Biology subjects

Palanca, A.

Publications and source records attributed to Palanca, A..

3 recordsLinked to original sources

bioRxiv2025

Cardiac fibrosis inhibitor CTPR390 prevents structural and morphological changes in collagen and fibroblasts of engineered human connective tissue

Cardiac fibrosis is a key characteristic of heart failure, with no effective treatment available. Using three-dimensional human models and cutting-edge biotechnology to evaluate new therapies offers a significant advancement. CTPR390, an experimental anti-fibrotic inhibitor targeting Hsp90, has shown success in animal models, but remains unexplored in human cardiac models. This study evaluated a cardiac three-dimensional engineered connective tissue (ECT) model treated with CTPR390, focusing on changes in the extracellular matrix and fibroblasts. Results showed that CTPR390 prevented architectural changes in TGF{beta}1-activated ECT, preserving tissue perimeter, collagen fibers alignment while reducing percentage of structured areas and degree of collagen structuration. Additionally, the treatment reduced cell area of elongated fibroblasts under tension, without changes in the internal rounded cells devoid of tension. Fibroblast recruitment to tension areas was diminished, showing biomechanical behavior similar to control ECT. This treatment also lowered the gene and protein expression of key pro-fibrotic markers. For the first time, advanced biotechnology was employed to detect the detailed structure of tissue fibrosis reduction after administering CTPR390, representing a significant advancement toward clinical application for cardiac fibrosis treatment. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=56 SRC="FIGDIR/small/633162v2_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@1f84961org.highwire.dtl.DTLVardef@19999eeorg.highwire.dtl.DTLVardef@1491286org.highwire.dtl.DTLVardef@5f2968_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2022

Systematic analysis of YFP gene traps reveals common discordance between mRNA and protein across the nervous system

While post-transcriptional control is thought to be required at the periphery of neurons and glia, its extent is unclear. Here, we investigate systematically the spatial distribution and expression of mRNA at single molecule sensitivity and their corresponding proteins of 200 YFP trap protein trap lines across the intact Drosophila nervous system. 98% of the genes studied showed discordance between the distribution of mRNA and the proteins they encode in at least one region of the nervous system. These data suggest that post-transcriptional regulation is very common, helping to explain the complexity of the nervous system. We also discovered that 68.5% of these genes have transcripts present at the periphery of neurons, with 9.5% at the glial periphery. Peripheral transcripts include many potential new regulators of neurons, glia and their interactions. Our approach is applicable to most genes and tissues and includes powerful novel data annotation and visualisation tools for post-transcriptional regulation. Brief outlineA novel high resolution and sensitive approach to systematically co-visualise the distribution of mRNAs and proteins in the intact nervous system reveals that post-transcriptional regulation of gene expression is very common. The rich data landscape is provided as a browsable resource (link), using Zegami, a cloud-based data exploration platform (link). Our solution provides a paradigm for the characterisation of post-transcriptional regulation of most genes and model systems. HighlightsO_LI196/200 (98%) Drosophila genes show discordant RNA and protein expression in at least one nervous system region C_LIO_LI137/200 (68.5%) mRNAs are present in at least one synaptic compartment C_LIO_LINovel localised mRNA and protein discovered in periphery of glial processes C_LIO_LINew paradigm for analysis of post-transcriptional regulation and data exploration C_LI

cell biology↗

bioRxiv2020

CryoSIM: super resolution 3D structured illumination cryogenic fluorescence microscopy for correlated ultra-structural imaging

Rapid cryo-preservation of biological specimens is the gold standard for visualising cellular structures in their true structural context. However, current commercial cryo-fluorescence microscopes are limited to low resolutions. To fill this gap, we have developed cryoSIM, a microscope for 3D super-resolution fluorescence cryo-imaging for correlation with cryo electron microscopy or cryo soft X-ray tomography. We provide the full instructions for replicating the instrument mostly from off-the-shelf components and accessible, user-friendly open source Python control software. Therefore, cryoSIM democratises the ability to detect molecules using super-resolution fluorescence imaging of cryo-preserved specimens for correlation with their cellular ultrastructure.

cell biology↗