IRCCS San Raffaele Scientific Institute Showcase

Raw images and dataset of densitometric analysis used for the generation of the figure 1 of the paper by Pelucchi S, Ravasi G, Piperno A. Ceruloplasmin variants might have different effects in different iron overload disorders. J Hepatol. 2021, 75:1003-1004. doi: 10.1016/j.jhep.2021.05.005. This paper is associated to the project "Blood-cerebrospinal fluid-barrie defect as gate for targeting by liver-directed ceruloplasmin gene replacement therapy in the rare disease aceruloplasminemia" supported by Italian Ministry of Health, with the grant RF-2018-1236671 to Massimo ALESSIO as principal investigator at the IRCCS-San Raffaele Hospital, Milano, Italy.

Cell migration is orchestrated by molecular networks supporting motility. The scaffolds ERC1/ELKS and Liprin-α1 sustain cell migration and invasion by assembling dynamic plasma membrane-associated platforms. ERC1/ELKS forms cytoplasmic condensates with liquid–like behavior. In this study we tested whether the ability of ERC1 to form condensates is relevant to its function in cell motility. We identified the shortest N-terminal region of ERC1 sufficient to drive phase separation in vitro and in cells. Fluorescence recovery after photobleaching confirmed the dynamic behavior of ERC1(1-244) condensates. Surprisingly, deletion of ERC1(1-244) including an intrinsically disordered region did not abolish the ability of ERC1DΔN to form condensates. Although the interactions of ERC1ΔN with partners were unaffected, the biophysical properties of ERC1ΔN condensates were altered, with consequences on cell motility. These findings highlight the importance of ERC1/ELKS to assemble functional networks, and show that altering the properties of ERC1–driven condensates interferes with tumor cell motility.

TITLE: Efficacy and safety of anti-CD45–saporin as conditioning agent for RAG deficiency Maria Carmina Castiello, Marita Bosticardo, Nicolò Sacchetti, Enrica Calzoni, Elena Fontana, Yasuhiro Yamazaki, Elena Draghici, Cristina Corsino , Ileana Bortolomai, Lucia Sereni, Hsin-Hui Yu, Paolo Uva, Rahul Palchaudhuri, David T. Scadden, Anna Villa, Luigi D. Notarangelo. PMID: 32387109 Background: Mutations in the recombinase-activating genes cause severe immunodeficiency, with a spectrum of phenotypes ranging from severe combined immunodeficiency to immune dysregulation. Hematopoietic stem cell transplantation is the only curative option, but a high risk of graft failure and poor immune reconstitution have been observed in the absence of myeloablation. Objectives: Our aim was to improve multilineage engraftment; we tested nongenotoxic conditioning with anti-CD45 mAbs conjugated with saporin CD45 (CD45-SAP). Methods: Rag1-KO and Rag1-F971L mice, which represent models of severe combined immune deficiency and combined immune deficiency with immune dysregulation, respectively, were conditioned with CD45-SAP, CD45-SAP plus 2 Gy of total body irradiation (TBI), 2 Gy of TBI, 8 Gy of TBI, or no conditioning and treated by using transplantation with lineage-negative bone marrow cells from wild-type mice. Flow cytometry and immunohistochemistry were used to assess engraftment and immune reconstitution. Antibody responses to 2,4,6-trinitrophenyl-conjugated keyhole limpet hemocyanin were measured by ELISA, and presence of autoantibody was detected by microarray. Results: Conditioning with CD45-SAP enabled high levels of multilineage engraftment in both Rag1 mutant models, allowed overcoming of B- and T-cell differentiation blocks and thymic epithelial cell defects, and induced robust cellular and humoral immunity in the periphery. Conclusions: Conditioning with CD45-SAP allows multilineage engraftment and robust immune reconstitution in mice with either null or hypomorphic Rag mutations while preserving thymic epithelial cell homeostasis.

Raw data to reprlicate the analyses conducted in "68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in Recurrent Prostate Cancer: Diagnostic Performance and Association with Clinical and Histopathological Data"

J Transl Autoimmun . 2021 Nov 1;4:100131. doi: 10.1016/j.jtauto.2021.100131. eCollection 2021. Intrinsic factor autoantibodies by luminescent immuno-precipitation system in patients with corpus atrophic gastritis Ilaria Marzinotto et al

Data related to manuscript "HNF4α, SP1 and c-myc are master regulators of CNS autoimmunity" by Colombo et al, J Autoimmun. 2023 Jul;138:103053. doi: 10.1016/j.jaut.2023.103053.

In the manuscript "Tolerogenic IL-10-engineered dendritic cell-based therapy to restore antigen-specific tolerance in T cell mediated diseases" published in Journal of Autoimmunity on May 22 2023 (doi: 10.1016/j.jaut.2023.103051). We describe the in vitro generation of dendritic cells genetically modified to render them pro-tolerogenic and able to modulate unwanted immune responses to auto-antigens both in vitro and in vivo. Raw data for each main figure published in the manuscript are available in the relative.csv file. Read the Read_me.rtf file for more details and for the accession numbers of NGS data deposited at GEO.

Database for patients included in the prospective phase 2 study PSMA-RGS (GR2018-12368369). Data dictionary is included in the name of the variables and the coding is separated by an underscore. Enclosed you can also find a CSV file with the coding.

Irisin is a circulating myokine released from skeletal muscles after physical exercise. Irisin production decreases during the course of chronic kidney disease (CKD) as a potential consequence of sarcopenia and physical inactivity. In the light of the potential role of irisin in cardiovascular disease of CKD patients, we studied the relationship of serum irisin with cardiovascular risk in a sample of patients at different stages of CKD not undergoing dialysis (n=79). Our findings suggest that serum irisin may be a marker of cardiovascular outcome in CKD patients. doi: 10.1053/j.jrn.2021.05.007 PMID: 34294556

The dataset includes 172 subjects for a total of 519 fetal rs-fMRI scans with respective brain segmentations. Brain segmentations were obtained with the RS-FetMRI package (https://github.com/NicoloPecco/RS-FetMRI). For each subject the gestational week at scan is reported as the last two digits of the file name. The RF-2016-02364081 DL dataset has been used to train and test deep learning architectures (i.e. Swin-UNETR, UNTER, CNN, GAN) on a fetal brain extraction task for the study titled ‘Optimizing performance of transformer-based models for fetal brain MR image segmentation’. Pretrain weights of Swin-UNETR best model can be found on the ‘weight’ folder (Fetal_pretrain.pth).