A proposito dell’attribuzione a Eckhart delle Collationes tramandate dal codice Cusano 21

This paper examines the attribution to Eckhart of the unpublished collationes contained in the MS Bernkastel-Kues, Bibliothek des St. Nikolaus-Hospitals 21. Eckhart’s authorship was excluded by Koch, but is plausible from the point of view of the history of the manuscript tradition. The paper announces the discovery of a series of similar collationes in a Lüneburg manuscript of Franciscan origin and highlights, through the edition of the texts relating to Advent, some parallels between both works, probably depending on the use of a common source

04/02/2003 - Stars Of The Chinese Golden Dragon Acrobats To Perform At EIU.pdf

Nuova interpretazione di un noto passo su Tommaso d'Aquini in Seuse, Horologium sapientia

Cognitive Reserve Index as predictor of the performance of neurologically healthy participants on a new test of non-verbal intelligence

openNel corso dello sviluppo della ricerca scientifica in ambito psicologico, si è data sempre più importanza al ruolo ricoperto dall'intelligenza non-verbale. Si è cercato di creare nuovi test che si adattassero alla misurazione di questo costrutto, dove primeggia il "Test delle Matrici di Raven". Lo studio presentato in questo elaborato si inserisce nel contesto della standardizzazione di nuovi test neuropsicologici, che possano descrivere in modo accurato la condizione del paziente in esame. Siamo stati guidati da tre obiettivi. Il primo era creare un test con una distribuzione "open", ovvero accessibile a chi lo necessita. Il secondo era ottenere una taratura italiana e aggiornata, rappresentativa della popolazione attuale. Il terzo era indagare l'effetto della riserva cognitiva sulla prestazione al test, attraverso la somministrazione del CRIq (Nucci et al., 2012). Durante la somministrazione del nuovo test delle matrici GAB-30, si sottoponevano al partecipante neurologicamente indenne anche il consenso informato, la scheda anamnestica, il MoCA (Nasreddine et al, 1996), e il CRIq. I dati ottenuti si sono poi analizzati attraverso analisi statistiche con il software JASP. In particolare, ci si è soffermati sull'indagine dell'influenza del CRIq sulla prestazione. I risultati hanno mostrato come né il punteggio totale del CRIq né i vari sotto-test possano definirsi predittori significativi della prestazione al GAB-30. Questo significa che il GAB-30 rientra all'interno dei test "equi culturalmente", in cui scolarità, attività lavorative, attività del tempo libero incidono in modo irrilevante sulla prestazione al test

Can We Still Trust Docking Results? An Extension of the Applicability of DockBench on PDBbind Database

The number of entries in the Protein Data Bank (PDB) has doubled in the last decade, and it has increased tenfold in the last twenty years. The availability of an ever-growing number of structures is having a huge impact on the Structure-Based Drug Discovery (SBDD), allowing investigation of new targets and giving the possibility to have multiple structures of the same macromolecule in a complex with different ligands. Such a large resource often implies the choice of the most suitable complex for molecular docking calculation, and this task is complicated by the plethora of possible posing and scoring function algorithms available, which may influence the quality of the outcomes. Here, we report a large benchmark performed on the PDBbind database containing more than four thousand entries and seventeen popular docking protocols. We found that, even in protein families wherein docking protocols generally showed acceptable results, certain ligand-protein complexes are poorly reproduced in the self-docking procedure. Such a trend in certain protein families is more pronounced, and this underlines the importance in identification of a suitable protein\ufffdligand conformation coupled to a well-performing docking protocol

Revisiting the Allosteric Regulation of Sodium Cation on the Binding of Adenosine at the Human A2A Adenosine Receptor: Insights from Supervised Molecular Dynamics (SuMD) Simulations

One of the most intriguing findings highlighted from G protein-coupled receptor (GPCR) crystallography is the presence, in many members of class A, of a partially hydrated sodium ion in the middle of the seven transmembrane helices (7TM) bundle. In particular, the human adenosine A2A receptor (A2A AR) is the first GPCR in which a monovalent sodium ion was crystallized in a distal site from the canonical orthosteric one, corroborating, from a structural point of view, its role as a negative allosteric modulator. However, the molecular mechanism by which the sodium ion influences the recognition of the A2A AR agonists is not yet fully understood. In this study, the supervised molecular dynamics (SuMD) technique was exploited to analyse the sodium ion recognition mechanism and how its presence influences the binding of the endogenous agonist adenosine. Due to a higher degree of flexibility of the receptor extracellular (EC) vestibule, we propose the sodium-bound A2A AR as less efficient in stabilizing the adenosine during the different steps of binding

