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San Raffaele Open Research Data Repository

IRCCS San Raffaele Scientific Institute Showcase

San Raffaele Open Research Data Repository (ORDR) is an institutional platform which allows to store preserve and share research data. ORDR is powered by the Digital Commons Data repository platform.

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  • A functional interaction between liprin-alpha1 and B56gamma regulatory subunit of protein phosphatase 2A supports tumor cell motility
    PLEASE REFER TO THE PUBLICATION: Journal: Communications Biology. DOI : 10.1038/s42003-022-03989-3 Title : A functional interaction between liprin-α1 and B56γ regulatory subunit of protein phosphatase 2A supports tumor cell motility. Scaffold liprin-alpha1 is required to assemble dynamic plasma membrane-associated platforms (PMAPs) at the front of migrating breast cancer cells, to promote protrusion and invasion. We show that the N-terminal region of liprin-alpha1 contains an LxxIxE motif interacting with B56 regulatory subunits of serine/threonine protein phosphatase 2A (PP2A). The specific interaction of B56gamma with liprin-alpha1 requires an intact motif, since two point mutations strongly reduce the interaction. B56gamma mediates the interaction of liprin-alpha1 with the heterotrimeric PP2A holoenzyme. Most B56gamma protein is recovered in the cytosolic fraction of invasive MDA-MB-231 breast cancer cells, where B56gamma is complexed with liprin-alpha1. While mutation of the short linear motif (SLiM) does not affect localization of liprin-alpha1 to PMAPs, localization of B56gamma at these sites specifically requires liprin-alpha1. Silencing of B56gamma or liprin-alpha1 inhibits to similar extent cell spreading on extracellular matrix, invasion, motility and lamellipodia dynamics in migrating MDA-MB-231 cells, suggesting that B56gamma-PP2A is a novel component of the PMAPs machinery regulating tumor cell motility. In this direction, inhibition of cell spreading by silencing liprin-alpha1 is not rescued by expression of B56gamma binding-defective liprin-alpha1 mutant. We propose that liprin-alpha1-mediated recruitment of PP2A via B56gamma regulates cell motility by controlling protrusion in migrating MDA-MB-231 cells.
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  • Unconventional platelet activation in COVID-19 (DOI 10.1111/jth.15575)
    FILE "patients and controls data" correspond to the row data of patients and controls (figures 1 and 2 and tables 1-3) FILE "in vitro exp" correspond to the row data of in vitro experiments (figures 3, 4 and 5)
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  • Therapeutic advantages of combined gene/cell therapy strategies in a murine model of GM2 gangliosidosis
    Genetic deficiency of β-N-acetylhexosaminidase (Hex) functionality leads to accumulation of GM2 ganglioside in Tay-Sachs disease and Sandhoff disease (SD), which presently lack approved therapies. Current experimental gene therapy (GT) approaches with adeno-associated viral vectors (AAVs) still pose safety and efficacy issues, supporting the search for alternative therapeutic strategies. Here we leveraged the lentiviral vector (LV)-mediated intracerebral (IC) GT platform to deliver Hex genes to the CNS and combined this strategy with bone marrow transplantation (BMT) to provide a timely, pervasive, and long-lasting source of the Hex enzyme in the CNS and periphery of SD mice. Combined therapy outperformed individual treatments in terms of lifespan extension and normalization of the neuroinflammatory/neurodegenerative phenotypes of SD mice. These benefits correlated with a time-dependent increase in Hex activity and a remarkable reduction in GM2 storage in brain tissues that single treatments failed to achieve. Our results highlight the synergic mode of action of LV-mediated IC GT and BMT, clarify the contribution of treatments to the therapeutic outcome, and inform on the realistic threshold of corrective enzymatic activity. These results have important implications for interpretation of ongoing experimental therapies and for design of more effective treatment strategies for GM2 gangliosidosis.
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  • Microglia-specific overexpression of α-synuclein leads to severe dopaminergic neurodegeneration by phagocytic exhaustion and oxidative toxicity
