Enrichments of post‐translational modifications in proteomic studies

More than 300 different protein post‐translational modifications are currently known, but only a few have been extensively investigated because modified proteoforms are commonly present in sub‐stoichiometry amount. For this reason, improvement of specific enrichment techniques is particularly useful for the proteomic characterization of post‐translationally modified proteins. Enrichment proteomic strategies could help the researcher in the challenging issue to decipher the complex molecular cross‐talk existing between the different factors influencing the cellular pathways. In this review the state of art of the platforms applied for the enrichment of specific and most common post‐translational modifications, such as glycosylation and glycation, phosphorylation, sulfation, redox modifications (i.e. sulfydration and nitrosylation), methylation, acetylation, and ubiquitinylation, are described. Enrichments strategies applied to characterize less studied post‐translational modifications are also briefly discussed.     

Healthy Properties of a New Formulation of Pomegranate-Peel Extract in Mice Suffering from Experimental Autoimmune Encephalomyelitis

A new formulation of a pomegranate-peel extract (PEm) obtained by PUAE (Pulsed Ultrasound-Assisted Extraction) and titrated in both ellagic acid (EA) and punicalagin is proposed, characterized and then analyzed for potential health properties in mice suffering from the experimental autoimmune encephalomyelitis (EAE). PEm effects were compared to those elicited by a formulation containing EA (EAm). Control and EAE mice were chronically administered EAm and Pem dissolved in the drinking water, starting from the day 10 post-immunization (d.p.i.), with a “therapeutic” protocol to deliver daily 50 mg/kg of EA. Treated EAE mice did not limit their daily access to the beverage, nor did they show changes in body weight, but they displayed a significant amelioration of “in vivo” clinical symptoms. “Ex vivo” histochemical analysis showed that spinal-cord demyelination and inflammation in PEm and EAm-treated EAE mice at 23 ± 1 d.p.i. were comparable to those in the untreated EAE animals, while microglia activation (measured as Ionized Calcium Binding Adaptor 1, Iba1 staining) and astrocytosis (quantified as glial fibrillar acid protein, GFAP immunopositivity) significantly recovered, particularly in the gray matter. EAm and PEm displayed comparable efficiencies in controlling the spinal pathological cellular hallmarks in EAE mice, and this would support their delivery as dietary supplementation in patients suffering from multiple sclerosis (MS).     

NO in Viral Infections: Role and Development of Antiviral Therapies

Nitric oxide is a ubiquitous signaling radical that influences critical body functions. Its importance in the cardiovascular system and the innate immune response to bacterial and viral infections has been extensively investigated. The overproduction of NO is an early component of viral infections, including those affecting the respiratory tract. The production of high levels of NO is due to the overexpression of NO biosynthesis by inducible NO synthase (iNOS), which is involved in viral clearance. The development of NO-based antiviral therapies, particularly gaseous NO inhalation and NO-donors, has proven to be an excellent antiviral therapeutic strategy. The aim of this review is to systematically examine the multiple research studies that have been carried out to elucidate the role of NO in viral infections and to comprehensively describe the NO-based antiviral strategies that have been developed thus far. Particular attention has been paid to the potential mechanisms of NO and its clinical use in the prevention and therapy of COVID-19.     

H,C, N and S stable isotopes and mineral profiles to objectively guarantee the authenticity of grated hard cheeses

In compliance with the European law (EC No. 510/2006), geographical indications and designations of origin for agricultural products and foodstuffs must be protected against mislabelling. This is particularly important for PDO hard cheeses, as Parmigiano Reggiano, that can cost up to the double of the no-PDO competitors.     

