University of Milano-Bicocca Showcase

Homology model and Molecular dynamics simulations for the AhR:ARNT:DRE complex in presence or absence of the TCDD ligand

Chemotherapy-induced peripheral neurotoxicity is one of the most common dose-limiting toxicities of several widely used anticancer drugs such as platinum derivatives (cisplatin) and taxanes (paclitaxel). Several molecular mechanisms related to the onset of neurotoxicity have already been proposed, most of them having the sensory neurons of the dorsal root ganglia (DRG) and the peripheral nerve fibers as principal targets. In this study we explore chemotherapy-induced peripheral neurotoxicity beyond the neuronocentric view, investigating the changes induced by paclitaxel (PTX) and cisplatin (CDDP) on satellite glial cells (SGC) in the DRG and their crosstalk. Rats were chronically treated with PTX (10 mg/Kg, 1qwx4) or CDDP (2 mg/Kg 2qwx4) or respective vehicles. Morpho-functional analyses were performed to verify the features of drug-induced peripheral neurotoxicity. Qualitative and quantitative immunohistochemistry, 3D immunofluorescence, immunoblotting, and transmission electron microscopy analyses were also performed to detect alterations in SGCs and their interconnections. We demonstrated that PTX, but not CDDP, produces a strong activation of SGCs in the DRG, by altering their interconnections and their physical contact with sensory neurons. SGCs may act as principal actors in PTX-induced peripheral neurotoxicity, paving the way for the identification of new druggable targets for the treatment and prevention of chemotherapy-induced peripheral neurotoxicity.

A new synthetic, multi-purpose dataset - called ENRICH - for testing photogrammetric and computer vision algorithms. Compared to existing datasets, ENRICH offers higher resolution images also rendered with different lighting conditions, camera orientation, scales, and field of view. Specifically, ENRICH is composed of three sub-datasets: ENRICH-Aerial, ENRICH-Square, and ENRICH-Statue, each exhibiting different characteristics. The proposed dataset is useful for several photogrammetry and computer vision-related tasks, such as the evaluation of hand-crafted and deep learning-based local features, effects of ground control points (GCPs) configuration on the 3D accuracy, and monocular depth estimation. Each zip file in the root is relative to a specific dataset: - ENRICH-Aerial, is an aerial image block of the city of Launceston, Australia. The acquisition is performed by simulating a typical oblique aerial camera with five views (nadir and four oblique views). - ENRICH-Square, is a ground-level dataset of a square captured by four cameras, each one moving on a different path with different focal length, orientation, and lighting conditions. - ENRICH-Statue, is a ground-level dataset portraying a statue (placed in the center of the ENRICH-Square scene), acquired using four cameras moving on different paths with different focal lengths, orientations, and lighting conditions. Be sure to check the README file in the dataset root for information on folder structure and file contents. Please refer to the related paper (https://doi.org/10.1016/j.isprsjprs.2023.03.002) for information about the generation method and the purpose of ENRICH.

Included in this folder are the original labels of the pictures, as well as the organized tables used for the statistics with additional information for each image, such as the coordinates or depth.

We propose a Bayesian Reduction for Amplified Quantization in Umap Embedding (BRAQUE) as an integrative novel approach, from data preprocessing to phenotype classification. BRAQUE starts with an innovative preprocessing, named Lognormal Shrinkage, able to enhance input fragmentation by fitting a lognormal mixture model and shrinking each component towards its median, in order to help further clustering step in finding more separated and clear clusters. The BRAQUE’s pipeline consist of a dimensionality reduction step performed using UMAP, and a clustering performed using HDBSCAN on UMAP embedding. These SUPPLEMENTAL DATA contain the csv image data files for seven lymphoid tissues, the antibody list and an MTA agreement letter for the CyBorgh software.

Codes and database originated for the manuscript published in the DOI article: 10.1016/j.jdeveco.2023.103053

These are supplemental data to the manuscript entitled: A DNA damage response-like phenotype defines a novel subset of colon cancer. A third of de-novo presentations of colorectal cancer display foci of positivity for ℽH2AX, pCHK2, pNBS1 in the absence of apoptosis or senescence associated p21/CDKN1A. This phenotype is reminiscent of an ongoing DNA damage response (DDR). The TP53 status, the chromosome 20q amplification or the microsatellite instability gene status did not correlate with the DDR phenotype, except for a preferential association with MSH2/MSH6 inactivation and conserved MLH1. Additional lesions of DDR-associated genes may be responsible for this phenotype, which is absent from the remaining cases in this cohort. The outcome, after adjuvant treatment with DNA-damaging drugs, did not differentiate this group from the remaining cases. DDR+ colorectal cancers may be amenable to personalized therapy by targeting the DDR.

Original (Italian) and English translation of the questionnaires used to perform the study. Original dataset used to perform the analysis (in Italian)

Tubulointerstitial fibrosis is observed in diabetic nephropathy. It is still debated whether tubular cells, undergoing epithelial-mesenchymal transition (EMT) in high glucose (HG) conditions, may contribute to interstitial fibrosis development. In this study, we investigated the phenotypic and molecular EMT-like changes and the alteration of inflammatory and fibrogenic secretome induced by HG in human primary tubular cell cultures. Taking advantage of this in vitro cell model composed of proximal and distal tubular cells, we showed that HG-treated tubular cells acquired a fibroblast-like morphology with cytoplasmic stress fibers, maintaining the expression of the epithelial markers specific of proximal and distal tubular cells. HG increased Snail1, miRNA210 and Vimentin mesenchymal markers, decreased N-cadherin expression and migration ability of primary tubular cells, while E-cadherin expression and focal adhesion distribution were not affected. Furthermore, HG treatment of tubular cells altered the inflammatory cytokine secretion creating a secretome able to enhance the proliferation and migration of fibroblasts. Our findings show that HG promotes an activated state of partial EMT in human tubular primary cells and induces a pro-inflammatory and pro-fibrogenic microenvironment, supporting the active role of tubular cells in diabetic nephropathy onset.

Metabolite library built from NMR spectra for metabolomic analysis of cheese whey permeate (CWP) using the Simple Mixture Analysis (SMA) tool implemented in MestreNova 14.3 software. Metabolites included: 2,3-Butandiol, Acetate, Alanine, Betaine, Choline, Citrate, Creatine, Creatinine, Ethanol, Fumarate, Hippurate, Lactate, Lactose, Orotate, Succinate, α-D-Galactose, β-D-Galactose Sample CWP in PB 10 mM (10% D2O) pH 7.4, TSP (1mM), Diluition Factor (10%) File included: SMA library .exp files and optimized .cmp files