The Impact of the ‘Mis-Peptidome’ on HLA Class I-Mediated Diseases: Contribution of ERAP1 and ERAP2 and Effects on the Immune Response

The strong association with the Major Histocompatibility Complex (MHC) class I genes represents a shared trait for a group of autoimmune/autoinflammatory disorders having in common immunopathogenetic basis as well as clinical features. Accordingly, the main risk factors for Ankylosing Spondylitis (AS), prototype of the Spondyloarthropathies (SpA), the Behçet’s disease (BD), the Psoriasis (Ps) and the Birdshot Chorioretinopathy (BSCR) are HLA-B*27, HLA-B*51, HLA-C*06:02 and HLA-A*29:02, respectively. Despite the strength of the association, the HLA pathogenetic role in these diseases is far from being thoroughly understood. Furthermore, Genome-Wide Association Studies (GWAS) have highlighted other important susceptibility factors such as Endoplasmic Reticulum Aminopeptidase (ERAP) 1 and, less frequently, ERAP2 that refine the peptidome presented by HLA class I molecules to CD8⁺ T cells. Mass spectrometry analysis provided considerable knowledge of HLA-B*27, HLA-B*51, HLA-C*06:02 and HLA-A*29:02 immunopeptidome. However, the combined effect of several ERAP1 and ERAP2 allelic variants could generate an altered pool of peptides accounting for the “mis-immunopeptidome” that ranges from suboptimal to pathogenetic/harmful peptides able to induce non-canonical or autoreactive CD8⁺ T responses, activation of NK cells and/or garbling the classical functions of the HLA class I molecules. This review will focus on this class of epitopes as possible elicitors of atypical/harmful immune responses which can contribute to the pathogenesis of chronic inflammatory diseases.     

AXL Receptor in Breast Cancer: Molecular Involvement and Therapeutic Limitations

Breast cancer was one of the first malignancies to benefit from targeted therapy, i.e., treatments directed against specific markers. Inhibitors against HER2 are a significant example and they improved the life expectancy of a large cohort of patients. Research on new biomarkers, therefore, is always current and important. AXL, a member of the TYRO-3, AXL and MER (TAM) subfamily, is, today, considered a predictive and prognostic biomarker in many tumor contexts, primarily breast cancer. Its oncogenic implications make it an ideal target for the development of new pharmacological agents; moreover, its recent role as immune-modulator makes AXL particularly attractive to researchers involved in the study of interactions between cancer and the tumor microenvironment (TME). All these peculiarities characterize AXL as compared to other members of the TAM family. In this review, we will illustrate the biological role played by AXL in breast tumor cells, highlighting its molecular and biological features, its involvement in tumor progression and its implication as a target in ongoing clinical trials.     

Autonomic Nervous System in Obesity and Insulin-Resistance—The Complex Interplay between Leptin and Central Nervous System

The role of the autonomic nervous system in obesity and insulin-resistant conditions has been largely explored. However, the exact mechanisms involved in this relation have not been completely elucidated yet, since most of these mechanisms display a bi-directional effect. Insulin-resistance, for instance, can be caused by sympathetic activation, but, in turn, the associated hyperinsulinemia can activate the sympathetic branch of the autonomic nervous system. The picture is made even more complex by the implicated neural, hormonal and nutritional mechanisms. Among them, leptin plays a pivotal role, being involved not only in appetite regulation and glucose homeostasis but also in energy expenditure. The purpose of this review is to offer a comprehensive view of the complex interplay between leptin and the central nervous system, providing further insights on the impact of autonomic nervous system balance on adipose tissue and insulin-resistance. Furthermore, the link between the circadian clock and leptin and its effect on metabolism and energy balance will be evaluated.     

Mechanical behavior of cold-water fish gelatin gels crosslinked with 1,4-butanediol diglycidyl ether

In this work, chemical crosslinking with 1,4-butanediol diglycidyl ether (BDDGE) is used as strategy to enhance mechanical performance of fish gelatin (FG) gels in order to meet the properties' range of mammalian gelatin physical gels. Joint analysis of free amino groups, swelling ratio, and total soluble material indicates that crosslinking degree increases with increasing FG concentration and it is favored by a 0.2 BDDGE/FG ratio. Increasing crosslinking degree enhances gel indentation strength and shear modulus (μ) while decreases fracture toughness (G_IC). Measured μ and G_IC values lies within the range exhibited by mammalian gelatin physical gels, but the relationship between these parameters is opposite. This is due to the different fracture mechanisms occurring in chemically crosslinked and physical gels.     

Isothermal crystallization of PLA: Nucleation density and growth rates of α and α' phases

From a technological point of view, poly(lactic acid) (PLA) is one of the most important polymers produced from renewable sources, due to its versatility, relatively acceptable processability, and low cost. However, a significant limitation exists in its slow crystallization kinetics, which results in amorphous products having low mechanical properties and thermal resistance. For this reason, quantitative knowledge of the phenomenon of crystallization kinetics is fundamental. In this work, the crystallization kinetics in quiescent conditions of a commercial grade of PLA was analyzed in terms of nucleation and growth rates by direct morphological observations at different crystallization temperatures (T_c) and by calorimetric analysis in isothermal and non-isothermal conditions. The optical analysis showed a spherulitic morphology with radial growth of the lamellae. The analysis of the growth rate evidenced the α/α'-crystals polymorphism with a transition temperature of ~120°C. Based on experimental observation, the crystallization kinetics of the two crystalline phases were assessed.     