The Influence of Different Bleaching Protocols on Dentinal Enzymatic Activity: An In Vitro Study

This study aimed to investigate matrix metalloproteinase (MMP) activity in human dentin using in-situ and gelatin zymography, after at-home and in-office bleaching, related to their clinical exposure times. Dentin specimens (n = 5) were treated with 35% hydrogen peroxide (50 min per session/4 sessions), 10% carbamide peroxide (180 min/21 sessions), or no treatment. All were subjected to in-situ zymography. Dentin slices were, subsequently, obtained, covered with fluorescein-conjugated gelatin, and examined with confocal laser-scanning microscopy. The fluorescence intensity was quantified and statistically analyzed using one-way ANOVA and Bonferroni tests (α = 0.05). Furthermore, gelatin zymography was performed on protein extracts obtained from dentin powder (N = 8 teeth), treated with hydrogen peroxide or carbamide peroxide, with different exposure times (10/50 min for hydrogen peroxide; 252/1260 min for carbamide peroxide). The results of the in-situ zymography showed no statistical differences between the bleached specimens and the control group, with a medium level of gelatinolytic activity expressed in the dentin tubules. The results of gelatin zymography showed an increased expression of pro-MMP-9 in carbamide peroxide groups. The expression of pro-MMP-2 decreased in all the experimental groups. The bleaching treatments performed on the enamel of sound teeth do not influence dentinal enzymatic activity. However, when unprotected dentin tissue is bleached, matrix metalloproteinases are more expressed, particularly when carbamide peroxide is used, proportional to the exposure time.     

Therapeutic Potential of Highly Selective A3 Adenosine Receptor Ligands in the Central and Peripheral Nervous System

Ligands of the G_i protein-coupled adenosine A₃ receptor (A₃R) are receiving increasing interest as attractive therapeutic tools for the treatment of a number of pathological conditions of the central and peripheral nervous systems (CNS and PNS, respectively). Their safe pharmacological profiles emerging from clinical trials on different pathologies (e.g., rheumatoid arthritis, psoriasis and fatty liver diseases) confer a realistic translational potential to these compounds, thus encouraging the investigation of highly selective agonists and antagonists of A₃R. The present review summarizes information on the effect of latest-generation A₃R ligands, not yet available in commerce, obtained by using different in vitro and in vivo models of various PNS- or CNS-related disorders. This review places particular focus on brain ischemia insults and colitis, where the prototypical A₃R agonist, Cl-IB-MECA, and antagonist, MRS1523, have been used in research studies as reference compounds to explore the effects of latest-generation ligands on this receptor. The advantages and weaknesses of these compounds in terms of therapeutic potential are discussed.     

Essential collections for equilibrium concepts

The aim of this study is to identify and characterize the parts of an extensive form game that are ??relevant?? to determining whether the outcome of a certain strategy profile is an equilibrium outcome. We formally define what we mean by ??relevant?? and refer to the associated collection of information sets as essential. We apply this idea to a number of classic equilibrium concepts and discuss some implications of our approach.     

Accelerated Koenigs-Knorr glucuronidation of a deactivated nitrophenol: unveiling the role of polyamine additive 1,1,4,7,10,10-hexamethyltriethylenetetramine through design of experiments

1,1,4,7,10,10-Hexamethyltriethylenetetramine (HMTTA) emerged from a limited parallel screening of selected polyamines as the most appropriate additive for an especially problematic Koenigs-Knorr glucuronidation. This initial finding rapidly evolved into a reliable and high-yielding procedure through the use of two sets of experimental designs. The detailed effect of the stoichiometry of reagents and the amount of amine additive on reaction yield was elucidated. The complexity of the response surface for product yield, described by a third-order polynomial equation, together with ancillary kinetic experiments evidenced the multiple role of HMTTA in the present glucuronidation process.     

Abelian fourfold of Mumford-type and Kuga-Satake varieties

Let X be a complex abelian fourfold of Mumford-type and let V = H¹(X, ). The complex Mumford-Tate group of X is isogenous to SL(2)³. We recover information about the Hodge structure of X using representations of the Lie algebras (2)³ and (8) acting on V . Using these techniques we show that there is a Kuga-Satake variety A associated to X in such a way that A is isogenous to X³².