Targeting Methyltransferases in Human Pathogenic Bacteria: Insights into Thymidylate Synthase (TS) and Flavin-Dependent TS (FDTS)

In cells, thymidylate synthases provide the only de novo source of 2'-deoxythymidine-5'-monophosphate (dTMP), required for DNA synthesis. The activity of these enzymes is pivotal for cell survival and proliferation. Two main families of thymidylate synthases have been identified in bacteria, folate-dependent thymidylate synthase (TS) and flavin-dependent TS (FDTS). TS and FDTS are highly divergent enzymes, characterized by exclusive catalytic mechanisms, involving different sets of cofactors. TS and FDTS mechanisms of action have been recently revised, providing new perspectives for the development of antibacterial drugs targeting these enzymes. Nonetheless, some catalytic details still remain elusive. For bacterial TSs, half-site reactivity is still an open debate and the recent evidences are somehow controversial. Furthermore, different behaviors have been identified among bacterial TSs, compromising the definition of common mechanisms. Moreover, the redox reaction responsible for the regeneration of reduced flavin in FDTSs is not completely clarified. This review describes the recent advances in the structural and functional characterization of bacterial TSs and FDTSs and the current understanding of their mechanisms of action. Furthermore, the recent progresses in the development of inhibitors targeting TS and FDTS in human pathogenic bacteria are summarized

O-ZONE: affordable stratospheric air dynamic sampling device

The current situation regarding air pollution, global warming and the world approaching the point of no return have led the United Nations to focus on improving the environmental situation through the SDGs [1]. In line with these ambitions, O-ZONE team, was born in 2019 with the clear objective of taking concrete action against climate change [2]. The team's goal is to build a compact, low-cost, and reusable device to sample stratospheric pollutants, at various altitudes and thus provide air quality indications in mid-range areas for monitoring, prevention, and rapid intervention in case of unpredictable events. The O-ZONE team was therefore born as an idea of some students from the Aerospace Engineering course at the same University. The students took part in the REXUS/BEXUS project by Swedish National Space Agency (SNSA), Deutsches Zentrum für Luft- und Raumfahrt (DLR) and European Space Agency (ESA) [3]. As in each of these projects, the team tackled the various steps of space missions but, in this case, with extra constraints. They had to work during the lockdown with various complications due to the pandemic. Although the launch was delayed, the students carried on with their motivation and then launched their device on board the BEXUS 30. The prototype launched in Kiruna - Sweden (at the Esrange base), and which reached an altitude of 27.8 km, is a sampling system for Volatile Organic Compounds (VOCs), such as NOX and SOX, Particulate Matter (PM) and Chlorofluorocarbons (CFCs) responsible for the depletion of the Ozone layer [4]. These types of samplers [2] fill the technological gap in atmospheric analysis; the current state of the art allows air to be monitored only statically from ground stations or by satellite analysis [5], while O-ZONE presents an accessible, easy-to-use and rapid in situ sampling method. This paper describes the technical specifications and design aspects of the device and the experience that has allowed the students to grow as a team, especially in terms of personal skills and the ability to work with concurrent engineering and interdisciplinarity. Finally, the experiment results will be shown

Epilepsy, Antiepileptic Drugs, and Aggression: An Evidence-Based Review.

Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, and we present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases

Effect of nanostructured surfaces on ejection forces in micro-injection molding

openL’industria della plastica è una tra le industrie che più è cresciuta nel XXI secolo con una richiesta di componenti prodotti tramite il processo di stampa a iniezione che è in continuo aumento, essendo questa la tecnologia la più efficiente per produrre articoli di diversa forma e complessità a costi contenuti. Negli ultimi anni si è assistito ad un innalzamento degli standard qualitativi richiesti a fronte di una necessità di componenti sempre più piccoli, ponendo nuove e complicate sfide tecnologiche. In particolare, la miniaturizzazione della parte spesso porta all’acuirsi delle criticità che si riscontrano durante il processo di estrazione, a causa di forze più elevate che inducono indesiderate deformazioni sul componente. L’eiezione della parte, nella maggior parte dei casi, è ancora affidata a dei semplici estrattori che, per limiti tecnologici o geometrici, spesso applicano la forza in posizioni non ottimali, favorendo la distorsione. Lo scopo di questo studio è stato quello di utilizzare le LIPSS (Laser Induced Periodic Surface Structures) per diminuire l’effettiva area di contatto tra polimero e stampo, sfruttando la scarsa capacità della plastica di riprodurre le nanostrutture, minimizzando così le forze di estrazione.The plastics industry is one of the industries that has grown the most in the 21st century with a demand for components produced through the injection molding process that is continuously increasing, this technology being the most efficient to produce items of different shapes and complexity at low costs. In recent years there has been a rise in the quality standards required against a need for ever smaller components, presenting new and complicated technological challenges. In particular, the miniaturization of the part often leads to the aggravation of criticalities encountered during the ejection process, due to higher forces that induce unwanted deformations on the component. The ejection of the part, in most cases, is still performed by simple extractors that, due to technological or geometric limitations, often apply the force in non-optimal positions, favoring distortion. The aim of this study was to use LIPSS (Laser Induced Periodic Surface Structures) to reduce the effective contact area between polymer and mold, exploiting the poor ability of plastics to reproduce nanostructures, thus minimizing ejection forces

Overview of spacecraft fragmentation testing

Spacecraft fragmentation due to collisions with space debris is a major concern for space agencies and commercial entities, since the production of collisional fragments is one of the major sources of space debris. It is in fact believed that, in certain circumstances, the increase of fragmentation events could trigger collisional cascade that makes the future debris environmental not sustainable. Experimental studies have shown that the fragmentation process is highly complex and influenced by various factors, such as the material properties, the velocity and angle of the debris impact and the point of collision (e.g. central, glancing, on spacecraft appendages). In recent years, numerous impact tests have been performed, varying one or more of these parameters to better understand the physics behind these phenomena. In this context some tests have been also performed at the hypervelocity impact facility of the university of Padova. This paper provides an overview of the main experiments performed, the most critical issues observed and proposes some future directions for further research. Moreover, it summarizes the current state of research in spacecraft fragmentation, including the methods and techniques used to simulate debris impacts, the characterization of fragment properties and the analysis of the resulting debris cloud