Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia

The C-terminal aminoacidic sequence from NPM1-mutated protein, absent in normal human tissues, may serve as a leukemia-specific antigen and can be considered an ideal target for NPM1-mutated acute myeloid leukemia (AML) immunotherapy. Different in silico instruments and in vitro/ex vivo immunological platforms have identified the most immunogenic epitopes from NPM1-mutated protein. Spontaneous development of endogenous NPM1-mutated-specific cytotoxic T cells has been observed in patients, potentially contributing to remission maintenance and prolonged survival. Genetically engineered T cells, namely CAR-T or TCR-transduced T cells, directed against NPM1-mutated peptides bound to HLA could prospectively represent a promising therapeutic approach. Although either adoptive or vaccine-based immunotherapies are unlikely to be highly effective in patients with full-blown leukemia, these strategies, potentially in combination with immune-checkpoint inhibitors, could be promising in maintaining remission or preemptively eradicating persistent measurable residual disease, mainly in patients ineligible for allogeneic hematopoietic stem cell transplant (HSCT). Alternatively, neoantigen-specific donor lymphocyte infusion derived from healthy donors and targeting NPM1-mutated protein to selectively elicit graft-versus-leukemia effect may represent an attractive option in subjects experiencing post-HSCT relapse. Future studies are warranted to further investigate dynamics of NPM1-mutated-specific immunity and explore whether novel individualized immunotherapies may have potential clinical utility in NPM1-mutated AML patients.     

Analysis of extra virgin olive oils from stoned olives

This paper focuses on comparing the main chemical characteristics of 16 fresh commercial samples of extra virgin olive oil obtained from four harvest years (1999–2002) and derived from both stoned and whole fruits. The qualitative and quantitative contents of minor polar compounds (MPCs) together with other reference analytical parameters (acidity, peroxides, UV absorption values and Rancimat test) were evaluated. An investigation of the MPCs and oil composition obtained from only stoned olives was also carried out. The acidity values of the oils from stoned fruits were always similar to or lower than those of the corresponding oils from whole fruits. For almost all the samples from stoned olives a better resistance to oxidation was revealed in comparison with the corresponding traditional oils. Five pairs obtained from the 2000 and 2001 harvests showed higher concentrations of both MPCs and hydroxytyrosol derivatives in the oils from stoned fruits, in agreement with their higher Rancimat values. Overall, our findings with regard to acidity values, % hydrolysis, the Rancimat test and the qualitative and quantitative distribution of MPCs suggest a higher antioxidant capacity of the oils from stoned olives. Copyright © 2004 Society of Chemical Industry     

Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG2T(G3T)3] and Its Derivatives with an Abasic Site Replacing Single Thymidine

In this paper, we report our investigations on five {"type":"entrez-nucleotide","attrs":{"text":"T30175","term_id":"612273"}}T30175 analogues, prepared by replacing sequence thymidines with abasic sites (S) one at a time, in comparison to their natural counterpart in order to evaluate their antiproliferative potential and the involvement of the residues not belonging to the central core of stacked guanosines in biological activity. The collected NMR (Nuclear Magnetic Resonance), CD (Circular Dichroism), and PAGE (Polyacrylamide Gel Electrophoresis) data strongly suggest that all of them adopt G-quadruplex (G4) structures strictly similar to that of the parent aptamer with the ability to fold into a dimeric structure composed of two identical G-quadruplexes, each characterized by parallel strands, three all-anti-G-tetrads and four one-thymidine loops (one bulge and three propeller loops). Furthermore, their antiproliferative (MTT assay) and anti-motility (wound healing assay) properties against lung and colorectal cancer cells were tested. Although all of the oligodeoxynucleotides (ODNs) investigated here exhibited anti-proliferative activity, the unmodified {"type":"entrez-nucleotide","attrs":{"text":"T30175","term_id":"612273"}}T30175 aptamer showed the greatest effect on cell growth, suggesting that both its characteristic folding in dimeric form and its presence in the sequence of all thymidines are crucial elements for antiproliferative activity. This straightforward approach is suitable for understanding the critical requirements of the G-quadruplex structures that affect antiproliferative potential and suggests its application as a starting point to facilitate the reasonable development of G-quadruplexes with improved anticancer properties.     

Measurements of size distribution nanoparticles in ultraviolet‐curable methacrylate‐based boehmite nanocomposites

A deep study on the possibility to increase the quality of the dispersion of organically modified Boehmite nanoparticles into photo‐polymerizable methacrylic‐siloxane monomers, to be used as coatings, was conducted using unconventional indirect analyses. The nanocomposite were produced using two different procedures, starting from the conventional “solvent dispersion method.” The two procedures used differ for the technique used to obtain the dispersion of Boehmite, i.e., sonication or magnetic stirring and for the time used in each procedure. The efficiency of each method of preparation of nanostructured systems was analyzed, both in the liquid (uncured) and ultraviolet (UV) cured state. First, dynamic light scattering and rheological measurements were performed on the liquid suspensions, supplying experimental data used in proper theoretical models to estimate the dimensions and distribution of Boehmite particles. The suspensions obtained with the two different methods were, then, UV cured obtaining thin and thick films, on which scanning electron microscopy and transmittance measurements were performed. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Multifunctional cotton fabrics

Electrically conductive fabrics were produced by deposition of a thin film of doped polypyrrole on the surface of cotton fibres. In situ oxidative chemical polymerisation were carried out in aqueous solutions of pyrrole, oxidant and doping agents, at room temperature. Polypyrrole-coated fibres were characterized by Light Microscopy, SEM, EDX, FTIR and TGA. Moreover, fabric samples were also evaluated for moisture regain, electrical resistivity, heat generation and antibacterial activity. PPy alters the combustion process of cellulose fibres that maintain the fibrous shape after heating in air. Moreover, it seems that PPy is really an antibacterial agent, apart from the oxidant or dopant used. The results highlight potential applications as technical textiles with antistatic (low electrical resistance), heat generation, hygroscopy, antibacterial and high temperature resistance properties.     

In-House Validation and Comparison of Two Wheat (<Emphasis Type="Italic">Triticum aestivum</Emphasis>) Taxon-Specific Real-Time PCR Methods for GMO Quantification Supported by Droplet Digital PCR

Common wheat is one of the most important staple food crops worldwide. However, unlike other important staple crops such as maize or soybean, genetically modified (GM) wheat is not yet present in the global food market. Nonetheless, in the recent past, the adventitious presence of GM glyphosate-tolerant volunteers was reported in open wheat fields in the USA. The European Union Reference Laboratory for GM Food and Feed (EURL-GMFF) was therefore called to develop a strategy to detect such unauthorised GM wheat in wheat samples by using both taxon-specific and screening tests. Two candidate common wheat taxon-specific real-time PCR methods were suggested, one targeting ssII-D gene coding for starch synthase and the other targeting waxy-D1 gene, coding for granule-bound starch synthase. In the present study, the two above-mentioned real-time PCR taxon-specific methods were in-house verified and compared, proposing droplet digital PCR (ddPCR) as a new tool for supporting the application of the European Network of GMO Laboratories (ENGL) established method performance criteria. Preliminary performance data of waxy-D1 and ssII-D methods in ddPCR format are shown too to give a contribution to the bridging process from the consolidated to the emerging quantitative PCR methodology.