Investigating the neurovascular coupling in the cerebellar granular layer.

The neurovascular coupling (NVC) or functional hyperemia is the mechanism whereby neuronal activity controls cerebral blood flow (CBF). The tight coupling between neuronal activation and blood vessels diameter modifications ensures the proper supply of oxygen and nutrients to the central nervous system. In the brain, CBF adaptations are governed by vasoactive agents and their action on the vascular system (Iadecola, 2017). This phenomenon is also involved in the genesis of the blood-oxygen-level-dependent (BOLD) signals used by neuroimaging techniques, like functional magnetic resonance imaging (fMRI), to map changes in brain activity. Although being highly investigated, the interpretation of activity-dependent BOLD responses is widely debated (Hall et al., 2016). The complexity of investigating BOLD neurophysiological basis, i.e. NVC mechanisms, resulted in the inability to define a comprehensive theory for BOLD signals interpretation. In this work of thesis, the attention was focused on NVC mechanisms in the cerebellum. In this region, NVC has been previously investigated in the molecular layer, where interneurons activation has been found as the main player, unlike Purkinje cells spiking activity (Cauli et al., 2004; Thomsen et al., 2004). Surprisingly, there was no information about the role of the granular layer in cerebellar NVC before our investigations. In the granular layer, NVC is mediated by granule cells through an NMDA receptor/NO-dependent system acting on pericytes (Mapelli et al., 2017). The latter are contractile cells able to regulate the caliber of brain capillaries (Attwell et al., 2016),which are thought to be involved in the genesis of BOLD signals (Hall et al., 2016). Recent investigations using human fMRI demonstrated that cerebellar vermis lobule V and hemisphere lobule VI showed respectively linear and non-linear BOLD responses during the same motor task performance (Alahmadi et al., 2017). In mouse cerebellar slices, vermis lobule V and hemisphere lobule VI responded with different non-linear neurovascular events to several frequency patterns of neuronal activation, suggesting that NVC and thus BOLD signals might be region-dependent in the cerebellum (Gagliano et al., 2018 in preparation). In conclusion, granule cells, pericytes and capillaries may drive the basic neurovascular mechanisms of the cerebellum, but different cerebellar regions (vermis and hemisphere) could differently contribute to the genesis of cerebellar BOLD signals. These results might reflect different functions of these cerebellar areas following the same input

Investigating the neurovascular coupling in the cerebellar granular layer.

The neurovascular coupling (NVC) or functional hyperemia is the mechanism whereby neuronal activity controls cerebral blood flow (CBF). The tight coupling between neuronal activation and blood vessels diameter modifications ensures the proper supply of oxygen and nutrients to the central nervous system. In the brain, CBF adaptations are governed by vasoactive agents and their action on the vascular system (Iadecola, 2017). This phenomenon is also involved in the genesis of the blood-oxygen-level-dependent (BOLD) signals used by neuroimaging techniques, like functional magnetic resonance imaging (fMRI), to map changes in brain activity. Although being highly investigated, the interpretation of activity-dependent BOLD responses is widely debated (Hall et al., 2016). The complexity of investigating BOLD neurophysiological basis, i.e. NVC mechanisms, resulted in the inability to define a comprehensive theory for BOLD signals interpretation. In this work of thesis, the attention was focused on NVC mechanisms in the cerebellum. In this region, NVC has been previously investigated in the molecular layer, where interneurons activation has been found as the main player, unlike Purkinje cells spiking activity (Cauli et al., 2004; Thomsen et al., 2004). Surprisingly, there was no information about the role of the granular layer in cerebellar NVC before our investigations. In the granular layer, NVC is mediated by granule cells through an NMDA receptor/NO-dependent system acting on pericytes (Mapelli et al., 2017). The latter are contractile cells able to regulate the caliber of brain capillaries (Attwell et al., 2016),which are thought to be involved in the genesis of BOLD signals (Hall et al., 2016). Recent investigations using human fMRI demonstrated that cerebellar vermis lobule V and hemisphere lobule VI showed respectively linear and non-linear BOLD responses during the same motor task performance (Alahmadi et al., 2017). In mouse cerebellar slices, vermis lobule V and hemisphere lobule VI responded with different non-linear neurovascular events to several frequency patterns of neuronal activation, suggesting that NVC and thus BOLD signals might be region-dependent in the cerebellum (Gagliano et al., 2018 in preparation). In conclusion, granule cells, pericytes and capillaries may drive the basic neurovascular mechanisms of the cerebellum, but different cerebellar regions (vermis and hemisphere) could differently contribute to the genesis of cerebellar BOLD signals. These results might reflect different functions of these cerebellar areas following the same input

