A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls

The most frequently used biomarkers to support the diagnosis of Alzheimer’s Disease (AD) are Aβ42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyloid deposition. These tests are rather complex and invasive and not easily applicable to clinical practice. Circulating non-coding RNAs, which are inherently stable and easy to manage, have been reported as promising biomarkers for central nervous system conditions. Recently, circular RNAs (circRNAs) as a novel class of ncRNAs have gained attention. We carried out a pilot study on five participants with AD and five healthy controls (HC) investigating circRNAs by Arraystar Human Circular RNA Microarray V2.0. Among them, 26 circRNAs were differentially expressed (FC ≥ 1.5, p < 0.05) in participants with AD compared to HC. From a top 10 of differentially expressed circRNAs, a validation study was carried out on four up-regulated (hsa_circRNA_050263, hsa_circRNA_403959, hsa_circRNA_003022, hsa_circRNA_100837) and two down-regulated (hsa_circRNA_102049, hsa_circRNA_102619) circRNAs in a larger population. Moreover, five subjects with mild cognitive impairment (MCI) were investigated. The analysis confirmed the upregulation of hsa_circRNA_050263, hsa_circRNA_403959, and hsa_circRNA_003022 both in subjects with AD and in MCI compared to HCs. We also investigated all microRNAs potentially interacting with the studied circRNAs. The GO enrichment analysis shows they are involved in the development of the nervous system, and in the cellular response to nerve growth factor stimuli, protein phosphorylation, apoptotic processes, and inflammation pathways, all of which are processes related to the pathology of AD.     

Distribution of KIR Genes and Their HLA Ligands in Different Viral Infectious Diseases: Frequency Study in Sicilian Population

Natural killer (NK) cells play a role in defence against viral infections by killing infected cells or by producing cytokines and interacting with adaptive immune cells. Killer immunoglobulin-like receptors (KIRs) regulate the activation of NK cells through their interaction with human leucocyte antigens (HLA). Ninety-six Sicilian patients positive to Human Immunodeficiency Virus-1 (HIV) and ninety-two Sicilian patients positive to SARS-CoV-2 were genotyped for KIRs and their HLA ligands. We also included fifty-six Sicilian patients with chronic hepatitis B (CHB) already recruited in our previous study. The aim of this study was to compare the distribution of KIR–HLA genes/groups of these three different infected populations with healthy Sicilian donors from the literature. We showed that the inhibitory KIR3DL1 gene and the KIR3DL1/HLA-B Bw4 pairing were more prevalent in individual CHB. At the same time, the frequency of HLA-C2 was increased in CHB compared to other groups. In contrast, the HLA-C1 ligand seems to have no contribution to CHB progression whereas it was significantly higher in COVID-19 and HIV-positive than healthy controls. These results suggest that specific KIR–HLA combinations can predict the outcome/susceptibility of these viral infections and allows to plan successful customized therapeutic strategies.     

MCD Diet Rat Model Induces Alterations in Zinc and Iron during NAFLD Progression from Steatosis to Steatohepatitis

We evaluate the effects of the methionine-choline-deficient (MCD) diet on serum and hepatic zinc (Zn) and iron (Fe) and their relationships with matrix metalloproteinases (MMPs) and their modulators (TIMPs and RECK) as well as hepatic fatty acids using male Wistar rats fed 2-, 4- and 8-week MCD diets. Serum and hepatic Zn decrease after an 8-week MCD diet. Serum Fe increases after an 8-week MCD diet and the same occurs for hepatic Fe. An increase in hepatic MMP activity, associated with a decrease in RECK and TIMPs, is found in the MCD 8-week group. Liver Fe shows a positive correlation versus MMPs and RECK, and an inverse correlation versus TIMPs. A positive correlation is found comparing liver Zn with stearic, vaccenic and arachidonic acids, and an inverse correlation is found with linolenic and docosatetraenoic acids. An opposite trend is found between liver Fe versus these fatty acids. During NAFLD progression from steatosis to steatohepatitis, MCD rats exhibit an increase in Zn and a decrease in Fe levels both in serum and tissue associated with alterations in hepatic MMPs and their inhibitors, and fatty acids. The correlations detected between Zn and Fe versus extracellular matrix modulators and fatty acids support their potential role as therapeutic targets.     

