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The main research question of this contribution, from the legal perspective, is how reconciling the free flow of information with the protection of personal data. These two interests are often seen as conflicting. Several conceptual and mental steps are, in our view, necessary to go beyond the antagonism and to see a more productive relationship. We propose five steps to answer this question

The two European Courts (the European Court of Human Rights, ECtHR and, to a lesser degree, the European Union Court of Justice, EUCJ) have contributed greatly to the development of a legal framework for surveillance by either law enforcement agencies in the criminal law area or by secret services. Both courts put great emphasis on a system of control ex ante and post hoc by independent supervisory authorities. A complex and controversial issue remains whether the human rights to privacy, respect of communications, and to an effective remedy (enshrined in Article 8 and 13 of European Convention on Human Rights (ECHR)), requires judicial review as a necessary safeguard for secret surveillance or alternatively, at which conditions, parallel systems of non-judicial review can be accepted as adequate safeguards against illegitimate interference in citizens’ private life. The European Courts have not yet established a clear doctrine in determining suitable thresholds and parameters. In particular, the ECtHR has a flexible approach in interpreting article 8 and 13 ECHR, depending on several factors (“vital” interests at stake, political considerations, etc.). In general terms, the Court has shown a preference towards judiciary oversight, but in the European legal order there are several examples of alternative oversight systems assessed positively by the Court, such as the quasi-judiciary systems (where the independency of the supervisory body, its wide jurisdiction, its power to data access and its power to effective reactions are proved) or the system of oversight set by Data Protection Authorities in the EU member states. However, in recent judgements of the ECtHR and the EUCJ we see an increasing emphasis on declaring the necessity of a “good enough” judicial (ex ante or post hoc) control over surveillance, meaning not simply a judicial control, but a system of oversight (judicial, quasi-judicial, hybrid) which can provide an effective control over surveillance, supported by empirical checks in the national legal system at issue.

The N-ter domain in HuPrP regulates the folding mechanism by tuning the long-range μs–ms dynamics. Removal of the N-ter domain triggers the formation of a stable β-enriched intermediate state inducing amyloid aggregates with HuPrPSc seeding activity.

Humans are estimated to consume several grams per week of nanoplastics (NPs) through exposure to a variety of contamination sources. Nonetheless, the effects of these polymeric particles on living systems are still mostly unknown. Here, by means of CD, NMR and TEM analyses, we describe at an atomic resolution the interaction of ubiquitin with polystyrene NPs (PS-NPs), showing how a hard protein corona is formed. Moreover, we report that in human HeLa cells exposure to PS-NPs leads to a sensible reduction of ubiquitination. Our study overall indicates that PS-NPs cause significant structural effects on ubiquitin, thereby influencing one of the key metabolic processes at the base of cell viability.

The overexpression of PED/PEA15, the phosphoprotein enriched in diabetes/phosphoprotein enriched in the astrocytes 15 protein (here referred simply to as PED), observed in some forms of type II diabetes, reduces the transport of insulin-stimulated glucose by binding to the phospholipase D1 (PLD1). The inhibition of the PED/PLD1 interaction was shown to restore basal glucose transport, indicating PED as a pharmacological target for the development of drugs capable of improving insulin sensitivity and glucose tolerance. We here report the identification and selection of PED ligands by means of NMR screening of a library of small organic molecules, NMR characterization of the PED/PLD1 interaction in lysates of cells expressing PLD1, and modulation of such interactions using BPH03, the best selected ligand. Overall, we complement the available literature data by providing detailed information on the structural determinants of the PED/PLD1 interaction in a cellular lysate environment and indicate BPH03 as a precious scaffold for the development of novel compounds that are able to modulate such interactions with possible therapeutic applications in type II diabetes.

