La collezione storica degli strumenti di fisica dell'Università di Palermo

L'articolo descrive la composizione e la storia della collezione di strumenti dell'Istituto di Fisica dell'Università di Palerm

Due 'paradossi meccanici' della Collezione Storica degli Strumenti di Fisica dell'Universit\`a di Palermo

Many instruments of the Historical Collection of the Physics Instruments of the University of Palermo date back to the early nineteenth century, when experimental Physics begun to be taught in university studies by using instruments and apparatuses in the classroom to illustrate the laws of Physics. Among the various instruments belonging to the Collection, there are also the so-called 'paradoxes', instruments with surprising properties that do not seem to follow the laws of Physics. In this article we analyze two 'mechanical paradoxes' of the Collection and discuss their possible educational use.Comment: 11 Pages, in Italian, 9 Figures. Accepted for publication in Quaderni di Ricerca in Didattica (Science), special Issue in Italian languag

Detailed Soluble Proteome Analyses of a Dairy-Isolated Enterococcus faecalis: A Possible Approach to Assess Food Safety and Potential Probiotic Value

Enterococci are common inhabitants of the gastrointestinal tracts of humans and animals and thanks to their capability to tolerate different environmental conditions and their high rates of gene transfer, they are able to colonize various ecological niches, as food matrices. Enterococcus faecalis bacteria are defined as controversial microorganisms. From one side they are used as food starters, bio-control agents and probiotics to improve human or animal health. From the other side, in the last two decades enterococci have emerged as important nosocomial pathogens, because bearing high-level of resistance to antibiotics and several putative virulence factors. In this study, the soluble proteome quantitation data (LC-MS/MS) of the food-isolated strain E. faecalis D27 (dairy-isolate) was compared with the soluble proteome quantitation data of the pathogenic E. faecalis UW3114 (urinary tract infection isolate) and with the one of the health promoting strain E. faecalis Symbioflor1, respectively. The comparison of cytosolic protein expression profiles highlighted statistically significant changes in the abundance of proteins mainly involved in specific metabolic pathways, nutrient transport, stress response, and cell wall modulation. Moreover, especially in the dairy isolate and the clinical isolate, several proteins with potential pathogenic implications were found, such as serine proteases, von Willebrand factor, serine hydrolase with beta lactamase activity, efflux transporter, and proteins involved in horizontal gene transfer. The analysis of the extracellular proteome provided interesting results concerning proteins involved in bacterial communication, such as pheromones and conjugative elements and also proteins able to interact with human components. The phenotypic characterization evaluating (i) biofilm formation (ii) hemolytic activity on blood agar plates (iii) protease activity (iv) gelatinase (v) antibiotic resistance pattern, enabled us to elucidate the risks associated with the poor characterized foodborne E. faecalis D27

Musculoskeletal disorders and incongruous postures in workers on ropes: A pilot study

Background: Occupational hazards believed to cause musculoskeletal disorders in rope workers are traditionally associated with maintaining incongruous postures for prolonged periods of time. Design and methods: A cross-sectional survey was conducted on 132 technical operators in the wind energy and acrobatic construction sectors, who work on ropes, analysing the ergonomic characteristics of the environments, the way in which tasks are carried out, the strain perceived by individual workers, and assessing the presence of any musculoskeletal disorders (MSDs) by means of an objective examination focused on the anatomical districts that were the object of our study. Results: Analysis of the data obtained showed that there were differences in the perception of the level of physical intensity and perceived exertion between the groups of workers. Statistical analysis also revealed a significant association between the frequency of MSDs analysed and perceived exertion. Discussion: The most significant finding to emerge from this study is the high prevalence of MSDs of the cervical spine (52.94%), the upper limbs (29.41%), and the dorso-lumbar spine (17.65%). These values differ from those classically found in those exposed to the risk of conventional manual handling of loads. Conclusions: The high prevalence of disorders of the cervical spine, the scapulo-humeral girdle and the upper limbs, indicates the need to consider the forced position to be assumed for a large part of the work activity, staticity, and the inability to move the lower limbs for long periods as the predominant risk in rope work

Musculoskeletal disorders and incongruous postures in workers on ropes: A pilot study

