ROLE OF FERROPORTIN-MEDIATED IRON RELEASE FROM MACROPHAGES IN TISSUE HOMEOSTASIS AND REPAIR

Macrophages are essential in the inflammatory response and also have a critical function in body iron homeostasis. Moreover, it is known that iron metabolism is important in the context of inflammation. Indeed, it has been demonstrated that, in line with their functions, distinct macrophage populations, such as M1 and M2 polarized cells, differ in the expression of genes involved in iron homeostasis as well as in the expression of immunoregulatory genes. The functional significance of these differencies are not completely understood: we hypotized that iron released by M2 macrophages could promote cell proliferation and extracellular matrix deposition in the resolution phase of inflammation. Moreover, in line with the increasing awareness that macrophages have an important trophic role in addition to their immunological function, macrophages may play a role of \u201clocal iron redistributors\u201d in tissues, where they would manage iron availability for neighbouring cells. Therefore, the major aim of this project was to exploit a mouse model of impaired iron release from macrophages, caused by deletion of Ferroportin (Fpn), to understand the functions of macrophage iron in two situations of tissue repair: cutaneous wound healing and liver fibrosis. The characterization of mice with loss of macrophage Fpn showed that they are affected by transient alopecia caused by impaired hair follicle growth. The local impairment of iron distribution due to macrophage Fpn inactivation was accompanied by cellular iron deprivation and decreased proliferation in adjacent epithelial cells. By exposing mice to an iron-restricted diet we concluded that hair loss was not related to hypoferremia/anemia. Taken together, these results suggest that iron retention in resident macrophages has detrimental effects on tissue homeostasis by inhibiting the proliferation of hair follicle cells. We observed a considerable delay in the closure of excisional skin wounds of Fpnfl/flLysCre/- mice compared to controls, with defective granulation tissue formation and diminished fibroplasia. Moreover, the development of both lymphatic and blood vascular network was impaired. Conversely, inactivation of Fpn in macrophages had no impact on inflammatory processes accompanying wound healing, such as production of inflammatory molecules, content of leukocyte subsets and macrophage polarization. Altogether, these results indicate that, though it does not interfere with immune cells recruitment and local activation, Fpn deletion in macrophages impairs blood vessels formation and stromal cells proliferation, leading to delayed skin repair. Fpn inactivation in macrophages had no impact on inflammation, steatosis and fibrosis associated with exposition to the MCD diet, a model of non-alcoholic steatohepatitis. Levels of inflammatory and fibrogenic markers did not show significant differences between Fpnfl/flLysCre/- mice and controls. Interestingly, the levels of transaminases were significantly lower in mice with Fpn inactivation in macrophages, suggesting a different susceptibility to liver damage. These data suggest that, in this model, Fpn deletion in macrophages does not affect the inflammatory response to liver damage and fibrogenesis. The different susceptibility to liver damage and the different results we observed in the cutaneous wound healing and in the process of hepatic fibrosis should be further explored, perhaps using another model of fibrosis. In conclusion, the results reported in this thesis indicate that the macrophage trophic function in skin homeostasis and healing is iron and Fpn-dependent

Automated efficiency loss analysis by luminescence image reconstruction using generative adversarial networks

Identifying solar cell efficiency shortfalls in production lines is crucial to troubleshoot and optimize manufacturing processes. With the adoption of luminescence imaging as a key end-of-line characterization tool, a wealth of information is available to evaluate cell performance and classify defects, suitable for user input-free deep-learning analysis. We propose an automated reconstruction method, based on state-of-the-art generative adversarial networks, to remove defective regions in luminescence images. The reconstructed and original images are compared to estimate the efficiency loss. The method is validated on intentionally damaged cells by reconstructing defect-free images and then predicting the efficiency loss. The method can differentiate between different types of defects and pinpoint the defects that lead to the highest efficiency shortfall, enabling manufacturers to troubleshoot production lines in a fast and cost-effective manner. The proposed approach unlocks the potential of luminescence imaging as an effective end-of-line characterization tool

Finding the trigger to Iapetus' odd global albedo pattern: Dynamics of dust from Saturn's irregular satellites

