Modulation of LPS-induced nitric oxide production in intestinal cells by hydroxytyrosol and tyrosol metabolites:Insight into the mechanism of action

At intestinal level, after acute or chronic exposure to iNOS-derived NO, a toxic mechanism of action leads to inflammation and degenerative diseases. The aim of this study was to investigate the effect of glucuronide and sulfate metabolites of the extra virgin olive oil phenols tyrosol (Tyr) and hydroxytyrosol (HT), in comparison with their parent compounds, on the release of NO following exposure to a pro-inflammatory stimulus, the bacterial lipopolysaccharide (LPS). Human colon adenocarcinoma cells (Caco-2), differentiated as normal enterocytes, were treated with pathological concentrations of LPS, in order to stimulate iNOS pathway, which involves NF-ĸB activation through IĸBα phosphorylation and subsequent degradation induced by Akt or MAPKs. All the tested metabolites inhibited NO release induced by LPS, acting as inhibitors of iNOS expression, with an efficacy comparable to that of the parent compounds. HT and Tyr metabolites were effective in the inhibition of IĸBα degradation. No one of the compounds was able to inhibit Akt activation, whereas they modulated p38 and ERK1/2 MAPK. Obtained data show that HT and Tyr metabolites are able to prevent a pathological NO overproduction at intestinal level, where they concentrate, thus significantly contributing to the protective activity exerted by their parent compounds against inflammation

Ostracod and Foraminifer Responses to Late Pleistocene–Holocene Volcanic Activity in Northern Victoria Land as Recorded in Ross Sea (Antarctica) Marine Sediments

The impacts on ostracods and foraminifers caused by three Late Quaternary ashfalls of different intensities and recovered in the ANTA02-NW2 core sediments (Drygalski Basin, western Ross Sea) were analysed for the first time. Albeit with different timing, both associations demonstrated similar response patterns associated with the deposition of material from volcanic eruptions. In particular, based on the palaeontological evidence, it was possible to divide the cores into four intervals/phases recording the evolution of the ecosystem before and after the deposition events: (1) Pre-extinction phase (high abundance and high diversity values). (2) Extinction phase, characterised by the complete disappearance of ostracod fauna; the foraminiferal assemblage, although not entirely absent, records extremely low values of abundance and diversity (survivor assemblage). (3) Recovery phase (increasing abundance and diversity values), characterised by the recolonisation of some opportunistic taxa; species such as Australicythere devexa and Australicythere polylyca dominate the ostracod assemblage. (4) Post-extinction phase (high abundance and high diversity values), with the return to an environmental equilibrium characterised by the colonisation of specialised taxa such as Argilloecia sp., Cytheropteron sp., Echinocythereis sp., and Hemicytherura spp. Our results may aid in the understanding of how communities (i.e., ostracods and foraminifers) recovered after the impact of direct deposits of volcanic ash into ocean waters. The mechanisms by which disappearance and/or mortality was induced are still not clear. The release of toxic metals during the reaction of the volcanic ash with seawater, the resulting chemical alteration in the seawater, and the change in pH, together with the possible suppression of planktonic organisms, may have caused the two main extinction phases recorded by the ANTA02-NW2 core sediments

A Service-Oriented Approach to Crowdsensing for Accessible Smart Mobility Scenarios

This work presents an architecture to help designing and deploying smart mobility applications. The proposed solution builds on the experience already matured by the authors in different fields: crowdsourcing and sensing done by users to gather data related to urban barriers and facilities, computation of personalized paths for users with special needs, and integration of open data provided by bus companies to identify the actual accessibility features and estimate the real arrival time of vehicles at stops. In terms of functionality, the first "monolithic" prototype fulfilled the goal of composing the aforementioned pieces of information to support citizens with reduced mobility (users with disabilities and/or elderly people) in their urban movements. In this paper, we describe a service-oriented architecture that exploits the microservices orchestration paradigm to enable the creation of new services and to make the management of the various data sources easier and more effective. The proposed platform exposes standardized interfaces to access data, implements common services to manage metadata associated with them, such as trustworthiness and provenance, and provides an orchestration language to create complex services, naturally mapping their internal workflow to code. The manuscript demonstrates the effectiveness of the approach by means of some case studies