Background:Occupational hazards believed to cause musculoskeletal disorders in rope workers are traditionally associated with maintaining incongruous postures for prolonged periods of time. Design and methods:A cross-sectional survey was conducted on 132 technical operators in the wind energy and acrobatic construction sectors, who work on ropes, analysing the ergonomic characteristics of the environments, the way in which tasks are carried out, the strain perceived by individual workers, and assessing the presence of any musculoskeletal disorders (MSDs) by means of an objective examination focused on the anatomical districts that were the object of our study. Results:Analysis of the data obtained showed that there were differences in the perception of the level of physical intensity and perceived exertion between the groups of workers. Statistical analysis also revealed a significant association between the frequency of MSDs analysed and perceived exertion. Discussion:The most significant finding to emerge from this study is the high prevalence of MSDs of the cervical spine (52.94%), the upper limbs (29.41%), and the dorso-lumbar spine (17.65%). These values differ from those classically found in those exposed to the risk of conventional manual handling of loads. Conclusions:The high prevalence of disorders of the cervical spine, the scapulo-humeral girdle and the upper limbs, indicates the need to consider the forced position to be assumed for a large part of the work activity, staticity, and the inability to move the lower limbs for long periods as the predominant risk in rope work

COVID-19 Pandemic: New Prevention and Protection Measures

As of the end of February 2021, more than 420,000,000 confirmed cases of COVID-19 have been reported worldwide, with 5,856,224 deaths. Transmission of the different genetically engineered variants of SARS-CoV-2, which have been isolated since the beginning of the pandemic, occurs from one infected person to another by the same means: the airborne route, indirect contact, and occasionally the fecal–oral route. Infection is asymptomatic or may present with flulike symptoms such as fever, cough, and mild to moderate and severe respiratory distress, requiring hospitalization and assisted ventilation support. To control the spread of COVID-19, the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) have indicated that the appropriate use of personal protective equipment (PPE), as well as the adoption of effective hygiene systems, is one of the primary prevention measures for the entire population. Companies and institutions around the world are therefore trying to find the best ways to reorganize their operations, minimizing the risk of infection among their employees, in order to protect their health and prevent internal outbreaks of SARS-CoV-2, including through the development of new technologies that could also be an innovative and driving factor for the relaunch of companies in a more sustainable, ethically correct, and safe for the health of employees perspective. On the basis of the above premises, in view of the coexistence with SARS-CoV-2 that will most likely accompany us in the coming years, and in view of the vaccination campaign adopted worldwide, the purpose of our narrative review is to update the previous operational protocols with the latest scientific knowledge to be adopted in the workplace even when the emergency crisis is over

HIV-1-induced nuclear invaginations mediated by VAP-A, ORP3, and Rab7 complex explain infection of activated T cells

The mechanism of human immunodeficiency virus 1 (HIV-1) nuclear entry, required for productive infection, is not fully understood. Here, we report that in HeLa cells and activated CD4+ T cells infected with HIV-1 pseudotyped with VSV-G and native Env protein, respectively, Rab7+ late endosomes containing endocytosed HIV-1 promote the formation of nuclear envelope invaginations (NEIs) by a molecular mechanism involving the VOR complex, composed of the outer nuclear membrane protein VAP-A, hyperphosphorylated ORP3 and Rab7. Silencing VAP-A or ORP3 and drug-mediated impairment of Rab7 binding to ORP3-VAP-A inhibited the nuclear transfer of the HIV-1 components and productive infection. In HIV-1-resistant quiescent CD4+ T cells, ORP3 was not hyperphosphorylated and neither VOR complex nor NEIs were formed. This new cellular pathway and its molecular players are potential therapeutic targets, perhaps shared by other viruses that require nuclear entry to complete their life cycle

Discovery of the 3-Amino-1,2,4-triazine-Based Library as Selective PDK1 Inhibitors with Therapeutic Potential in Highly Aggressive Pancreatic Ductal Adenocarcinoma

