Effects of animacy on the processing of morphological Number: a cognitive inheritance?

Language encodes into morphology part of the information present in the referential world. Some features are marked in the great majority of languages, such as the numerosity of the referents that is encoded in morphological Number. Other features do not surface as frequently in morphological markings, yet they are pervasive in natural languages. This is the case of animacy, that can ground Gender systems as well as constrain the surfacing of Number. The diffusion of numerosity and animacy could mirror their biological salience at the extra-linguistic cognitive level. Human extra-linguistic numerical abilities are phylogenetically ancient and are observed in non-human animal species, especially when counting salient animate entities such as social companions. Does the saliency of animacy influence the morphological encoding of Number in language processing? We designed an experiment to test the encoding of morphological Number in language processing in relation to animacy. In Italian, Gender and Number are mandatorily expressed in a fusional morpheme. In some nouns denoting animate referents, Gender encodes the sex of referents and is semantically interpretable. In some other animate nouns and in inanimate nouns, Gender is uninterpretable at the semantic level. We found that it is easier to inflect for Number nouns when the inflectional morpheme is interpretable with respect to a semantic feature related to animacy. We discuss the possibility that the primacy of animacy in counting is mirrored in morphological processing and that morphology is designed to easily express information that is salient from a cognitive point of view

A recombination-based method to characterize human BRCA1 missense variants

Purpose. Many missense variants in BRCA1 are of unclear clinical significance. Functional and genetic approaches have been proposed for elucidating the clinical significance of such variants. The purpose of the present study was to evaluate BRCA1 missense variants for their effect on both Homologous Recombination (HR) and Non Homologous End Joining (NHEJ). Methods. HR frequency evaluation: HeLaG1 cells, containing a stably integrated plasmid that allows to measure HR events by gene conversion events were transfected with the pcDNA3β expression vector containing the BRCA1-wild type (BRCA1-WT) or the BRCA1-Unclassified Variants (BRCA1-UCVs). The NHEJ was measured by a random plasmid integration assay. Results. This assays suggested a BRCA1 involvement mainly in the NHEJ. As a matter of fact, the Y179C and the A1789T variant altered significantly the NHEJ activity as compared to the wild type, suggesting that they may be related to BRCA1 associated pathogenicity by affecting this function. The variants N550H and I1766S, and the mutation M1775R did not alter the NHEJ frequency. Conclusions. These data, beside proposing a method for the study of BRCA1 variants effect on HR and NHEJ, highlighted the need for a range of functional assays to be performed in order to identify variants with altered function

Enhancing Historic Houses as a marketing product. The case of Associazione Ville Borbone e Dimore Storiche della Versilia.

This thesis arises from my experience of internship in the cultural Association Ville Borbone e Dimore Storiche della Versilia and, above all, from my curiosity of seeing tourism as something different from the classic standardization of it. I would like to suggest this kind of tourism to a target of tourists which is interested in history and culture and that want to have an authentic experience, appreciating and admiring the majesty of villas and dwellings

Cognitive and communicative pressures in the emergence of grammatical structure: A closer look at whether number sense is encoded in privileged ways

open3siembargoed_20210707Franzon F.; Zanini C.; Rugani R.Franzon, F.; Zanini, C.; Rugani, R

Do non-verbal number systems shape grammar? Numerical cognition and Number morphology compared

Number morphology (e.g., singular vs. plural) is a part of the grammar that captures numerical information. Some languages have morphological Number values, which express few (paucal), two (dual), three (trial) and sometimes (possibly) four (quadral). Interestingly, the limit of the attested morphological Number values matches the limit of non-verbal numerical cognition. The latter is based on two systems, one estimating approximate numerosities and the other computing exact numerosities up to three or four. We compared the literature on nonverbal number systems with data on Number morphology from 218 languages. Our observations suggest that nonverbal numerical cognition is reflected as a core part of language

