Quantitative analysis of extensional joints in the southern Adriatic foreland (Italy), and the active tectonics of the Apulia region

The Adriatic foreland of the Apennines comes ashore only in Apulia (easternmost Italy). Its southern part, our study area, lacks any structural analysis devoted to define its recent-to-active tectonics. Throughout the Quaternary, this region was affected by mild brittle deformation with rare faults, characterized by small displacement, and widespread extension joints, frequently organized in sets. Therefore, we conducted a quantitative and systematic analysis of the joint sets affecting Quaternary deposits, by applying an inversion technique ad hoc to infer the orientation and ratio of the principal stress axes, R = (σ2 - σ3)/(σ1 - σ3). Within a general extensional regime, we recognized three deformational events of regional significance. The oldest event, constrained to the early and middle part of the Middle Pleistocene, is characterized by variable direction of extension and R between 0.64-0.99. The penultimate event, dated late Middle Pleistocene, is characterized by an almost uniaxial tension, with a horizontal σ3 striking ~N43°E; R is high, between 0.85-0.99. The most recent event is characterized by the lowermost R values, that never exceed 0.47 and are frequently <0.30, indicating a sort of horizontal „radial‟ extension. This event is not older than the Late Pleistocene and possibly reflects the active stress field still dominating the entire study area

Quantitative analysis of extensional joints in the southern Adriatic foreland (Italy), and the active tectonics of the Apulia region

The Adriatic foreland of the Apennines comes ashore only in Apulia (easternmost Italy). Its southern part, our study area, lacks any structural analysis devoted to define its recent-to-active tectonics. Throughout the Quaternary, this region was affected by mild brittle deformation with rare faults, characterized by small displacement, and widespread extension joints, frequently organized in sets. Therefore, we conducted a quantitative and systematic analysis of the joint sets affecting Quaternary deposits, by applying an inversion technique ad hoc to infer the orientation and ratio of the principal stress axes, R = (σ2 − σ3)/(σ1 − σ3). Within a general extensional regime, we recognized three deformational events of regional significance. The oldest event, constrained to the early and middle part of the Middle Pleistocene, is characterized by variable direction of extension and R between 0.64 and 0.99. The penultimate event, dated late Middle Pleistocene, is characterized by an almost uniaxial tension, with a horizontal σ3 striking ∼N43°E; R is high, between 0.85 and 0.99. The most recent event is characterized by the lowermost R values, that never exceed 0.47 and are frequently <0.30, indicating a sort of horizontal ‘radial’ extension. This event is not older than the Late Pleistocene and possibly reflects the active stress field still dominating the entire study area

Canonical and noncanonical roles of Fanconi anemia proteins: Implications in cancer predisposition

Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder characterized by the variable presence of congenital somatic abnormalities, bone marrow failure (BMF), and a predisposition to develop cancer. Monoallelic germline mutations in at least five genes involved in the FA pathway are associated with the development of sporadic hematological and solid malignancies. The key function of the FA pathway is to orchestrate proteins involved in the repair of interstrand cross-links (ICLs), to prevent genomic instability and replication stress. Recently, many studies have highlighted the importance of FA genes in noncanonical pathways, such as mitochondria homeostasis, inflammation, and virophagy, which act, in some cases, independently of DNA repair processes. Thus, primary defects in DNA repair mechanisms of FA patients are typically exacerbated by an impairment of other cytoprotective pathways that contribute to the multifaceted clinical phenotype of this disease. In this review, we summarize recent advances in the understanding of the pathogenesis of FA, with a focus on the cytosolic noncanonical roles of FA genes, discussing how they may contribute to cancer development, thus suggesting opportunities to envisage novel therapeutic approaches