Pyruvate dehydrogenase kinases (PDKs) are serine/threonine kinases, that are directly involved in altered cancer cell metabolism, resulting in cancer aggressiveness and resistance. Dichloroacetic acid (DCA) is the first PDK inhibitor that has entered phase II clinical; however, several side effects associated with weak anticancer activity and excessive drug dose (100 mg/kg) have led to its limitation in clinical application. Building upon a molecular hybridization approach, a small library of 3-amino-1,2,4-triazine derivatives has been designed, synthesized, and characterized for their PDK inhibitory activity using in silico, in vitro, and in vivo assays. Biochemical screenings showed that all synthesized compounds are potent and subtype-selective inhibitors of PDK. Accordingly, molecular modeling studies revealed that a lot of ligands can be properly placed inside the ATP-binding site of PDK1. Interestingly, 2D and 3D cell studies revealed their ability to induce cancer cell death at low micromolar doses, being extremely effective against human pancreatic KRAS mutated cancer cells. Cellular mechanistic studies confirm their ability to hamper the PDK/PDH axis, thus leading to metabolic/redox cellular impairment, and to ultimately trigger apoptotic cancer cell death. Remarkably, preliminary in vivo studies performed on a highly aggressive and metastatic Kras-mutant solid tumor model confirm the ability of the most representative compound 5i to target the PDH/PDK axis in vivo and highlighted its equal efficacy and better tolerability profile with respect to those elicited by the reference FDA approved drugs, cisplatin and gemcitabine. Collectively, the data highlights the promising anticancer potential of these novel PDK-targeting derivatives toward obtaining clinical candidates for combatting highly aggressive KRAS-mutant pancreatic ductal adenocarcinomas

Structural Manipulations of Marine Natural Products Inspire a New Library of 3-Amino-1,2,4-Triazine PDK Inhibitors Endowed with Antitumor Activity in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the main aggressive types of cancer, characterized by late prognosis and drug resistance. Among the main factors sustaining PDAC progression, the alteration of cell metabolism has emerged to have a key role in PDAC cell proliferation, invasion, and resistance to standard chemotherapeutic agents. Taking into account all these factors and the urgency in evaluating novel options to treat PDAC, in the present work we reported the synthesis of a new series of indolyl-7-azaindolyl triazine compounds inspired by marine bis-indolyl alkaloids. We first assessed the ability of the new triazine compounds to inhibit the enzymatic activity of pyruvate dehydrogenase kinases (PDKs). The results showed that most of derivatives totally inhibit PDK1 and PDK4. Molecular docking analysis was executed to predict the possible binding mode of these derivatives using ligand-based homology modeling technique. Evaluation of the capability of new triazines to inhibit the cell growth in 2D and 3D KRAS-wild-type (BxPC-3) and KRAS-mutant (PSN-1) PDAC cell line, was carried out. The results showed the capacity of the new derivatives to reduce cell growth with a major selectivity against KRAS-mutant PDAC PSN-1 on both cell models. These data demonstrated that the new triazine derivatives target PDK1 enzymatic activity and exhibit cytotoxic effects on 2D and 3D PDAC cell models, thus encouraging further structure manipulation for analogs development against PDA

Imidazo[2,1-b] [1,3,4]thiadiazoles with antiproliferative activity against primary and gemcitabine-resistant pancreatic cancer cells

A new series of eighteen imidazo [2,1-b] [1,3,4]thiadiazole derivatives was efficiently synthesized and screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. Two out of eighteen derivatives, compounds 12a and 12h, showed remarkably cytotoxic activity with the half maximal inhibitory concentration values (IC50) ranging from 0.23 to 11.4 mM, and 0.29e12.2 mM, respectively. However, two additional compounds, 12b and 13g, displayed remarkable in vitro antiproliferative activity against pancreatic ductal adenocarcinoma (PDAC) cell lines, including immortalized (SUIT-2, Capan-1, Panc-1), primary (PDAC-3) and gemcitabine-resistant (Panc-1R), eliciting IC50 values ranging from micromolar to sub-micromolar level, associated with significant reduction of cell-migration and spheroid shrinkage. These remarkable results might be explained by modulation of key regulators of epithelial-to-mesenchymal transition (EMT), including E-cadherin and vimentin, and inhibition of metalloproteinase-2/-9. High-throughput arrays revealed a significant inhibition of the phosphorylation of 45 tyrosine kinases substrates, whose visualization on Cytoscape highlighted PTK2/FAK as an important hub. Inhibition of phosphorylation of PTK2/FAK was validated as one of the possible mechanisms of action, using a specific ELISA. In conclusion, novel imidazothiadiazoles show potent antiproliferative activity, mediated by modulation of EMT and PTK2/FAK