The Role of Glucocorticoid Receptor in the Pathophysiology of Pituitary Corticotroph Adenomas

Adrenocorticotropic Hormone (ACTH)-secreting pituitary adenomas are rare tumors characterized by autonomous ACTH secretion with a consequent increase in circulating cortisol levels. The resulting clinical picture is called Cushing’s disease (CD), a severe condition burdened with high morbidity and mortality. Apart from increased cortisol levels, CD patients exhibit a partial resistance to the negative glucocorticoid (GC) feedback, which is of paramount clinical utility, as the lack of suppression after dexamethasone administration is one of the mainstays for the differential diagnosis of CD. Since the glucocorticoid receptor (GR) is the main regulator of negative feedback of the hypothalamic–pituitary–adrenal axis in normal conditions, its implication in the pathophysiology of ACTH-secreting pituitary tumors is highly plausible. In this paper, we review GR function and structure and the mechanisms of GC resistance in ACTH-secreting pituitary tumors and assess the effects of the available medical therapies targeting GR on tumor growth.     

Probiotics Function in Preventing Atopic Dermatitis in Children

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by relapsing eczematous injuries and severe pruritus. In the last few years, the AD prevalence has been increasing, reaching 20% in children and 10% in adults in high-income countries. Recently, the potential role of probiotics in AD prevention has generated considerable interest. As many clinical studies show, the gut microbiota is able to modulate systemic inflammatory and immune responses influencing the development of sensitization and allergy. Probiotics are used increasingly against AD. However, the molecular mechanisms underlying the probiotics mediated anti-allergic effect remain unclear and there is controversy about their efficacy. In this narrative review, we examine the actual evidence on the effect of probiotic supplementation for AD prevention in the pediatric population, discussing also the potential biological mechanisms of action in this regard.     

How Important Are Genes to Achieve Longevity?

Several studies on the genetics of longevity have been reviewed in this paper. The results show that, despite efforts and new technologies, only two genes, APOE and FOXO3A, involved in the protection of cardiovascular diseases, have been shown to be associated with longevity in nearly all studies. This happens because the genetic determinants of longevity are dynamic and depend on the environmental history of a given population. In fact, population-specific genes are thought to play a greater role in the attainment of longevity than those shared between different populations. Hence, it is not surprising that GWAS replicated associations of common variants with longevity have been few, if any, as these studies pool together different populations. An alternative way might be the study of long-life families. This type of approach is proving to be an ideal resource for uncovering protective alleles and associated biological signatures for healthy aging phenotypes and exceptional longevity.     

On-column Refolding of Diphtheria Toxin Variant CRM197 by Different Metal-Chelating Affinity Chromatography Matrices

We have previously shown that the diphtheria toxin variant CRM 197 （cross-reacting material 197） can be overexpressed in Escherichia coli at high levels, yielding insoluble aggregates, which were solubilized using urea. This study reports a comparison of three matrices suitable for the purification and refolding of recombinant CRM197 by metal-chelating affinity chromatography, Moreover, we show that refolded CRM197 features enzymatic activity.     

Application of Central Composite Design to evaluate the antilisterial activity of hydro-alcohol berry extract of Myrtus communis L.

The antimicrobial activity of the hydro-alcohol extract of Myrtus communis L. (ME) berries was investigated against six Listeria monocytogenes strains (2 type strains and 4 isolates). Sub-lethal ME concentrations reduced L. monocytogenes counts by at least 2 log cycles. A Central Composite Design was used to investigate the combined effects of sub-lethal concentrations of ME (0.039–0.195 mL/100 mL), NaCl (0–2.0 g/100 mL) and pH (5.0–7.0) on strains growth. ME affected growth parameters, generally extending lag phase length and reducing maximum growth, sometimes with interactive effects with pH. The highest ME concentrations (0.117–0.195 mL/100 mL) combined with the lowest pH values (5.0–6.0) strongly reduced or even inhibited strains growth.     

Multibody modelling of N DOF robot arm assigned to milling manufacturing. Dynamic analysis and position errors evaluation

Nowadays, with the large use of robot manipulators in the most different fields of industrial production, two main aims must be commonly reached: robot dynamic behavior improvement and end-effector position errors reduction. For a N DOF robot arm, in case of specific applications such as milling manufacturing, one of the main source of end-effector position errors can be identified with joint compliances. This aspect, well known in literature, has been confirmed by experimental tests and measurements carried out on a specific robot assigned to non-standard milling manufacturing of marble objects (sculptures realization). To approach and analyze this issue the authors chose the multibody simulation environment. Hence, the authors developed a parametric modelling procedure that, by determining the robot characteristics through CAD model and technical data sheet investigation, provides reliable multibody dynamic models of generic N DOF robot arms. In this modelling approach the robot geometry construction is based on a standard strategy typical of this research field (i.e. Denavit-Hartenberg, Veitschegger-Wu). The developed procedure enables to obtain robot representation at various complexity levels according to the number of modelled robot components and actuation typology (Motion laws defined both in displacement or applied torque). Eventually, for a specific test case, the authors were able to correctly simulate the robot dynamic behavior, as it was demonstrated by numerical/experimental comparison. In this way the influence of the joint compliance behavior and actuator rotational inertia effects on end-effector position accuracy was analyzed.     

A deletional frameshift mutation in spectrin beta-gene associated with hereditary elliptocytosis in spectrin Napoli

We studied a clinically manifest, dominantly transmitted elliptocytosis in an Italian family. We found a new spectrin variant, designated spectrin Napoli. Its beta-chain was truncated in its C-terminal region (apparent MW 216 kD). It displayed a low expression level (15%). There was a 8 nt deletion: CTTTTGAGAAGT-->CTGT (nt 6255-6262), starting after codon 2053. This deletion was followed by a 54 nt (18 amino acids) missense sequence and terminated by the TGA triplet which normally overlaps codons 2074 and 2075 (CTTGAG). The overall length of the mutated beta-chain was comparable to that found in spectrin Nice, spectrin Tokyo and spectrin Tandil, which are other variants with truncated beta-chains; however, a distinct nonsense codon was used in spectrin Napoli.