Recent Developments in EU Environmental Policy and Legislation

This section describes the significant political initiatives and acts of legislation in the environmental field adopted in the period from September 2022 until June 2023

‘Urgenda-Style’ Strategic Climate Change Litigation in Italy: A Tale of Human Rights and Torts?

This contribution addresses the first strategic climate change litigation filed against the Italian State, the Giudizio Universale case. Giudizio Universale’s legal architecture is largely akin to other landmark cases filed in Europe, such as Urgenda in The Netherlands and Klimaatzaak in Belgium. Accordingly, Giudizio Universale is grounded on the state’s breach of international and EU obligations, the encroachment of human rights enshrined in the European Convention on Human Rights and the Italian Constitution, and the consequent attribution of domestic tort liability to the state under the Italian Civil Code. This article thus examines the main arguments raised in Giudizio Universale in light of the underlying domestic human rights and tort liability regimes. It first investigates the interplay between the breach of climate change obligations and human rights infringement as presented in the complaint to understand whether, and to what extent, Italian courts could give deference to an ‘Urgenda-style’ claim. Second, it unpacks the existing interpretation of tort liability as applied to state liability vis-à-vis its citizens by Italian courts. Third, it factors Giudizio Universale in the recent Italian Constitutional reform, which explicitly introduced the protection of the environment, biodiversity and ecosystems, as well as a reference to the ‘interests of future generations’, into the fundamental principles of the Italian Constitution. Overall, the article concludes that several limitations exist in the Italian legal system in the pursuance of strategic climate litigation against the state for its (in)action against climate change. One of the merits of the Giudizio Universale case, however, is that it challenges these limitations to provide another suitable tool for ensuring protection against the climate emergency

Cationic carbosilane dendrimers and oligonucleotide binding: an energetic affair

GENERATION 2 CATIONIC CARBOSILANE DENDRIMERS HOLD GREAT PROMISE AS INTERNALIZING AGENTS FOR GENE THERAPY AS THEY PRESENT LOW TOXICITY AND RETAIN AND INTERNALIZE GENETIC MATERIAL AS OLIGONUCLEOTIDE OR SIRNA. IN THIS WORK WE CARRIED OUT A COMPLETE IN SILICO STRUCTURAL AND ENERGETICAL CHARACTERIZATION OF THE INTERACTIONS OF A SET OF 2G CARBOSILANE DENDRIMERS, SHOWING DIFFERENT AFFINITY TOWARDS TWO SINGLE STRAND OLIGONUCLEOTIDE (ODN) SEQUENCES IN VITRO. OUR SIMULATIONS PREDICT THAT THESE FOUR DENDRIMERS AND THE RELEVANT ODN COMPLEXES ARE CHARACTERIZED BY SIMILAR SIZE AND SHAPE, AND THAT THE MOLECULE-SPECIFIC ODN BINDING ABILITY CAN BE RATIONALIZED ONLY CONSIDERING A CRITICAL MOLECULAR DESIGN PARAMETER: THE NORMALIZED EFFECTIVE BINDING ENERGY \u394GBIND,EFF/NEFF I.E., THE PERFORMANCE OF EACH ACTIVE INDIVIDUAL DENDRIMER BRANCH DIRECTLY INVOLVED IN A BINDING INTERACTIO

Antifungal and antimycobacterial activity of new N1-[1-aryl-2-(1H-Imidazol-1-yl and 1H-1,2,4-triazol-1-yl)-ethylidene]-pyridine-2-carboxamidrazone derivatives: A combined experimental and computational approach.

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Hitting the right spot: mechanism of action of OPB‐31121, a novel and potent inhibitor of the Signal Transducer and Activator of Transcription 3 (STAT3)

STAT3 is a key element in many oncogenic pathways and, like other transcription factors, is an attractive target for development of novel anticancer drugs. However, interfering with STAT3 functions has been a difficult task and very few small molecule inhibitors have made their way to the clinic. OPB‐31121, an anticancer compound currently in clinical trials, has been reported to affect STAT3 signaling, although its mechanism of action has not been unequivocally demonstrated. In this study, we used a combined computational and experimental approach to investigate the molecular target and the mode of interaction of OPB‐31121 with STAT3. In parallel, similar studies were performed with known STAT3 inhibitors (STAT3i) to validate our approach. Computational docking and molecular dynamics simulation (MDS) showed that OPB‐31121 interacted with high affinity with the SH2 domain of STAT3. Interestingly, there was no overlap of the OPB‐31121 binding site with those of the other STAT3i. Computational predictions were confirmed by in vitro binding assays and competition experiments along with site‐directed mutagenesis of critical residues in the STAT3 SH2 domain. Isothermal titration calorimetry experiments demonstrated the remarkably high affinity of OPB‐31121 for STAT3 with Kd (10 nM) 2–3 orders lower than other STAT3i. Notably, a similar ranking of the potency of the compounds was observed in terms of inhibition of STAT3 phosphorylation, cancer cell proliferation and clonogenicity. These results suggest that the high affinity and efficacy of OPB‐ 31121 might be related to the unique features and mode of interaction of OPB‐31121 with STAT3. These unique characteristics make OPB‐31121 a promising candidate for further development and an interesting lead for designing new, more effective STAT3i

Role of Rad51 and DNA repair in cancer: A molecular perspective

The maintenance of genome integrity is essential for any organism survival and for the inheritance of traits to offspring. To the purpose, cells have developed a complex DNA repair system to defend the genetic information against both endogenous and exogenous sources of damage. Accordingly, multiple repair pathways can be aroused from the diverse forms of DNA lesions, which can be effective per se or via crosstalk with others to complete the whole DNA repair process. Deficiencies in DNA healing resulting in faulty repair and/or prolonged DNA damage can lead to genes mutations, chromosome rearrangements, genomic instability, and finally carcinogenesis and/or cancer progression. Although it might seem paradoxical, at the same time such defects in DNA repair pathways may have therapeutic implications for potential clinical practice. Here we provide an overview of the main DNA repair pathways, with special focus on the role played by homologous repair and the RAD51 recombinase protein in the cellular DNA damage response. We next discuss the recombinase structure and function per se and in combination with all its principal mediators and regulators. Finally, we conclude with an analysis of the manifold roles that RAD51 plays in carcinogenesis, cancer progression and anticancer drug resistance, and conclude this work with a survey of the most promising therapeutic strategies aimed at targeting RAD51 in experimental oncology