibrational probes
Probes with reversible fluorescence are useful in super-resolution microscopy, but lack sufficient chemical specificity. Here, the authors engineer alkyne tagged diarylethene to realize photo-switchable stimulated Raman scattering probes with high chemical resolution, for applications in living cells.
- Jianpeng Ao
- , Xiaofeng Fang
- & Minbiao Ji
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Article
| Open AccessA choreography of centrosomal mRNAs reveals a conserved localization mechanism involving active polysome transport
Centrosomes function as microtubule organizing centers where several mRNAs accumulate. By employing high-throughput single molecule FISH screening, the authors discover that 8 human mRNAs localize to centrosomes with unique cell cycle dependent patterns using an active polysome targeting mechanism.
- Adham Safieddine
- , Emeline Coleno
- & Edouard Bertrand
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Article
| Open AccessExon junction complex dependent mRNA localization is linked to centrosome organization during ciliogenesis
Exon junction complexes (EJCs) that mark untranslated mRNA are involved in transport, translation and nonsense-mediated mRNA decay. Here the authors show centrosomal localization of EJCs which appears to be required for both the localization of NIN mRNA around centrosomes and ciliogenesis.
- Oh Sung Kwon
- , Rahul Mishra
- & Hervé Le Hir
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Article
| Open AccessReal-time interleaved spectroscopic photoacoustic and ultrasound (PAUS) scanning with simultaneous fluence compensation and motion correction
Spectroscopic photoacoustic imaging has been limited by wavelength-dependent fluence variations and tissue motion. Here, the authors achieve real-time fluence and motion correction in vivo by using a wavelength-tunable laser, sequential scan of a narrow beam and partial image reconstruction for each pulse.
- Geng-Shi Jeng
- , Meng-Lin Li
- & Matthew O’Donnell
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Article
| Open AccessProtein identification by 3D OrbiSIMS to facilitate in situ imaging and depth profiling
Label-free protein characterization at surfaces requires digestion or matrix application prior to mass spectrometry. Here, the authors report the assignment of undigested proteins at surfaces by de novo sequencing and apply the methodology to a protein monolayer biochip and for in situ depth profiling of proteins through human skin.
- Anna M. Kotowska
- , Gustavo F. Trindade
- & David J. Scurr
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Article
| Open AccessTurn-on chemiluminescence probes and dual-amplification of signal for detection of amyloid beta species in vivo
Detection of amyloid beta deposits is often performed with fluorescent compounds that bind plaques. Here the authors develop turn-on chemiluminescent probes that bind amyloid beta plaques in vivo, and amplify the signal via chemiluminescence resonance energy transfer to the plaque-binding fluorescent molecule CRANAD-3.
- Jing Yang
- , Wei Yin
- & Chongzhao Ran
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Article
| Open AccessA nanobody-based fluorescent reporter reveals human α-synuclein in the cell cytosol
α-Syn in CSF is a biomarker of neurodegenerative diseases; however, the detection of clinically relevant species is difficult. Here, the authors create a nanobody biosensor that reveals the presence of α-Syn in cells, which allow the detection of transmittable forms of α-Syn present in human CSF.
- Christoph Gerdes
- , Natalia Waal
- & Felipe Opazo
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Article
| Open AccessTarget-responsive vasoactive probes for ultrasensitive molecular imaging
Noninvasive detection of molecular targets in living subjects could provide valuable insights into healthy function and disease. Here, the authors develop vasoactive imaging probes which allow wide-field in vivo mapping of nanomolar-level molecular species in rat brain.
- Robert Ohlendorf
- , Agata Wiśniowska
- & Alan Jasanoff
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Article
| Open AccessNucleoplasmic signals promote directed transmembrane protein import simultaneously via multiple channels of nuclear pores
The contribution of central and peripheral channels of nuclear pores to transport of transmembrane proteins is unclear. Here the authors show that most inner nuclear membrane proteins use only peripheral channels, but some extend nuclear localization signals into the central channel for directed nuclear transport.
- Krishna C. Mudumbi
- , Rafal Czapiewski
- & Weidong Yang
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Article
| Open AccessPositron emission tomography imaging of novel AAV capsids maps rapid brain accumulation
Adeno-associated viruses (AAVs) can be targeted in a tissue-specific manner, but their tissue accumulation cannot be assessed in a non-invasive manner. Here the authors conjugate a multivalent chelator labelled with Cu-64 to the surface of AAVs and image the brain accumulation of the PHB.eB capsid by PET.
- Jai Woong Seo
- , Elizabeth S. Ingham
- & Katherine W. Ferrara
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Article
| Open AccessMaltotriose-based probes for fluorescence and photoacoustic imaging of bacterial infections
Sensitive diagnostic tools for bacterial infections of wounds and surgical sites are necessary to enable early detection and determine optimal means of treatment. Here, the authors develop a fluorescent and optoacoustic probe based on a maltotriose scaffold, which is selectively taken up by gram-positive and gram-negative bacteria.
