SPECIALIZED FUNCTIONS OF LAMINA PROPRIA ANTIGEN-PRESENTING CELLS IN THE MAINTENANCE OF INTESTINAL IMMUNE-HOMEOSTASIS

The intestinal immune system is daily threatened by the exposure to potentially harmful agents, such as food antigens and the gut flora. They represent, indeed, a potent immunogenic stimulus that the immune system has to tolerate. In the Gut-Associated Lymphoid Tissue, the cooperation and mutual interaction of specific environmental factors and peculiar populations of antigen-presenting cells renders the gut a suitable site for the maintenance of a tolerogenic milieu, where immunosuppressive mechanisms keep at bay unwanted deleterious immune responses. The establishment of tolerance to food antigens mostly relies on the ability of specific subsets of mononuclear cells to take up antigens in the SI (Small Intestine) and to subsequently shape the immune response, which is initiated in the draining mesenteric lymph nodes. Here, we describe a subset of resident intestinal macrophages, expressing CX3CR1, which are committed to antigen uptake. Furthermore, we show that in the absence of functional CX3CR1 receptor, which impairs the ability of these cells to sample the intestinal lumen, decreased antigen uptake and failure in the establishment of oral tolerance is observed in CX3CR1-deficient mice. As CX3CR1+ cells are sessile and poorly able to prime T cells, we hypothesized the possibility of gap junction-mediated antigenic material transfer to CD103+ dendritic cells, which have been accounted for migratory tolerogenic cells. We show, indeed, that mononuclear cells from the SI can exchange peptides and gap-junction diffusible dyes. Furthermore, CX3CR1+ macrophages and CD103+ dendritic cells express a peculiar panel of connexins, among which connexin 43 is the most expressed. We then generated mice lacking connexin 43 in CD11c+ cells. These mice displayed no change in the frequency and activation state of the different populations of lamina propria cells but decreased the levels of peripheral T regulatory cells at steady-state. In addition, we observed impaired establishment of oral tolerance to ovalbumin. This indicates that DC-expression of Cx43 is required for the establishment of oral tolerance. Whether this is due to a lessening in antigen transfer which impinges on the ability of CD103+ dendritic cells to prime T cells towards a tolerogenic phenotype or to other Cx43-dependent functions of SI mononuclear cells are still open questions, which need to be addressed

A Model-Based methodology to support the Space System Engineering (MBSSE)

International audienceThis paper presents a model based methodology that relies on the sound basis of the most recent and widespread applicable system engineering standards and model based practices, The methodology has been defined to support domain specific space system engineering standards and practices and assessed through the application on industrial case studies. A complementary formal verification approach has also been experimented

The use of Th in HTR: State of the art and implementation in Th/Pu fuel cycles

Nowadays nuclear is the only greenhouse-free source that can appreciably respond to the increasing worldwide energy demand. The use of Thorium in the nuclear energy production may offer some advantages to accomplish this task. Extensive R&D on the thorium fuel cycle has been conducted in many countries around the world. Starting from the current nuclear waste policy, the EU-PUMA project focuses on the potential benefits of using the HTR core as a Pu/MA transmuter. In this paper the following aspects have been analysed: (1) the state-of-the-art of the studies on the use of Th in different reactors, (2) the use of Th in HTRs, with a particular emphasis on Th-Pu fuel cycles, (3) an original assessment of Th-Pu fuel cycles in HTR. Some aspects related to Thorium exploitation were outlined, particularly its suitability for working in pebble-bed HTR in a Th-Pu fuel cycle. The influence of the Th/Pu weight fraction at BOC in a typical HTR pebble was analysed as far as the reactivity trend versus burn-up, the energy produced per Pu mass, and the Pu isotopic composition at EOC are concerned. Although deeper investigations need to be performed in order to draw final conclusions, it is possible to state that some optimized Th percentage in the initial Pu/Th fuel could be suggested on the basis of the aim we are trying to reach

