A data-driven epidemic model to analyse the course of covid-19 in the Veneto region

The current COVID-19 pandemic is an unprecedented global health crisis, with severe economic impacts and social damages. Mathematical models are playing an important role in this ongoing emergency, providing scientific support to inform public policies worldwide. In this thesis work, an epidemic model for the spread of the novel Coronavirus disease in the Veneto region has been proposed. Starting from the available local Health System data to examine past year contagion numbers and other features potentiality, a SEIQRD (Susceptible Exposed Infected Quarantined Removed Deceased) compartmental schema has been designed generalizing the classic SIR model. Then, the infection dynamics have been practically implemented in two versions: as a Deterministic Equation-based formulation and as an Agent-based model. While the former has been maintained simple and computationally inexpensive in order to serve as a baseline and to quickly provide parameter estimates, for the latter a detailed metapopulation of agents with personalized attributes and network of contacts has been developed to recreate as realistic as possible simulations. Once these models have been trained and validated, they could became valuable tools for various types of analysis and predictions. In particular, the agent-based version, thanks to its flexibility as well as to its higher resolution, could be exploited for exclusive a posteriori evaluations of the effectiveness of the adopted containment measures in reducing the pandemic in Veneto.ope

Phosphate overload accelerates vascular aging in uremic patients

Vascular calcification is a very common event in atients affected by diabetes and chronic kidney disease (CKD). Recently, it has been well documented that abnormalities in mineral and bone metabolism in CKD patients are associated with increased morbidity and mortality. Elevated serum phosphate and calcium-phosphate product levels play an important role in the pathogenesis of vascular mineralization in uremic patients and also appear to be associated with increased cardiovascular mortality. Together with classical passive precipitation of calcium-phosphate in soft tissues, during the last decade it has been demonstrated that inorganic phosphate may cause extraskeletal calcification directly through a real “ossification” of the tunica media in the vasculature of CKD patients. Therefore, control of phosphate retention is now an even more crucial target of treatment in patients affected by chronic kidney disease

Familial ALS-superoxide dismutases associate with mitochondria and shift their redox potentials

Recent studies suggest that the toxicity of familial amyotrophic lateral sclerosis mutant Cu, Zn superoxide dismutase (SOD1) arises from its selective recruitment to mitochondria. Here we demonstrate that each of 12 different familial ALS-mutant SOD1s with widely differing biophysical properties are associated with mitochondria of motoneuronal cells to a much greater extent than wild-type SOD1, and that this effect may depend on the oxidation of Cys residues. We demonstrate further that mutant SOD1 proteins associated with the mitochondria tend to form cross-linked oligomers and that their presence causes a shift in the redox state of these organelles and results in impairment of respiratory complexes. The observation that such a diverse set of mutant SOD1 proteins behave so similarly in mitochondria of motoneuronal cells and so differently from wild-type SOD1 suggests that this behavior may explain the toxicity of ALS-mutant SOD1 proteins, which causes motor neurons to die

SILAC labeling coupled to shotgun proteomics analysis of membrane proteins of liver stem/hepatocyte allows to candidate the inhibition of TGF-beta pathway as causal to differentiation

International audienceDespite extensive research on hepatic cells precursors and their differentiated states, much remains to be learned about the mechanism underlying the self-renewal and differentiation. We apply the SILAC (stable isotope labeling by amino acids in cell culture) approach to quantitatively compare the membrane proteome of the resident liver stem cells (RLSCs) and their progeny spontaneously differentiated into epithelial/hepatocyte (RLSCdH). By means of nanoLC-MALDI-TOF/TOF approach, we identified and quantified 248 membrane proteins and 57 of them were found modulated during hepatocyte differentiation. Functional clustering of differentially expressed proteins by Ingenuity Pathway Analysis revealed that the most of membrane proteins found to be modulated are involved in cell-to-cell signaling/interaction pathways. Moreover, the upstream prediction analysis of proteins involved in cell-to-cell signaling and interaction unveiled that the activation of the mesenchymal to epithelial transition (MET), by the repression of TGFB1/Slug signaling, may be causal to hepatocyte differentiation. Taken together, this study increases the understanding of the underlying mechanisms modulating the complex biological processes of hepatic stem cell proliferation and differentiation

Biological properties of a human compact anti-ErbB2 antibody.

ErbB2 is a prognostic factor and target of therapy for many carcinomas. In contrast with the other ErbB receptors, ErbB2 lacks a soluble direct ligand, but it is the preferred co-receptor for the ErbB family members, forming heterodimers with more potent and prolonged signalling activity than that of homodimers. We recently produced a new anti-ErbB2 antibody, Erb-hcAb, by fusion of Erbicin, a human, anti-ErbB2 scFv, selectively cytotoxic to ErbB2-positive cells, and a human Fc domain. This fully human antitumour antibody represents a compact version of an IgG1, with the cytotoxicity of the scFv moiety on target cells, combined with the ability of the Fc moiety to induce both antibody- and complement-dependent cytotoxicity. Here, we describe the main properties of Erb-hcAb, using as a reference Herceptin, an anti-ErbB2 humanized monoclonal currently employed in clinical immunotherapy. We found that both bivalent Erb-hcAb and Herceptin increase receptor phosphorylation and downregulation, whereas monovalent Erbicin does not. These results correlate with the finding that Erb-hcAb is capable of inducing apoptosis and inhibiting cell cycle progression in ErbB2-positive cells. Its powerful in vitro antitumour action matched that observed in vivo in experiments with human ErbB2-positive tumour xenografts established in athymic mice. Finally, Erb-hcAb displays a glycosylation profile virtually superimposable to that of a human IgG. These findings suggest that Erb-hcAb is a very promising new agent for the immunotherapy of carcinomas that overexpress the ErbB2 receptor