- Aimen Zlitni
- , Gayatri Gowrishankar
- & Sanjiv Sam Gambhir
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Article
| Open AccessIn vivo imaging of phosphocreatine with artificial neural networks
Phosphocreatine plays a vital role in cellular energetic homeostasis, but there are no routine diagnostic tests to noninvasively map the distribution with clinically relevant spatial resolution. Here, the authors develop and validate a noninvasive approach for quantifying and imaging phosphocreatine, without contrast agents, on widely available clinical MRI scanners with artificial neural networks.
- Lin Chen
- , Michael Schär
- & Jiadi Xu
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Article
| Open AccessElucidating target specificity of the taccalonolide covalent microtubule stabilizers employing a combinatorial chemical approach
Taccalonolide microtubule stabilizers covalently bind β-tubulin and overcome taxane resistance mechanisms. Here, the authors synthesized fluorogenic taccalonolide probes and investigated the specificity of taccalonolide binding to β-tubulin and the molecular interactions between drug and target,
- Lin Du
- , Samantha S. Yee
- & April L. Risinger
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Article
| Open AccessSub-nanomolar sensitive GZnP3 reveals TRPML1-mediated neuronal Zn2+ signals
Numerous fluorescent Zn2+ sensors are available but most are unsuitable to detect physiological dynamics of cytosolic Zn2+. In this study, the authors present a genetically encoded sensor with sub-nanomolar sensitivity and show that Zn2 + is released from endolysosomal vesicles via TRPML1 in neurons.
- Taylor F. Minckley
- , Chen Zhang
- & Yan Qin
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Article
| Open AccessElectro-optic imaging enables efficient wide-field fluorescence lifetime microscopy
Nanosecond imaging techniques, such as fluorescence lifetime imaging microscopy (FLIM), are limited by low efficiency of current detectors. Here, the authors implement an electro-optic approach using Pockels cells for wide-field image gating and demonstrate high throughput FLIM on standard camera sensors.
- Adam J. Bowman
- , Brannon B. Klopfer
- & Mark A. Kasevich
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Article
| Open AccessQuantum biological tunnel junction for electron transfer imaging in live cells
Although quantum biological electron transfer is important in many biological processes, imaging of the events in live cells has remained challenging. Here, the authors demonstrate real-time optical detection of quantum biological electron tunnelling between nanoparticles and cytochrome c inside living cells.
- Hongbao Xin
- , Wen Jing Sim
- & Luke P. Lee
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Article
| Open AccessBioengineered bacterial vesicles as biological nano-heaters for optoacoustic imaging
Bacterial outer membrane vesicles (OMVs) are increasingly used as carriers for drug delivery. Here the authors encapsulate biopolymer melanin into OMVs, extending their use to optoacoustic imaging both in vitro and in vivo, and demonstrate the potential of this tool for photothermal therapy applications.
- Vipul Gujrati
- , Jaya Prakash
- & Vasilis Ntziachristos
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Article
| Open AccessHigh-resolution structure determination of sub-100 kDa complexes using conventional cryo-EM
Despite many recent advances in cryo-EM, imaging smaller macromolecules (below 100 kDa) has remained a challenge. Here the authors show that biological specimens amassing <100 kDa can be resolved to better than 3 Å resolution using conventional defocus-based single-particle analysis methods.
- Mark A. Herzik Jr.
- , Mengyu Wu
- & Gabriel C. Lander
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Article
| Open AccessIntensiometric biosensors visualize the activity of multiple small GTPases in vivo
FRET sensors hardly achieve visualization of spatiotemporal dynamics of protein activity in vivo. Here the authors present intensiometric small GTPase biosensors based on dimerization-dependent fluorescent proteins that enable monitoring of activity of small GTPases in the brains of behaving mice at a single spine resolution.
- Jihoon Kim
- , Sangkyu Lee
- & Won Do Heo
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Article
| Open AccessImplementation and benchmarking of a novel analytical framework to clinically evaluate tumor-specific fluorescent tracers
Fluorescent tracers are being tested in clinical trials to improve detection of tumor margins, but procedures are not standardised. Here, the authors develop an analytical framework that is compatible with the workflow in the operating theatre, and show that it leads to an 88% increase in intraoperative detection of tumor margins in patients with breast cancer.
- Marjory Koller
- , Si-Qi Qiu
- & Gooitzen M. van Dam
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Article
| Open AccessChiral DOTA chelators as an improved platform for biomedical imaging and therapy applications
MRI contrast agents containing the rare earth metal gadolinium are very effective, yet unstable and thus potentially hazardous. Here, the authors developed complexes between gadolinium and the scaffolding compound DOTA with increased stability, which also lend themselves to radiometal labelling.
