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The global spread of COVID-19 pandemic forced the scientific community to identify new ways of exchanging and transferring the scientific knowledge, also considering that the measures taken to combat the pandemic, such as travel restrictions, closed borders and gathering bans, led to cancellations of many conferences, meetings and workshops. The enhancement of the existing digital platforms and the development of new systems to share scientific knowledge has allowed the scientific community to "meet" again in new virtual environments (e.g., Zoom, Cisco WebEx, Live Stream, Demio, GoToWebinar Seminar, Google Hangouts, Skype, Microsoft Teams, etc.), providing an unprecedented opportunity to reform methods of organizing academic conferences in all disciplines.Starting from the review of the existing literature, this study aimed at investigating the impact of the spreading of virtual conferences on the field of research. The SWOT analysis was used to identify strengths and weaknesses of the scientific conferences organized in the new format, as well as opportunities and threats created by the socio-economic and political context in the era of the COVID-19 pandemic.

Il saggio ripercorre le principali tappe dello sviluppo della medicina del lavoro in Italia, facendo particolarmente riferimento all'attività delle principali istituzioni scientifiche in materia, l'International Commission on Occupational Health (ICOH) e la Società Italiana di Medicina del Lavoro - SIML.

Background The aim of this study is to illustrate the historical role of the International Commission on Occupational Health (ICOH) congresses as an arena where national and international occupational medicine can dialogue and as the first example of scientific transferability of the research and prevention results that have had such an impact on global public health. Methods We used the ICOH Heritage Repository, in which ICOH congress proceedings (from the first congress in Milan in 1906 to the last congress, held in Dublin in 2018), are organised in an orderly way, updated and easily accessible according to open access logic. Results We describe studies by three physicians who submitted significant scientific work to ICOH congresses, one on the battle against ancylostomiasis (Volante, 1906), the second (Quarelli, 1928) on carbon disulphide poisoning, and the third (Viola, 1969) on the carcinogenicity of vinyl chloride monomer. Priority is given to Italian cases, on account of the authors’ obvious familiarity with the issues. Conclusion The visibility offered in ICOH conferences and their published proceedings has boosted the international spread of their findings, contributing to the scientific transferability of the research results and influencing the development of policies and prevention interventions that have had a great impact on global public health.

NeuriteTracker is a computer vision approach used to analyze neuronal morphodynamics and to examine spatiotemporal Rho GTPase signaling networks regulating neurite outgrowth., Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth.

The open-source platform openBIS (open Biology Information System) offers an Electronic Laboratory Notebook and a Laboratory Information Management System (ELN-LIMS) solution suitable for the academic life science laboratories. openBIS ELN-LIMS allows researchers to efficiently document their work, to describe materials and methods and to collect raw and analyzed data. The system comes with a user-friendly web interface where data can be added, edited, browsed and searched., Bioinformatics, 32 (4), ISSN:1367-4803, ISSN:1460-2059

Deregulation of protein kinases is associated with numerous diseases, making them important targets for drug discovery. The majority of drugs target the catalytic site of these proteins, but due to the high level of similarity within the ATP binding sites of protein kinases, it is often difficult to achieve the required pharmacological selectivity. In this study, we describe the identification and subsequent analysis of water patterns in the ATP binding sites of 171 protein kinase structures, comprising 19 different kinases from various branches of the kinome, and demonstrate that structurally similar binding sites often have significantly different water patterns. We show that the observed variations in water patterns of different, but structurally similar kinases can be exploited in the structure-based design of potent and selective kinase inhibitors.

We describe herein the structure-activity relationship (SAR) and cocrystal structures of a series of Nek2 inhibitors derived from the published polo-like kinase 1 (Plk1) inhibitor (R)-1. Our studies reveal a nonlinear SAR for Nek2 and our cocrystal structures show that compounds in this series bind to a DFG-out conformation of Nek2 without extending into the enlarged back pocket commonly found in this conformation. These observations were further investigated, and structure-based design led to Nek2 inhibitors derived from (R)-1 with more than a hundred-fold selectivity against Plk1.

The design of biologically active compounds from ligand-free protein structures using a structure-based approach is still a major challenge. In this paper, we present a fast knowledge-based approach (HS-Pharm) that allows the prioritization of cavity atoms that should be targeted for ligand binding, by training machine learning algorithms with atom-based fingerprints of known ligand-binding pockets. The knowledge of hot spots for ligand binding is here used for focusing structure-based pharmacophore models. Three targets of pharmacological interest (neuraminidase, beta2 adrenergic receptor, and cyclooxygenase-2) were used to test the evaluated methodology, and the derived structure-based pharmacophores were used in retrospective virtual screening studies. The current study shows that structure-based pharmacophore screening is a powerful technique for the fast identification of potential hits in a chemical library, and that it is a valid alternative to virtual screening by molecular docking.

