The DivJ, CbrA and PleC system controls DivK phosphorylation and symbiosis in Sinorhizobium meliloti

Sinorhizobium meliloti is a soil bacterium that invades the root nodules it induces on Medicago sativa, whereupon it undergoes an alteration of its cell cycle and differentiates into nitrogen-fixing, elongated and polyploid bacteroid with higher membrane permeability. In Caulobacter crescentus, a related alphaproteobacterium, the principal cell cycle regulator, CtrA, is inhibited by the phosphorylated response regulator DivK. The phosphorylation of DivK depends on the histidine kinase DivJ, while PleC is the principal phosphatase for DivK. Despite the importance of the DivJ in C. crescentus, the mechanistic role of this kinase has never been elucidated in other Alphaproteobacteria. We show here that the histidine kinases DivJ together with CbrA and PleC participate in a complex phosphorylation system of the essential response regulator DivK in S. meliloti. In particular, DivJ and CbrA are involved in DivK phosphorylation and in turn CtrA inactivation, thereby controlling correct cell cycle progression and the integrity of the cell envelope. In contrast, the essential PleC presumably acts as a phosphatase of DivK. Interestingly, we found that a DivJ mutant is able to elicit nodules and enter plant cells, but fails to establish an effective symbiosis suggesting that proper envelope and/or low CtrA levels are required for symbiosis.National Institutes of Health (U.S.) (Grant GM31010

Selenium-containing glycoconjugates as antioxidants

Selenium (Se) is recognized as a trace element essential for human health; low Se levels are actually associated with several diseases.1 Many natural occurring Se compounds show redox and biologically capacities, thus stimulating synthesis of new molecules with the aim to spread antioxidant effects in biological systems.2 Most of these bioactive Se-containing molecules showed a strong therapeutic and biological relevance.3 In the framework aimed at discovering new efficacious antioxidants, the synthesis of new selenoglycoconjugates, consisting of monosaccharaides containing selenium bound to polyphenols, is of our interest with the aim to overcome the poor (poly)phenol bioavailability and to provide a synergistic antioxidant effect at once. The results herein reported open new and long- term perspectives in the seleno-sugars like antioxidants in biological medium.

Highly diastereoselective preparation of anti-α,β-dialkyl β-amino acids containing natural α-amino acid side chains

An efficient synthesis of anti-2-alkyl β3-amino acids was developed starting from the fully protected β3-amino acids. The strategy allows the introduction of the side chain of natural α-amino acids such as Ala, Phe and Ser at the C-2 position, with high diastereoselectivity. The preparation of 2-methyliden-β3-amino acids is also reported. This methodology does not need the use of expensive chiral reagents and/or chiral auxiliaries, and leads to compounds with orthogonal protecting groups. © 2007 Elsevier Ltd. All rights reserved

D-Glucosamine in a chimeric prolinamide organocatalyst for direct asymmetric aldol addition

O-TBDPS d-glucosamine coupled with l-proline is reported to act as an efficient organocatalyst in the accomplishment of direct aldol reactions. Excellent results, in terms of chemical yields, as well as diastereomeric and enantiomeric ratios, are reported for the catalyzed additions of cyclohexanone and acetone to variously substituted benzaldehydes. © 2012 Elsevier Ltd. All rights reserved

Finite Element Modeling Application in Forensic Practice: A Periprosthetic Femoral Fracture Case Study

The incidence of periprosthetic fractures has rapidly increased in the last two decades and has been the cause of a large number of revision surgeries and permanent physical disability for many patients, as well as a significant socioeconomic burden for many nations. This research deals with a periprosthetic femur fracture real event, occurred following a total hip arthroplasty and treated with one of the most widespread internal fixation methods: the implant of a periprosthetic femur plate system. A Finite Element analysis was performed to investigate the implanted femur plate break after a short follow-up and to understand the plate break causes. Such events are currently object of forensic debate as more and more often hospitals, surgeons, and medical device manufacturers are denounced by patients to whom similar events occur. In this work, different load situations acting on the femur during daily and incidental activities were simulated, in order to validate the correct behavior of the plate, according to the intended use recommended by the manufacturer. The analysis demonstrates that the plate failure can occur in situations of unconventional loading such as that caused by stumbling and in presence of incomplete bone healing

