Bottom-up Geopolitics and Everyday Brexits at the Gibraltar-Spain Border

Brexit has opened doors for renewed attention to contested, multi-scalar geopolitical forces grounded in everyday life in borderlands. In this paper, we aim to unravel ‘everyday Brexits’ in the Gibraltar–La Línea (Spain) borderlands. By studying the 2019 commemoration of the historic 1969 border closure, we concentrate on how local borderwork by residents is mobilised for bottom-up geopolitics in the context of Brexit negotiations. We use a conceptual approach that focuses on multiple layerings of the border and the selectivity of stakeholders to select among these layers to pursue their interests. Based on on-site observations, in-depth interviews, and informal conversations with residents and key actors of La Línea and Gibraltar, we argue that Brexit has increased the tension of already loaded core-periphery relations in Spain. Brexit does not represent a sudden disruption. Rather, we show how Brexit allowed the bottom-up geopolitical mobilisation of latent, strongly historically embedded and continuous cross-borders sentiments of residents. This mobilisation could potentially challenge local cross-border power relations. In the final analysis, we conclude that the bottom-up geopolitics of ‘ordinary’ residents through everyday bordering processes is central to geopolitics research, including with regard to Brexit and in particular for non-British geographies affected by Brexit

Cuban Migrants and the Making of Havana\u27s Property Market

The emerging literature on the globalization of real estate has addressed how internationally circulating capital has increasingly found its ways into housing markets of the Global South . With relatively underdeveloped financial and real estate markets, these countries have discursively and materially been rebranded as emerging markets, that is, they have been shaped into frontiers in the global urbanization of capital. In this paper we scrutinize the transnational real estate networks that shape and reshape the Cuban housing market. First, we reconstruct how, following the 2011 legalization of housing prices set between buyers and sellers, Cuban migrants and a few foreign investors, in cooperation with Cubans residing in Cuba, are buying properties in Cuba\u27s cities, beach resorts and other towns. Second, we explore the economic and extra-economic motives behind such transnational property transactions, highlighting how residential properties are bought and converted into private restaurants or hotels. Central to our analysis is that the present development is not simply shaped by local or national demand and processes but also by international investment. We contend that a pattern of economic globalization unfolds where transnational remittances, rather than institutional investments or mortgage finance, steer Cuba\u27s emerging property market, along with local investments among Cuban citizens

L’INSEGNAMENTO DELLA PRAGMATICA ITALIANA SU LIRA: COME REAGISCONO GLI UTENTI?

Nel presente contributo si riportano i risultati di uno studio che coinvolge un gruppo di parlanti non nativi dell’italiano ai quali è stato chiesto di sperimentare alcune delle proposte didattiche presenti sul sito LIRA (Lingua/cultura Italiana in Rete per l’Apprendimento), creato per favorire lo sviluppo e il mantenimento di competenze pragmatico-culturali in italiano L2. I materiali di LIRA sono raggruppati in aree tematiche che coprono un’ampia gamma di argomenti legati agli usi pragmalinguistici e alle norme sociopragmatiche dell’italiano, e sono costruiti a partire dacampioni di parlato spontaneo o semi-spontaneo e da documenti scritti autentici.Gli informanti sono stati invitati ad affrontare alcuni dei percorsi didattici di LIRA e la loro attività è stata monitorata per mezzo di protocolli di indagine introspettiva.I commenti mostrano come, nel complesso, tanto l’uso di input autentico quanto il ricorso a tipi di feedback che aprono al confronto invece di fornire un’unica soluzione corretta stimolino la riflessione e quindi contribuiscano allo sviluppo della consapevolezza sui fenomeni su cui si desidera attirare l’attenzione degli utenti. La scelta di fare affidamento esclusivamente su esempi autentici di uso della lingua consente inoltre di affrontare temi che vengono abitualmente trascurati nell’insegnamento dell’italiano a stranieri e che suscitano invece grande interesse e curiosità negli apprendenti. Teaching italian pragmatics using LIRA: how do users react?In this paper we report the results of a study involving a group of non-native speakers of Italian who were asked to do some of the educational proposals on the LIRA (Language / culture in Italian Network for Learning) site, created to encourage the development and maintenance of skills in pragmatic-cultural Italian L2. The LIRA materials are grouped into subject areas that cover a wide range of topics relating to Italian pragma-linguistic use and socio-pragmatic standards and are constructed from samples of spontaneous or semi-spontaneous speech and authentic written documents.The informants were invited to try some of the educational LIRA activities and they were monitored through introspective survey protocols.  The comments show that, overall, the use of real input, as well as the use of feedback open to comparison,(rather than providing a single correct solution) stimulated reflection and thus contributed to the development of awareness of the phenomena meant to attract the users’ attention. The decision to rely solely on authentic language also made it possible to address issues that are usually neglected in teaching Italian to foreigners and created great interest and curiosity in the learners

Scaffold-Hopping Strategies in Aurone Optimization: A Comprehensive Review of Synthetic Procedures and Biological Activities of Nitrogen and Sulfur Analogues

