Soft-Seeded Pomegranate (<Emphasis Type="Italic">Punica granatum</Emphasis> L.) Varieties: Preliminary Characterization and Quality Changes of Minimally Processed Arils During Storage

A preliminary characterization of two new soft-seeded pomegranate varieties (MR-100® and KINGDOM®) based on their main physico-chemical and nutritional parameters was reported. The two varieties showed significant differences (p ≤ 0.05) in polyphenols, anthocyanins and antioxidant activity. Kingdom pomegranate had higher polyphenols (2524.73 mg GAE/L), anthocyanins (752.49 mg C₃gE/L) and antioxidant activity (EC₅₀ 13.58 μL/mL) than MR-100 (1792.74 mg GAE/L, 141.29 mg C₃gE/L and EC₅₀ 47.53 μL/mL, respectively). Moreover, minimally processed arils of the two varieties were packaged in semipermeable and micro-perforated film at 5 °C, and the quality changes that occurred during storage condition (15 days) were investigated. During storage, Kingdom arils exhibited a better performance in terms of antioxidant activity, polyphenols and anthocyanin content with respect to MR-100. Furthermore, the packaging systems did not affect the estimated quality parameters for both varieties. Based on the sensory evaluation and microbial counts, both aril varieties reached, at 15-day storage, suitable values for commercial purpose.     

Histochemical characterization of the sialic acid residues in mouse colon mucins

The mucins of colonic murine mucus are highly O‐glycosilated sulfosialoglycoproteins. We have characterized the sialylation pattern of oligosaccharide chains of colonic murine mucins by conventional histochemical methods and by lectin histochemistry combined with chemical pretreatments and sialidase digestion. Oligosaccharide chains are strongly sulphated, with an increase of sulfation from the proximal toward the distal colon and a decrease of sialic acid expression and acetylation toward the distal colon. In the goblet cells of proximal colon, sialic acid bound α2,3 to Galβ1,3GalNAc subterminal dimers is diacetylated at C7,C8;C7,C9;C8,C9 or triacetylated at C7,8,9. In the distal colon, sialic acid‐linked α2,3 to Galβ1,3GalNAc subterminal dimers shows reduced O‐acetylation at C7 and/or C8, while acetyl substituents at C9 and at C4 are almost absent. Sialic acid is involved in different essential physiological functions; thus, alterations of its expression and acetylation in oligosaccharide chains of intestinal mucins are generally associated with diseases, such as ulcerative colitis and cancer. Mice may represent a suitable animal model to study alterations of oligosaccharidic chains in colonic mucins and lectin histochemistry combined with chemical pretreatments, and enzyme digestion may be a valuable tool for this study. Our present work may represent a landmark for further lectin histochemical studies to evaluate alterations of mouse colon mucins under different physiological, pathological, or experimental conditions, with possible translational value in humans. Microsc. Res. Tech., 2013. © 2012 Wiley Periodicals, Inc.     

Lipid characteristics of RSV-transformed Balb/c 3T3 cell lines with different spontaneous metastatic potentials

To determine whether a metastatic phenotype may be corelated with a characteristic lipid pattern, we compared the lipid composition of low metastasizing Balb/c 3T3 cells transformed by the B77 strain of Rous sarcoma virus (B77-3T3 cells) with that of a subclone isolated by growth in 0.6% agar, the B77-AA6 cells, which exhibit a high capacity for spontaneous metastasis. B77-3T3 cells revealed characteristics in their lipid composition common to other systems of transformed cells, i.e., an accumulation of ether-linked lipids, a reduction of the more complex gangliosides, an increase of oleic acid (18∶1) and a decrease of arachidonic (20∶4) and C22 polyunsaturated fatty acids in phospholipids. High metastatic B77-AA6 cells showed: a) an even more marked decrease of complex gangliosides; b) a more pronounced increase of 18∶1 and decrease of 20∶4 and 22 polyunsaturated fatty acids in certain phospholipid classes; and c) a higher percentage of alkyl-acyl subfractions in both phosphatidylcholine and phosphatidylethanolamine than B77-3T3 cells. Comparing the data for other systems of metastatic cells with those of lipid studies of spontaneously metastasizing B77-AA6 cell system leads us to conclude that the metastatic phenotype is characterized by a change in ether-linked lipids, rather than in fatty acids.     

