Development of a Device-Assisted Nerve-Regeneration Procedure in Disruptive Lesions of the Brachial Plexus.

Background:  We describe the development of a new surgical procedure to be used in the treatment of disruptive brachial plexus (BP) lesions. It is centered on an artificial device designed to assist nerve regeneration by providing a confined and protected environment. Nerve fibers can repair inside the device, while the adverse massive scar-tissue formation is limited to the outside of the device.

Multiplexed molecular descriptors of pressure ulcers defined by imaging mass spectrometry.

The pathogenesis of impaired healing within pressure ulcers remains poorly characterized and rarely examined. We describe the results of a pilot study that applies matrix-assisted laser desorption/ionization imaging mass spectrometry technology for direct tissue analysis to evaluate proteomic signatures ranging from 2 to 20 kDa and phospholipids from 300-1,200 Da in focal regions within the wound microenvironment. Distinguishing molecular differences were apparent between upper vs.

A proposal for mitochondrial processing peptidase catalytic mechanism.

The reaction mechanism of the Mitochondrial Processing Peptidase enzyme (MPP) was investigated by using hybrid density functional theory. This enzyme removes the NH(2)-terminal targeting signals of nuclear-encoded mitochondrial protein precursors in the mitochondrial matrix. The catalytic process was studied using a model for the active site consisting of 161 atoms locating all the stationary points on the potential energy curve and determining the main energetic, structural, and electronic features that drive the catalysis.

Spatial mapping by imaging mass spectrometry offers advancements for rapid definition of human skin proteomic signatures.

Investigations into the human skin proteome by classical analytical procedures have not addressed spatial molecular distributions in whole-skin biopsies. The aim of this study was to develop methods for the detection of protein signatures and their spatial disposition in human skin using advanced molecular imaging technology based on mass spectrometry technologies. This technology allows for the generation of protein images at specific molecular weight values without the use of antibody while maintaining tissue architecture.

Can human prolidase enzyme use different metals for full catalytic activity?

The catalytic hydrolysis of the Gly-Pro substrate by the bimetallic prolidase active site model cluster has been investigated at the DF/B3LYP level of theory, in order to provide fundamental insights into the still poorly understood mechanism of prolidase catalysis. To date, the majority of prolidases exhibits metal-dependent activity, requiring two divalent cations such as Zn(2+), Mn(2+), or Co(2+) for maximal activity. In addition, it has been shown recently that two different metal ions in the active site of human prolidase (Zn and Mn) can coexist, with the protein remaining partially active.

Waiting-time distributions of magnetic discontinuities: clustering or Poisson process?

Using solar wind data from the Advanced Composition Explorer spacecraft, with the support of Hall magnetohydrodynamic simulations, the waiting-time distributions of magnetic discontinuities have been analyzed. A possible phenomenon of clusterization of these discontinuities is studied in detail. We perform a local Poisson's analysis in order to establish if these intermittent events are randomly distributed or not.

Human insulin-degrading enzyme working mechanism.

The possible mechanism by which the insulin-degrading enzyme (IDE) zinc-binding protease carries out its catalytic function toward two peptides of different length, simulating a portion of B chain of insulin, was investigated on an enzymatic model consisting of 130 /159 atoms, using the density functional theory method and the hybrid exchange-correlation functional B3LYP in gas phase and in the protein environment. Based on the geometry and relative stabilities of minima and transition states on the potential energy profiles, we determined that proteolysis reaction is exothermic and proceeds quickly as the barrier in the rate-limiting step falls widely within the range of values expected for an enzymatic catalysis, both in vacuum and in protein medium.

Determination of the catalytic pathway of a manganese arginase enzyme through density functional investigation.

The catalytic mechanism of dimanganese-containing arginase enzyme has been investigated by DFT calculations. Two exchange-correlation functionals, B3 LYP and MPWB1 K, have been used to construct the potential energy profiles for the hydrolysis of an arginine substrate performed by an arginase active site model system. Two reaction mechanisms have been investigated, one involving a water molecule (mechanism 1) and the other involving a hydroxide ion (mechanism 2) as nucleophilic agent.

