22 research outputs found

    Evolution of complexity in the zebrafish synapse proteome

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    The proteome of human brain synapses is highly complex and mutated in over 130 diseases. This complexity arose from two whole genome duplications early in the vertebrate lineage. Zebrafish are used in modelling human diseases, however its synapse proteome is uncharacterised and whether the teleost-specific genome duplication (TSGD) influenced complexity is unknown. We report the characterisation of the proteomes and ultrastructure of central synapses in zebrafish and analyse the importance of the TSGD. While the TSGD increases overall synapse proteome complexity, the Post Synaptic Density (PSD) proteome of zebrafish has lower complexity than mammals. A highly conserved set of ~1000 proteins is shared across vertebrates. PSD ultrastructural features are also conserved. Lineage-specific proteome differences indicate vertebrate species evolved distinct synapse types and functions. The datasets are a resource for a wide range of studies and have important implications for the use of zebrafish in modelling human synaptic diseases

    Spatial distribution of surface temperature and land cover: A study concerning Sardinia, Italy

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    Land surface temperature (LST) is a key climate variable that has been studied mainly at the urban scale and in the context of urban heat islands. By analyzing the connection between LST and land covers, this study shows the potential of LST to analyze the relation between urbanization and heating phenomena at the regional level. Land cover data, drawn from Copernicus, and LST, retrieved from Landsat 8 satellite images, are analyzed through a methodology that couples GIS and regression analysis. By looking at the Italian island of Sardinia as a case study, this research shows that urbanization and the spatial dynamics of heating phenomena are closely connected, and that intensively farmed areas behave quite similarly to urban areas, whereas forests are the most effective land covers in mitigating LST, followed by areas covered with Mediterranean shrubs. This leads to key policy recommendations that decision makers could implement to mitigate LST at the regional scale and that can, in principle, be exported to regions with similar climate and land covers. The significance of this study can be summed up in a novel approach to analyze the relationship between LST and land covers that uses freely available spatial data and therefore can easily be replicated in other regional contexts to derive appropriate policy recommendations

    Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry

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    To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90)+HLA-DRAhi sublining fibroblasts, IL1B+ pro-inflammatory monocytes, ITGAX+TBX21+ autoimmune-associated B cells and PDCD1+ peripheral helper T (TPH) cells and follicular helper T (TFH) cells. We defined distinct subsets of CD8+ T cells characterized by GZMK+, GZMB+, and GNLY+ phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed IL6 expression to THY1+HLA-DRAhi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.</p

    Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry.

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    To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90)HLA-DRA sublining fibroblasts, IL1B pro-inflammatory monocytes, ITGAXTBX21 autoimmune-associated B cells and PDCD1 peripheral helper T (T) cells and follicular helper T (T) cells. We defined distinct subsets of CD8 T cells characterized by GZMK, GZMB, and GNLY phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed IL6 expression to THY1HLA-DRA fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis
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