Analisi dei cambiamenti di uso del suolo nell’area montuosa e collinare dell’Emilia-Romagna nel periodo 1954-1994

Lo scopo di questo studio è stato la realizzazione di una banca dati multitemporale di uso del suolo per i territori montuosi e collinari della Regione Emilia-Romagna, relativa al periodo 1954-1994. Tale banca dati riporta gli attributi relativi all’uso del suolo del 1954-55 e 1994 e consente di analizzare i cambiamenti di estensione, tipologia e localizzazione delle classi di uso del suolo. I dati più recenti sono quelli relativi alla banca dati vettoriale di uso del suolo del 1994 già pubblicata dalla Regione Emilia-Romagna. I dati del 1954 sono stati ottenuti dall’interpretazione e delineazione visuale di ortofoto ottenute da foto aeree pancromatiche del volo G.A.I. del 1954- 1955. È stata utilizzata una nomenclatura di uso del suolo a priori gerarchica a due livelli comparabile con quella della banca dati del 1994. I risultati dimostrano che in quaranta anni, l’area indagata ha subito una significativa evoluzione di uso del suolo. Le aree a seminativo ed a foresta sono aumentate, a scapito delle aree a coltivazione parcellizzata e specializzata e di cespuglieto

Hypoxia shapes autophagy in LPS-activated dendritic cells

During their lifespan, dendritic cells (DCs) are exposed to different pO2 levels that affect their differentiation and functions. Autophagy is one of the adaptive responses to hypoxia with important implications for cell survival. While the autophagic machinery in DCs was shown to impact signaling of TLRs, its regulation by the MD-2/TLR4 ligand LPS is still unclear. The aim of this study was to evaluate whether LPS can induce autophagy in DCs exposed to either aerobic or hypoxic conditions. Using human monocyte-derived DCs and the combination of immunofluorescence confocal analysis, measure of mitochondrial membrane potential, Western blotting, and RT-qPCR, we showed that the ability of LPS to modulate autophagy was strictly dependent upon pO2 levels. Indeed, LPS inhibited autophagy in aerobic conditions whereas the autophagic process was induced in a hypoxic environment. Under hypoxia, LPS treatment caused a significant increase of functional lysosomes, LC3B and Atg protein upregulation, and reduction of SQSTM1/p62 protein levels. This selective regulation was accompanied by activation of signalling pathways and expression of cytokines typically associated with DC survival. Bafilomycin A1 and chloroquine, which are recognized as autophagic inhibitors, confirmed the induction of autophagy by LPS under hypoxia and its impact on DC survival. In conclusion, our results show that autophagy represents one of the mechanisms by which the activation of the MD-2/TLR4 ligand LPS promotes DC survival under hypoxic conditions

The Activity of Special Continuity Care Units in the City of Florence During the COVID-19 Pandemic

Objectives: Worldwide, countries adopted different strategies in primary care (PC) to cope with the COVID-19 pandemic. This study aims to describe and evaluate the functions and activity load of a specific PC organizational model called “Special Continuity Care Units” (SCCU) in Florence, Italy, and to investigate the characteristics of the COVID-19 patients assisted by the service.Methods: The retrospective cross-sectional design used daily updated reports by SCCU team members to evaluate the activity load. The retrospective cohort study analyzed data of the demographics, clinical characteristics, and process outcomes of patients assisted during the second pandemic wave.Results: The analysis shows how the service activity load changed along with the epidemiological trend. Regarding people assisted by the SCCU, the median follow-up duration of symptoms was 6 days; male gender and being symptomatic were predictors of hospitalization.Conclusion: Some key characteristics can be described as indispensable in PC services facing health emergencies: model flexibility, the availability of resources, networking among services to enhance coordination and resource optimization, and close collaboration with general practitioners

Hypoxia enhances the expression of RNASET2 in human monocyte-derived dendritic cells: Role of PI3K/AKT pathway

Hypoxia is a key component of the tumor microenvironment (TME) and promotes not only tumor growth and metastasis, but also negatively affects infiltrating immune cells by impairing host immunity. Dendritic cells (DCs) are the most potent antigen-presenting cells and their biology is weakened in the TME in many ways, including the modulation of their viability. RNASET2 belongs to the T2 family of extracellular ribonucleases and, besides its nuclease activity, it exerts many additional functions. Indeed, RNASET2 is involved in several human pathologies, including cancer, and it is functionally relevant in the TME. RNASET2 functions are not restricted to cancer cells and its expression could be relevant also in other cell types which are important players in the TME, including DCs. Therefore, this study aimed to unravel the effect of hypoxia (2% O2) on the expression of RNASET2 in DCs. Here, we showed that hypoxia enhanced the expression and secretion of RNASET2 in human monocyte-derived DCs. This paralleled the HIF-1α accumulation and HIF-dependent and-independent signaling, which are associated with DCs’ survival/autophagy/apoptosis. RNASET2 expression, under hypoxia, was regulated by the PI3K/AKT pathway and was almost completely abolished by TLR4 ligand, LPS. Taken together, these results highlight how hypoxia-dependent and-independent pathways shape RNASET2 expression in DCs, with new perspectives on its implication for TME and, therefore, in anti-tumor immunity

Inhibition of melanoma cell migration and invasion targeting the hypoxic tumor associated caxii

