Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.     

FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective

Irisin, the circulating peptide originating from fibronectin type III domain-containing protein 5 (FNDC5), is mainly expressed by muscle fibers under peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) control during exercise. In addition to several beneficial effects on health, physical activity positively affects nervous system functioning, particularly the hippocampus, resulting in amelioration of cognition impairments. Recently, FNDC5/irisin detection in hippocampal neurons and the presence of irisin in the cerebrospinal fluid opened a new intriguing chapter in irisin history. Interestingly, in the hippocampus of mice, exercise increases FNDC5 levels and upregulates brain-derived neurotrophic factor (BDNF) expression. BDNF, displaying neuroprotection and anti-inflammatory effects, is mainly produced by microglia and astrocytes. In this review, we discuss how these glial cells can morphologically and functionally switch during neuroinflammation by modulating the expression of a plethora of neuroprotective or neurotoxic factors. We also focus on studies investigating the irisin role in neurodegenerative diseases (ND). The emerging involvement of irisin as a mediator of the multiple positive effects of exercise on the brain needs further studies to better deepen this issue and the potential use in therapeutic approaches for neuroinflammation and ND.     

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.     

Immiscible PHB/PBS and PHB/PBSA blends: morphology,phase composition and modelling of elastic modulus

This paper reports the thermal, morphological and mechanical properties of environmentally friendly poly(3-hydroxybutyrate) (PHB)/poly(butylene succinate) (PBS) and PHB/poly[(butylene succinate)-co-(butylene adipate)] (PBSA) blends, prepared by melt mixing. The blends are known to be immiscible, as also confirmed by the thermodynamic analysis here presented. A detailed quantification of the crystalline and amorphous fractions was performed, in order to interpret the mechanical properties of the blends. As expected, the ductility increased with increasing PBS or PBSA amount, but in parallel the decrease in the elastic modulus appeared limited. Surprisingly, the elastic modulus was found properly described by the rule of mixtures in the whole composition range, thus attesting mechanical compatibility between the two blend components. This unusual behavior has been explained as due to co-continuous morphology, present in a wide composition range, but also at the same time as the result of shrinkage occurring during sequential crystallization of the two components, which can lead to physical adhesion between matrix and dispersed phase. For the first time, the elastic moduli of the crystalline and mobile amorphous fractions of PBS and PBSA and of the mobile amorphous fraction of PHB at ambient temperature have been estimated through a mechanical modelling approach. © 2021 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.     

1,2,4-Oxadiazole Topsentin Analogs with Antiproliferative Activity against Pancreatic Cancer Cells,Targeting GSK3β Kinase

A new series of topsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,2,4-oxadiazole moiety, was efficiently synthesized. All derivatives were pre-screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. The five most potent compounds were further investigated in various pancreatic ductal adenocarcinoma (PDAC) cell lines, including SUIT-2, Capan-1, and Panc-1 cells, eliciting EC₅₀ values in the micromolar and sub-micromolar range, associated with significant reduction of cell migration. These remarkable results might be explained by the effects of these new topsentin analogues on epithelial-to-mesenchymal transition markers, including SNAIL-1/2 and metalloproteinase-9. Moreover, flow cytometric analysis after Annexin V-FITC and propidium iodide staining demonstrated that these derivatives enhanced apoptosis of PDAC cells. Keeping with these data, the PathScan intracellular signaling and ELISA array revealed cleavage of caspase-3 and PARP and a significant inhibition of GSK3β phosphorylation, suggesting this kinase as a potential downstream target of our novel compounds. This was further supported by a specific assay for the evaluation of GSK3β activity, showing IC₅₀ values for the most active compounds against this enzyme in the micromolar range.     

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.     

Mass spectrometry in the diagnosis of thyroid disease and in the study of thyroid hormone metabolism

The importance of thyroid hormones in the regulation of development, growth, and energy metabolism is well known. Over the last decades, mass spectrometry has been extensively used to investigate thyroid hormone metabolism and to discover and characterize new molecules involved in thyroid hormones production, such as thyrotropin-releasing hormone. In the earlier period, the quantification methods, usually based on gas chromatography–mass spectrometry, were complicated and time consuming. They were mainly focused on basic research, and were not suitable for clinical diagnostics on a routine basis. The development of the modern mass spectrometers, mainly coupled to liquid chromatography, enabled simpler sample preparation procedures, and the accurate quantification of thyroid hormones, of their precursors, and of their metabolites in biological fluids, tissues, and cells became feasible. Nowadays, molecules of physiological and pathological interest can be assayed also for diagnostic purposes on a routine basis, and mass spectrometry is slowly entering the clinical laboratory. This review takes stock of the advancements in the field of thyroid metabolism that were carried out with mass spectrometry, with special focus on the use of this technique for the quantification of molecules involved in thyroid diseases.     