Deregulation of protein kinases is associated with numerous diseases, making them important targets for drug discovery. The majority of drugs target the catalytic site of these proteins, but due to the high level of similarity within the ATP binding sites of protein kinases, it is often difficult to achieve the required pharmacological selectivity. In this study, we describe the identification and subsequent analysis of water patterns in the ATP binding sites of 171 protein kinase structures, comprising 19 different kinases from various branches of the kinome, and demonstrate that structurally similar binding sites often have significantly different water patterns. We show that the observed variations in water patterns of different, but structurally similar kinases can be exploited in the structure-based design of potent and selective kinase inhibitors.

We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2.

The HSF1-mediated stress response pathway is steadily gaining momentum as a critical source of targets for cancer therapy. Key mediators of this pathway include molecular chaperones such as heat shock protein (HSP) 90. There has been considerable progress in targeting HSP90 and the preclinical efficacy and signs of early clinical activity of HSP90 inhibitors have provided proof-of-concept for targeting this group of proteins. The HSP70 family of molecular chaperones are also key mediators of the HSF-1-stress response pathway and have multiple additional roles in protein folding, trafficking and degradation, as well as regulating apoptosis. Genetic and biochemical studies have supported the discovery of HSP70 inhibitors which have the potential for use as single agents or in combination to enhance the effects of classical chemotherapeutic or molecularly targeted agents including HSP90 inhibitors. Here we provide a perspective on the progress made so far in designing agents which target the HSP70 family.

The design of biologically active compounds from ligand-free protein structures using a structure-based approach is still a major challenge. In this paper, we present a fast knowledge-based approach (HS-Pharm) that allows the prioritization of cavity atoms that should be targeted for ligand binding, by training machine learning algorithms with atom-based fingerprints of known ligand-binding pockets. The knowledge of hot spots for ligand binding is here used for focusing structure-based pharmacophore models. Three targets of pharmacological interest (neuraminidase, β2 adrenergic receptor, and cyclooxygenase-2) were used to test the evaluated methodology, and the derived structure-based pharmacophores were used in retrospective virtual screening studies. The current study shows that structure-based pharmacophore screening is a powerful technique for the fast identification of potential hits in a chemical library, and that it is a valid alternative to virtual screening by molecular docking.

4 pags, 2 figs, 1 tab. -- Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.febslet.2008.05.035, Mistletoe lectin is a potent biohazard. Lectin activity in the toxic dimer primarily originates from the 2γ-subdomain (Tyr-site) of the B-subunit. Crystallographic information on lectin-sugar complexes is available only at acidic pH, where lectin activity is low. Thus, we mapped ligand-binding properties including comparison to ricin's Tyr-site at neutral pH. Using these results and molecular dynamics simulations, a local conformational change was rendered likely. The obtained structural information is valuable for the design of potent inhibitors. © 2008 Federation of European Biochemical Societies., This work was supported by DGICYT (BQU2003-03550-C03-03 and BFU2006-10288/BMC), the research initiative LMUexcellent and an EC Marie Curie Research Training Network Grant (Contract No. MRTN-CT-2005-019561)

Water molecules play a crucial role in mediating the interaction between a ligand and a macromolecular receptor. An understanding of the nature and role of each water molecule in the active site of a protein could greatly increase the efficiency of rational drug design approaches: if the propensity of a water molecule for displacement can be determined, then synthetic effort may be most profitably applied to the design of specific ligands with the displacement of this water molecule in mind. In this paper, a thermodynamic analysis of water molecules in the binding sites of six proteins, each complexed with a number of inhibitors, is presented. Two classes of water molecules were identified: those conserved and not displaced by any of the ligands, and those that are displaced by some ligands. The absolute binding free energies of 54 water molecules were calculated using the double decoupling method, with replica exchange thermodynamic integration in Monte Carlo simulations. It was found that conserved water molecules are on average more tightly bound than displaced water molecules. In addition, Bayesian statistics is used to calculate the probability that a particular water molecule may be displaced by an appropriately designed ligand, given the calculated binding free energy of the water molecule. This approach therefore allows the numerical assessment of whether or not a given water molecule should be targeted for displacement as part of a rational drug design strategy.

2,4- and 4,6-Diamino-substituted pyrimidines are known for their biological activity in many therapeutic areas. A novel solid-phase synthesis of this class of compounds by nucleophilic aromatic substitution has been set up and the reactivity of differently substituted solid-supported pyrimidines with properly selected amines has been studied. Using this methodology a small library of diamino-substituted pyrimidines has been prepared.