Biofilm producing Salmonella typhi: Chronic colonization and development of gallbladder cancer

Salmonella enterica subspecies enterica serovar Typhi is the aetiological agent of typhoid or enteric fever. In a subset of individuals, S. Typhi colonizes the gallbladder causing an asymptomatic chronic infection. Nonetheless, these asymptomatic carriers provide a reservoir for further spreading of the disease. Epidemiological studies performed in regions where S. Typhi is endemic, revealed that the majority of chronically infected carriers also harbour gallstones, which in turn, have been indicated as a primary predisposing factor for the onset of gallbladder cancer (GC). It is now well recognised, that S. Typhi produces a typhoid toxin with a carcinogenic potential, that induces DNA damage and cell cycle alterations in intoxicated cells. In addition, biofilm production by S. Typhi may represent a key factor for the promotion of a persistent infection in the gallbladder, thus sustaining a chronic local inflammatory response and exposing the epithelium to repeated damage caused by carcinogenic toxins. This review aims to highlight the putative connection between the chronic colonization by highly pathogenic strains of S. Typhi capable of combining biofilm and toxin production and the onset of GC. Considering the high risk of GC associated with the asymptomatic carrier status, the rapid identification and profiling of biofilm production by S. Typhi strains would be key for effective therapeutic management and cancer prevention

Boost Full Bridge Bidirectional DC/DC Converter for Supervised Aeronautical Applications

The More Electrical Aircraft concept requires electronic devices able to efficiently and safely convert electrical power between different voltage levels. The entire realization of a bidirectional DC/DC converter, from design to validation phase, is here discussed in detail. First, a boost full bridge electrical structure is selected, adopting a Parallel Input Parallel Output (PIPO) interleaving technique and an optimal turns ratio selection for the transformers in order to reduce both weight and size of the equipment. Next, modulation schemes in both step-down and step-up modes are discussed. Successively ad hoc PI regulators for both operative modes are presented. A key idea of the paper is that the converter behavior must be related not only to the control strategy but also to a global supervision logic able to safely conduct the converter operations and to react from external stimuli. Thus, a finite state machine (FSM) approach is employed. An innovative strategy called buffer mode is presented, defined as an intelligent combination of buck and boost modes. Extensive simulations and experimental results are shown, in order to confirm the effectiveness of the proposed approach

Accurate energies of hydrogen bonded nucleic acid base pairs and triplets in tRNA tertiary interactions

Tertiary interactions are crucial in maintaining the tRNA structure and functionality. We used a combined sequence analysis and quantum mechanics approach to calculate accurate energies of the most frequent tRNA tertiary base pairing interactions. Our analysis indicates that six out of the nine classical tertiary interactions are held in place mainly by H-bonds between the bases. In the remaining three cases other effects have to be considered. Tertiary base pairing interaction energies range from −8 to −38 kcal/mol in yeast tRNA(Phe) and are estimated to contribute roughly 25% of the overall tRNA base pairing interaction energy. Six analyzed posttranslational chemical modifications were shown to have minor effect on the geometry of the tertiary interactions. Modifications that introduce a positive charge strongly stabilize the corresponding tertiary interactions. Non-additive effects contribute to the stability of base triplets

Definizione delle situazioni geomorfologiche rilevanti in due diverse AMP secondo la metodologia CARLIT = Definition of relevant geomorphological situations in two different MPAs with CARLIT methodology

Macroalgae is a biological key element for the assessment of the Ecological Status in coastal waters according to the European Water Framework Directive (2000/60/EC). Here we propose the monitoring of North Sardinia coastal water quality based on CARLIT methodology. A study on the geomorphological factors of two MPAs was made as a first step for the assessment of Reference Conditions fulfils the requirements of the WFD

Coordinatively unsaturated ruthenium complexes as efficient alkyne-azide cycloaddition catalysts

The performance of 16-electron ruthenium complexes with the general formula Cp*Ru(L)X (in which L = phosphine or N-heterocyclic carbene ligand; X = Cl or OCH2CF3) was explored in azide−alkyne cycloaddition reactions that afford the 1,2,3- triazole products. The scope of the Cp*Ru(PiPr3)Cl precatalyst was investigated for terminal alkynes leading to new 1,5-disubstituted 1,2,3-triazoles in high yields. Mechanistic studies were conducted and revealed a number of proposed intermediates. Cp*Ru- (PiPr3)(η2-HCCPh)Cl was observed and characterized by 1H, 13C, and 31P NMR at temperatures between 273 and 213 K. A rare example of N,N-κ2-phosphazide complex, Cp*Ru(κ2-iPr3PN3Bn)Cl, was fully characterized, and a single-crystal X-ray diffraction structure was obtained. DFT calculations describe a complete map of the catalytic reactivity with phenylacetylene and/or benzylazide.Publisher PDFPeer reviewe