Can subpyriporphyrin and its boron complex be proposed as photosensitizers in photodynamic therapy ? A first principle time dependent study.

Density functional theory (DFT) and its time-dependent approach (TDDFT) in conjunction with the PBE0 exchange-correlation functional have been employed to characterize the structural and electronic properties of a new synthesized homologue of a triphyrin, in which a pyrrole ring has been substituted with a pyridine moiety, and its boron complex. Absorption spectra have been computed for different isomers of the free compound as well as for the corresponding boron containing system. The solvent effects have been evaluated through the polarizable continuum model (PCM).

On the Pt(+) and Rh(+) Catalytic Activity in the Nitrous Oxide Reduction by Carbon Monoxide.

Nitrous oxide activation by CO in the presence of platinum and rhodium monocations was elucidated by density functional methods for ground and first excited states. Platinum and rhodium cations fulfill the thermodynamic request for the oxygen-atom transport that allows the catalytic cycle to be completed, but actually, just the first one meaningfully improves the kinetics of the process. For both catalysts, the reaction pathways show the only activation barrier in correspondence of nitrogen release and monoxide cation formation.

Reaction mechanism of molybdoenzyme formate dehydrogenase.

Formate dehydrogenase is a molybdoenzyme of the anaerobic formate hydrogen lyase complex of the Escherichia coli microorganism that catalyzes the oxidation of formate to carbon dioxide. The two proposed mechanisms of reaction, which differ in the occurrence of a direct coordination or not of a SeCys residue to the molybdenum metal during catalysis were analyzed at the density functional level in both vacuum and protein environments. Some DF functionals, in addition to the very popular B3LYP one, were employed to compute barrier heights.

First-principle time-dependent study of magnesium-containing porphyrin-like compounds potentially useful for their application in photodynamic therapy.

Geometry optimization, singlet-triplet energy gap, and electronic absorption spectra calculation of complexes formed by Mg ion and porphyrin, porphyrazin, chlorine, bacteriochlorine, texaphyrin, phthalocyanine, naphthalocyanine, and anthracocyanine ligands have been carried out to elucidate their potentiality as photosensitizers in photodynamic therapy (PDT). The study has been performed employing the density functional theory (DFT) and its time-dependent approach (TDDFT) in conjunction with the PBE0 exchange-correlation functional and extended TZVP all-electron basis sets. The solvent effects have been evaluated throughout the polarizable continuum model (PCM).

On the Catalytic Role of Ge(+) and Se(+) in the Oxygen Transport Activation of N2O by CO.

The different reactivity of two first row cations selenium and germanium, in activating the reduction of nitrous oxide by carbon monoxide, was theoretically investigated at the density functional level using large basis sets and pseudopotential for metal atoms. In the two examined cases, the reaction mechanisms appeared to be quite different. Germanium shows a very good performance as far as thermodynamic and kinetic aspects are concerned.

Negative charged threonine 95 of c-Jun is essential for c-Jun N-terminal kinase-dependent phosphorylation of threonine 91/93 and stress-induced c-Jun biological activity.

Activation of c-Jun, a major component of the AP-1 transcription factor, represents a paradigm for transcriptional response to stress. Transactivation of c-Jun is regulated by Jun-N-terminal kinases (JNKs) through phosphorylation at serine 63 and 73 (S63/S73), as well as at threonine 91 and 93 (T91/T93). How these two groups of phosphoacceptor sites respond to different grades of genotoxic stress and whether DNA-damage pathways influence the extent of their JNK-dependent phosphorylations remain to be elucidated.

A comparative study of the antioxidant power of flavonoid catechin and its planar analogue.

The antioxidant ability of the flavanol catechin and its planar derivative, catechin 1 (PC1), was explored using the DF/B3LYP theoretical approach. Their potentiality in the hydrogen abstraction and electron transfer reactions, the main working mechanisms of antioxidants, was evaluated by computing the values of two key parameters, which are the OH bond dissociation energy and the ionization potential. Results indicated that the effect of a planar arrangement in the catechin molecule is small in the case of the hydrogen abstraction but greater for the electron transfer, since the in vacuo ionization potential value decreases by about 3 kcal/mol.

