Geohazard features of the north-western Sicily and Pantelleria

9 pages, 3 figures, supplemental material https://doi.org/10.1080/17445647.2024.2342931.-- Data availability statement: Department of Earth and Marine Science of the University of Palermo for institutional purposes, so their access will be available by contacting the reference people (attilio.sulliunipa.it) upon reasonable requestWe present maps of geohazard features identified across north-western Sicily and Pantelleria in the framework of the Magic project (MArine Geohazard along Italian Coasts), which involved Italian marine geological researchers in 2007-2013. These seafloor features were recognized using high-resolution bathymetry data and rely on the morphological expression of the seafloor and shallow sub-surface processes. The north-western Sicily is a complex continental margin, affected by morphodynamic, depositional, and tectonic processes. The Egadi offshore is controlled by fault escarpments and alternating retreating and progradational processes. Ustica and Pantelleria submerged edifices show the effect of volcanic activity. The Ustica seafloor is interested in volcanic, tectonic, and gravitational instability processes, while the Pantelleria offshore underwent erosive-depositional processes and the effect of bottom currents. Two levels of interpretation are represented: the physiographic domain at a scale of 1:250.000 and the morphological units and morpho-bathymetric elements at a 1:100.000 scaleThe Magic Project has been funded by the Italian Civil Protection Department. [...] With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)Peer reviewe

Metastatic group 3 medulloblastoma is driven by PRUNE1 targeting NME1-TGF-β-OTX2-SNAIL via PTEN inhibition.

Genetic modifications during development of paediatric groups 3 and 4 medulloblastoma are responsible for their highly metastatic properties and poor patient survival rates. PRUNE1 is highly expressed in metastatic medulloblastoma group 3, which is characterized by TGF-β signalling activation, c-MYC amplification, and OTX2 expression. We describe the process of activation of the PRUNE1 signalling pathway that includes its binding to NME1, TGF-β activation, OTX2 upregulation, SNAIL (SNAI1) upregulation, and PTEN inhibition. The newly identified small molecule pyrimido-pyrimidine derivative AA7.1 enhances PRUNE1 degradation, inhibits this activation network, and augments PTEN expression. Both AA7.1 and a competitive permeable peptide that impairs PRUNE1/NME1 complex formation, impair tumour growth and metastatic dissemination in orthotopic xenograft models with a metastatic medulloblastoma group 3 cell line (D425-Med cells). Using whole exome sequencing technology in metastatic medulloblastoma primary tumour cells, we also define 23 common 'non-synonymous homozygous' deleterious gene variants as part of the protein molecular network of relevance for metastatic processes. This PRUNE1/TGF-β/OTX2/PTEN axis, together with the medulloblastoma-driver mutations, is of relevance for future rational and targeted therapies for metastatic medulloblastoma group 3

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5-11 December, to 17.5% (25/143 samples) in the week 12-18, to 65.9% (89/135 samples) in the week 19-25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased from one in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons. In conclusion, we designed an RT-qPCR assay capable to detect the Omicron variant, which can be successfully used for the purpose of wastewater-based epidemiology. We also described the history of the introduction and diffusion of the Omicron variant in the Italian population and territory, confirming the effectiveness of sewage monitoring as a powerful surveillance tool

The metastasis suppressor protein NM23-H1 interacts with PI3K catalytic subunit p110α and impairs PI3K-Akt axis