Maternal immune activation disrupts dopamine system in the offspring

Background: In utero exposure to maternal viral infections is associated with a higher incidence of psychiatric disorders with a supposed neurodevelopmental origin, including schizophrenia. Hence, immune response factors exert a negative impact on brain maturation that predisposes the offspring to the emergence of pathological phenotypes later in life. Although ventral tegmental area dopamine neurons and their target regions play essential roles in the pathophysiology of psychoses, it remains to be fully elucidated how dopamine activity and functionality are disrupted in maternal immune activation models of schizophrenia. Methods: Here, we used an immune-mediated neurodevelopmental disruption model based on prenatal administration of the polyriboinosinic-polyribocytidilic acid in rats, which mimics a viral infection and recapitulates behavioral abnormalities relevant to psychiatric disorders in the offspring. Extracellular dopamine levels were measured by brain microdialysis in both the nucleus accumbens shell and the medial prefrontal cortex, whereas dopamine neurons in ventral tegmental area were studied by in vivo electrophysiology. Results: Polyriboinosinic-polyribocytidilic acid-treated animals, at adulthood, displayed deficits in sensorimotor gating, memory, and social interaction and increased baseline extracellular dopamine levels in the nucleus accumbens, but not in the prefrontal cortex. In polyriboinosinic-polyribocytidilic acid rats, dopamine neurons showed reduced spontaneously firing rate and population activity. Conclusions: These results confirm that maternal immune activation severely impairs dopamine system and that the polyriboinosinic-polyribocytidilic acid model can be considered a proper animal model of a psychiatric condition that fulfills a multidimensional set of validity criteria predictive of a human patholog

The interplay of chemical structure, physical properties, and structural design as a tool to modulate the properties of melanins within mesopores

The design of modern devices that can fulfil the requirements for sustainability and renewable energy applications calls for both new materials and a better understanding of the mixing of existing materials. Among those, surely organic–inorganic hybrids are gaining increasing attention due to the wide possibility to tailor their properties by accurate structural design and materials choice. In this work, we’ll describe the tight interplay between porous Si and two melanic polymers permeating the pores. Melanins are a class of biopolymers, known to cause pigmentation in many living species, that shows very interesting potential applications in a wide variety of fields. Given the complexity of the polymerization process beyond the formation and structure, the full understanding of the melanins’ properties remains a challenging task. In this study, the use of a melanin/porous Si hybrid as a tool to characterize the polymer’s properties within mesopores gives new insights into the conduction mechanisms of melanins. We demonstrate the dramatic effect induced on these mechanisms in a confined environment by the presence of a thick interface. In previous studies, we already showed that the interactions at the interface between porous Si and eumelanin play a key role in determining the final properties of composite materials. Here, thanks to a careful monitoring of the photoconductivity properties of porous Si filled with melanins obtained by ammonia-induced solid-state polymerization (AISSP) of 5,6-dihydroxyindole (DHI) or 1,8-dihydroxynaphthalene (DHN), we investigate the effect of wet, dry, and vacuum cycles of storage from the freshly prepared samples to months-old samples. A computational study on the mobility of water molecules within a melanin polymer is also presented to complete the understanding of the experimental data. Our results demonstrate that: (a) the hydration-dependent behavior of melanins is recovered in large pores (≈ 60 nm diameter) while is almost absent in thinner pores (≈ 20 nm diameter); (b) DHN-melanin materials can generate higher photocurrents and proved to be stable for several weeks and more sensitive to the wet/dry variations

Micro-scale {UHI} risk assessment on the heat-health nexus within cities by looking at socio-economic factors and built environment characteristics: The Turin case study (Italy)

Today the most substantial threats facing cities relate to the impacts of climate change. Extreme temperature such as heat waves and the occurrence of Urban Heat Island (UHI) phenomena, present the main challenges for urban planning and design. Climate deterioration exacerbates the already existing weaknesses in social systems, which have been created by changes such as population increases and urban sprawl. Despite numerous attempts by researchers to assess the risks associated with the heat-health nexus in urban areas, no common metrics have yet been defined yet. The objective of this study, therefore, is to provide an empirical example of a flexible and replicable methodology to estimate the micro-scale UHI risks within an urban context which takes into account all the relevant elements regarding the heat-health nexus. For this purpose, the city of Turin has been used as a case study. The methodological approach adopted is based on risk assessment guidelines suggested and approved by the most recent scientific literature. The risk framework presented here used a quantitative estimate per each census tract within the city based on the interaction of three main factors: hazard, exposure, and vulnerability. Corresponding georeferenced maps for each indicator have been provided to increase the local knowledge on the spatial distribution of vulnerability drivers. The proposed methodology and the related findings represent an initial stage of the urban risk investigation within the case study. This will include participatory processes with local policymakers and health-stakeholders with a view to guiding the local planning agenda of climate change adaptation and resilience strategies in the City of Turin