STEPS TOWARDS A UNIFIED THEORY OF PSYCHOPATHOLOGY: THE PHASE SPACE OF MEANING MODEL

none6noThe hypothesis of a general psychopathology factor (p factor) has been advanced in recent years. It is an innovation with breakthrough potential, in the perspective of a unified view of psychopathology; however, what remains a controversial topic is how its nature might be conceptualized. The current paper outlines a semiotic, embodied and psychoanalytic conceptualization of psychopathology – the Phase Space of Meaning (PSM) model – aimed at providing ontological grounds to the p factor hypothesis. Framed within a more general model of how the mind works, the PSM model maintains that the p factor can be conceived as the empirical marker of the degree of rigidity of the meaning-maker’s way of interpreting experience, namely of the dimensions of meanings used to map the environment’s variability. As to the clinical implications, two main aspects are outlined. First, according PSM model, psychopathology is not an invariant condition, and does not have a set dimensionality, but is able to vary it locally, in order to address the requirement of situated action. Second, psychopathology is conceived as one of the mind’s modes of working, rather than the manifestation of its disruption. Finally, the puzzling issue of the interplay between stability and variability in the evolutionary trajectories of patients along with their life events is addressed and discussed.openVenuleo, C.; Salvatore, G.; Andrisano-Ruggieri, R.; Marinaci, T.; Cozzolino, M.; Salvatore, S.Venuleo, C.; Salvatore, G.; Andrisano-Ruggieri, R.; Marinaci, T.; Cozzolino, M.; Salvatore, S

The extreme hyper-reactivity of Cys94 in lysozyme avoids its amorphous aggregation

Many proteins provided with disulfde bridges in the native state undergo amorphous irreversible aggregation when these bonds are not formed. Here we show that egg lysozyme displays a clever strategy to prevent this deleterious aggregation during the nascent phase when disulfdes are still absent. In fact, when the reduced protein assembles into a molten globule state, its cysteines acquire strong hyper-reactivity towards natural disulfdes. The most reactive residue, Cys94, reacts with oxidized glutathione (GSSG) 3000 times faster than an unperturbed protein cysteine. A low pKa of its sulfydryl group (6.6/7.1) and a productive complex with GSSG (KD=0.3mM), causes a fast glutathionylation of this residue (t1/2=3s) and a complete inhibition of the protein aggregation. Other six cysteines display 70 times higher reactivity toward GSSG. The discovery of extreme hyper-reactivity in cysteines only devoted to structural roles opens new research felds for Alzheimer’s and Parkinson diseases

Promising Perspectives on the Use of Fullerenes as Efficient Containers for Beryllium Atoms

The possibility of using fullerenes as containers for toxic beryllium atoms is studied by a multi-scale approach in which first-principles and classical molecular dynamics simulations are combined. By studying the energetics, electronic and spectroscopic properties of Be-fullerene systems and by simulating their interaction at finite temperature in vacuo and in representative biological environments it is concluded that: i) Be endohedral complexes can be obtained by implanting Be atoms at energies >2.3 eV that is consistent with laser implantation technologies; ii) it is in principle possible to distinguish stable endohedral complexes from metastable exohedral ones by optical absorption, suggesting that optical spectroscopy can be a valuable a non-destructive technique to assist the synthesis and the control of implanted films iii) the Be-endohedral complexes are long-lived and thermodynamically stable and can confine beryllium both in vacuo and in aqueous solution; iv) Be@C60 complexes are likely unable to penetrate the selectivity filters of a prototypical protein showing that fullerene prevents undesired interactions with biomolecules and toxicity effects of Be2+ related to replacement of the Ca2+. Overall, these results provide an assessment on the possibility to encapsulate Be atoms into fullerenes by ion implantation to synthesize inert and highly stable and safe molecular containers for toxic beryllium radionuclides. Great opportunities are expected for the realization and application of Be-C60 complexes to nanotechnology and nanomedicine with particularly appealing perspectives in the field of neutron capture therapy of cancer

Combination of humic biostimulants with a microbial inoculum improves lettuce productivity, nutrient uptake, and primary and secondary metabolism

Biostimulants of natural origin represent a growing ecological strategy to increase crops productivity, especially when applied in combination with microbial bioeffectors. We studied the effect of biostimulants such as Potassium Humates (KH) from Leonardite and Compost Tea (CT) from green compost on both productivity and nutritional status of lettuce plants, as well as on the primary and secondary metabolism of treated plants, when amended either alone or in combination with a commercial microbial inoculum (M+), mainly based on arbuscular mycorrhizal fungi (Micosat TabPlus)