Effect of cavosurface angle beveling on the exposure angle of enamel prisms in different cavity sizes

The quality of the micromechanical retention between the enamel prisms exposed through acid etching and adhesive system can be influenced by the relationship between the angle of the exposed enamel prisms and the external surface/restorative material. Therefore, the aim of the present study was to determine the influence of the enamel cavosurface beveling in different cavity sizes on the angle relation between enamel prisms and the restorative material. For this research, 30 human permanent molars were used and divided into three groups according the isthmus aperture of class I cavities (1/4, 1/3, and 1/2 of the intercuspal distance). Cavosurface angle beveling was performed in each tooth buccal or palatal/lingual side, and a resin composite restoration was placed. Each restored tooth was sectioned in buccal/palatal direction followed by analysis in scanning electron microscope. Means of the angles observed between enamel prisms and the restorative material were registered and statistically analyzed by Kruskal‐Wallis test. Results showed higher mean angle values for beveled groups when comparing with the values observed in the unbeveled margins (p < .05) regardless of the isthmus aperture, being 1/4 (beveled = 48.36°; unbeveled = 20.71°), 1/3 (beveled = 39.75°; unbeveled = 29.15°), and 1/2 (beveled = 37.02°; unbeveled = 26.34°). It was also observed that in some unbeveled cavities, there were the presence of laterally exposed enamel prisms (0°), mainly in more conservative cavities. It was concluded that the presence of higher angles values occurred in the samples with beveled margins, without presence of laterally exposed enamel prisms.     

The evaluation of a social adaptive website for cultural events

In this paper, we present an evaluation of a social adaptive website in the domain of cultural events, iCITY DSA, which provides information about cultural resources and events that promote the cultural heritage in the city of Turin. Using this evaluation, our objective was to investigate the actual usage of a social adaptive website, in an effort to discover the real behavior of users, the unforeseen correlations among user actions and the consequent interactive behavior, the accuracy of both system and social recommendations and their impact on the users themselves, and the role of tagging in the user modeling process. The major contributions of the paper are manifold: insights into user interactions with social adaptive systems; guidelines for future designs; evaluation of the tagging activity and tag meanings in relation to the application domain and thus their impact on the representation of the user model; and a demonstration of how a combination and interplay of evaluation methodologies (e.g., quantitative and qualitative) can enhance our comprehension of evaluation data.     

Development and characterisation of a Y2Ti2O7-based glass-ceramic as a potential oxidation protective coating for titanium suboxide (TiOx)

A silica-based glass-ceramic, with Y₂Ti₂O₇ as the major crystalline phase, is designed, characterised and tested as an oxidation-protective coating for a titanium suboxide (TiO_x) thermoelectric material at temperatures of up to 600 °C. The optimised sinter-crystallisation treatment temperatures are found to be 1300 °C and 855 °C for a duration of 30 min, and this treatment leads to a glass-ceramic with cubic Y₂Ti₂O₇ and CaAl₂Si₂O₈ as crystalline phases. An increase of ~270 °C in the dilatometric softening temperature is observed after devitrification of the parent glass, thus further extending its working temperature range.Excellent adhesion of the glass-ceramic coating to the thermoelectric material is maintained after exposure to a temperature of 600 °C for 120 h under oxidising conditions, thus confirming the effectiveness of the T1 glass-ceramic in protecting the TiO_x material.     

Antioxidant packaging development and optimization using agroindustrial wastes

The increasing use of non-biodegradable materials and the difficulty in recycling most of the available packaging have been pushing the development of biodegradable packaging. In this study, the potential uses of agroindustrial wastes to produce biodegradable films with antioxidant capacity were investigated. Starch films were produced by casting method using bran from jaboticaba peel, mango peel, and broccoli stalk. The influence of the concentration or type of bran in the properties of the films was evaluated through a central composite design. The results were analyzed by response surface and desirability function. Except for elongation and water solubility, the fitted equations were predictive in all studied properties. The films prepared from a higher concentration of mango peel exhibited better antioxidant capacity, while the broccoli stalk had no significant effect on antioxidant properties. The optimal formulation of the film (2.8% of jaboticaba peel and 20.0% of mango peel) and their predicted response variables (0.8 MPa for tensile strength, 40.0 MPa for Young's modulus, 4.5 mg/ml for IC₅₀, and 41.6% for inhibition percentage) were defined according to the results. The optimization was satisfactory and the film presented high antioxidant capacity and moderate mechanical properties, proving to be an alternative to replace plastic packaging.     

Characterisation of oleoresins extracted from tomato waste by liquid and supercritical carbon dioxide

Tomato waste is characterised by high amounts of bioactive compounds, such as carotenoids, polyphenols and essential fatty acids. In this work, oleoresins were produced from tomato waste (skins + seeds) and skins using carbon dioxide under liquid and supercritical conditions. The use of ethanol as a co-solvent was also evaluated. Compositions of the oleoresins were analysed and compared to oleoresin obtained by means of an organic solvent, which was used as the control. Oleoresin extraction from the waste by liquid and supercritical CO₂ provided the highest yields (12.5%–12.9%). The extracts obtained from the skins with supercritical CO₂ without ethanol had the highest content of α- and γ-tocopherols (80 and 575 mg/100 g oleoresin, respectively), while lycopene and β-carotene were found at 205 and 75 mg/100 g oleoresin, respectively. The highest quantity of polyphenols (9305 mg GAE/100 g oleoresin) was found in the oleoresin extracted from skin by supercritical CO₂ with ethanol. All oleoresins were characterised by a high antioxidant activity, which improved with the synergy of carotenoids, tocopherols and polyphenols.