The Promise of Preventive Cancer Vaccines

Years of unsuccessful attempts at fighting established tumors with vaccines have taught us all that they are only able to truly impact patient survival when used in a preventive setting, as would normally be the case for traditional vaccines against infectious diseases. While true primary cancer prevention is still but a long-term goal, secondary and tertiary prevention are already in the clinic and providing encouraging results. A combination of immunopreventive cancer strategies and recently approved checkpoint inhibitors is a further promise of forthcoming successful cancer disease control, but prevention will require a considerable reduction of currently reported toxicities. These considerations summed with the increased understanding of tumor antigens allow space for an optimistic view of the future

Extended endoscopic endonasal transsphenoidal approach to the suprasellar area: Anatomic considerations - Part I

INTRODUCTION: Interest in using the extended endonasal transsphenoidal approach for management of suprasellar lesions, with either a microscopic or endoscopic technique, has increased in recent years. The most relevant benefit is that this median approach permits the exposure and removal of suprasellar lesions without the need for brain retraction. MATERIALS AND METHODS: Fifteen human cadaver heads were dissected to evaluate the surgical key steps and the advantages and limitations of the extended endoscopic endonasal transplanum sphenoidale approach. We compared this with the transcranial microsurgical view of the suprasellar area as explored using the bilateral subfrontal microsurgical approach, and with the anatomy of the same region as obtained through the endoscopic endonasal route. RESULTS: Some anatomic conditions can prevent or hinder use of the extended endonasal approach. These include a low level of sphenoid sinus pneumatization, a small sella size with small distance between the internal carotid arteries, a wide intercavernous sinus, and a thick tuberculum sellae. Compared with the subfrontal transcranial approach, the endoscopic endonasal approach offers advantages to visualizing the subchiasmatic, retrosellar, and third ventricle areas. CONCLUSION: The endoscopic endonasal transplanum sphenoidale technique is a straight, median approach to the midline areas around the sella that provides a multiangled, close-up view of all relevant neurovascular structures. Although a lack of adequate instrumentation makes it impossible to manage all structures that are visible with the endoscope, in selected cases, the extended endoscopic endonasal approach can be considered part of the armamentarium for surgical treatment of the suprasellar area

Stereoselectivity in Metallocene-Catalyzed Coordination Polymerization of Renewable Methylene Butyrolactones: From Stereo-random to Stereo-perfect Polymers

Coordination polymerization of renewable α-methylene-γ-(methyl)butyrolactones by chiral C2-symmetric zirconocene catalysts produces stereo-random, highly stereo-regular, or perfectly stereo-regular polymers, depending on the monomer and catalyst structures. Computational studies yield a fundamental understanding of the stereocontrol mechanism governing these new polymerization reactions mediated by chiral metallocenium catalysts

Unusual C–C Bond Cleavage in the Formation of Amine-Bis(phenoxy) Group 4 Benzyl Complexes: Mechanism of Formation and Application to Stereospecific Polymerization

Group 4 tetrabenzyl compounds MBn4 (M = Zr, Ti), upon protonolysis with an equimolar amount of the tetradentate amine-tris(phenol) ligand N[(2,4-tBu2C6H2(CH2)OH]3 in toluene from −30 to 25 °C, unexpectedly lead to amine-bis(phenoxy) dibenzyl complexes, BnCH2N[(2,4-tBu2C6H2(CH2)O]2MBn2 (M = Zr (1), Ti (2)) in 80% (1) and 75% (2) yields. This reaction involves an apparent cleavage of the >NCH2–ArOH bond (loss of the phenol in the ligand) and formation of the >NCH2–CH2Bn bond (gain of the benzyl group in the ligand). Structural characterization of 1 by X-ray diffraction analysis confirms that the complex formed is a bis(benzyl) complex of Zr coordinated by a newly derived tridentate amine-bis(phenoxy) ligand arranged in a mer configuration in the solid state. The abstractive activation of 1 and 2 with B(C6F5)3·THF in CD2Cl2 at room temperature generates the corresponding benzyl cations {BnCH2N[(2,4-tBu2C6H2(CH2)O]2MBn(THF)}+[BnB(C6F5)3]− (M = Zr (3), Ti, (4)). These cationic complexes, along with their analogues derived from (imino)phenoxy tri- and dibenzyl complexes, [(2,6-iPr2C6H3)N═C(3,5-tBu2C6H2)O]ZrBn3 (5) and [2,4-Br2C6H2(O)(6-CH2(NC5H9))CH2N═CH(2-adamantyl-4-MeC6H2O)]ZrBn2 (6), have been found to effectively polymerize the biomass-derived renewable β-methyl-α-methylene-γ-butyrolactone (βMMBL) at room temperature into the highly stereoregular polymer PβMMBL with an isotacticity up to 99% mm. A combined experimental and DFT study has yielded a mechanistic pathway for the observed unusual C–C bond cleavage in the present protonolysis reaction between ZrBn4 and N[(2,4-tBu2C6H2(CH2)OH]3 for the formation of complex 1, which involves the benzyl radical and the Zr(III) species, resulting from thermal and photochemical decomposition of ZrBn4, followed by a series of reaction sequences consisting of protonolysis, tautomerization, H-transfer, oxidation, elimination, and radical coupling