Effect of counterion on the catalytic activity of NHC-gold(I) in A3 coupling reactions

Synthetic A3-coupling represents an efficient and environmentally convenient procedure for the production of propargylamines, relevant intermediates for the preparation of pharmacologically active substances. Gold(I) complexes of general formula NHC-Au-X have been synthesized, characterized, and tested in the A3-coupling reaction of benzaldehyde, piperidine and phenylacetylene on varying the anionic fragment X as halogenide (Cl, Br, I), acetate (OAc), hexafluorophosphate (PF6) or phenylacetylide (-C≡CPh), with 5-dichloro[N-methyl, N’(2-hydroxy-2-phenyl)ethyl imidazole-2-ylidene as NHC ligand. The kinetic profiles were interpreted with DFT (Density Functional Theory) studies on bond dissociation energies (BDE) of the counterion as well as on the relative stability of the neutral NHC-Au-X complexes with respect to their ionic forms [Au(NHC)2]+[AuX2]-

Impact of therapeutic choices on outcome of osteomyelitis caused by MRSA

Fifty-four patients with chronic osteomyelitis sustained by methicillin-resistant staphylococcus were treated with daptomycin, linezolid, or teicoplanin and observed over time. Median time to CRP normalization was 7 weeks for daptomycin, 8 weeks for linezolid, and 12 weeks for teicoplanin (X2 =14.1; p < 0.001). Cure rate (intention to treat analysis) was 83% for the cases receiving teicoplanin, 77% for those receiving linezolid and 92% for those receiving daptomycin. We conclude that daptomycin and linezolid have to be considered at least equivalent to teicoplanin for the treatment of MRSA osteomyelitis

Outcomes of decompression for lumbar spinal canal stenosis based upon preoperative radiographic severity

BACKGROUND: The relationship between severity of preoperative radiographic findings and surgical outcomes following decompression for lumbar degenerative spinal canal stenosis is unclear. Our aim in this paper was to gain insight into this relationship. We determined pre-operative radiographic severity on MRI scans using strict methodological controls and correlated such severity with post-operative outcomes using prospectively collected data. METHODS: Twenty-seven consecutive patients undergoing decompression for isolated degenerative spinal canal stenosis at L4-L5 were included. We measured cross-sectional area on MRI using the technique of Hamanishi. We categorized the severity of stenosis using Laurencin and Lipson's 'Stenosis Ratio'. We determined pre-operative status (prospectively) and post-operative outcomes using Weiner and Fraser's 'Neurogenic Claudication Outcome Score'. We determined patient satisfaction using standardized questionnaires. Each of these is a validated measure. Formal statistical evaluation was undertaken. RESULTS: No patients (0 of 14) with a greater than 50% reduction in cross-sectional area on pre-operative MRI had unsatisfactory outcomes. In contrast, outcomes for patients with less than or equal to 50% reduction in cross-sectional area had unsatifactory outcomes in 6 of 13 cases, with all but one negative outcome having a cross-sectional area reduction between 32% and 47%. CONCLUSION: The findings suggest that there appears to be a relationship between severity of stenosis and outcomes of decompressive surgery such that patients with a greater than 50% reduction in cross sectional area are more likely to have a successful outcome

Quantitative radiologic criteria for the diagnosis of lumbar spinal stenosis: a systematic literature review

Background: Beside symptoms and clinical signs radiological findings are crucial in the diagnosis of lumbar spinal stenosis (LSS). We investigate which quantitative radiological signs are described in the literature and which radilogical criteria are used to establish inclusion criteria in clincical studies evaluating different treatments in patients with lumbar spinal stenosis. Methods: A literature search was performed in Medline, Embase and the Cochrane library to identify papers reporting on radiological criteria to describe LSS and systematic reviews investigating the effects of different treatment modalities. Results: 25 studies reporting on radiological signs of LSS and four systematic reviews related to the evaluation of different treatments were found. Ten different parameters were identified to quantify lumbar spinal stenosis. Most often reported measures for central stenosis were antero-posterior diameter (< 10 mm) and cross-sectional area (< 70 mm2) of spinal canal. For lateral stenosis height and depth of the lateral recess, and for foraminal stenosis the foraminal diameter were typically used. Only four of 63 primary studies included in the systematic reviews reported on quantitative measures for defining inclusion criteria of patients in prognostic studies. Conclusions: There is a need for consensus on well-defined, unambiguous radiological criteria to define lumbar spinal stenosis in order to improve diagnostic accuracy and to formulate reliable inclusion criteria for clinical studies

Structural and Functional Similarities between Osmotin from Nicotiana Tabacum Seeds and Human Adiponectin

Osmotin, a plant protein, specifically binds a seven transmembrane domain receptor-like protein to exert its biological activity via a RAS2/cAMP signaling pathway. The receptor protein is encoded in the gene ORE20/PHO36 and the mammalian homolog of PHO36 is a receptor for the human hormone adiponectin (ADIPOR1). Moreover it is known that the osmotin domain I can be overlapped to the β-barrel domain of adiponectin. Therefore, these observations and some already existing structural and biological data open a window on a possible use of the osmotin or of its derivative as adiponectin agonist. We have modelled the three-dimensional structure of the adiponectin trimer (ADIPOQ), and two ADIPOR1 and PHO36 receptors. Moreover, we have also modelled the following complexes: ADIPOQ/ADIPOR1, osmotin/PHO36 and osmotin/ADIPOR1. We have then shown the structural determinants of these interactions and their physico-chemical features and analyzed the related interaction residues involved in the formation of the complexes. The stability of the modelled structures and their complexes was always evaluated and controlled by molecular dynamics. On the basis of these results a 9 residues osmotin peptide was selected and its interaction with ADIPOR1 and PHO36 was modelled and analysed in term of energetic stability by molecular dynamics. To confirm in vivo the molecular modelling data, osmotin has been purified from nicotiana tabacum seeds and its nine residues peptide synthesized. We have used cultured human synovial fibroblasts that respond to adiponectin by increasing the expression of IL-6, TNF-alpha and IL-1beta via ADIPOR1. The biological effect on fibroblasts of osmotin and its peptide derivative has been found similar to that of adiponectin confirming the results found in silico