: Aurones, particular polyphenolic compounds belonging to the class of minor flavonoids and overlooked for a long time, have gained significative attention in medicinal chemistry in recent years. Indeed, considering their unique and outstanding biological properties, they stand out as an intriguing reservoir of new potential lead compounds in the drug discovery context. Nevertheless, several physicochemical, pharmacokinetic, and pharmacodynamic (P3) issues hinder their progression in more advanced phases of the drug discovery pipeline, making lead optimization campaigns necessary. In this context, scaffold hopping has proven to be a valuable approach in the optimization of natural products. This review provides a comprehensive and updated picture of the scaffold-hopping approaches directed at the optimization of natural and synthetic aurones. In the literature analysis, a particular focus is given to nitrogen and sulfur analogues. For each class presented, general synthetic procedures are summarized, highlighting the key advantages and potential issues. Furthermore, the biological activities of the most representative scaffold-hopped compounds are presented, emphasizing the improvements achieved and the potential for further optimization compared to the aurone class

Bioisosteric heterocyclic analogues of natural bioactive flavonoids by scaffold-hopping approaches: State-of-the-art and perspectives in medicinal chemistry

: The flavonoid family is a set of well-known bioactive natural molecules, with a wide range of potential therapeutic applications. Despite the promising results obtained in preliminary in vitro/vivo studies, their pharmacokinetic and pharmacodynamic profiles are severely compromised by chemical instability. To address this issue, the scaffold-hopping approach is a promising strategy for the structural optimization of natural leads to discover more potent analogues. In this scenario, this Perspective provides a critical analysis on how the replacement of the chromon-4-one flavonoid core with other bioisosteric nitrogen/sulphur heterocycles might affect the chemical, pharmaceutical and biological properties of the resulting new chemical entities. The investigated derivatives were classified on the basis of their biological activity and potential therapeutic indications. For each session, the target(s), the specific mechanism of action, if available, and the key pharmacophoric moieties were highlighted, as revealed by X-ray crystal structures and in silico structure-based studies. Biological activity data, in vitro/vivo studies, were examined: a particular focus was given on the improvements observed with the new heterocyclic analogues compared to the natural flavonoids. This overview of the scaffold-hopping advantages in flavonoid compounds is of great interest to the medicinal chemistry community to better exploit the vast potential of these natural molecules and to identify new bioactive molecules

Formaldehyde in Hospitals Induces Oxidative Stress: The Role of GSTT1 and GSTM1 Polymorphisms

Despite the toxicity and health risk characteristics of formaldehyde (FA), it is currently used as a cytological fixative and the definition of safe exposure levels is still a matter of debate. Our aim was to investigate the alterations in both oxidative and inflammatory status in a hospital working population. The 68 workers recruited wore a personal air-FA passive sampler, provided a urine sample to measure 15-F2t-Isoprostane (15-F2t-IsoP) and malondialdehyde (MDA) and a blood specimen to measure tumour necrosis factor α (TNFα). Subjects were also genotyped for GSTT1 (Presence/Absence), GSTM1 (Presence/Absence), CYP1A1 exon 7 (A > G), and IL6 (−174, G > C). Workers were ex post split into formalin-employers (57.3 μg/m3) and non-employers (13.5 μg/m3). In the formalin-employers group we assessed significantly higher levels of 15-F2t-IsoP, MDA and TNFα (2t-IsoP (p = 0.027) and MDA (p GSTT1 Null (p = 0.038), GSTM1 Null (p = 0.031), and CYP1A1 exon 7 mutation carrier (p = 0.008) workers, compared to the wild type subjects. This study confirms the role of FA in biomolecular profiles alterations, highlighting how low occupational exposure can also result in measurable biological outcomes

Vibropolyfection: coupling polymer-mediated gene delivery to mechanical stimulation to enhance transfection of adherent cells

Background: With the success of recent non-viral gene delivery-based COVID-19 vaccines, nanovectors have gained some public acceptance and come to the forefront of advanced therapies. Unfortunately, the relatively low ability of the vectors to overcome cellular barriers adversely affects their effectiveness. Scientists have thus been striving to develop ever more effective gene delivery vectors, but the results are still far from satisfactory. Therefore, developing novel strategies is probably the only way forward to bring about genuine change. Herein, we devise a brand-new gene delivery strategy to boost dramatically the transfection efficiency of two gold standard nucleic acid (NA)/polymer nanoparticles (polyplexes) in vitro. Results: We conceived a device to generate milli-to-nanoscale vibrational cues as a function of the frequency set, and deliver vertical uniaxial displacements to adherent cells in culture. A short-lived high-frequency vibrational load (t= 5 min, f= 1,000 Hz) caused abrupt and extensive plasmalemma outgrowths but was safe for cells as neither cell proliferation rate nor viability was affected. Cells took about 1 hr to revert to quasi-naIve morphology through plasma membrane remodeling. In turn, this eventually triggered the mechano-activated clathrin-mediated endocytic pathway and made cells more apt to internalize polyplexes, resulting in transfection efficiencies increased from 10-to100-fold. Noteworthy, these results were obtained transfecting three cell lines and hard-to-transfect primary cells. Conclusions: In this work, we focus on a new technology to enhance the intracellular delivery of NAs and improve the transfection efficiency of non-viral vectors through priming adherent cells with a short vibrational stimulation. This study paves the way for capitalizing on physical cell stimulation(s) to significantly raise the effectiveness of gene delivery vectors in vitro and ex vivo