A critical assessment of the mechanistic aspects in HAYNES 188 during low-cycle fatigue in the range 25 °C to 1000 °C

The low-cycle fatigue (LCF) behavior of a wrought cobalt-base superalloy, Haynes 188, has been investigated over a range of temperatures between 25 °C and 1000 °C employing a triangular waveform and a constant strain amplitude of ±0.4 pct. Correlations between macroscopic cyclic deformation and fatigue life with the various microstructural phenomena were enabled through scanning electron microscopy (SEM) and transmission electron microscopy (TEM), detailing the crack initiation and propagation modes, deformation substructure, and carbide precipitation. Cyclic stress response varied as a complex function of temperature. Dynamic strain aging (DSA) was found to occur over a wide temperature range between 300 °C and 750 °C. In the DSA domain, the alloy exhibited marked cyclic hardening with a pronounced maximum at 650 °C. Dynamic strain aging has been documented through the occurrence of serrated yielding, inverse temperature dependence of maximum cyclic stress, and cyclic inelastic strain developed at half of the fatigue life. Additionally, the alloy also displayed a negative strain rate sensitivity of cyclic stress in the DSA regime. These macroscopic features in the DSA domain were accompanied by the substructure comprised of coplanar distribution of dislocations associated with the formation of pileups, stacking faults, and very high dislocation density. Toward the end of the DSA domain, dislocation pinning by M₂₃C₆ precipitates occurred predominantly. The deformation behavior below and above the DSA domain has also been investigated in detail. The temperature dependence of LCF life showed a maximum at ≈300 °C. The drastic reduction in life between 300 °C and 850 °C has been ascribed primarily to the deleterious effects of DSA on crack initiation and propagation, while the lower life at temperatures less than 200 °C has been attributed to the combined influence of low ductility and larger cyclic response stress.     

Target Hopping as a Useful Tool for the Identification of Novel EphA2 Protein–Protein Antagonists

Lithocholic acid (LCA), a physiological ligand for the nuclear receptor FXR and the G‐protein‐coupled receptor TGR5, has been recently described as an antagonist of the EphA2 receptor, a key member of the ephrin signalling system involved in tumour growth. Given the ability of LCA to recognize FXR, TGR5, and EphA2 receptors, we hypothesized that the structural requirements for a small molecule to bind each of these receptors might be similar. We therefore selected a set of commercially available FXR or TGR5 ligands and tested them for their ability to inhibit EphA2 by targeting the EphA2‐ephrin‐A1 interface. Among the selected compounds, the stilbene carboxylic acid GW4064 was identified as an effective antagonist of EphA2, being able to block EphA2 activation in prostate carcinoma cells, in the micromolar range. This finding proposes the “target hopping” approach as a new effective strategy to discover new protein–protein interaction inhibitors.     

The MITC9 <Emphasis Type="Italic">shell</Emphasis> element in <Emphasis Type="Italic">plate</Emphasis> bending: mathematical analysis of a simplified case

We consider the 9-node shell element referred to as the MITC9 shell element in plate bending solutions and present a simplified mathematical analysis. The element uses bi-quadratic interpolations of the rotations and transverse displacement, and the “rotated Raviart-Thomas” interpolations for the transverse shear stresses. A rigorous mathematical analysis of the element is still lacking, even for the simplified case of plate solutions (that is, flat shells), although the numerical evidence suggests a good and reliable behavior. Here we start such an analysis by considering a very simple particular case; namely, a rectangular plate, clamped all around the boundary, and solved with a uniform decomposition. Moreover, we consider only the so-called limit case, corresponding to the limit equations that are obtained for the thickness t going to zero. While the mathematical analysis of the limit case is simpler, such analysis, in general, gives an excellent indication of whether shear locking is present in the real case t > 0. We detail that the element in the setting considered shows indeed optimal behavior.     

Immune Aging and Immunotherapy in Cancer

Immune functions decline as we age, while the incidence of cancer rises. The advent of immune checkpoint blockade (ICB) has not only revolutionized cancer therapy, but also spawned great interest in identifying predictive biomarkers, since only one third of patients show treatment response. The aging process extensively affects the adaptive immune system and thus T cells, which are the main target of ICB. In this review, we address age-related changes regarding the adaptive immune system with a focus on T cells and their implication on carcinogenesis and ICB. Differences between senescence, exhaustion, and anergy are defined and current knowledge, treatment strategies, and studies exploring T cell aging as a biomarker for ICB are discussed. Finally, novel approaches to improve immunotherapies and to identify biomarkers of response to ICB are presented and their potential is assessed in a comparative analysis.