The development of new formulations can be driven by the knowledge of host–guest complexes using cyclodextrins which have the ability to include guest molecules within their hydrophobic cavities, improving the physicochemical properties of the guest. To rationally explore new pesticide formulations, the effects of cyclodextrins on the properties of such guest molecules need to be explored. Imidacloprid is a neonicotinoid systemic insecticide used worldwide. In this study, the inclusion complexes of Imidacloprid (IMI) with β-cyclodextrin (β-CD) were prepared in the solid state by co-precipitation and the physical mixing method, with a stoichiometry of 1:1 and 1:2 molar ratios. The obtained products, Imidacloprid:β-cyclodextrin inclusion complex (IMI:β-CD), were characterized in the solid state by Fourier transform-infrared (FT-IR) spectroscopy and X-ray powder diffractometry (XRD). In solution, the 1:1 stoichiometry for the inclusion complexes was established by the Job plot method, and the binding constant of IMI:β-CD was determined by UV–vis titration. The toxicity was determined in producers and primary consumers of the freshwater trophic chain, the green alga Raphidocelis subcapitata and the rotifer Brachionus calyciflorus, respectively. The results indicated that Imidacloprid forms inclusion complexes with CDs showing improved physicochemical properties compared to free Imidacloprid. The formation of the inclusion complex reduced the chronic toxicity in rotifers when IMI concentrations were close to those of environmental concern (tenths/hundredths of micromoles/L). Therefore, CD inclusion complexes could provide important advantages to be considered for the future industrial production of new formulations.

In this paper, we present a fundamental framework for defining different types of explanations of AI systems and the criteria for evaluating their quality. Starting from a structural view of how explanations can be constructed, i.e., in terms of an explanandum (what needs to be explained), multiple explanantia (explanations, clues, or parts of information that explain), and a relationship linking explanandum and explanantia, we propose an explanandum-based typology and point to other possible typologies based on how explanantia are presented and how they relate to explanandia. We also highlight two broad and complementary perspectives for defining possible quality criteria for assessing explainability: epistemological and psychological (cognitive). These definition attempts aim to support the three main functions that we believe should attract the interest and further research of XAI scholars: clear inventories, clear verification criteria, and clear validation methods.

An unprecedented effort to tackle the ongoing COVID-19 pandemic has characterized the activity of the global scientific community over the last two years. Hundreds of published studies have focused on the comprehension of the immune response to the virus and on the definition of the functional role of SARS-CoV-2 proteins. Proteins containing zinc fingers, both belonging to SARS-CoV-2 or to the host, play critical roles in COVID-19 participating in antiviral defenses and regulation of viral life cycle. Differentially expressed zinc finger proteins and their distinct activities could thus be important in determining the severity of the disease and represent important targets for drug development. Therefore, we here review the mechanisms of action of host and viral zinc finger proteins in COVID-19 as a contribution to the comprehension of the disease and also highlight strategies for therapeutic developments.

Asthma is characterized by chronic inflammation and a variable degree of airway hyperresponsiveness (AHR). Our previous papers documented a role for Nociceptin/Orphanin FQ (N/OFQ) and its receptor N/OFQ peptide (NOP) in AHR. Therefore, the aim of this study was to improve the bioavailability of N/OFQ by developing solid lipid nanoparticles (SLNs). N/OFQ-loaded SLNs were prepared by the Quasi Emulsion Solvent Diffusion (QESD) technique and then characterized. Brown Norway rats were sensitized to ovalbumin (OVA) and treated with an intratracheal administration of saline solution or N/OFQ-SLN. Then, 24 h after the last challenge, functional histological and molecular evaluations were performed. SLNs showed a mean diameter of 233 ± 0.03 nm, a polydispersity index (PDI) value around 0.28 ± 0.02 and a drug release percentage of 84.3. The in vitro release of N/OFQ from SLNs showed that the release of the peptide starts already after two hours of incubation. Animals receiving N/OFQ-SLN showed a significative decrease in allergen-induced AHR compared to the control group. These results showed the positive effects of N/OFQ-SLNs on the inflammatory process and on the mechanical properties of the airways, suggesting that the innovative nanotechnological approach may be therapeutically beneficial for asthmatic patients. © 2022 by the authors.