- Lixiong Dai
- , Chloe M. Jones
- & Ga-Lai Law
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Article
| Open AccessDirection of actin flow dictates integrin LFA-1 orientation during leukocyte migration
Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for cell migration. Here the authors show that actin flow can orient cell surface integrins during leukocyte migration, suggesting integrin activation by cytoskeletal force.
- Pontus Nordenfelt
- , Travis I. Moore
- & Timothy A. Springer
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Article
| Open AccessImaging of pH in vivo using hyperpolarized 13C-labelled zymonic acid
Local pH alterations can be manifestations of pathologies such as cancer, inflammation and ischaemia. Here Düwelet al. show hyperpolarized 13C-labelled zymonic acid can be used as a non-invasive probe to map and measure pH in vivo, suggesting it as a candidate for clinical imaging and a diagnostic tool.
- Stephan Düwel
- , Christian Hundshammer
- & Franz Schilling
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Article
| Open AccessLive cell imaging of single genomic loci with quantum dot-labeled TALEs
Visualizing single genomic loci in living cells remains technically challenging. Here the authors adopt a strategy of labelling a pair of transcription activator-like effectors (TALEs) with differently coloured quantum dots and use them to identify integrated HIV-1 proviral DNA sequences in living cells.
- Yingxin Ma
- , Mingxiu Wang
- & Zongqiang Cui
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Article
| Open AccessQuantitative volumetric Raman imaging of three dimensional cell cultures
Advances in chemical imaging capability can add to our understanding of complex cellular systems. Here the authors develop a framework for label-free quantitative volumetric Raman spectroscopic imaging and use it to visualize and quantify biomolecules in various 3D cellular systems.
- Charalambos Kallepitis
- , Mads S. Bergholt
- & Molly M. Stevens
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Article
| Open AccessLive cell imaging of low- and non-repetitive chromosome loci using CRISPR-Cas9
CRISPR-Cas9 has been used to image repetitive loci in live cells to explore genome organization. Here the authors demonstrate the imaging of low-repeat regions with a single-guide RNA and the imaging of a non-repetitive region, allowing the tracking of transcriptionally active and inactive regions.
- Peiwu Qin
- , Mahmut Parlak
- & Mazhar Adli
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Article
| Open AccessMolecular imaging with engineered physiology
The vasculature produces strong endogenous contrast in magnetic resonance imaging (MRI). Here Desai et al. report genetically encoded imaging probes derived from the vasodilator, calcitonin gene-related peptide, which allows visualization of molecular events via haemodynamic changes in optical imaging or MRI.
- Mitul Desai
- , Adrian L. Slusarczyk
- & Alan Jasanoff
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Article
| Open AccessIn vivo imaging of clock gene expression in multiple tissues of freely moving mice
The circadian rhythms of peripheral clocks are difficult to study. Here the authors demonstrate a technique to image clock gene expression simultaneously in various tissues of freely moving mice, and use it to show that a long duration light pulse resets the rhythms in the olfactory bulb faster than other tissues.
- Toshiyuki Hamada
- , Kenneth Sutherland
- & Ken-ichi Honma
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Article
| Open AccessIn vivo nanoparticle-mediated radiopharmaceutical-excited fluorescence molecular imaging
Insufficient imaging sensitivity can make it challenging to assess early stage tumour lesions in vivo. Here, the authors present the radiopharmaceutical-excited fluorescence imaging technique that can detect tumour lesions less than 2 mm in size in living mice.
- Zhenhua Hu
- , Yawei Qu
- & Jie Tian
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Article |
In-cell NMR reveals potential precursor of toxic species from SOD1 fALS mutants
Mutations in the enzyme superoxide dismutase 1 (SOD1) underlie a form of neurodegenerative disease called amyotrophic lateral sclerosis. Here the authors employ in-cell NMR to show that SOD1 mutants adopt unstructured conformations that are unable to bind zinc and may form toxic SOD1 aggregates.
- Enrico Luchinat
- , Letizia Barbieri
- & Lucia Banci
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Article
| Open AccessIn vivo single-molecule imaging identifies altered dynamics of calcium channels in dystrophin-mutant C. elegans
Single molecule fluorescence microscopy is a powerful technique to study protein dynamics in cells, but it has not been applied to adult animals. The authors use complementation-activated light microscopy in C. elegansto discover that dystrophin regulates the diffusion properties of voltage-dependent calcium ion channels at the surface of body-wall muscle cells.
- Hong Zhan
- , Ramunas Stanciauskas
- & Fabien Pinaud
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Article
| Open AccessQuantitative super-resolution imaging of Bruchpilot distinguishes active zone states
Complex molecular interactions occur in the active zone cytomatrix (CAZ) within the presynaptic terminal to regulate synaptic plasticity. Here, the authors use imaging techniques to show that the CAZ is composed of units containing on average 137 Bruchpilot proteins, many of which are arranged into clusters.
- Nadine Ehmann
- , Sebastian van de Linde
- & Robert J. Kittel