New insights into key determinants for adenosine 1 receptor antagonists selectivity using supervised molecular dynamics simulations

Adenosine receptors (ARs), like many otherGprotein-coupledreceptors (GPCRs), are targets of primary interest indrug design. However, one of the main limits for the development of drugs for this class of GPCRs is the complex selectivity profile usually displayed by ligands. Numerous efforts have been madefor clarifying the selectivity of ARs, leading to the development of many ligand-based models. The structure of the AR subtype A1 (A1AR) has been recently solved,providing important structural insights. In the present work, we rationalized the selectivity profile of two selective A1AR and A2AAR antagonists, investigating their recognition trajectories obtained by Supervised Molecular Dynamics from an unbound state and monitoring the role of the water molecules in the binding site

Targeting Protein Kinase CK1\u3b4 with Riluzole: Could It Be One of the Possible Missing Bricks to Interpret Its Effect in the Treatment of ALS from a Molecular Point of View?

Riluzole, approved by the US Food and Drug Administration (FDA) in 1995, is the most widespread oral treatment for the fatal neurodegenerative disorder amyotrophic lateral sclerosis (ALS). The drug, whose mechanism of action is still obscure, mitigates progression of the illness, but unfortunately with only limited improvements. Herein we report the first demonstration, using a combination of computational and in vitro studies, that riluzole is an ATP-competitive inhibitor of the protein kinase CK1 isoform\u2005\u3b4, with an IC50 value of 16.1\u2005\u3bcm. This allows us to rewrite its possible molecular mechanism of action in the treatment of ALS. The inhibition of CK1\u3b4 catalytic activity indeed links the two main pathological hallmarks of ALS: transactive response DNA-binding protein of 43\u2005kDa (TDP-43) proteinopathy and glutamate excitotoxicity, exacerbated by the loss of expression of glial excitatory amino acid transporter-2 (EAAT2)

The Multifaceted Role of GPCRs in Amyotrophic Lateral Sclerosis: A New Therapeutic Perspective?

Amyotrophic lateral sclerosis (ALS) is a degenerating disease involving the motor neurons, which causes a progressive loss of movement ability, usually leading to death within 2 to 5 years from the diagnosis. Much effort has been put into research for an effective therapy for its eradication, but still, no cure is available. The only two drugs approved for this pathology, Riluzole and Edaravone, are onlyable to slow down the inevitable disease progression. As assessed in the literature, drug targets such as protein kinases have already been extensively examined as potential drug targets for ALS, with some molecules already in clinical trials. Here, we focus on the involvement of another very important and studied class of biological entities, G protein-coupled receptors (GPCRs), in the onset and progression of ALS. This workaimsto give an overview of what has been already discovered on the topic, providing useful information and insights that can be used by scientists all around the world who are putting efforts into the fight against this very important neurodegenerating disease

Photoidentification catalog of Cuvier's beaked whale (Ziphius cavirostris) in the Ligurian Sea

A photo-ID catalog of Cuvier's beaked whales was compiled by analyzing data collected in the Ligurian Sea from 1998 to 2007. Data were collected during dedicated surveys for beaked whales, opportunistic whale watching cruises, and during several tagging efforts. A total of 2,300 photographs was collected and referenced to time and GPS position. Of these photographs, 650 were of sufficient quality to use for photo-identification. Photographs were divided into four categories, based on scarring and pigmentation patterns: very distinctive (heavily scarred and/or bold pigmentation), distinctive (many distinct scars and/or bold pigmentation), slightly distinctive (few scars and lack of bold pigmentation), and not distinctive (no scars and solid brown animal). 127 individual whales were identified, of which 10 were classified as adult males, 3 as adult females, 3 as calves, and 27 as immature whales, based on the above criteria. An additional 26 whales were classified as possible males, and 28 as possible females. During the 9 year study period, 34 whales were resighted, and the longest time between resights was 7 years