Ruolo di varianti missenso del gene BRCA1 nella riparazione del danno al DNA

RIASSUNTO BRCA1 (Breast Cancer Gene 1) è un gene di suscettibilità al carcinoma mammario e ovarico umano. Mutazioni nonsenso o frameshift che producono un codone di stop prematuro ed una proteina BRCA1 tronca e mutazioni missenso che causano cambiamenti amminoacidici deleteri, predispongono allo sviluppo del tumore della mammella e dell’ovaio. D’altra parte non è ancora stato chiarito il ruolo patologico di molte varianti missenso ricorrenti in famiglie con storia di tumore alla mammella e all’ovaio. Un metodo per caratterizzarle è quello di valutare l’effetto della proteina variante rispetto alla forma wildtype nelle funzioni biologiche che BRCA1 svolge tramite saggi funzionali. BRCA1 mappa in posizione 17q21 e codifica per una proteina nucleare che agisce da soppressore tumorale. Questa proteina è lunga 1863 amminoacidi e presenta differenti domini funzionali, che, attraverso l’interazione con partner specifici sono coinvolti nella regolazione della trascrizione, nel controllo del ciclo cellulare, nel pathway di ubiquitinazzione delle proteine e nel mantenimento della stabilità genomica mediante riparazione del danno al DNA tramite ricombinazione omologa (Homologous Recombination, HR) e mediante ricombinazione non omologa o (Non Homologous End Joining, NHEJ). Lo scopo del lavoro di tesi è stato quello di valutare il potenziale ruolo patogenetico di varianti missenso (UCVs) del gene BRCA1 identificate in individui con storia familiare di cancro alla mammella e all’ovaio. In particolare è stato valutato l’effetto dell’overespressione di BRCA1 wt e delle forme varianti sul meccanismo di ricombinazione omologa (error-free) e non omologa (error-prone). A tal fine sono state utilizzate due strategie sperimentali: 1. Per valutare il ruolo di BRCA1 wt e mutato nel pathway della ricombinazione omologa sono state utlizzate cellule della linea HeLaG1, un clone cellulare derivato dalla linea HeLa che ha un substrato di ricombinazione integrato nel proprio genoma. Il substrato contiene due geni di resistenza all’igromicina difettivi per l’inserzione di una sequenza linker. Come prodotto dell’evento di ricombinazione omologa si ottiene la formazione di un gene di resistenza all’igromicina attivo, che permette la selezione dei ricombinanti. In questo modo è stata valutata la capacità delle cellule di formare colonie in igromicina e calcolata la frequenza di ricombinazione omologa come rapporto delle colonie di cellule resistenti all’antibiotico per l’avvenuta integrazione del plasmide, rispetto al totale delle cellule vitali piastrate. L’effettiva espressione della proteina BRCA1 wt e mutata è stata valutata mediante la tecnica del Western Blot utilizzando l’anticorpo Ab-4 specifico per l’esone centrale della proteina in questione. 2. Per valutare la NHEJ si è ricorsi al metodo di valutazione della integrazione random nel genoma di una cellula umana di sequenze di DNA plasmidico. Il saggio si basa sulla trasfezione del vettore pBlue-puro il quale contiene un gene di resistenza ad un antibiotico sotto il controllo di un forte promotore virale e sequenze non omologhe alle sequenze umane. La non omologia di sequenza consente solo l’integrazione random del plasmide nel genoma delle cellule trasfettate per NHEJ. Questo saggio permette di valutare la frequenza dell’evento di NHEJ come rapporto delle colonie di cellule resistenti all’antibiotico per l’avvenuta integrazione del plasmide, rispetto al totale delle cellule vitali piastrate. Il saggio è stato effettuato nella linea epiteliale HeLa derivata da un carcinoma della cervice uterina. La linea esprime una forma wt della proteina BRCA1. E’ stata effettuata una co-trasfezione transiente di un vettore di espressione per il gene BRCA1 wildtype o mutato, con il plasmide pBLue-puro ed è stata valutata la capacità delle cellule di formare colonie in puromicina. Inoltre è stata valutata l’espressione del transgene BRCA1 wt e mutato mediante la tecnica del Western Blot, utilizzando lo stesso anticorpo precedentemente indicato. I risultati ottenuti possono fornire delle valide indicazioni sul potenziale ruolo di BRCA1 e delle varianti missenso studiate nei due principali pathway cellulari di ricombinazione