Saccharomyces cerevisiae and Hanseniaspora uvarum mixed starter cultures: Influence of microbial/physical interactions on wine characteristics

The growing trend in the wine industry is the revaluation of the role of non-Saccharomyces yeasts, promoting the use of these yeasts in association with Saccharomyces cerevisiae. Non-Saccharomyces yeasts contribute to improve wine complexity and organoleptic composition. However, the use of mixed starters needs to better understand the effect of the interaction between these species during alcoholic fermentation. The aim of this study is to evaluate the influence of mixed starter cultures, composed by combination of different S. cerevisiae and Hanseniaspora uvarum strains, on wine characteristics and to investigate the role of cell-to-cell contact on the metabolites produced during alcoholic fermentation. In the first step, three H. uvarum and two S. cerevisiae strains, previously selected, were tested during mixed fermentations in natural red grape must in order to evaluate yeast population dynamics during inoculated fermentation and influence of mixed starter cultures on wine quality. One selected mixed starter was tested in a double-compartment fermentor in order to compare mixed inoculations of S. cerevisiae/H. uvarum with and without physical separation. Our results revealed that physical contact between S. cerevisiae and H. uvarum affected the viability of H. uvarum strain, influencing also the metabolic behaviour of the strains. Although different researches are available on the role of cell-to-cell contact-mediated interactions on cell viability of the strains included in the mixed starter, to our knowledge, very few studies have evaluated the influence of cell-to-cell contact on the chemical characteristics of wine.     

Optimizing the lignin based synthesis of flexible polyurethane foams employing reactive liquefying agents

The present work is focused on the optimization of a green process based on the employment of by‐products obtained from wood treatments as raw materials for producing flexible polyurethane foams. More specifically, lignin was employed in flexible polyurethane foams in order to partially replace the usual fossil polyols; therefore glycerol (GLY) and glycerin polyglycidyl ether (EJ 300) were used as the polyol fraction for lignin liquefaction. Polypropylene glycol triol was used as a chain extender in different ratios with liquefaction solvents, and polymeric diphenylmethane diisocyanate as an isocyanate fraction. Liquefaction of lignin was performed by microwave irradiation, thus reducing the processing time and energy required compared to present industrial production processes. All the foams were produced in controlled expansion through the adoption of a ‘one‐shot’ approach, using water as a blowing agent and with an isocyanate index (NCO/OH) of less than 100 to improve the flexibility of the foam. This approach allowed for the substitution of up to 12% of common petro derived polyol with commercial soda lignin. Finally, the foams were characterized, presenting properties that could be modulated as a function of lignin content, GLY/EJ 300 ratio and isocyanate index. The qualities of the foams were compatible with existing materials used for furniture and for the interiors of car seats and couches. © 2015 Society of Chemical Industry     

Towards controlled cationic polymer growth from inorganic oxide defects: Directing the mechanism of polystyrene grafting from γ-irradiated silica

Most studies on surface-initiated controlled polymerizations for the synthesis of polymeric covalent organic-inorganic hybrid materials focus on chemical methods requiring specific modifications of the inorganic substrate. Few mechanistically-aware approaches have been undertaken towards exploiting the reactivity of defects induced by physical techniques such as ionizing radiations or UV–Vis light. Within this framework, we take grafted polymerization of styrene from γ-irradiated silica as a mechanistic testing ground where para- and diamagnetic silica defects are present, and polymerization proceeds through both radical and cationic mechanisms, resulting in a bimodal molecular weight distribution. We show that these mechanistic intricacies can be sorted out by resorting to the chemical arsenal developed in the last decades for controlled polymerizations. Specifically, we obtained a silica-polystyrene grafted material by cationic grafting from at 30 °C, a unimodal molecular weight distribution, and a relatively high molecular weight (Mn = 7.4 kDa) with a PDI of 1.68.