323,116 research outputs found
Precariato, sicurezza e regolarità del lavoro. Atti del convegno tenutosi a Bologna il 13 dicembre 2006
No full textSYNTHESIS AND BIOLOGICAL EVALUATION OF NEW INHIBITORS OF ENZYMES INVOLVED IN c-di-GMP METABOLISM
No full textRecently, much attention has been focused on the need for new antimicrobial agents with new targets or mechanisms of action against multidrug-resistant bacteria. Heavy antibiotic use and person to person spread of bacteria have greatly increased antibiotic resistance due to genetic mutation and this problem is continually increasing in severity. Biofilm-forming bacteria, resistant to antibiotics, cause over 65% of hospital infections. Biofilms are structural communities of bacterial cells enclosed in a self-produced polymeric matrix and adherent to an inhert or living surface. In the biofilm, bacteria are 1000-times more resistant to conventional antibiotic treatment. Despite the central role that bacterial biofilm plays in infection, there is currently no anti-biofilm drugs in clinical use. Therefore, the development of original compounds that specifically target the formation of biofilm is of great need in view of a rational use of antibiotics.
Cyclic di-GMP (c-di-GMP) is a second messenger unique of bacteria that plays a central role in biofilm formation and also in the expression of virulence traits. Synthesis of c-di-GMP occurs via diguanylate cyclase enzymes (DCGs), while degradation of c-di-GMP occurs via phosphodiesterase enzymes (PDE). Small molecules interfering with c-di-GMP metabolism could potentially inhibit biofilm formation and virulence in a variety of bacteria. Inhibition of bacteria virulence rather than growth is an alternative strategy that allows to combat bacterial infections without exerting strong selective pressure for the bacteria to evolve resistance mechanisms. The exact details of c-di-GMP signaling is currently being studied by several laboratories and it is expected that analogs of c-di-GMP or other small molecules able to inhibit the enzymes involved in the c-di-GMP metabolism will become useful as either antivirulence or antibiofilm drugs. To date, only few molecular scaffolds have been identified and new small molecules that are able to prevent or destroy biofilm formation are needed.
Based on these findings new c-di-GMP analogs have been synthesized and their ability to inhibit both PDE or DCG enzymes has been evaluated using an innovative approach to follow the enzymatic c-di-GMP formation and degradation in real-time.(1) The enzymes assayed are RocR and the cytoplasmatic portion of PA1120 from P. aeruginosa (PDE and DCG, respectively) and PleD from C. crescentus, as a reference of DCGs. The newly synthesized compounds showing the highest activity in vitro are currently being analyzed for their ability to inhibit c-di-GMP signaling, biofilm formation and/or virulence factors production in vivo, using the human pathogen P. aeruginosa as model bacterium. Results of these studies will be discussed.
(1) Stelitano, V, et al. Nucleic Acids Res. 2013, 41, e79
Allosteric control in the synthesis and sensing of cyclic-di-GMP
No full textCyclic-di-GMP (c-di-GMP) is considered one of the most important regulators of bacterial adaptation strategies such as persistence, cytotoxicity, development and biofilm formation. C-di-GMP is synthesized by diguanylate cyclases (DGCs), containing GGDEF domain and degraded by specific phosphodiesterases (PDEs), containing EAL or HD-GYP signatures. The relevance of c-di-GMP is linked to its amazing capacity to interact with a large repertoire of proteins and nucleic acids using different binding modes; its conformational plasticity is likely at the basis of its extraordinary success as a signal molecule (1). Activaction/deactivation of individual proteins is likely to be controlled by a combination of c-di-GMP affinity and binding mode, producing a variety of allosteric control mechanisms, few of them characterized in detail biochemically. In this study, we focused on the biochemistry of c-di-GMP by studying the protein domains involved in its synthesis and degradation, which are supposed to interact to each other allosterically. To derive the principles governing protein/c-di-GMP interaction and catalysis, we have produced an array of small molecules, mostly c-di-GMP analogues, and studies their binding affinities for the active and inhibitory sites of GGDEF diguanylate cyclases (PleD, YfiN) (2,3) also in comparison with EAL phosphodiesterases (RocR) (4). Moreover, to determine the molecular determinants of the crosstalk between GGDEF and EAL domains, we focus on the characterization of the structure and function of different hybrid proteins, harboring both domains fused in tandem. 1. Romlig, U., Galperin, M.Y:, Gomelsky, M. (2013) Mol. Biol. Rev. 77:1-52. 2. Chan, C., Paul, R., Samoray, D., Amiot, N.C., Giese, B., et al (2004) Proc Natl Acad Sci USA 101: 17084-17089. 3. Giardina, G., Paiardini, A., Fernicola, S., Franceschini, S., Rinaldo, S., Stelitano, V., Cutruzzolà, F. (2013) PLoS One 8:e81324. 4. Rao, F., Yang, Y., Qi, Y., Liang, Z.X. (2008) J Bacteriol. 190:3622-3
Rimedi e sanzioni nella cd. "riforma Bersani"
No full textLa cd."riforma Bersani" aggredisce mil fenomeno del lavoro sommerso sul duplice versante dei "rimedi" e delle "sanzioni". Sul primo versante, irrobustisce la responsabilità solidale tra imprenditori nelle catene di appalti; sul secondo, introduce una "maxisanzione" amministrativa contro il lavoro sommerso.
