Il potere performativo della Parola Divina nei miti di Creazione del Vicino Oriente Antico

Objective: This thesis aims at identifying and analyze the role of the "Creative Word" or "Performative Word" in myths of creation of the Ancient Near East., through the study of two specific cases: the Memphite Theology in Egypt and the Enuma Eliš in Mesopotamia. Methods: Two case studies were selected according to the definition of the concept of “performativity”, both in cultural and linguistic studies, and through the application of a rigorous methodology for comparisons in humanities. The analysis of the two case studies was preceded by a brief summary and a comparison between the so called “Ritual of the Opening/Washing of the Mouth” in Mesopotamia (mīs pî) and in Egypt (wp·t-rȝ). This comparison was useful for understanding the approach of these two cultures to the same problem: the attribution of a performative value to a cultural/artistic product. The texts were extensively studied in two separate chapters, in which they have been explained according to their respective cultural and chronological backgrounds. In addition to the description of their contexts, they have also been related to other documents with the same cultural provenance (Egypt, Mesopotamia) sharing different degrees of affinity with our two initial texts. Considering all the peculiarities of the two myths (structure and length of the narratives, complexity, language, fruition), their analysis did not develop in a perfectly mirrored way, but on a number of specific issues that have been identified within each text. The comparison was conducted mainly on the analysis of the similarities and differences found in these highlighted topics (linguistic features; how to create; creation as a "divine plan"; terminology; legacy). Conclusions The comparative activity has shown that both traditions shared and elaborated the concept of “Performative Word”, yet in two very different and peculiar ways, specific of the single context. At the end of our investigation it has been possible to draw several conclusions regarding the legacy produced by these two important documents, in relation to other texts written several centuries later than the period in which these phenomena have been produced and enjoyed by an ancient audience

Analysing stress field conditions of the Colima Volcanic Complex (Mexico) by integrating finite-element modelling (FEM) simulations and geological data

In recent decades, finite-element modelling (FEM) has become a very popular tool in volcanological studies and has even been used to describe complex system geometries by accounting for multiple reservoirs, topography, and het- erogeneous distribution of host rock mechanical properties. In spite of this, the influence of geological information on numerical simulations is still poorly considered. In this work, 2D FEM of the Colima Volcanic Complex (Mexico) is pro- vided by using the Linear Static Analysis (LISA) software in order to investigate the stress field conditions with increas- ingly detailed geological data. By integrating the published geophysical, volcanological, and petrological data, we mod- elled the stress field considering either one or two magma chambers connected to the surface via dykes or isolated (not connected) in the elastic host rocks (considered homoge- neous and non-homogeneous). We also introduced tectonic disturbance, considering the effects of direct faults bordering the Colima Rift and imposing an extensional far-field stress of 5 MPa. We ran the model using the gravity in calculations. Our results suggest that an appropriate set of geological data is of pivotal importance for obtaining reliable numerical out- puts, which can be considered a proxy for natural systems. Beside and beyond the importance of geological data in FEM simulations, the model runs using the complex feeding system geometry and tectonics show how the present-day Col- ima volcanic system can be considered in equilibrium from a stress state point of view, in agreement with the long-lasting open conduit dynamics that have lasted since 1913

Myb-binding protein 1A (MYBBP1A) is essential for early embryonic development, controls cell cycle and mitosis, and acts as a tumor suppressor

MYBBP1A is a predominantly nucleolar transcriptional regulator involved in rDNA synthesis and p53 activation via acetylation. However little further information is available as to its function. Here we report that MYBBP1A is developmentally essential in the mouse prior to blastocyst formation. In cell culture, down-regulation of MYBBP1A decreases the growth rate of wild type mouse embryonic stem cells, mouse embryo fibroblasts (MEFs) and of human HeLa cells, where it also promotes apoptosis. HeLa cells either arrest at G2/M or undergo delayed and anomalous mitosis. At mitosis, MYBBP1A is localized to a parachromosomal region and gene-expression profiling shows that its down-regulation affects genes controlling chromosomal segregation and cell cycle. However, MYBBP1A down-regulation increases the growth rate of the immortalized NIH3T3 cells. Such Mybbp1a down-regulated NIH3T3 cells are more susceptible to Ras-induced transformation and cause more potent Ras-driven tumors. We conclude that MYBBP1A is an essential gene with novel roles at the pre-mitotic level and potential tumor suppressor activity.NHMRC: This work was supported by Associazione Italiana Ricerche sul Cancro (AIRC) grant 8929 and European Community FP7 201681 ‘‘Prepobedia’’ to FB, the Australian National Health and Medical Research Council to RK and TJG (project ID000115). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Disruption of semantic metwork in mild Alzheimer's disease revealed by resting-state fMRI

Subtle semantic deficits can be observed in Alzheimer's disease (AD) patients even in the early stages of the illness. In this work, we tested the hypothesis that the semantic control network is deregulated in mild AD patients. We assessed the integrity of the semantic control system using resting-state functional magnetic resonance imaging in a cohort of patients with mild AD (n = 38; mean mini-mental state examination = 20.5) and in a group of age-matched healthy controls (n = 19). Voxel-wise analysis spatially constrained in the left fronto-temporal semantic control network identified two regions with altered functional connectivity (FC) in AD patients, specifically in the pars opercularis (POp, BA44) and in the posterior middle temporal gyrus (pMTG, BA21). Using whole-brain seed-based analysis, we demonstrated that these two regions have altered FC even beyond the semantic control network. In particular, the pMTG displayed a wide-distributed pattern of lower connectivity to several brain regions involved in language-semantic processing, along with a possibly compensatory higher connectivity to the Wernicke's area. We conclude that in mild AD brain regions belonging to the semantic control network are abnormally connected not only within the network, but also to other areas known to be critical for language processing

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19