This thesis documents a novel interaction between the catalytic subunit of PI3K class I subunit alpha p110α (PI3KCA) and the anti-metastatic protein NM23-H1 (NDPKA) and analyzes the functional consequences of this interaction. A yeast two hybrid screening of a cDNA library derived from an immortalized lymphoblastoid cell line (LCL) using NM23-H1 as “bait”, identified the PI3K Class I catalytic subunit p110α (PI3KCA) as a strong binding partner. The interaction was validated by GST pull down and two-way co-immunoprecipitation experiments. Among the various components that regulate PI3K signalling, class I p110α is associated with neoplastic progression because it is frequently mutated or overexpressed in different types of tumors. NM23-H1 is a well characterized protein with different enzymatic activities (nucleoside diphosphate kinase, protein histidine kinase, serine/threonine protein kinase, 3'-5' exonuclease) and with metastasis suppressor activity in different tumors. Loss of function NM23-H1 mutants, which determine the Killer of Prune phenotype in Drosophila, abrogate completely the anti-metastatic activity and do not interact with PI3K p110α. HEK293T, MDA-MB435 and MDA-MB231 cell lines stably expressing NM23H1 inhibit Akt phosphorylation induced by the Epidermal growth factor (EGF). Under the same conditions NM23-H1 protein mutants fail to inhibit EGF-induced AKT phosphorylation. NM23H1 knockdown in HEK293T cell lines stimulates Akt phosphorylation. The main functional consequence of NM23 and p110α interaction is the inhibition of cell motility and clonogenic potential. In fact, in MDA-MB435 cells expressing p110α, wild type NM23H1, not the mutants, counteracts the enhancement of motility, invasion, adhesion, and the formation of filopodia (cell motility structures) induced by expression of p110α. These results provide a new mechanism that explains the NM23-H1anti-metastatic properties during cancer progression and pave the way to a novel translational perspective

Geohazard features of the north-western Sicily and Pantelleria

We present maps of geohazard features identified across north-western Sicily and Pantelleria in the framework of the Magic project (MArine Geohazard along Italian Coasts), which involved Italian marine geological researchers in 2007-2013. These seafloor features were recognized using high-resolution bathymetry data and rely on the morphological expression of the seafloor and shallow sub-surface processes. The north-western Sicily is a complex continental margin, affected by morphodynamic, depositional, and tectonic processes. The Egadi offshore is controlled by fault escarpments and alternating retreating and progradational processes. Ustica and Pantelleria submerged edifices show the effect of volcanic activity. The Ustica seafloor is interested in volcanic, tectonic, and gravitational instability processes, while the Pantelleria offshore underwent erosive-depositional processes and the effect of bottom currents. Two levels of interpretation are represented: the physiographic domain at a scale of 1:250.000 and the morphological units and morpho-bathymetric elements at a 1:100.000 scale.</p

Metastatic group 3 medulloblastoma is driven by PRUNE1 targeting NME1-TGF-β-OTX2-SNAIL via PTEN inhibition

Genetic modifications during development of paediatric groups 3 and 4 medulloblastoma are responsible for their highly metastatic properties and poor patient survival rates. PRUNE1 is highly expressed in metastatic medulloblastoma group 3, which is characterized by TGF-β signalling activation, c-MYC amplification, and OTX2 expression. We describe the process of activation of the PRUNE1 signalling pathway that includes its binding to NME1, TGF-β activation, OTX2 upregulation, SNAIL (SNAI1) upregulation, and PTEN inhibition. The newly identified small molecule pyrimido-pyrimidine derivative AA7.1 enhances PRUNE1 degradation, inhibits this activation network, and augments PTEN expression. Both AA7.1 and a competitive permeable peptide that impairs PRUNE1/NME1 complex formation, impair tumour growth and metastatic dissemination in orthotopic xenograft models with a metastatic medulloblastoma group 3 cell line (D425-Med cells). Using whole exome sequencing technology in metastatic medulloblastoma primary tumour cells, we also define 23 common 'non-synonymous homozygous' deleterious gene variants as part of the protein molecular network of relevance for metastatic processes. This PRUNE1/TGF-β/OTX2/PTEN axis, together with the medulloblastoma-driver mutations, is of relevance for future rational and targeted therapies for metastatic medulloblastoma group 3.Genetic modifications during development of paediatric groups 3 and 4 medulloblastoma are responsible for their highly metastatic properties and poor patient survival rates. PRUNE1 is highly expressed in metastatic medulloblastoma group 3, which is characterized by TGF-β signalling activation, c-MYC amplification, and OTX2 expression. We describe the process of activation of the PRUNE1 signalling pathway that includes its binding to NME1, TGF-β activation, OTX2 upregulation, SNAIL (SNAI1) upregulation, and PTEN inhibition. The newly identified small molecule pyrimido-pyrimidine derivative AA7.1 enhances PRUNE1 degradation, inhibits this activation network, and augments PTEN expression. Both AA7.1 and a competitive permeable peptide that impairs PRUNE1/NME1 complex formation, impair tumour growth and metastatic dissemination in orthotopic xenograft models with a metastatic medulloblastoma group 3 cell line (D425-Med cells). Using whole exome sequencing technology in metastatic medulloblastoma primary tumour cells, we also define 23 common 'non-synonymous homozygous' deleterious gene variants as part of the protein molecular network of relevance for metastatic processes. This PRUNE1/TGF-β/OTX2/PTEN axis, together with the medulloblastoma-driver mutations, is of relevance for future rational and targeted therapies for metastatic medulloblastoma group 3. 10.1093/brain/awy039-video1 awy039media1 574205353400