A novel role for RecA under non-stress: promotion of swarming motility in Escherichia coli K-12

BACKGROUND: Bacterial motility is a crucial factor in the colonization of natural environments. Escherichia coli has two flagella-driven motility types: swimming and swarming. Swimming motility consists of individual cell movement in liquid medium or soft semisolid agar, whereas swarming is a coordinated cellular behaviour leading to a collective movement on semisolid surfaces. It is known that swimming motility can be influenced by several types of environmental stress. In nature, environmentally induced DNA damage (e.g. UV irradiation) is one of the most common types of stress. One of the key proteins involved in the response to DNA damage is RecA, a multifunctional protein required for maintaining genome integrity and the generation of genetic variation. RESULTS: The ability of E. coli cells to develop swarming migration on semisolid surfaces was suppressed in the absence of RecA. However, swimming motility was not affected. The swarming defect of a ΔrecA strain was fully complemented by a plasmid-borne recA gene. Although the ΔrecA cells grown on semisolidsurfaces exhibited flagellar production, they also presented impaired individual movement as well as a fully inactive collective swarming migration. Both the comparative analysis of gene expression profiles in wild-type and ΔrecA cells grown on a semisolid surface and the motility of lexA1 [Ind-] mutant cells demonstrated that the RecA effect on swarming does not require induction of the SOS response. By using a RecA-GFP fusion protein we were able to segregate the effect of RecA on swarming from its other functions. This protein fusion failed to regulate the induction of the SOS response, the recombinational DNA repair of UV-treated cells and the genetic recombination, however, it was efficient in rescuing the swarming motility defect of the ΔrecA mutant. The RecA-GFP protein retains a residual ssDNA-dependent ATPase activity but does not perform DNA strand exchange. CONCLUSION: The experimental evidence presented in this work supports a novel role for RecA: the promotion of swarming motility. The defective swarming migration of ΔrecA cells does not appear to be associated with defective flagellar production; rather, it seems to be associated with an abnormal flagellar propulsion function. Our results strongly suggest that the RecA effect on swarming motility does not require an extensive canonical RecA nucleofilament formation. RecA is the first reported cellular factor specifically affecting swarming but not swimming motility in E. coli. The integration of two apparently disconnected biologically important processes, such as the maintenance of genome integrity and motility in a unique protein, may have important evolutive consequences

Some Regularity Properties on Bolza problems in the Calculus of Variations

The paper summarizes the main core of the last results that we obtained in [4, 8, 17] on the regularity of the value function for a Bolza problem of a one-dimensional, vectorial problem of the calculus of variations. We are concerned with a nonautonomous Lagrangian that is possibly highly discontinuous in the state and velocity variables, nonconvex in the velocity variable and non coercive. The main results are achieved under the assumption that the Lagrangian is convex on the one-dimensional lines of the velocity variable and satisfies a local Lipschitz continuity condition w.r.t. the time variable, known in the literature as Property (S), and strictly related to the validity of the Erdmann-Du-Bois Reymond equation. Under our assumptions, there exists a minimizing sequence of Lipschitz functions. A first consequence is that we can exclude the presence of the Lavrentiev phenomenon. Moreover, under a further mild growth assumption satisfied by the minimal length functional, fully described in the paper, the above sequencemay be taken with the same Lipschitz rank, even when the initial datum and initial value vary on a compact set. The Lipschitz regularity of the value function follows

Non-occurrence of gap for one-dimensional non-autonomous functionals

Let F(y):=∫tTL(s,y(s),y′(s))ds be a positive functional defined on the space W1,p([t, T] ; Rn) (p≥ 1) of Sobolev functions with, possibly, one or both end point conditions. It is important, especially for the applications, to be able to approximate the infimum of F with the values of F along a sequence of Lipschitz functions satisfying the same boundary condition(s). Sometimes this is not possible, i.e., the so called Lavrentiev phenomenon occurs. This is the case of the seemingly innocent Manià’s Lagrangian L(s,y,y′)=(y3-s)2(y′)6 and boundary data y(0) = 0 , y(1) = 1 ; nevertheless in this situation the phenomenon does not occur with just the end point condition y(1) = 1. The paper focuses about the different set of conditions that are needed to avoid the Lavrentiev phenomenon for problems depending on the number of end point conditions that are considered. Under minimal assumptions on the (possibly) extended value, Lagrangian, we ensure the non-occurrence of the Lavrentiev phenomenon with just one end point condition, thus extending a milestone result by Alberti and Serra Cassano to non-autonomous case. We then introduce an additional hypothesis, satisfied when the Lagrangian is bounded on bounded sets, in order to ensure the non-occurrence of the phenomenon when dealing with both end point conditions; the result gives some new light even in the autonomous case