    Recent findings in human samples and animal models support the involvement of inflammation in the development of Parkinson’s disease. Nevertheless, it is currently unknown whether microglial activation constitutes a primary event in neurodegeneration. We generated a new mouse model by lentiviral-mediated selective α-synuclein (αSYN) accumulation in microglial cells. Surprisingly, these mice developed progressive degeneration of dopaminergic (DA) neurons without endogenous αSYN aggregation. Transcriptomics and functional assessment revealed that αSYN-accumulating microglial cells developed a strong reactive state with phagocytic exhaustion and excessive production of oxidative and proinflammatory molecules. This inflammatory state created a molecular feed-forward vicious cycle between microglia and IFNγ-secreting immune cells infiltrating the brain parenchyma. Pharmacological inhibition of oxidative and nitrosative molecule production was sufficient to attenuate neurodegeneration. These results suggest that αSYN accumulation in microglia induces selective DA neuronal degeneration by promoting phagocytic exhaustion, an excessively toxic environment and the selective recruitment of peripheral immune cells.
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  • Deletion of a pseudogene within a fragile site triggers the oncogenic expression of the mitotic CCSER1 gene
    Paper published (10.26508/lsa.202101019)
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  • R Status is a Relevant Prognostic Factor for Recurrence and Survival After Pancreatic Head Resection for Ductal Adenocarcinoma
    Data refer to the paper doi: 10.1245/s10434-020-09467-6 Data were collected in a prospective database maintained at the Division of Pancreatic Surgery, San Raffaele Scientific Institute, Milan, Italy. Patients with a histologic diagnosis of PDAC in the head of the pancreas who underwent pancreatoduodenectomy or total pancreatectomy were eligible for the study. Only patients with a minimum follow-up period of 12 months were included unless they had died within 1 year after surgery because of tumor recurrence
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  • Long-Term Survivors after Upfront Resection for Pancreatic Ductal Adenocarcinoma: An Actual 5-Year Analysis of Disease-Specific and Post-Recurrence Survival
    Data refer to the paper doi: 10.1245/s10434-021-10401-7 Data refer to patients who underwent upfront surgical resection for pancreatic ductal adenocarcinoma between 2009 and 2014
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  • The role of acinar content at pancreatic resection margin in the development of postoperative pancreatic fistula and acute pancreatitis after pancreaticoduodenectomy
    Data refer to the paper doi: 10.1016/j.surg.2021.03.047 Data from 388 consecutive patients who underwent pancreaticoduodenectomy in the period 2018–2019. Pancreatic section margins were histologically assessed for acinar, fibrosis, and fat content.
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  • ACHIEVING VIROLOGICAL CONTROL IN PAN-RESISTANT HIV-1 INFECTION: A CASE SERIES
    We report findings from heavily treatment-experienced PLWH with a pan-resistant HIV-1 infection, who achieved virological control once introduced injections of ibalizumab, that is free from cross-resistance with all the antiretroviral drugs available and ensures patient adherence due to a close monitoring attributable to the route of administration, combined with recycled enfuvirtide and an optimized background regimen, selected on the basis of an accurate evaluation of resistance mutations. Please refer to DOI: https://doi.org/10.1016/j.ebiom.2022.103906
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  • data for "Integration of clinical and multi-omics multiple sclerosis data into a predictive algorithm of disease activity to accelerate personalized medicine" (GR-2016-02363997)
    Data refer to the results obtained within the GR-2016-02363997 project funded by the Italian Ministry of Health. Main aim was to combine clinical data with genetic variants, transcriptomic and T lymphocyte repertoires signatures to dissect the biological basis of multiple sclerosis (MS) inflammatory activity. Two sets of patients were analysed: i) Extended cohort, for the identification of genetic biomarkers, ii) Core Cohort, for the identification of genetic, transcriptomic and immune repertoires biomarkers. Each patient was classified according to the NEDA (No Evidence of Disease Activity) criterion at 4- year follow-up, while time to first relapse (TTFR) was considered as secondary outcome. Data includes: - Results: GR-2016-02363997_results.pdf - uploaded documents.pdf - Genetic data: GEN_top_SNPs_geno.ped; GEN_top_SNPs_geno.map; GEN_var.txt; GEN_gene-wise.txt - Transcriptomic data: EXPR_topRNA_CPM.txt; EXPR_var.txt - Immunosequencing data: IMMSEQ_diversity.txt; IMMSEQ_trbd.txt; IMMSEQ_trbj.txt; IMMSEQ_trbv.txt; IMMSEQ_var.txt
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