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.     

Gastric Adenocarcinomas and Signet-Ring Cell Carcinoma: Unraveling Gastric Cancer Complexity through Microbiome Analysis—Deepening Heterogeneity for a Personalized Therapy

Gastric cancer (GC) is the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. With the advances of the omic studies, a heterogeneous GC landscape has been revealed, with significant molecular diversity. Given the multifaceted nature of GC, identification of different patient subsets with prognostic and/or predictive outcomes is a key aspect to allow tailoring of specific treatments. Recently, the involvement of the microbiota in gastric carcinogenesis has been described. To deepen this aspect, we compared microbiota composition in signet-ring cell carcinoma (SRCC) and adenocarcinoma (ADC), two distinct GC subtypes. To this purpose, 10 ADC and 10 SRCC and their paired non-tumor (PNT) counterparts were evaluated for microbiota composition through 16S rRNA analysis. Weighted and unweighted UniFrac and Bray–Curtis dissimilarity showed significant community-level separation between ADC and SRCC. Through the LEfSe (linear discriminant analysis coupled with effect size) tool, we identified potential microbial biomarkers associated with GC subtypes. In particular, SRCCs were significantly enriched in the phyla Fusobacteria, Bacteroidetes, Patescibacteria, whereas in the ADC type, Proteobacteria and Acidobacteria phyla were found. Overall, our data add new insights into GC heterogeneity and may contribute to deepening the GC classification.     

Graphene nanoplatelets composite membranes for thermal comfort enhancement in performance textiles

The advent of 2D nanostructured materials as advanced fillers for polymer matrix composites has opened the doors to a plethora of new industrial applications requiring both electric and thermal management. Unique properties, in fact, can arise from accurate selection and processing of 2D fillers and their matrix. Here, we report an innovative family of nanocomposite membranes based on polyurethane (PU) and graphene nanoplatelets (GNPs), designed to improve thermal comfort in functional textiles. GNP particles were thoroughly characterized (through Raman, atomic force microscopy, high-resolution TEM, scanning electron microscope), and showed high crystallinity (I_D/I_G = 0.127), low thickness (D50 < 6–8 layers), and high lateral dimensions (D50 ≈ 3 μm). When GNPs were loaded (up to 10% wt/wt) into the PU matrix, their homogeneous dispersion resulted in an increase of the in-plane thermal conductivity of composite membranes up to 471%. The thermal dissipation of membranes, alone or coupled with cotton fabric, was further evaluated by means of an ad hoc system designed to simulate a human forearm. The results obtained provide a new strategy for the preparation of membranes suitable for technical textiles, with improved thermal comfort.     

Polycyclic aromatic hydrocarbon (PAH) content of soil and olives collected in areas contaminated with creosote released from old railway ties

Simple sample preparation procedures involving sonication and solid phase extraction (SPE), followed by reversed-phase high performance liquid chromatography (HPLC) and spectrofluorometric detection, were used to analyse polycyclic aromatic hydrocarbons (PAHs) in soil and olives collected in areas contaminated with creosote-treated railway ties. Very high PAH contents (with amounts ranging from 114.7 to 2157.2 and from 167.3 to 3121.8 microg kg(-1) dry weight for total light PAHs and total heavy PAHs, respectively) were found in soil sampled up to 1 m from the source of contamination. The PAH load decreased rapidly with the distance from the railway ties. High amounts of light PAHs, up to 6359.9 microg kg(-1), were also found in oil extracted from olives collected in a rural area where old railway ties were stored. No appreciable transfer of heavy PAHs and benzo[a]pyrene was observed in oil samples.     

Kinetics of 4-nitrophenol biodegradation in a sequencing batch reactor

In this paper, the biodegradation process of 4-nitrophenol (4NP) in a sequencing batch reactor has been investigated. Kinetic tests have been carried out on biomass grown on mixed substrate (4NP plus biogenic substrate) both in the presence of a biogenic substrate fraction in the feed and with 4NP as the sole carbon source. Removal kinetics for all tests is well described by the typical substrate inhibition pattern as predicted by the Haldane equation. In both sets, estimated kinetic parameters are very similar: no beneficial effect of the biogenic fraction is observed on the 4NP removal while increasing trend of 4NP maximum removal rate with the 4NP/COD(TOT) ratio in the feed has been observed. This finding has been modelled by estimating the fraction of the total biomass involved in 4NP biodegradation as a function of 4NP concentration in the feed. High removal rates, short acclimation times and good settling characteristics of produced sludge (observed during the whole working period) confirm the suitability of periodic systems in enhancing the bacterial potentialities for biodegradation of xenobiotic compounds.     

Intrinsic Fluorescence of the Active and the Inactive Functional Forms of Human Thymidylate Synthase

The observables associated with protein intrinsic fluorescence – spectra, time decays, anisotropies – offer opportunities to monitor in real time and non-invasively a protein‘s functional form and its interchange with other forms with different functions. We employed these observables to sketch the fluorometric profiles of two functional forms of human thymidylate synthase (hTS), a homodimeric enzyme crucial for cell proliferation and thus targeted by anticancer drugs. The protein takes an active and an inactive form. Stabilization of the latter by peptides that, unlike classical hTS inhibitors, bind it at the monomer/monomer interface offers an alternative inhibition mechanism that promises to avoid the onset of drug resistance in anticancer therapy. The fluorescence features depicted herein can be used as tools to identify and quantify each of the two protein forms in solution, thus making it possible to investigate the kinetic and thermodynamic aspects of the active/inactive conformational interchange. Two examples of fluorometrically monitored interconversion kinetics are provided.     

Partial replacement of sodium chloride with potassium chloride in marinated rabbit meat

This study was aimed at evaluating the consequences of sodium chloride reduction by potassium chloride up to 50% on technological, sensorial and microbiological traits of marinated rabbit meat. In total, 226 rabbit loin meat samples were obtained and subjected to vacuum tumbling using solutions with different NaCl/KCl ratios. Replacing of sodium chloride up to 30% by potassium chloride did not change microbiological traits (total aerobic mesophilic and lactic acid bacteria maximum cell loads), sensorial acceptability (perceived saltiness and overall liking) and technological traits (pH, colour, texture, cooking loss and yield). Otherwise, reduction in sodium chloride to 50% significantly decreased perceived saltiness (4.15 vs. 4.73; P < 0.05) and reduced microbial shelf life by 1 day when compared to control, even if there was still no effect on technological traits. In conclusion, it is feasible imparting an added value for processed rabbit meat products by reduction in sodium content that could increase market interest.     

Persistent organic pollutants in farmed European sea bass (Dicentrarchus labrax,Linnaeus, 1758) from Sicily (Italy)

Farmed European sea bass (Dicentrarchus labrax, Linnaeus, 1758) were collected during 2016 from one Sicilian fish farm that uses two different rearing systems – sea cage and concrete tank – for determination of polychlorinated biphenyls (PCB), organochlorine pesticides (OCP) and polycyclic aromatic hydrocarbons (PAH) residues by HRGC-MS/MS. Moreover, commercial feed was analysed. This study aimed to determine whether the different rearing systems affect the concentration of these compounds, and to assess the safety of cultured fish. PCBs represent the pollutants with the highest concentration; in particular, PCB138 and 153 have the highest concentration in almost all samples. Among OCPs, only 4,4′-DDE, 4,4′-DDD and 4,4′-DDT residues have been detected. Concerning PAHs, only fluorene and phenanthrene were detected, in both rearing systems. Although some residues of organic pollutants were found in the analysed samples, they were always below the MRLs, so the results suggest that farmed sea bass are safe for human consumption.