NMDARs Mediate the Role of Monoamine Oxidase A in Pathological Aggression

This is the publisher's version, also available electronically from http://www.jneurosci.org/content/32/25/8574Converging evidence shows that monoamine oxidase A (MAO A), the key enzyme catalyzing serotonin (5-hydroxytryptamine; 5-HT) and norepinephrine (NE) degradation, is a primary factor in the pathophysiology of antisocial and aggressive behavior. Accordingly, male MAO A-deficient humans and mice exhibit an extreme predisposition to aggressive outbursts in response to stress. As NMDARs regulate the emotional reactivity to social and environmental stimuli, we hypothesized their involvement in the modulation of aggression mediated by MAO A. In comparison with WT male mice, MAO A KO counterparts exhibited increases in 5-HT and NE levels across all brain regions, but no difference in glutamate concentrations and NMDAR binding. Notably, the prefrontal cortex (PFC) of MAO A KO mice exhibited higher expression of NR2A and NR2B, as well as lower levels of glycosylated NR1 subunits. In line with these changes, the current amplitude and decay time of NMDARs in PFC was significantly reduced. Furthermore, the currents of these receptors were hypersensitive to the action of the antagonists of the NMDAR complex (dizocilpine), as well as NR2A (PEAQX) and NR2B (Ro 25-6981) subunits. Notably, systemic administration of these agents selectively countered the enhanced aggression in MAO A KO mice, at doses that did not inherently affect motor activity. Our findings suggest that the role of MAO A in pathological aggression may be mediated by changes in NMDAR subunit composition in the PFC, and point to a critical function of this receptor in the molecular bases of antisocial personality

Respects of human rights and perception of quality of care, the users' point of view comparing mental health and other health facilities in a region of Italy

This work is part of a research project that aims to measure organisational well-being, human rights respect and quality of care in mental health services in Sardinia, Italy, country that has replaced long-stay psychiatric hospitals with community mental health services. Previous contributions have seen Italian health professionals and users as the most satisfied and optimistic about the quality of the mental health care provided and the respect they offer for service users' rights. Our aim is to confirm these findings by comparing experiences of users of mental health services with those of other care services in the same region. Our findings indicate that mental health services users show higher level of satisfaction for care and higher perception of users' human rights respect compared to non-mental health facilities users. They also have greater satisfaction with organisational aspects of services and they are more convinced that the health professionals rights are respected. In contrast, they are less satisfied with the resources available for care centres than other users and require more professional psychosocial support. We want to allow future comparisons to other regions on quality assessment through the perception of users and worker on respect for standards and human rights

Maternal immune activation impairs endocannabinoid signaling in the mesolimbic system of adolescent male offspring

Prenatal infections can increase the risk of developing psychiatric disorders such as schizophrenia in the offspring, especially when combined with other postnatal insults. Here, we tested, in a rat model of prenatal immune challenge by the viral mimic polyriboinosinic-polyribocytidilic acid, whether maternal immune activation (MIA) affects the endocannabinoid system and endocannabinoid-mediated modulation of dopamine functions. Experiments were performed during adolescence to assess i) the behavioral endophenotype (locomotor activity, plus maze, prepulse inhibition of startle reflex); ii) the locomotor activity in response to Δ9-Tetrahydrocannabinol (THC) and iii) the properties of ventral tegmental area (VTA) dopamine neurons in vivo and their response to THC; iv) endocannabinoid-mediated synaptic plasticity in VTA dopamine neurons; v) the expression of cannabinoid receptors and enzymes involved in endocannabinoid synthesis and catabolism in mesolimbic structures and vi) MIA-induced neuroinflammatory scenario evaluated by measurements of levels of cytokine and neuroinflammation markers. We revealed that MIA offspring displayed an altered locomotor activity in response to THC, a higher bursting activity of VTA dopamine neurons and a lack of response to cumulative doses of THC. Consistently, MIA adolescence offspring showed an enhanced 2-arachidonoylglycerol-mediated synaptic plasticity and decreased monoacylglycerol lipase activity in mesolimbic structures. Moreover, they displayed a higher expression of cyclooxygenase 2 (COX-2) and ionized calcium-binding adaptor molecule 1 (IBA-1), associated with latent inflammation and persistent microglia activity. In conclusion, we unveiled neurobiological mechanisms whereby inflammation caused by MIA influences the proper development of endocannabinoid signaling that negatively impacts the dopamine system, eventually leading to psychotic-like symptoms in adulthood