Persistence and degradation are important factors in determining the safe use of such synthetic products, and numerous studies have been addressed to develop pesticide remediation methods aimed at ameliorating these features. In this frame, the use of different cyclodextrins (CDs) molecules has attracted considerable attention due to their well-known non-toxic nature, limited environmental impact, and capability to reduce the environmental and health risks of pesticides. CDs appear to be a valuable tool for the elimination of pesticides from polluted areas as well as for better pesticide formulations that positively influence their hydrolysis or degradation. The present work investigates the interaction between β-cyclodextrins and three commonly used pesticides (i.e., chlorpropham, monuron, and propanil) both in solution and in the solid state by means of UV-Vis, FT-IR, and X-ray powder diffractometry. We show that such interactions result in all three cases in the formation of inclusion complexes with a 1:1 stoichiometry and binding constants (Kb) of 369.9 M−1 for chlorpropham, 292.3 M−1 for monuron, and 298.3 M−1 for propanil. We also report the energy-minimized structures in silico for each complex. Our data expand and complement the available literature data in indicating CDs as a low-cost and very effective tool capable of modulating the properties that determine the environmental fate of pesticides.

Rispetto alle realtà mesopotamica, egiziana, ebraica non troviamo sostanziali diversità ideologiche nella Grecia già indoeuropeizzata. *Per designare il signore, il sovrano, in greco esistono due termini: basileús e wánaks . Il rapporto tra i titoli è stato chiarito da Benveniste in speciale riferimento agli usi micenei: «Sembre che il basileús sia solo un capo locale, un notabile, non un re. egli non sembra dotato di nessuna autorità politica. Invece il wánaks è considerato come il detentore del potere regale, anche se non si può definire ancora la vastità del suo territorio». Va poi rilevato chewánaks è inoltre una qualificazione divina riservata alle divinità maggiori. Nell’epopea omerica tale rapporto viene rispettato. Solowánaks «designa la realtà del potere regale;basileús è solo un titolo tradizionale che detiene il capo del génos, ma che non corrisponde a una sovranità territoriale e che molte persone possono possedere nello stesso luogo». L’esercizio del potere è prerogativa esclusiva delwánaks. Il re esercita il suo potere per volere di Zeus. Dal dio celeste gli vengono gli atributi della sua funzione, come lo scettro.«Tutto ciò che è e tutto ciò che possiede, le sue insegne e i suoi poteri, gli sono conferiti dagli dei, ma non li detiene in virtù di un ascendenza divina»; Tutta l’autorità degli ordini del re si fonda sul fatto che questi non sono che la traduzione del volere divino. Nel mondo minoico-miceneo, dunque, al pari di tutte le coeve civiltà dell’età del bronzo, il potere politico economico è saldamente nelle mani di un re. Questi è il centro della società, la sua stanza e il suo trono sono il centro dinamico del palazzo. La rilevanza sul piano religioso di tali individui è manifestata soprattutto dai sepolcri. La specialità del loro corredo ma anche le raffigurazioni cultuali che li accompagnano. «Se gli anelli d’oro, che venivano sepolti appunto solo nelle tombe dei nobili, di re e regine, recano impresse tanto spesso scene cultuali, anche questo indica l’importanza delle cerimonie per i potenti» Compared to the Mesopotamian, Egyptian and Jewish realities we do not find substantial ideological differences in the already Indo-Europeanized Greece. *There are two terms in Greek to designate the lord, the sovereign: basileús and wánaks . The relationship between the titles was clarified by Benveniste with special reference to Mycenaean customs: «It seems that the basileús is only a local chief, a notable, not a king. he does not seem endowed with any political authority. Instead the wánaks is considered as the holder of royal power, even if the vastness of his territory cannot yet be defined». It should also be noted that chewánaks is also a divine qualification reserved for major deities. In the Homeric epic this relationship is respected. Solowánaks "designates the reality of royal power; basileús is only a traditional title which holds the head of the génos, but which does not correspond to a territorial sovereignty and which many people can possess in the same place". The exercise of power is the exclusive prerogative of the wánaks. The king exercises his power at the behest of Zeus. The attributes of his function, such as the scepter, come to him from the celestial god. ; The whole authority of the king's orders rests on the fact that they are but the translation of the divine will. In the Minoan-Mycenaean world, therefore, like all the contemporary civilizations of the Bronze Age, political and economic power is firmly in the hands of a king. This is the center of society, his room and his throne are the dynamic center of the palace. The religious relevance of these individuals is shown above all by the sepulchres. The specialty of their equipment but also the cultic representations that accompany them. «If the gold rings, which were buried only in the tombs of nobles, kings and queens, so often bear cult scenes, this also indicates the importance of ceremonies for the powerful»

