OHB-I Nanosatellite Constellation for Earth Observation: A Contribution to Iride

IRIDE is an End-To-End System consisting of: Several LEO constellations (Upstream Segment). A ground operational infrastructure (Downstream Segment). Services for the Italian public administration (Service Segment). IRIDE is unique since it provides microwave imaging (Synthetic Aperture Radar, SAR), optical imaging at various spatial resolutions and in different frequency ranges, including panchromatic, multispectral, hyperspectral, and infrared bands

The Antifungal Antibiotic Filipin as a Diagnostic Tool of Cholesterol Alterations in Lysosomal Storage Diseases and Neurodegenerative Disorders

Cholesterol is the most considerable member of a family of polycyclic compounds understood as sterols, and represents an amphipathic molecule, such as phospholipids, with the polar hydroxyl group located in position 3 and the rest of the molecule is completely hydrophobic. In cells, it is usually present as free, unesterified cholesterol, or as esterified cholesterol, in which the hydroxyl group binds to a carboxylic acid and thus generates an apolar molecule. Filipin is a naturally fluorescent antibiotic that exerts a primary antifungal effect with low antibacterial activity, interfering with the sterol stabilization of the phospholipid layers and favoring membrane leakage. This polyene macrolide antibiotic does not bind to esterified sterols, but only to non-esterified cholesterol, and it is commonly used as a marker to label and quantify free cholesterol in cells and tissues. Several lines of evidence have indicated that filipin staining could be a good diagnostic tool for the cholesterol alterations present in neurodegenerative (e.g., Alzheimer’s Disease and Huntington Disease) and lysosomal storage diseases (e.g., Niemann Pick type C Disease and GM1 gangliosidosis). Here, we have discussed the uses and applications of this fluorescent molecule in lipid storage diseases and neurodegenerative disorders, exploring not only the diagnostic strength of filipin staining, but also its limitations, which over the years have led to the development of new diagnostic tools to combine with filipin approach

Altered development of cerebellar granule neurons in a mouse model of Niemann-Pick type C1 disease

Niemann-Pick type C1 disease (NPCD), also called “Juvenile Alzheimer’s Disease”, is a lysosomal cholesterol storage disorder due to mutations in the NPC1 gene, presenting visceral/neurological impairments associated with cognitive decline. NPC1 neurodegeneration is characterized by the presence of amyloid-β deposition and tau aggregations, alike to Alzheimer's disease. Unfortunately, the molecular mechanisms that cause neurodegeneration in this disease are currently unknown. Studying the cerebellar development in Npc1 mutant mice, we observed a defective proliferation of granule neurons (GNs)1, concomitant with the dysregulation of Sonic Hedgehog (Shh) and Brain Derived Neurotrophic factor (BDNF) expression, that affects the size of cerebellar lobules2 . Aims: In light of the relevance of BDNF in a wide range of neurophysiological processes, as neuronal migration, differentiation and degeneration3, we analyzed BDNF-TrkB signaling during the first weeks of postnatal life, in a milder mouse model, Npc1nmf164, harboring a missense mutation in a region where a high proportion of human mutations are found and associated with a slower disease progression. Materials and Methods: In order to study the expression and localization of BDNF/TrkB, we performed Western Blot and Immunofluorescence analyses in cerebellar samples of wt and Npc1nmf164mice. Cerebellar neuron responsiveness to BDNF was investigated by chemotaxis assay in in vitro culture, while neuronal differentiation was studied by detailed dendritic branching analysis of Golgi-stained GNs. Results: We observed an altered expression/localization of BDNF and its receptor TrkB, at the very early stages of cerebellar development. Furthermore, purified GNs from Npc1nmf164 mice, in the presence of exogenous BDNF, exhibit a reduced chemotaxis response, dependent on altered TrkB receptor trafficking. Using Golgi staining, we observed that mature GNs present an abnormal dendritic morphology. Discussion These data raising the possibility that morpho-functional anomalies in granule neurons largely anticipate the overt manifestation of symptoms in adult NPC1 patients. Our focus on very early morphological/ biochemical defects, which precede neurodegeneration in adults, is relevant for identifying predictive markers, useful for NPC1 disease treatment. Thus, given the potential of BDNF to protect synapses against various toxic insults, manipulation of BDNF could represent a valid therapeutic approach for a variety of neurological disorders, including NPC1 disease. Conclusions: Here, we propose that an altered BDNF signaling is a part of complex cerebellar deficits, which may be predictive of symptomatic events in NPCD, as well as the progressive neurodegeneration of Purkinje cells in adulthood

Reduced Cerebellar BDNF Availability Affects Postnatal Differentiation and Maturation of Granule Cells in a Mouse Model of Cholesterol Dyshomeostasis

: Niemann-Pick type C1 (NPC1) disease is a lysosomal lipid storage disorder due to mutations in the NPC1 gene resulting in the accumulation of cholesterol within the endosomal/lysosomal compartments. The prominent feature of the disorder is the progressive Purkinje cell degeneration leading to ataxia.In a mouse model of NPC1 disease, we have previously demonstrated that impaired Sonic hedgehog signaling causes defective proliferation of granule cells (GCs) and abnormal cerebellar morphogenesis. Studies conducted on cortical and hippocampal neurons indicate a functional interaction between Sonic hedgehog and brain-derived neurotrophic factor (BDNF) expression, leading us to hypothesize that BDNF signaling may be altered in Npc1 mutant mice, contributing to the onset of cerebellar alterations present in NPC1 disease before the appearance of signs of ataxia.We characterized the expression/localization patterns of the BDNF and its receptor, tropomyosin-related kinase B (TrkB), in the early postnatal and young adult cerebellum of the Npc1nmf164 mutant mouse strain.In Npc1nmf164 mice, our results show (i) a reduced expression of cerebellar BDNF and pTrkB in the first 2 weeks postpartum, phases in which most GCs complete the proliferative/migrative program and begin differentiation; (ii) an altered subcellular localization of the pTrkB receptor in GCs, both in vivo and in vitro; (iii) reduced chemotactic response to BDNF in GCs cultured in vitro, associated with impaired internalization of the activated TrkB receptor; (iv) an overall increase in dendritic branching in mature GCs, resulting in impaired differentiation of the cerebellar glomeruli, the major synaptic complex between GCs and mossy fibers