Expression of Tight Junction and Drug Efflux Transporter Proteins in an in vitro Model of Human Blood–Brain Barrier

Interendothelial cell tight junctions (TJs) proteins contribute to maintain the structural and functional integrity of the blood–brain barrier (BBB) and several efflux transporters regulate transport of compounds across BBB. A unique double compartment-model of the BBB, consisting of cerebral endothelial cells isolated from cryopreserved human glial tumors, alone and in the presence of human astroglial cells derived from the same tissue preparation was established. Endothelial cell viability and transendothelial electrical resistance (TEER) were measured in this model and three representative TJ proteins – occludin (OCLN), zonula occludens-1 (ZO-1) and claudin-5 (CLN-5) – as well as several drug efflux transporters – P-glycoprotein (P-gp), multidrug resistance protein-1 and 2 (MRP-1 and MRP-2), organic anion-transporting polypeptide-1 and 3 (oatp1 and oatp3) were analyzed at both the protein and gene transcript level. Functional activity of P-gp and MRP-1 was also assessed. Endothelial cell viability as well as TEER significantly increased in the presence of glial cells. A significant increase of expression of OCLN, ZO-1, and CLN-5 proteins as well as of several drug transporter proteins except oatp3 and MRP-1, was also found in the presence of glial cells. All the gene transcripts protein analyzed were found to be significantly increased in the presence of glial cells. A suitable functional activity of P-gp and MRP-1 was also found. These results demonstrate that this brain endothelium culture system mimics a physiologically relevant situation and may therefore provide a new tool for studying the effects of biological fluids such as serum and cerebrospinal fluid from patients with neurological disorders underlying a BBB alteration in disease pathogenesis

Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study

Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with still unknown etiology. We aimed at investigating the association between environmental and occupational factors with ALS risk. Methods: We performed a population-based case-control study in four Italian provinces (Catania, Modena, Novara, and Reggio Emilia) by administration of tailored questionnaires to ALS cases (n = 95) and randomly selected population referents (n = 135). We estimated ALS risk by calculating the odds ratio (OR) with its 95% confidence interval (CI) using an unconditional logistic regression model. Results: We found a positive association with disease risk for history of occupation in the agricultural sector (OR = 2.09, 95% CI 0.79-7.54), especially for longer than 10 years (OR = 2.72, 95% 1.02-7.20). Overall occupational exposure to solvents also suggested a positive association, especially for thinners (OR = 2.27, 95% CI 1.14-4.54) and paint removers (OR = 2.01, 95% CI 0.90-4.48). Both occupational and environmental exposure to electromagnetic fields show a slightly increased risk with OR = 1.69 (95% CI 0.70-4.09) and 2.41 (95% CI 1.13-5.12), respectively. Occupational but not environmental exposure to pesticides (OR = 1.22, 95% CI 0.63-2.37), particularly fungicides, and exposure to metals (OR = 4.20, 95% CI 1.88-9.38), particularly lead, mercury, and selenium, showed an imprecise but positive association. Finally, there was an indication of increased risk for living in proximity to water bodies. Conclusions: Despite the caution that needs to be used due to some study limitations, such as the low number of exposed subjects and the possibility of recall bias, these results suggest the potential role of some environmental and occupational factors in ALS etiology

Clinical and Lifestyle Factors and Risk of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study

Background: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease of the motor neurons. The etiology of ALS remains largely unknown, particularly with reference to the potential environmental determinants. Methods: We performed a population-based case-control study in four provinces from both Northern and Southern Italy in order to assess non-genetic ALS risk factors by collecting through tailored questionnaires information about clinical and lifestyle factors. We estimated ALS risk by calculating odds ratio (OR) with its 95% confidence interval (CI) using unconditional logistic regression models adjusted for sex, age and educational attainment. Results: We recruited 230 participants (95 cases and 135 controls). We found a possible positive association of ALS risk with trauma, particularly head trauma (OR = 2.61, 95% CI 1.19-5.72), electric shock (OR = 2.09, 95% CI 0.62-7.06), and some sports, although at a competitive level only. In addition, our results suggest an increased risk for subjects reporting use of private wells for drinking water (OR = 1.38, 95% CI 0.73-2.27) and for use of herbicides during gardening (OR = 1.95, 95% CI 0.88-2.27). Conversely, there was a suggestion of an inverse association with overall fish consumption (OR = 0.27, 95% CI 0.12-0.60), but with no dose-response relation. Consumption of some dietary supplements, namely those containing amino acids and, in the Southern Italy population, vitamins and minerals such as selenium, seemed associated with a statistically imprecise increased risk. Conclusions: Our results suggest a potential etiologic role a number of clinical and lifestyle factors with ALS risk. However, caution is needed due to some study limitations. These include the small sample size and the low number of exposed subjects, which affect statistical precision of risk estimates, the potential for exposure misclassification, and the uncertainties about mechanisms underpinning the possible association between these factors and disease risk

Potential for a Circular Autopoietic Economy on Canavese Territory

The aim of this gigamap is to describe and summarize a student work carried out during the semester course Open Systems Design at Politecnico Torino. The map is one of the outputs from an analysis of the Canavese, Piedmont region and subsequently an in-depth study of the relationships and “flows” with certain “currencies” between some selected economic and public actors. Canavese is a historical-geographical area located in the province of Turin, Italy; it’s full of great natural and geological spots, with a strong enogastronomic identity, historical re-enactments, a well-known manufacture sector like the ceramic of Castellamonte, as well as the leading high-tech branch like Arduino. Through the approach deriving from systemic design, it was possible to identify some strategies for the creation of new networks aimed at transforming the economy and production processes from linear to circular approach. Five types of “circular flows” were assessed and “designed into” the current linear system, thus proposing an improved economy based on circularity: flows of matter (energy/CO2, water, materials), economic flows, and social flows. The Gigamap will be presented to stakeholders in a public hearing and supposedly be used to illustrate and incubate a circular economy that is more resilient and more regenerative. Reading the map The reading should start at the top left, where the abstract is located, next, there is an outline that shows the connections between the five topics investigated. Subsequently, there is a timeline with some fundamental events in the history of the Canavese. In the center there is the circularity map with the main cities, focusing on new opportunities of circular flows between the 15 analysed economic actors. At the bottom, some general data and on the right a brief description of the role and territorial qualities of the companies. Lastly, there is a summary of the emerging properties

Black holes, gravitational waves and fundamental physics: a roadmap

The grand challenges of contemporary fundamental physics—dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem—all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'