Probabilistic analysis of weather data for a hybrid solar/wind energy system

In this paper, a procedure for the probabilistic treatment of solar irradiance and wind speed data is reported as a method of evaluating, at a given site, the electric energy generated by both a photovoltaic system and a wind system. The aim of the proposed approach is twofold: first, to check if the real probability distribution functions (PDFs) of both clearness index and wind speed overlap with Hollands and Huget and Weibull PDFs, respectively; and then to find the parameters of these two distributions that best fit the real data. Further, using goodness-of-fit tests, these PDFs are compared with another set of very common PDFs, namely the Gordon and Reddy and Lognormal functions, respectively. The results inform the design of a pre-processing stage for the input of an algorithm that probabilistically optimizes the design of hybrid solar wind power systems. In this paper, the validity of the proposed procedure was tested using long-term meteorological data from Acireale (Italy). Copyright © 2010 John Wiley & Sons, Ltd

Conversion of Organic Dyes into Pigments: Extraction of Flavonoids from Blackberries (Rubus ulmifolius) and Stabilization

The blackberry’s color is composed mainly of natural dyes called anthocyanins. Their color is red–purple, and they can be used as a natural colorant. Anthocyanins are flavonoids, which are products of plants, and their colors range from orange and red to various shades of blue, purple and green, according to pH. In this study, the chemical composition of an extract obtained from blackberries was defined by LC-ESI/LTQOrbitrap/MS in positive and negative ionization mode. Furthermore, we investigated the adsorption process of blackberry extract using several inorganic fillers, such as metakaolin, silica, Lipari pumice, white pozzolan and alumina. The pigments exhibit different colors as a function of their interactions with the fillers. The analysis of the absorption data allowed the estimation of the maximum adsorbing capacity of each individual filler tested. Through thermogravimetric measurements (TGA), the thermal stability and the real adsorption of the organic extract were determine

An assessment study of evaporation rate models on a water basin with floating photovoltaic plants

Under the general topic of the impact of floating PV systems (FPVs) on water basins, the present study aims to model and analyze the effect of FPVs on the evaporation rate of water surfaces. The estimation of the evaporation of the water surface of a basin is usually calculated using mathematical evaporation models that require knowledge of some parameters (i.e. solar radiation, humidity, air temperature, water temperature, wind velocity). Thus, in the first section of this study some evaporative models (EVM) for free water basin have been examined to evaluate which are the environmental variables used. On the basis of this analysis, new numerical models for the calculation of the daily evaporation rate have been developed using the DoE method (3 models) and the linear regression method (2 models). The results of the developed models have been compared with the experimental measurements carried out by an evaporimeter, such comparison has highlighted the robustness of the proposed numerical models. Moreover, for estimating the evaporation rate in water basins partially covered by FPVs further three numerical methods are proposed. Finally, the evaporation rates, arising by the installation of different typology of FPVs on water basins, have been evaluated as function of the energy balance on the water surface. It is possible to highlight that the amount of evaporated water depends not only on the percentage of surface covered but also on the characteristics of floating systems. Covering only 30% of the surface of a basin, it is possible to obtain up to 49% reduction in evaporation

Lethal Hydrogen Sulfide poisoning in open space: an atypical case of asphyxiation of two workers

Hydrogen sulfide is one of the most dangerous toxic gases that has led to the deaths in confined spaces of many workers. We report an atypical case of a fatal accident of H2S poisoning in an open space when two workers dide during the opening of a hatch on a tanker truck filled with leachate water. Despite being utdoors, the two workers, were suddenly and quickly overhelmed by a lethal cloud of H2S,which escaped like a geyser from the hatch and hovered over the top of the tanker making it impossible for them to survive. the first operator was engulfed by the sudden flow of lethal gas near the hatch while the second worker, who came to his aid, immediately lopst consciousness and fell off the tanker onto the ground. Environmental toxicological analyses were carried out on the air near the hatch and inside the tanker 2h, 20 days and 70 days after the accident. Toxicological analyses on the blood were also carried out but unfortunately, no urine samples was available. The thiosulfate, detected by GC/MS analysis after derivatization of PFBBr, was found to be 0.01 and 0.04mM/L. These values are included in the medium-low lethal values of occupational fatalities involving H2S reported in the literature

Job performance in chronic hepatitis C virus patients treated with pegylated interferon-α2b plus ribavirin: an observational study

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Non-Linear Frequency Dependence of Neurovascular Coupling in the Cerebellar Cortex Implies Vasodilation-Vasoconstriction Competition