Gata2 related conditions and predisposition to pediatric myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are hematopoietic disorders rare in childhood, often occurring in patients with inherited bone marrow failure syndromes or germinal predisposition syndromes. Among the latter, one of the most frequent involves the gene GATA binding protein 2 (GATA2), coding for a transcriptional regulator of hematopoiesis. The genetic lesion as well as the clinical phenotype are extremely variable; many patients present hematological malignancies, especially MDS with the possibility to evolve into acute myeloid leukemia. Variable immune dysfunction, especially resulting in B-and NK-cell lymphopenia, lead to severe infections, including generalized warts and mycobacterial infection. Defects of alveolar macrophages lead to pulmonary alveolar proteinosis through inadequate clearance of surfactant proteins. Currently, there are no clear guidelines for the monitoring and treatment of patients with GATA2 mutations. In patients with MDS, the only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT) that restores normal hematopoiesis preventing the progression to acute myeloid leukemia and clears long-standing infections. However, to date, the donor type, conditioning regimen, and the optimal time to proceed to HSCT, as well as the level of chimerism needed to reverse the phenotype, remain unclear highlighting the need for consensus guidelines

Integration of multiple platforms for the analysis of multifluorescent marking technology applied to pediatric GBM and dipg

The intratumor heterogeneity represents one of the most difficult challenges for the development of effective therapies to treat pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG). These brain tumors are composed of heterogeneous cell subpopulations that coexist and cooperate to build a functional network responsible for their aggressive phenotype. Understanding the cellular and molecular mechanisms sustaining such network will be crucial for the identification of new therapeutic strategies. To study more in-depth these mechanisms, we sought to apply the Multifluorescent Marking Technology. We generated multifluorescent pGBM and DIPG bulk cell lines randomly expressing six different fluorescent proteins and from which we derived stable optical barcoded single cell-derived clones. In this study, we focused on the application of the Multifluorescent Marking Technology in 2D and 3D in vitro/ex vivo culture systems. We discuss how we integrated different multimodal fluorescence analysis platforms, identifying their strengths and limitations, to establish the tools that will enable further studies on the intratumor heterogeneity and interclonal interactions in pGBM and DIPG

Expanding the spectrum of EWSR1-PATZ1 rearranged CNS tumors: An infantile case with leptomeningeal dissemination

We report on a case of EWSR1-PATZ1 rearranged brain tumor occurring in a 17 month-old child, originally interpreted as an infantile glioblastoma. Our case shows important analogies with the 2 previously reported cases, including the intraventricular location, the histologic appearance (pushing borders, oligodendrocyte-like morphology, rich vascular network) and the glioneural immunophenotype, supporting the role of these features as relevant clues to the diagnosis. On the other hand, our case displays unique characteristics, i.e. the onset in an infant, the presence of a focal high-grade component and the leptomeningeal dissemination, pointing to the importance of considering this entity in the differential diagnosis of an infantile glial/glioneural tumor

Tidal notches in Mediterranean Sea: a comprehensive analysis

Recent works (Evelpidou et al., 2012) suggest that the modern tidal notch is disappearing worldwide due sea level rise over the last century. In order to assess this hypothesis, we measured modern tidal notches in several of sites along the Mediterranean coasts. We report observations on tidal notches cut along carbonate coasts from 73 sites from Italy, France, Croatia, Montenegro, Greece, Malta and Spain, plus additional observations carried outside the Mediterranean. At each site, we measured notch width and depth, and we described the characteristics of the biological rim at the base of the notch. We correlated these parameters with wave energy, tide gauge datasets and rock lithology. Our results suggest that, considering \u2018the development of tidal notches the consequence of midlittoral bioerosion\u2019 (as done in Evelpidou et al., 2012) is a simplification that can lead to misleading results, such as stating that notches are disappearing. Important roles in notch formation can be also played by wave action, rate of karst dissolution, salt weathering and wetting and drying cycles. Of course notch formation can be augmented and favoured also by bioerosion which can, in particular cases, be the main process of notch formation and development. Our dataset shows that notches are carved by an ensemble rather than by a single process, both today and in the past, and that it is difficult, if not impossible, to disentangle them and establish which one is prevailing. We therefore show that tidal notches are still forming, challenging the hypothesis that sea level rise has drowned them