The leading face of Saturn's moon Iapetus, Cassini Regio, has an albedo only one tenth that on its trailing side. The origin of this enigmatic dichotomy has been debated for over forty years, but with new data, a clearer picture is emerging. Motivated by Cassini radar and imaging observations, we investigate Soter's model of dark exogenous dust striking an originally brighter Iapetus by modeling the dynamics of the dark dust from the ring of the exterior retrograde satellite Phoebe under the relevant perturbations. In particular, we study the particles' probabilities of striking Iapetus, as well as their expected spatial distribution on the Iapetian surface. We find that, of the long-lived particles (greater than about 5 microns), most particle sizes (greater than about 10 microns) are virtually certain to strike Iapetus, and their calculated distribution on the surface matches up well with Cassini Regio's extent in its longitudinal span. The satellite's polar regions are observed to be bright, presumably because ice is deposited there. Thus, in the latitudinal direction we estimate polar dust deposition rates to help constrain models of thermal migration invoked to explain the bright poles (Spencer & Denk 2010). We also analyze dust originating from other irregular outer moons, determining that a significant fraction of that material will eventually coat Iapetus--perhaps explaining why the spectrum of Iapetus' dark material differs somewhat from that of Phoebe. Finally we track the dust particles that do not strike Iapetus, and find that most land on Titan, with a smaller fraction hitting Hyperion. As has been previously conjectured, such exogenous dust, coupled with Hyperion's chaotic rotation, could produce Hyperion's roughly isotropic, moderate-albedo surface.Comment: Accepted for publication in Icaru

Saturn's icy satellites and rings investigated by Cassini - VIMS. III. Radial compositional variability

In the last few years Cassini-VIMS, the Visible and Infared Mapping Spectrometer, returned to us a comprehensive view of the Saturn's icy satellites and rings. After having analyzed the satellites' spectral properties (Filacchione et al. (2007a)) and their distribution across the satellites' hemispheres (Filacchione et al. (2010)), we proceed in this paper to investigate the radial variability of icy satellites (principal and minor) and main rings average spectral properties. This analysis is done by using 2,264 disk-integrated observations of the satellites and a 12x700 pixels-wide rings radial mosaic acquired with a spatial resolution of about 125 km/pixel. The comparative analysis of these data allows us to retrieve the amount of both water ice and red contaminant materials distributed across Saturn's system and the typical surface regolith grain sizes. These measurements highlight very striking differences in the population here analyzed, which vary from the almost uncontaminated and water ice-rich surfaces of Enceladus and Calypso to the metal/organic-rich and red surfaces of Iapetus' leading hemisphere and Phoebe. Rings spectra appear more red than the icy satellites in the visible range but show more intense 1.5-2.0 micron band depths. The correlations among spectral slopes, band depths, visual albedo and phase permit us to cluster the saturnian population in different spectral classes which are detected not only among the principal satellites and rings but among co-orbital minor moons as well. Finally, we have applied Hapke's theory to retrieve the best spectral fits to Saturn's inner regular satellites using the same methodology applied previously for Rhea data discussed in Ciarniello et al. (2011).Comment: 44 pages, 27 figures, 7 tables. Submitted to Icaru

Characterization of Whole Grain Pasta: Integrating Physical, Chemical, Molecular, and Instrumental Sensory Approaches

The consumption of whole-grain foodincluding pastahas been increasing steadily. In the case of whole-grain pasta, given the many different producers, it seems important to have some objective parameters to define its overall quality. In this study, commercial whole-grain pasta samples representative of the Italian market have been characterized from both molecular and electronic-senses (electronic nose and electronic tongue) standpoint in order to provide a survey of the properties of different commercial samples. Only 1 pasta product showed very low levels of heat damage markers (furosine and pyrraline), suggesting that this sample underwent to low temperature dry treatment. In all samples, the furosine content was directly correlated to protein structural indices, since protein structure compactness increased with increasing levels of heat damage markers. Electronic senses were able to discriminate among pasta samples according to the intensity of heat treatment during the drying step. Pasta sample with low furosine content was discriminated by umami taste and by sensors responding to aliphatic and inorganic compounds. Data obtained with this multidisciplinary approach are meant to provide hints for identifying useful indices for pasta quality. Practical ApplicationAs observed for semolina pasta, objective parameters based on heat-damage were best suited to define the overall quality of wholegrain pasta, almost independently of compositional differences among commercial samples. Drying treatments of different intensity also had an impact on instrumental sensory traits that may provide a reliable alternative to analytical determination of chemical markers of heat damage in all cases where there is a need for avoiding time-consuming procedures