RETURN TO WORK IN ITALIAN CANCER SURVIVORS: THE INNOVATIVE SOCIAL-HEALTH CARE NETWORK

The Local Health Authority of Reggio Emilia, supported by the Manodori Foundation, decided to implement this innovative social-health care pathway that was created together with other 14 organizations in the Province of Reggio Emilia: they are Associations, labor union, training institutions, social cooperatives, and so on… Together, we created a network to address the need to go back to work of cancer patients. What happens to the working age patients with cancer in Reggio Emilia? First of all first of all the HCPs who meet the patients for diagnostic or curative reasons ask for information about the work situation. On the basis of this very first information collected, if the patient is judged at risk to lose the job he is referred to the network hub of UNA MANO: the Informa-salute service. Here, a Nurse, together with other trained personnel, make the first true assessment of the risk to lose the job. If the patients is judged at low risk, he still receive information regarding… If the patient is judged at risk to lose the job, he is sent to the OT that make a deep, second level of assessment. After this, if the risk is confirmed as moderate, the patients will received a personalized intervention targeted to… If the risk is judged very high, or the patient as already lost the job, the social part of the network is activated to implement a personalized intervention targeted to

First report on Copepoda and Ostracoda (Crustacea) from northern Apenninic springs (N. Italy): a faunal and biogeographical account

The microcrustacean fauna of rheocrene and rheo-limnocrene springs in a protected area of the northern Apennines (Italy) was investigated for the first time. All springs are located in the catchments of the rivers Parma and Enza at altitudes between 800 and 1609 m a.s.l. Several of these springs are still in pristine condition while others are artificially modified or impacted to some degree. Surveys were carried out from April to June 2007. The sampling methods used for invertebrate fauna were: moss washing, artificial traps, and inserting drift tubes at the discharge point. A total of 14 harpacticoid, five cyclopoid, and 13 ostracod taxa were identified. Ostracods were mainly represented by crenophilic taxa; of particular interest was the collection of a specimen belonging to Pseudolimnocythere, a stygobiont genus with only two living species and a reduced distribution. Faunal affinities between northern Apenninic springs and those in other Italian mountain systems are discussed. The investigated ecosystems support a high microcrustacean diversity that must be adequately preserved due to the increasing direct and indirect impacts on mountain springs and groundwater resources

VOC Air Pollution in Urban Areas – A Microscale Model experimentally validated

Previous theoretical and experimental studies (S. T. A.- Università di Pisa (DIMNP), 1998; Agostini E., M. Corezzi, I. Ciucci, M. Mazzini 2003; Agostini E., I. Ciucci, M. Mazzini, S. Strinati, 2003) even if partial, evidenced the problem of atmospheric pollution by Volatile Organic Compounds (VOC) in Livorno (Tuscany). This pollution is caused mainly by the presence of an important refinery, other industries and traffic. Other relevant VOC emission sources are linked to port activities and to numerous small companies using paints and solvents. Figure 1 shows the map of Livorno, situated on the Tyrrhenian sea. This is a simple site from the orography point of view, except for the southern zone where a promontory and a chain of hills impose a more complex pattern of air fluxes. The industrial zone is localized in the north of the map and the harbour activities along the coast (west area). It’s difficult to define a specific zone for the companies using solvents and paints, even though a grater concentration is present around the axis Viale Carducci – Piazza Repubblica – Via Grande. The map outlines also the air pollution measurement stations managed by ARPAT (points) and the meteorological stations (crosses). The simulation of the emission scenario, was done by using ISC3 (U. S. Environmental Protection Agency) code for treating diffuse sources and CALINE4 (California Department of Transportation) for those related to traffic on main roads. The research work focuses the attention on the results of model validation by experimental data obtained along the roads of the studied area. The possibility to extend the application of this model to sites with similar orography and town-planning characteristics is also discussed in the aim of obtaining information about the level of atmospheric pollution on sites where there aren’t measurement stations

Effects of Acetyl-L-Carnitine on Oxidative Stress in Amyotrophic Lateral Sclerosis Patients: Evaluation on Plasma Markers and Members of the Neurovascular Unit