Modelling the evolution of oxidative browning during storage of white wines: effects of packaging and closures

Shelf life of products is a key parameter for any company at local and international level that wish to improve their competitiveness; thus, there is a need to search for methods that allow one to predict the shelf life of bottled wines. In this view, the progress of chemical oxidative reactions of six Italian white wines during storage (10 months after bottling), in different packaging, was monitored by means of selected oenological parameters. The optical density at 420 nm, an index of browning, showed a progressive increase that fitted the zero‐order kinetic rate. The onset of wine browning was further tested by means of accelerated ageing in controlled temperature conditions which results, modelled using the rate constants approach, showed an Arrhenius‐like dependence from temperature, allowing to estimate apparent activation energies of oxidative chemical browning (range: 46.8–88.3 kJ mol^?1). Kinetic and thermodynamic approach provided a useful tool to predict quality changes of white wines during storage with respect to packaging conditions.     

Specificity of Infant Digestive Conditions: Some Clues for Developing Relevant In Vitro Models

Digestion of nutrients is an essential function of the newborn infant gut to allow growth and development and understanding infant digestive function is essential to optimize nutrition and oral drug delivery. Ethical considerations prohibit invasive in vivo trials and as a consequence in vitro assays are often conducted. However, the choice of in vitro model parameters are not supported by an exhaustive analysis of the literature and do not mimic precisely the digestive conditions of the infant. This review contains a compilation of the studies which characterized the gastroduodenal conditions in full-term or preterm infants of variable postnatal age from birth up to six months. Important data about healthy full-term infants are reported. The enzymatic (type of enzymes and level of activity) and nonenzymatic (milk-based diet, frequency of feeding, bile salt concentrations) conditions of digestion in infants are shown to differ significantly from those in adults. In addition, the interindividual and developmental variability of the digestive conditions in infants is also highlighted.     

Antineurogenic phenotypes induced by truncated Notch proteins indicate a role in signal transduction and may point to a novel function for Notch in nuclei

Loss of any one of several neurogenic genes of Drosophila results in overproduction of embryonic neuroblasts at the expense of epidermoblasts. In this paper a variety of altered Notch proteins are expressed in transgenic flies. Dominant lethal, antineurogenic phenotypes were produced by expression of three classes of mutant proteins: (1) a protein comprised of the cytoplasmic domain of Notch and devoid of sequences permitting membrane association; (2) a transmembrane protein lacking the extracellular, lin12/Notch repeats; and (3) transmembrane proteins carrying amino acid substitutions replacing one or both extracellular cysteines thought to be involved in Notch dimerization. These Notch proteins not only suppress the neural hypertrophy observed in Notch- embryos, but also generate a phenotype in which elements of the embryonic nervous system are underproduced. Action of the intracellular cdc10 repeats appears to be essential for wild-type Notch function or for the antineurogenic activity of these proteins. The activities of the dominant, gain-of-function proteins indicate that Notch functions as a signal transducing receptor during ectoderm development. Production of antineurogenic Notch proteins in embryos deficient for the other neurogenic genes allowed functional dependencies to be established. Delta, mastermind, bigbrain, and neuralized appear to function in elaboration of a signal upstream of Notch. Genes of the Enhancer of split complex act after Notch. The cytoplasmic domain of Notch contains nuclear localization sequences that function in cultured cells, and one of the Notch antineurogenic proteins, the cytoplasmic domain, accumulates in nuclei in vivo.     

On the role of the calcination step in the preparation of active (superacid) sulfated zirconia catalysts

In the preparation of active SO₄-ZrO₂ catalysts, several steps involving various chemical and/or physical processes are necessary. In particular it has been reported that, after sulfation of amorphous Zr hydrates, a calcination atT _calc>773 K is needed to guarantee the crystallization of ZiO₂ in the tetragonal phase. By the use of a stabilized tetragonal ZrO₂, it is here demonstrated that a calcination atT _calc>773 K is indeed necessary for all SO₄-ZrO₂ systems, and that its actual role is the selective elimination of sulfates from highly energetic crystallographic defects. The calcination step atT _calc>773 K so creates the conditions for the formation of strong Lewis acid centres, that are necessary in the catalytic process, and the presence of which is here monitored spectroscopically by the reversible adsorption of carbon monoxide.     

GUEST EDITORIAL: PAPERS IN SENSING AND IN REASONING (MARCO SOMALVICO MEMORIAL ISSUE)

Recently, we observed a great movement of Internet users from blogs and wiki to Myspace, Facebook, Twitter, and Plurk. To increase profit margins, identifying the service factors that attract customers to join a new virtual community is crucial for website enterprises. Most works focus on social networks, success factors, and reasons for participating. Relatively few works have attempted to address this issue. Additionally, feature selection techniques have been widely used to extract crucial attributes. However, domain knowledge, which is hard to obtain, is needed to select meaningful features. Therefore, this work proposes a Kano's model based Neural Network (KANN) method combining Kano's model and neural networks to identify the key service factors. Finally, a real case study of a survey of virtual community users is provided to identify the key service factors.