COVID-19: opinions and behavior of Italian general population during the first epidemic phase

On January 9, 2020, the World Health Organization (WHO) declared that Chinese health authorities had identified a new coronavirus strain never before isolated in humans, the 2019-nCoV later redefined SARS-CoV-2, that still today represent a public health problem. The present survey started on 10 February 2020 with the aim of a) assessing the risk perception in healthcare workers and young students, following the evolution of attitudes, perception and knowledge over time, b) provide useful information to the general population during survey

COVID-19: opinions and behavior of Italian general population during the first epidemic phase

Background and aim: On January 9, 2020, the World Health Organization (WHO) declared that Chinese health authorities had identified a new coronavirus strain never before isolated in humans, the 2019-nCoV later redefined SARS-CoV-2, that still today represent a public health problem. The present survey started on 10 February 2020 with the aim of a) assessing the risk perception in healthcare workers and young students, following the evolution of attitudes, perception and knowledge over time, b) provide useful information to the general population during survey. Results: A study sample consisting of 4116 Italian individuals of both sexes was enrolled. High levels of risk perception, low perception of self-efficacy and low levels of knowledge scores (24.55 ± 5.76 SD) were obtained indicating the need for continuous population monitoring as well as further communication strategies carried out at institution levels. Conclusion: The results of the present study could help public health authorities in carrying out informative campaigns for general population and could be an important tool in evaluating public knowledge and misperceptions during the management of the COVID-19. (www.actabiomedica.it)

Metastatic group 3 medulloblastoma is driven by PRUNE1 targeting NME1–TGF-β–OTX2–SNAIL via PTEN inhibition

Genetic modifications during development of paediatric groups 3 and 4 medulloblastoma are responsible for their highly metastatic properties and poor patient survival rates. PRUNE1 is highly expressed in metastatic medulloblastoma group 3, which is characterized by TGF-β signalling activation, c-MYC amplification, and OTX2 expression. We describe the process of activation of the PRUNE1 signalling pathway that includes its binding to NME1, TGF-β activation, OTX2 upregulation, SNAIL (SNAI1) upregulation, and PTEN inhibition. The newly identified small molecule pyrimido-pyrimidine derivative AA7.1 enhances PRUNE1 degradation, inhibits this activation network, and augments PTEN expression. Both AA7.1 and a competitive permeable peptide that impairs PRUNE1/NME1 complex formation, impair tumour growth and metastatic dissemination in orthotopic xenograft models with a metastatic medulloblastoma group 3 cell line (D425-Med cells). Using whole exome sequencing technology in metastatic medulloblastoma primary tumour cells, we also define 23 common 'non-synonymous homozygous' deleterious gene variants as part of the protein molecular network of relevance for metastatic processes. This PRUNE1/TGF-β/OTX2/PTEN axis, together with the medulloblastoma-driver mutations, is of relevance for future rational and targeted therapies for metastatic medulloblastoma group 3