A general route to D- and L-six-membered nucleoside analogues

A simple synthetic route for novel L-(as well as D-) six-membered nucleosides is described. Particularly, we have provided a general approach to the synthesis of azasugar-based nucleosides, which preparation has been easily achieved starting from the coupling of our three carbon homologating agent 1 with the well known Garner aldehyde 4. Further suitable and stereocontrolled functionalizations of the intermediate 9 will provide, after the base insertion, a wide class of six membered modified azanucleosides to be tested as NRTIs. Copyright © Taylor & Francis Group, LLC

An expeditious procedure for the synthesis of isotopically labelled fatty acids: Preparation of 2,2-d2-nonadecanoic acid

We describe a new synthetic path for the preparation of isotopically labelled saturated odd-numbered fatty acids by a homologation procedure for the direct conversion of carboxylic acids into their 2,2-dideuterated homologues. This process can be used to obtain both odd- and even-numbered 2,2-dideuterated fatty acids starting from carboxylic acids. Furthermore, the reiteration of this process can also be used for the synthesis of polydeuterated fatty acids in which the heavy atoms are placed on adjacent carbon atoms or differently arranged in the molecule. Copyright © 2006 John Wiley & Sons, Ltd

Steroid-fullerene hybrids as promising derivatives with potential application in medicinal chemistry and materials science

In recent years, fullerenes have gained great interest because their structure enables the development of novel applications based on their chemical and physical properties.1 With a focus on their small size and special structure, there have been considerable reports on their ability to scavenge free radicals, visualize biological processes, and neuroprotective activity. Furthermore, their ability to capture radicals makes them good antioxidants, for developing potential drugs to treat neurodegenerative diseases.2 On the other hand, fullerene derivatives have been used as acceptor materials in solar cells for over two decades, following the demonstration of the first proof-of-concept devices at the end of the last century.3 This work aimed to obtain structurally novel compounds, based on generating molecular hybrids, with applications as anti amyloid-β (Aβ) peptide aggregates and as acceptor material in organic solar cells. For this purpose, fullerenes were covalently bonded to malonyl conjugates substituted with fragments such as steroids and seleno-sugars. Different strategies were designed for obtaining malonyl-steroids and seleno-sugars, as well as for their coupling reaction. The covalent attachment of the conjugates to [60]fullerene was performed by Bingel-Hirsch cyclopropanation. In addition, theoretical calculations at the DFT level of theory were used to predict the synthesized hybrids' molecular structures and to estimate their physicochemical properties. Theoretical calculations based on CNDOL Fockian together with configuration interaction of single excitations (CIS), as well as the experimental results obtained such as TEM and cyclic voltammetry demonstrated that one can be considered an appealing candidate with applications for photovoltaic devices. Molecular docking was employed to determine the potential application of these fullerene derivatives to treat neurodegenerative diseases, focusing on the interaction of these molecules with the (Aβ) peptide

Diastereo- and enantioselective direct aldol reactions in aqueous medium: A new highly efficient proline-sugar chimeric catalyst

A new synthetic catalyst, capable of acting like an enzyme in the accomplishment of direct aldol reactions, is presented. Excellent results, in terms of chemical yields and diastereo-/enantiomeric ratios, are reported for the catalyzed additions of cyclohexanone to variously substituted benzaldehydes. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Synthesis of 4-deoxy-L-(and D-)hexoses from chiral noncarbohydrate building blocks

4-Deoxy-L-hexoses were synthesized starting from our previously reported reagent 1 and (R)-benzyl glycidyl ether, which led in few steps to a substituted dihydropyran 6. The stereocontrolled hydroxylation of the latter afforded the corresponding 4-deoxy-L-hexoses 7a, 9, and 11. The same procedure, starting from (S)-benzyl glycidyl ether, enabled the preparation of their D-series enantiomers