Background: Intratumoral hypoxia contributes to cancer progression and poor prognosis. Carbonic anhydrases IX (CAIX) and XII (CAXII) play pivotal roles in tumor cell adaptation and survival, as aberrant Hedgehog (Hh) pathway does. In malignant melanoma both features have been investigated for years, but they have not been correlated before and/or identified as a potential pharmacological target. Here, for the first time, we demonstrated that malignant melanoma cell motility was impaired by targeting CAXII via either CAs inhibitors or through the inhibition of the Hh pathway. Methods: We tested cell motility in three melanoma cell lines (WM-35, SK-MEL28, and A375), with different invasiveness capabilities. To this end we performed a scratch assay in the presence of the smoothened (SMO) antagonist cyclopamine (cyclo) or CAs inhibitors under normoxia or hypoxia. Then, we analyzed the invasiveness potential in the cell lines which were more affected by cyclo and CAs inhibitors (SK-MEL28 and A375). Western blot was employed to assess the expression of the hypoxia inducible factor 1α, CAXII, and FAK phosphorylation. Immunofluorescence staining was performed to verify the blockade of CAXII expression. Results: Hh inhibition reduced melanoma cell migration and CAXII expression under both normoxic and hypoxic conditions. Interestingly, basal CAXII expression was higher in the two more aggressive melanoma cell lines. Finally, a direct CAXII blockade impaired melanoma cell migration and invasion under hypoxia. This was associated with a decrease of FAK phosphorylation and metalloprotease activities. Conclusions: CAXII may be used as a target for melanoma treatment not only through its direct inhibition, but also through Hh blockade

Role of the Hedgehog Pathway and CAXII in Controlling Melanoma Cell Migration and Invasion in Hypoxia

Simple Summary Malignant melanoma is the leading cause of death among skin cancer patients due to its tendency to metastasize. Hypoxia, which is a common feature of the tumor microenvironment, as well as different alterations at the molecular level, may affect melanoma aggressiveness. The aims and the objectives of this work were to investigate whether and how the Hedgehog pathway and CAXII may control malignant melanoma cell migration and invasiveness either in normoxic or hypoxic conditions. To this end we evaluated the migratory and invasive capabilities of SK-MEL-28 and A375 cell lines, where the hedgehog pathways and CAXII were inhibited by short interfering RNA. Our results indicate that SMO and GLI1 silencing caused the downregulation of CAXII expression. Furthermore, the Hedgehog pathway and CAXII inhibition, resulted in impaired melanoma cell migration and invasion either under normoxic or hypoxic conditions. The fact that CAXII and the Hedgehog pathway are relevant in melanoma cell invasion may be exploited to discover novel and promising therapeutical targets for melanoma clinical management. Background: Malignant melanoma is the leading cause of death among skin cancer patients due to its tendency to metastasize. Alterations at the molecular level are often evident, which is why melanoma biology has garnered increasing interest. The hedgehog (Hh) pathway, which is essential for embryonic development, is aberrantly re-activated in melanoma and may represent a promising therapeutic target. In addition, carbonic anhydrase XII (CAXII) represents a poor prognostic target for hypoxic tumors, such as melanoma, and is involved in cell migration. Thus, we decided to investigate whether and how the Hh pathway and CAXII may control melanoma cell migration and invasiveness. Methods: The migratory and invasive capabilities of SK-MEL-28 and A375 cell lines, either un-transfected or transiently transfected with Smoothened (SMO), GLI1, or CAXII siRNA, were studied under normoxic or hypoxic conditions. Results: For the first time, we showed that SMO and GLI1 silencing resulted in the downregulation of CAXII expression in both moderately and highly invasive melanoma cells under hypoxia. The Hh pathway as well as CAXII inhibition by siRNA resulted in impaired malignant melanoma migration and invasion. Conclusion: Our results suggest that CAXII and the Hh pathway are relevant in melanoma invasion and may be novel and promising therapeutical targets for melanoma clinical management

Hypoxia enhances the expression of RNASET2 in human monocyte-derived dendritic cells: Role of PI3K/AKT pathway

Hypoxia is a key component of the tumor microenvironment (TME) and promotes not only tumor growth and metastasis, but also negatively affects infiltrating immune cells by impairing host immunity. Dendritic cells (DCs) are the most potent antigen-presenting cells and their biology is weakened in the TME in many ways, including the modulation of their viability. RNASET2 belongs to the T2 family of extracellular ribonucleases and, besides its nuclease activity, it exerts many additional functions. Indeed, RNASET2 is involved in several human pathologies, including cancer, and it is functionally relevant in the TME. RNASET2 functions are not restricted to cancer cells and its expression could be relevant also in other cell types which are important players in the TME, including DCs. Therefore, this study aimed to unravel the effect of hypoxia (2% O2) on the expression of RNASET2 in DCs. Here, we showed that hypoxia enhanced the expression and secretion of RNASET2 in human monocyte-derived DCs. This paralleled the HIF-1\u3b1 accumulation and HIF-dependent and-independent signaling, which are associated with DCs\u2019 survival/autophagy/apoptosis. RNASET2 expression, under hypoxia, was regulated by the PI3K/AKT pathway and was almost completely abolished by TLR4 ligand, LPS. Taken together, these results highlight how hypoxia-dependent and-independent pathways shape RNASET2 expression in DCs, with new perspectives on its implication for TME and, therefore, in anti-tumor immunity

Energy-Efficient Train Control: A Practical Application

This research presents a practical application of the Energy Efficient Train Control (EETC) problem, which involves a collaboration between the Operations Research group of the University of Bologna and ALSTOM Ferroviaria SpA. The work is carried out within the framework of project Swift, funded by the Emilia-Romagna regional authority. Given a train running on a certain line, the problem requires to determine a speed profile that minimizes the traction energy consumption. In particular, we consider the setting of a real-time application, in which the speed profile has to be recomputed due to changes in the schedule caused by unpredictable events. We introduce three solution methods: a constructive heuristic, a multi-start randomized constructive heuristic, and a Genetic Algorithm. Numerical experiments are performed on real-life instances. The results show that high quality solutions are produced and that the computing time is suitable for real-time applications