Constitutive Endolysosomal Perforation in Neurons allows Induction of alpha-Synuclein Aggregation by Internalized Pre-Formed Fibrils DOI Creative Commons
Anwesha Sanyal, Gustavo Scanavachi, Elliott Somerville

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

ABSTRACT The endocytic pathway is both an essential route of molecular uptake in cells and a potential entry point for pathology-inducing cargo. cell-to-cell spread cytotoxic aggregates, such as those α-synuclein (α-syn) Parkinson’s Disease (PD), exemplifies this duality. Here we used human iPSC-derived induced neuronal model (iNs) prone to death mediated by aggregation late endosomes lysosomes endogenous α-syn, seeded internalized pre-formed fibrils α-syn (PFFs). This PFF-mediated was not observed with parental iPSCs or other non-neuronal cells. Using live-cell optical microscopy visualize the read out biosensors reporting endo-lysosome wounding, discovered that up about 10% iNs exhibited spontaneous constitutive perforations, regardless presence PFFs. absent cells, corresponded partial damage nanopores limiting membranes subset endolysosomes directly volumetric focused ion beam scanning electron (FIB-SEM) CA1 pyramidal neurons from mouse brain, found culture liver skin. We suggest compromised general are primary conduit cytosolic access PFFs entrapped within endo-lysosomal lumens, initiating aggregation. Significantly, eradicating intrinsic endolysosomal perforations inhibiting endosomal Phosphatidylinositol-3-Phosphate/Phosphatidylinositol 5-Kinase (PIKfyve kinase) using Apilimod Vacuolin-1 markedly reduced PFF-induced aggregation, despite continuing enter compartment. Crucially, intervention also diminished iN associated PFF incubation. Our results reveal surprising intrinsically perforated endo-lysosomes neurons, underscoring their crucial early involvement genesis toxic aggregates discovery offers basis employing PIKfyve kinase inhibition therapeutic strategy counteract synucleinopathies.

Language: Английский

The ImageJ ecosystem: Open‐source software for image visualization, processing, and analysis DOI Open Access

Alexandra B. Schroeder,

Ellen T. A. Dobson, Curtis Rueden

et al.

Protein Science, Journal Year: 2020, Volume and Issue: 30(1), P. 234 - 249

Published: Nov. 9, 2020

Abstract For decades, biologists have relied on software to visualize and interpret imaging data. As techniques for acquiring images increase in complexity, resulting larger multidimensional datasets, must adapt. ImageJ is an open‐source image analysis platform that has aided researchers with a variety of applications, driven mainly by engaged collaborative user developer communities. The close collaboration between programmers users resulted adaptations accommodate new challenges address the needs ImageJ's diverse base. consists many components, some relevant primarily developers vast collection user‐centric plugins. It available forms, including widely used Fiji distribution. We refer this entire codebase community as ecosystem. Here we review core features ecosystem highlight how responded technology advancements plugins tools recent years. These been developed several areas such visualization, segmentation, tracking biological entities large, complex datasets. Moreover, capabilities deep learning are being added ImageJ, reflecting shift bioimage towards exploiting artificial intelligence. facilitated profound architectural changes brought about ImageJ2 project. Therefore, also discuss contributions enhancing processing interoperability

Language: Английский

Citations

212
DeepImageJ: A user-friendly environment to run deep learning models in ImageJ DOI
Estibaliz Gómez‐de‐Mariscal,

Carlos García-López-de-Haro,

Wei Ouyang

et al.

Nature Methods, Journal Year: 2021, Volume and Issue: 18(10), P. 1192 - 1195

Published: Sept. 30, 2021

Language: Английский

Citations

195
Vimentin filaments integrate low-complexity domains in a complex helical structure DOI Creative Commons
Matthias Eibauer, Miriam S. Weber, Rafael Kronenberg‐Tenga

et al.

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: 31(6), P. 939 - 949

Published: April 17, 2024

Abstract Intermediate filaments (IFs) are integral components of the cytoskeleton. They provide cells with tissue-specific mechanical properties and involved in numerous cellular processes. Due to their intricate architecture, a 3D structure IFs has remained elusive. Here we use cryo-focused ion-beam milling, cryo-electron microscopy tomography obtain vimentin (VIFs). VIFs assemble into modular, intertwined flexible helical 40 α-helices cross-section, organized five protofibrils. Surprisingly, intrinsically disordered head domains form fiber lumen VIFs, while tails lateral connections between Our findings demonstrate how protein low sequence complexity can complement well-folded construct biopolymer striking strength stretchability.