The structural effects of zinc replacement by xenobiotic metal ions have been widely studied in several eukaryotic and prokaryotic zinc-finger-containing proteins. The prokaryotic zinc finger, that presents a bigger &beta, &beta, &alpha, domain with a larger hydrophobic core with respect to its eukaryotic counterpart, represents a valuable model protein to study metal ion interaction with metallo-proteins. Several studies have been conducted on Ros87, the DNA binding domain of the prokaryotic zinc finger Ros, and have demonstrated that the domain appears to structurally tolerate Ni(II), albeit with important structural perturbations, but not Pb(II) and Hg(II), and it is in vitro functional when the zinc ion is replaced by Cd(II). We have previously shown that Ros87 unfolding is a two-step process in which a zinc binding intermediate converts to the native structure thorough a delicate downhill folding transition. Here, we explore the folding/unfolding behaviour of Ros87 coordinated to Co(II), Ni(II) or Cd(II), by UV-Vis, CD, DSC and NMR techniques. Interestingly, we show how the substitution of the native metal ion results in complete different folding scenarios. We found a two-state unfolding mechanism for Cd-Ros87 whose metal affinity Kd is comparable to the one obtained for the native Zn-Ros87, and a more complex mechanism for Co-Ros87 and Ni-Ros87, that show higher Kd values. Our data outline the complex cross-correlation between the protein&ndash, metal ion equilibrium and the folding mechanism proposing such an interplay as a key factor in the proper metal ion selection by a specific metallo-protein.

Downhill folding has been defined as a unique thermodynamic process involving a conformations ensemble that progressively loses structure with the decrease of protein stability. Downhill folders are estimated to be rather rare in nature as they miss an energetically substantial folding barrier that can protect against aggregation and proteolysis. We have previously demonstrated that the prokaryotic zinc finger protein Ros87 shows a bipartite folding/unfolding process in which a metal binding intermediate converts to the native structure through a delicate barrier-less downhill transition. Significant variation in folding scenarios can be detected within protein families with high sequence identity and very similar folds and for the same sequence by varying conditions. For this reason, we here show, by means of DSC, CD and NMR, that also in different pH and ionic strength conditions Ros87 retains its partly downhill folding scenario demonstrating that, at least in metallo-proteins, the downhill mechanism can be found under a much wider range of conditions and coupled to other different transitions. We also show that mutations of Ros87 zinc coordination sphere produces a different folding scenario demonstrating that the organization of the metal ion core is determinant in the folding process of this family of proteins.

Ros/MucR is a widespread family of bacterial zinc-finger (ZF) containing proteins that integrate multiple functions such as virulence, symbiosis and/or cell cycle transcription. NMR solution structure of Ros DNA-binding domain (region 56–142, i.e. Ros87) has been solved by our group and shows that the prokaryotic ZF domain shows interesting structural and functional features that differentiate it from its eukaryotic counterpart as it folds in a significantly larger zinc-binding globular domain. We have recently proposed a novel functional model for this family of proteins suggesting that they may act as H-NS-‘like’ gene silencers. Indeed, the N-terminal region of this family of proteins appears to be responsible for the formation of functional oligomers. No structural characterization of the Ros N-terminal domain (region 1–55) is available to date, mainly because of serious solubility problems of the full-length protein. Here we report the first structural characterization of the N-terminal domain of the prokaryotic ZF family examining by means of MD and NMR the structural preferences of the full-length Ros protein from Agrobacterium tumefaciens.