Oxidative stress, the alteration of mitochondrial function, and the neurovascular unit (NVU), play a role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. We aimed to demonstrate the changes in the plasma redox system and nitric oxide (NO) in 32 new ALS-diagnosed patients in treatment with Acetyl-L-Carnitine (ALCAR) compared to healthy controls. We also evaluated the effects of plasma on human umbilical cord-derived endothelial vascular cells (HUVEC) and astrocytes. The analyses were performed at the baseline (T0), after three months (T1), and after six months (T2). In ALS patients at T0/T1, the plasma markers of lipid peroxidation, thiobarbituric acid reactive substances (TBARS) and 4-hydroxy nonenal (4-HNE) were higher, whereas the antioxidants, glutathione (GSH) and the glutathione peroxidase (GPx) activity were lower than in healthy controls. At T2, plasma TBARS and 4-HNE decreased, whereas plasma GSH and the GPx activity increased in ALS patients. As regards NO, the plasma levels were firmly lower at T0–T2 than those of healthy controls. Cell viability, and mitochondrial membrane potential in HUVEC/astrocytes treated with the plasma of ALS patients at T0–T2 were reduced, while the oxidant release increased. Those results, which confirmed the fundamental role of oxidative stress, mitochondrial function, and of the NVU in ALS pathogenesis, can have a double meaning, acting as disease markers at baseline and potential markers of drug effects in clinical practice and during clinical trial

Dual excitation multi-fluorescence flow cytometry for detailed analyses of viability and apoptotic cell transition

The discrimination of live/dead cells as well as the detection of apoptosis is a frequent need in many areas of experimental biology. Cell proliferation is linked to apoptosis and controlled by several genes. During the cell life, specific events can stimulate proliferation while others may trigger the apoptotic pathway. Very few methods (i.e. TUNEL) are now available for studies aimed at correlation between apoptosis and proliferation. Therefore, there is interest in developing new methodological approaches that are able to correlate apoptosis to the cell cycle phases. Recently new approaches have been proposed to detect and enumerate apoptotic cells by flow cytometry. Among these, the most established and applied are those based on the cell membrane modifications induced in the early phases of the apoptotic process. The dye pair Hoechst 33342 (HO) and Propidium Iodide (PI), thanks to their peculiar characteristics to be respectively permeable and impermeable to the intact cell membrane, seems to be very useful. Unfortunately the spectral interaction of these dyes generates a consistent "energy transfer" from HO to PI. The co-presence of the dyes in a nucleus results in a modification in the intensity of both the emitted fluorescences. In order to designate the damaged cells (red fluorescence) to the specific cell cycle phases (blue fluorescence), we have tested different staining protocols aimed to minimize the interference of these dyes as much as possible. In cell culture models, we are able to detect serum-starved apoptotic cells as well as to designate their exact location in the cell cycle phases using a very low PI concentration. Using a Partec PAS flow cytometer equipped with HBO lamp and argon ion laser, a double UV/blue excitation has been performed. This analytical approach is able to discriminate live blue cells from the damaged (blue-red) ones even at 0.05 ?g/mL PI. The same instrumental setting allows performing other multi-colour analyses including AnnexinV-FITC as well as the possibility to make a correlated analysis to phenotype markers

PM2.5 Size Distribution and Characterization by Carbon Isotope in Tuscany (Italy)

This study is focused on the numerical distribution and isotopic description of PM2.5 developed within the PATOS II (Particolato Atmosferico TOScana) regional project about the characterization and source apportionment of atmospheric aerosol (PM2.5) in Tuscany. PM isotopic analysis can play an important role in the individuation of primary and secondary sources and also in the determination of the natural/biogenic or anthropogenic/combustion contribution to the measured concentration. In addition, the PM2.5 particle number concentrations and the relative contribution of ultrafine particles are interpreted to identify the emission sources, the main atmospheric processes and the factors related with the dispersion of atmospheric pollutants. The analytical results in term of δ13C parameter show a greater variability in the urban and suburban background sites than in the urban traffic site, where the δ13C parameter does not vary significantly: this could be strictly correlated with traffic emissions and independently from the total particles number. On the contrary, urban and suburban background sites are affected by the meteorology and atmospheric processes. For this reason we can observe a wider variability in the δ13C values due to the contribution of different emissions sources. Despite all, in urban background we can observe lower δ13C values related with high number of total particles; this effect could be related with a traffic emission transport, because the δ13C parameter is similar to the δ13C value of urban traffic site