Neurovascular coupling (NVC) is the process associating local cerebral blood flow (CBF) to neuronal activity (NA). Although NVC provides the basis for the blood oxygen level dependent (BOLD) effect used in functional MRI (fMRI), the relationship between NVC and NA is still unclear. Since recent studies reported cerebellar non-linearities in BOLD signals during motor tasks execution, we investigated the NVC/NA relationship using a range of input frequencies in acute mouse cerebellar slices of vermis and hemisphere. The capillary diameter increased in response to mossy fiber activation in the 6-300 Hz range, with a marked inflection around 50 Hz (vermis) and 100 Hz (hemisphere). The corresponding NA was recorded using high-density multi-electrode arrays and correlated to capillary dynamics through a computational model dissecting the main components of granular layer activity. Here, NVC is known to involve a balance between the NMDAR-NO pathway driving vasodilation and the mGluRs-20HETE pathway driving vasoconstriction. Simulations showed that the NMDAR-mediated component of NA was sufficient to explain the time course of the capillary dilation but not its non-linear frequency dependence, suggesting that the mGluRs-20HETE pathway plays a role at intermediate frequencies. These parallel control pathways imply a vasodilation-vasoconstriction competition hypothesis that could adapt local hemodynamics at the microscale bearing implications for fMRI signals interpretation

Effect of extracellular matrix components on the expression of epithelial-to-mesenchymal transition markers in cultured human pancreatic ductal adenocarcinoma cells

Epithelial-to-mesenchymal transition (EMT) is a step-wise process leading to the phenotypic switch of epithelial to mesenchymal cells, providing these cells with a metastatic phenotype. During EMT epithelial cells loose adhesion by down regulation of E-cadherin and express N-cadherin, display cytoskeleton reorganization by expressing vimentin and α-smooth muscle actin (αSMA), acquire motile properties and become invasive by secretion of matrix metalloproteinases (MMPs). Cancer cell phenotype is influenced by the tumor microenvironment in relation to tumor progression, as well as to cell proliferation and invasion. The role of the extracellular matrix (ECM) in the microenvironment is particularly relevant in pancreatic ductal adenocarcinoma (PDAC) since this carcinoma is characterized by an intense desmoplastic reaction, representing the environment where the complex interplay between tumor cells, stromal fibroblasts and ECM components occurs. We aimed at analyzing in vitro the effect of the crosstalk between PDAC cells and their microenvironment by characterizing PDAC cell phenotype in cells cultured on different ECM proteins used as a substrate, in order to better understand the relationship between cancer cell behaviour and the proteins occurring in the desmoplastic tissue. We analyzed by immunofluorescence the expression of the main EMT markers such as E-cadherin, N-cadherin, β-catenin, αSMA, vimentin and collagen type I (COL-I) in PDAC cells cultured on laminin, fibronectin, COL-I and without coating (NC). Moreover, we investigated cell proliferation and MMPs activity in cell culture supernatants by SDS-zymography. Cell morphology was similar in PDAC cells cultured on laminin, fibronectin, COL-I, and in NC, as well as the E-cadherin/β-catenin complex, αSMA and COLI expression; by contrast, vimentin was undetectable in all the experimental conditions. N-cadherin was slightly detectable in cells cultured on fibronectin, COL-I, and laminin, and at lower extent in NC cells. Cell proliferation resulted similar in NC and in cells cultured on fibronectin, decreased on laminin and increased on COL-I. MMP-9 activity exhibited a similar trend, resulting similar on fibronectin, decreased on laminin and stimulated on COL-I. These preliminary results provide new insights in the characterization of the mutual effects elicited by the tumor-stroma interplay on the cancer cell, and will contribute to better understand the influence of the stroma on PDAC cancer cell phenotype, in order to develop new therapeutic strategies

Anaesthesiologic protocol for kidney transplantation in two patients with Fabry Disease: a case series

Fabry's Disease is a rare genetic syndrome, with a classic X-linked alpha -galactosidase A deficiency phenotype, responsible for glico-sphyngolypids metabolism impairment with clinical effects in several organs and functions. We describe the anaesthesiologic implications of two patients with Fabry disease who underwent a kidney transplantation from a deceased donor. We recommend careful preoperative evaluation, including cardiac sonography study and spirometry for Fabry disease patients, and according to our experience, we recommend advanced haemodynamic monitoring during surgery. Careful airway examination should be further performed, with particular attention to patient ventilability prediction and available alternative strategies for airway management in case of difficulties. A nephroprotective strategy and a particular care to the associated end-stage organ disease may significantly improve the long-term outcome of patients with Fabry Disease