A recombination-based method to characterize human BRCA1 missense variants

International audienceMany missense variants in BRCA1 are of unclear clinical significance. Functional and genetic approaches have been proposed for elucidating the clinical significance of such variants. The purpose of this study was to evaluate BRCA1 missense variants for their effect on both homologous recombination (HR) and non homologous end joining (NHEJ). HR frequency evaluation: HeLaG1 cells, containing a stably integrated plasmid that allows us to measure HR events by gene conversion events, were transfected with the pcDNA3β expression vector containing the BRCA1-wild-type () or the BRCA1-unclassified variants (BRCA1-UCVs). The NHEJ was measured by a random plasmid integration assay. The assays suggested a BRCA1 involvement mainly in the NHEJ. As a matter of fact, the Y179C and the A1789T variant significantly altered the NHEJ activity as compared to the wild type, suggesting that they may be related to BRCA1-associated pathogenicity by affecting this function. The variants N550H and I1766S, and the mutation M1775R did not alter the NHEJ frequency. These data, besides proposing a method for the study of BRCA1 variants' effect on HR and NHEJ, highlighted the need for a range of functional assays to be performed to identify variants with altered function

Hypothyroidism and metabolic cardiovascular disease

Cardiovascular disease (CVD) remains the leading cause of death worldwide, representing a major health issue of social and economic relevance. Both hyperthyroidism and hypothyroidism are very common in the adult population, and both disorders may contribute to the onset and progression of CVD. After a brief description of the role of thyroid hormones (THs) on the physiology of the cardiovascular system and the potential mechanism that links THs alterations with changes in cardiac function, blood pressure, endothelial function, and lipid levels, we review updated data about the clinical impact of overt hypothyroidism (OH) and subclinical hypothyroidism (SCH) on CV risk, CVD, and mortality. Furthermore, we summarize the current evidence for treating SCH with levothyroxine (L-T4). Several guidelines of distinguished endocrine societies recommend treatment for SCH with TSH higher than 10 mIU/L, where the benefit of L-T4 therapy is more evident for younger people, but still controversial in those aged over 65 years. Based on current knowledge, more research efforts are needed to better address the clinical management of CV risk and CVD in the elderly affected by SCH

Recent advances in the use of tyrosine kinase inhibitors against thyroid cancer

Introduction: Oncogenic tyrosine kinases (TK) are enzymes that play a key role in cell growth and proliferation and their mutations can lead to uncontrolled cell growth and development of aggressive cancer. This knowledge has led to the development of new classes of drugs, Tyrosine kinase inhibitors (TKI). They target oncogenic kinases who are associated with advanced radioactive iodine (RAI) refractory TC, which is not able to uptake RAI anymore and/or still grows between consecutive treatments with Iodine 131 (I131). Areas covered: Since Lenvatinib and Sorafenib approval, several other molecular inhibitors have been studied and then introduced for the treatment of aggressive and refractory thyroid cancer (TC), and, although the development of adverse effects or tumor resistance mechanisms, more and more compounds are still under investigation. The literature search was executed in PubMed and ClinicalTrials.gov to identify relevant articles and clinical trials published until December 2023. Expert opinion: In the context of clinical trials, driven by the presence of specific molecular mutations or even in the absence of both conditions, systemic therapy TKIs are valuable weapons to be used in patients affected by aggressive forms of TC, waiting for further expansion of the treatment landscape with more efficacious and safer drugs