Although similar in molecular composition, synapses can exhibit strikingly distinct functional transmitter release and plasticity characteristics. To determine whether ultrastructural differences co-define this functional heterogeneity, we combine hippocampal organotypic slice cultures, high-pressure freezing, freeze substitution, and 3D-electron tomography to compare two functionally distinct synapses: hippocampal Schaffer collateral and mossy fiber synapses. We find that mossy fiber synapses, which exhibit a lower release probability and stronger short-term facilitation than Schaffer collateral synapses, harbor lower numbers of docked synaptic vesicles at active zones and a second pool of possibly tethered vesicles in their vicinity. Our data indicate that differences in the ratio of docked versus tethered vesicles at active zones contribute to distinct functional characteristics of synapses.
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http://dx.doi.org/10.1016/j.celrep.2020.02.083 | DOI Listing |
Front Oncol
December 2024
Department of Integrative Translational Sciences, City of Hope, Beckman Research Institute, Duarte, CA, United States.
Over the past century, colorectal cancer (CRC) has become one of the most devastating cancers impacting the human population. To gain a deeper understanding of the molecular mechanisms driving this solid tumor, researchers have increasingly turned their attention to the tumor microenvironment (TME). Spatial transcriptomics and proteomics have emerged as a particularly powerful technology for deciphering the complexity of CRC tumors, given that the TME and its spatial organization are critical determinants of disease progression and treatment response.
View Article and Find Full Text PDFAdv Funct Mater
October 2024
Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA.
Traditional deep fluorescence imaging has primarily focused on red-shifting imaging wavelengths into the near-infrared (NIR) windows or implementation of multi-photon excitation approaches. Here, we combine the advantages of NIR and multiphoton imaging by developing a dual-infrared two-photon microscope to enable high-resolution deep imaging in biological tissues. We first computationally identify that photon absorption, as opposed to scattering, is the primary contributor to signal attenuation.
View Article and Find Full Text PDFDigit Health
December 2024
Department of Biological and Environmental Sciences and Technologies (DiSTeBA), Università del Salento, Lecce, Italy.
Objective: Osteoarthritis (OA), particularly knee OA, is a leading cause of disability and poses significant challenges in healthcare management. Mobile applications (apps) have emerged as potential tools to support therapeutic exercise by providing tailored programs, instructional content, and progress tracking. This systematic review evaluates the efficacy of mobile apps in enhancing therapeutic exercise for knee OA management.
View Article and Find Full Text PDFSpatially mapping the transcriptome and proteome in the same tissue section can significantly advance our understanding of heterogeneous cellular processes and connect cell type to function. Here, we present Deterministic Barcoding in Tissue sequencing plus (DBiTplus), an integrative multi-modality spatial omics approach that combines sequencing-based spatial transcriptomics and image-based spatial protein profiling on the same tissue section to enable both single-cell resolution cell typing and genome-scale interrogation of biological pathways. DBiTplus begins with reverse transcription for cDNA synthesis, microfluidic delivery of DNA oligos for spatial barcoding, retrieval of barcoded cDNA using RNaseH, an enzyme that selectively degrades RNA in an RNA-DNA hybrid, preserving the intact tissue section for high-plex protein imaging with CODEX.
View Article and Find Full Text PDFSingle-cell RNA sequencing (scRNA-seq) has revolutionized cell biology by enabling the profiling of transcriptomes at a single-cell resolution, leading to important discoveries that have advanced our understanding of cellular and tissue heterogeneity, developmental trajectories, and disease progression. Despite these important advances, scRNA-seq is limited to measuring the transcriptome providing a partial view of cellular function. To address this limitation, multimodal scRNA-seq assays have emerged, allowing for the simultaneous measurement of RNA expression and protein.
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