Proteomics of Aqueous Humor as a Source of Disease Biomarkers in Retinoblastoma

Aqueous humor (AH) can be easily and safely used to evaluate disease-specific biomarkers in ocular disease. The aim of this study was to identify specific proteins biomarkers in the AH of retinoblastoma (RB) patients at various stages of the disease. We analyzed the proteome of 53 AH samples using high-resolution mass spectrometry. We grouped the samples according to active vitreous seeding (Group 1), active aqueous seeding (Group 2), naive RB (group 3), inactive RB (group 4), and congenital cataracts as the control (Group 5). We found a total of 889 proteins in all samples. Comparative parametric analyses among the different groups revealed three additional proteins expressed in the RB groups that were not expressed in the control group. These were histone H2B type 2-E (HISTH2B2E), InaD-like protein (PATJ), and ubiquitin conjugating enzyme E2 V1 (UBE2V1). Upon processing the data of our study with the OpenTarget Tool software, we found that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and CD44 were more highly expressed in the RB groups. Our results provide a proteome database regarding AH related to RB disease that may be used as a source of biomarkers. Further prospective studies should validate our finding in a large cohort of RB patients.     

Acetylation-Specific Interference by Anti-Histone H3K9ac Intrabody Results in Precise Modulation of Gene Expression

Among Histone post-translational modifications (PTMs), lysine acetylation plays a pivotal role in the epigenetic regulation of gene expression, mediated by chromatin modifying enzymes. Due to their activity in physiology and pathology, several chemical compounds have been developed to inhibit the function of these proteins. However, the pleiotropy of these classes of proteins represents a weakness of epigenetic drugs. Ideally, a new generation of epigenetic drugs should target with molecular precision individual acetylated lysines on the target protein. We exploit a PTM-directed interference, based on an intrabody (scFv-58F) that selectively binds acetylated lysine 9 of histone H3 (H3K9ac), to test the hypothesis that targeting H3K9ac yields more specific effects than inhibiting the corresponding HAT enzyme that installs that PTM. In yeast scFv-58F modulates, gene expression in a more specific way, compared to two well-established HAT inhibitors. This PTM-specific interference modulated expression of genes involved in ribosome biogenesis and function. In mammalian cells, the scFv-58F induces exclusive changes in the H3K9ac-dependent expression of specific genes. These results suggest the H3K9ac-specific intrabody as the founder of a new class of molecules to directly target histone PTMs, inverting the paradigm from inhibiting the writer enzyme to acting on the PTM.     

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.     

Olive Oil in the Mediterranean Diet and Its Biochemical and Molecular Effects on Cardiovascular Health through an Analysis of Genetics and Epigenetics

Human nutrition is a relatively new science based on biochemistry and the effects of food constituents. Ancient medicine considered many foods as remedies for physical performance or the treatment of diseases and, since ancient times, especially Greek, Asian and pre-Christian cultures similarly thought that they had beneficial effects on health, while others believed some foods were capable of causing illness. Hippocrates described the food as a form of medicine and stated that a balanced diet could help individuals stay healthy. Understanding molecular nutrition, the interaction between nutrients and DNA, and obtaining specific biomarkers could help formulate a diet in which food is not only a food but also a drug. Therefore, this study aims to analyze the role of the Mediterranean diet and olive oil on cardiovascular risk and to identify their influence from the genetic and epigenetic point of view to understand their possible protective effects.     

Engineering Design Study on an Innovative Hydrokinetic Turbine with on Shore Foundation

Tidal currents are a resource of great potentiality and not yet fully explored. Several efforts have been made to exploit these resources, but the costs associated to the deployment of tidal plants in marine environments are usually too high. The aim of this work is to present a system able to handle with the above mentioned problems, through the development of a particular hydrokinetic turbine design. In previous works, the authors described a basic turbine configuration achieving interesting performances, although some operational inconveniences were detected. Those problems have been existing so the solution should be optimized and redesigned. As a result, a new design of the turbine is proposed, consisting of a double rotor spinning in opposite directions in order to balance the induced mechanical torque. From preliminary evaluations related to the Messina Strait tidal cycles （Punta Pezzo site, RC, Italy）, a single 12 m diameter turbine can supply a power of about 500 kW with a peak current speed of 3 m/s and deliver up to 450 MWh/year.     

Master equations for two qubits coupled via a nonlinear mode

A microscopic master equation describing the dynamics of two qubits coupled via a nonlinear mediator is constructed supposing that the two qubits, as well as the nonlinear mode, interact, each with its own independent bosonic bath. Generally speaking the master equation derived in this way represents a more appropriate tool for studying the dynamics of open quantum systems. Indeed we show that it is more complex than the phenomenological master equation, constructed simply adding ad hoc dissipative terms.     

Effect of saffron addition on the microbiological,physicochemical, antioxidant and sensory characteristics of yoghurt

The impact of added saffron on the characteristics of yoghurt was evaluated during storage. The fat content was lower in the saffron yoghurt. All colour variables were significantly affected by saffron and storage. From the 15th day of storage, bacterial numbers in the saffron yoghurt were higher than those of the control yoghurt. Sensory analysis data suggested that colour, odour and texture impacted consistently on the overall acceptability of the saffron yoghurt. Saffron addition significantly increased polyphenol content and antioxidant activity, providing evidence that the enrichment of natural yoghurt with saffron yields an innovative fermented product useful for supplementing antioxidant dietary intake.     

The interphase finite element

Mesomodelling of structures made of heterogeneous materials requires the introduction of mechanical models which are able to simulate the interactions between the adherents. Among these devices is quite popular the zero thickness interface (ZTI) model where the contact tractions and the displacement discontinuities are the primary static and kinematic variables. In some cases the joint response depends also on the internal stresses and strains within the thin layer adjacent to the joint interfaces. The interphase model, taking into account these additional variables, represents a sort of enhanced ZTI. In this paper a general theoretical formulation of the interphase model is reported and an original finite element, suitable for two-dimensional applications, is presented. A simple numerical experiment in plane stress state condition shows the relevant capabilities of the interphase element and allows to investigate its numerical performance. Some defects related to the shear locking of the element are resolved making use of well known numerical strategies. Finally, further numerical application to masonry structures are developed.