L'autore analizza i profili sanzionatori e promozionali della legge n. 248/2006, con specifico riferimento al contrasto del lavoro irregolare e alla tutela dei lavoratori nelle catene di appalt
Diffusive author(s), cohesive author: Analysis of S/N (1994)
No full textThis study indicates the ways in which various aspects of the author(s) are brought forth in Dumb type’s performance art, the S/N production. Previous research has suggested a non-hierarchical organization of Dumb type and the absence of a “privileged author” in Dumb type’s collaborative work, S/N. However, the results that I have investigated from member’s interviews on the creative process of S/N along with my analysis of the recorded images of S/N, indicate a different aspect of the author(s). First, S/N was created through, so to speak, the collective ideas of the members of Dumb type. Further, S/N has at least nine quotations from previous performances, installations, and printed writings, besides the work-in-progress technique. Explicating one of the “author functions” as given by Michel Foucault, each text has plural subjects of the author. However, it has been revealed from members’ interviews that Teiji Furuhashi had a decision-making role in selecting the members’ ideas within the performance. Since then, S/N has had plural subjects of creation; however, Furuhashi is one of the subjects of creation along with the “privileged author.” S/N has plural authors (diffusive authors) yet at the same time, it has a “privileged author,” Teiji Furuhashi (cohesive author)
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Progression of Lactobacillus plantarum prosthetic valve endocarditis followed by transesophageal echocardiogram
No full textEndocarditis due to Lactobacillus species is extremely rare. We report an uncommon case of Lactobacillus plantarum bioprosthetic aortic valve endocarditis, presenting with severe aortic steno-regurgitation, which responded to conventional medical and surgical treatment. This case provides a better understanding of the disease process of L. plantarum and highlights the role of transesophageal echocardiography in following the entire course of endocarditis. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases
The intestinal biofilm of pseudomonas aeruginosa and staphylococcus aureus is inhibited by antimicrobial peptides HBD-2 and HBD-3
No full textBackground: The intestinal microbiota is a very active microbial community interacting with the host in maintaining homeostasis; it acts in cooperation with intestinal epithelial cells, which protect the host from the external environment by producing a diverse arsenal of antimicrobial peptides (AMPs), including β-defensins-2 and 3 (HBD-2 and HBD-3), considered among the most studied in this category. However, there are some circumstances in which an alteration of this eubiotic state occurs, with the triggering of dysbiosis. In this condition, the microbiota loses its protective power, leading to the onset of opportunistic infections. In this scenario, the emergence of multi-drug resistant biofilms from Pseudomonas aeruginosa and Staphylococcus aureus is very frequent. Methods: We created a Caco-2 intestinal epithelial cell line stably transfected with the genes, encoding HBD-2 and HBD-3, in order to evaluate their ability to inhibit the intestinal biofilm formation of P. aeruginosa and S. aureus. Results: Both HBD-2 and HBD-3 showed anti-biofilm activity against P. aeruginosa and S. aureus. Conclusions: The exploitation of endogenous antimicrobial peptides as a new anti-biofilm therapy, in isolation or in combination with conventional antibiotics, can be an interesting prospect in the treatment of chronic and multi-drug resistant infections
HSV membrane glycoproteins, their function in viral entry and their use in vaccine studies
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