Language: Английский

Citations

31
BioImage Model Zoo: A Community-Driven Resource for Accessible Deep Learning in BioImage Analysis DOI Creative Commons
Wei Ouyang, Fynn Beuttenmueller, Estibaliz Gómez‐de‐Mariscal

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: June 8, 2022

Abstract Deep learning-based approaches are revolutionizing imaging-driven scientific research. However, the accessibility and reproducibility of deep workflows for imaging scientists remain far from sufficient. Several tools have recently risen to challenge democratizing learning by providing user-friendly interfaces analyze new data with pre-trained or fine-tuned models. Still, few existing models interoperable between these tools, critically restricting a model’s overall utility possibility validating reproducing analyses. Here, we present BioImage Model Zoo ( https://bioimage.io ): community-driven, fully open resource where standardized can be shared, explored, tested, downloaded further adaptation direct deployment in multiple end user-facing (e.g., ilastik, deepImageJ, QuPath, StarDist, ImJoy, ZeroCostDL4Mic, CSBDeep). To enable everyone contribute consume resources, provide model standard cross-compatibility, rich list example practical use-cases, developer documentation, accompanying infrastructure upload, download testing. Our contribution aims lay groundwork make methods microscopy findable, accessible, interoperable, reusable (FAIR) across software platforms.

Language: Английский

Citations

64
Interstitial boron-doped FeCoNiCr high entropy alloys with excellent electromagnetic-wave absorption and resistance to harsh environments DOI

Haoran Zhou,

Linwen Jiang,

Lei Jia

et al.

Journal of Alloys and Compounds, Journal Year: 2023, Volume and Issue: 959, P. 170579 - 170579

Published: May 15, 2023

Language: Английский

Citations

27
Live Microscopy of Multicellular Spheroids with the Multimodal Near-Infrared Nanoparticles Reveals Differences in Oxygenation Gradients DOI Creative Commons
Angela C. Debruyne, Irina A. Okkelman,

Nina Heymans

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(19), P. 12168 - 12186

Published: April 30, 2024

Assessment of hypoxia, nutrients, metabolite gradients, and other hallmarks the tumor microenvironment within 3D multicellular spheroid organoid models represents a challenging analytical task. Here, we report red/near-infrared (NIR) emitting cell staining with O2-sensitive nanoparticles, which enable measurements oxygenation on conventional fluorescence microscope. Nanosensor probes, termed "MMIR" (multimodal infrared), incorporate an NIR metalloporphyrin (PtTPTBPF) deep red aza-BODIPY reference dyes biocompatible polymer shell, allowing for oxygen gradient quantification via ratio phosphorescence lifetime readouts. We optimized techniques evaluated nanosensor probe characteristics cytotoxicity. Subsequently, applied nanosensors to live based HCT116, DPSCs, SKOV3 cells, at rest, treated drugs affecting respiration. found that growth medium viscosity, size, formation method influenced oxygenation. Some spheroids produced from HCT116 dental pulp stem cells exhibited "inverted" higher core levels than periphery. This contrasted frequently encountered "normal" hypoxia toward caused by diffusion. Further microscopy analysis demonstrated metabolic stratification spheroids: thus, autofluorescence FLIM NAD(P)H indicated glycolytic localization OxPhos-active Collectively, demonstrate strong potential NIR-emitting ratiometric advanced studies targeting quantitative real-time monitoring metabolism in complex tissue models.

Language: Английский

Citations

14
Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis DOI

Tinglv Fu,

Guorui Li, Donghang Li

et al.

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: 45(5), P. 1002 - 1018

Published: Jan. 15, 2024

Language: Английский

Citations

9
Ultrasound Neuromodulation of an Anti-Inflammatory Pathway at the Spleen Improves Experimental Pulmonary Hypertension DOI
Stefanos Zafeiropoulos, Umair Ahmed, Αlexandra Bekiaridou

et al.

Circulation Research, Journal Year: 2024, Volume and Issue: 135(1), P. 41 - 56

Published: May 7, 2024

Inflammation is pathogenically implicated in pulmonary arterial hypertension; however, it has not been adequately targeted therapeutically. We investigated whether neuromodulation of an anti-inflammatory neuroimmune pathway involving the splenic nerve using noninvasive, focused ultrasound stimulation spleen (sFUS) can improve experimental hypertension.

Language: Английский

Citations

9
Improved magneto-dielectric properties in Co substituted Cr ferrites for miniaturized antenna applications DOI

Shohanur Rahman Sagor,

Md. Abul Hossain, M. D. Hossain

et al.

Journal of Alloys and Compounds, Journal Year: 2025, Volume and Issue: unknown, P. 179152 - 179152

Published: Feb. 1, 2025

Language: Английский

Citations

1
Application of RSM- CCD methodology and Image J. for modeling and optimization of orchid protocorm encapsulation DOI Creative Commons
Zahra Mahdavi, Shirin Dianati Daylami, Ali Fadavi

et al.

Heliyon, Journal Year: 2025, Volume and Issue: unknown, P. e42744 - e42744

Published: Feb. 1, 2025

Language: Английский

Citations

1