On the origin of the different performance of iron and manganese monocations in catalyzing the nitrous oxide reduction by carbon oxide.

The potential energy profiles for the Fe+- and Mn+-assisted reduction of N2O by CO were studied at the B3LYP density functional level in order to get the differences in the reaction mechanisms determining the efficiency of iron and the inactivity of manganese as ionic catalysts. Both ground and excited states of cations were taken into account in view of a possible participation of the highest multiplicities to the reduction process. Results indicated that a spin inversion occurs in the rate-determining step of iron ion-catalyzed reaction that improves the performance of the cation.

Which one among Zn(II), Co(II), Mn(II), and Fe(II) is the most efficient ion for the methionine aminopeptidase catalyzed reaction?

The catalytic hydrolysis of a methionyl-peptide substrate by a methionine aminopeptidase active site model cluster was investigated at the DF/B3LYP level of theory, in the gas-phase and in the protein environment. Zn(II), Co(II), Mn(II), and Fe(II) transition metals were examined as the potential catalytic metals of this enzyme involved in protein maturation. Two different mechanisms in which Glu204 was present as protonated or deprotonated residue were considered.

CO2 Activation by Nb(+) and NbO(+) in the Gas Phase. A Case of Two-State Reactivity Process.

Gas-phase carbon dioxide activation by Nb(+) and NbO(+) was studied at the density functional level of theory using the hybrid exchange correlation functional B3LYP. Three reaction profiles corresponding to the quintet, triplet, and singlet multiplicities were investigated in order to ascertain the presence of some spin inversion during the CO2 reduction. Carbon dioxide activation mediated by metal cations was found to be an exothermic spin-forbidden process resulting from a crossing between quintet and triplet energetic profiles.

The preferred reaction path for the oxidation of methanol by PQQ-containing methanol dehydrogenase: addition-elimination versus hydride-transfer mechanism.

The catalytic oxidation of methanol to formaldehyde by pyrroloquinoline quinone (PQQ)-containing methanol dehydrogenase (MDH) was investigated at density functional B3LYP level. The still controversial addition-elimination and hydride-transfer reaction mechanisms were analysed. Computations performed in the gas phase and in the protein environment indicated that both suggested reaction sequences involve very high activation barriers.

A molecular dynamics simulation study of the solvent isotope effect on copper plastocyanin.

The effect of heavy water on the structure and dynamics of copper plastocyanin as well as on some aspects of the solvent dynamics at the protein-solvent interfacial region have been investigated by molecular dynamics simulation. The simulated system has been analyzed in terms of the atomic root mean square deviation and fluctuations, intraprotein H-bond pattern, dynamical cross-correlation map and the results have been compared with those previously obtained for plastocyanin in H2O (Ciocchetti et al. Biophys.

Gas and liquid phase acidity of natural antioxidants.

The gas phase and in solution absolute and relative acidities of nine natural systems contained in red and white wines were determined through theoretical B3LYP/6-311++G** calculations. The aim was to correlate these thermodynamic quantities to the ability that some of these compounds show in chelating metals ions to carry out an antioxidant action following a mechanism recently reported in the literature. Results indicated that both absolute and relative values are affected by molecular features such as electronic delocalization and conjugation and intramolecular hydrogen bonds.

Role of the metal ion in formyl-peptide bond hydrolysis by a peptide deformylase active site model.

The catalytic mechanism of peptide deformylase enzymes containing zinc, iron, cobalt, and nickel dications was explored in the gas phase and in the protein environment. The study was performed at the density functional level using three model systems to simulate the active site. The work had the aim to evaluate the effect of metal substitution on the hydrolytic properties and the possible different performances of the various catalysts.

Encoding the core electrons with graph concepts.

The core electron problem of atoms in chemical graph studies has always been considered as a minor problem. Usually, chemical graphs had to encode just a small set of second row atoms, i.e.

Electrical impedance tomography via filtered-back projection of fan current distribution: a numerical simulation.

An approach to electrical impedance tomography (EIT) data acquisition inspired by NMR-filtered back-projection imaging with fan isochromat distribution is proposed. A current projection is generated by injecting current at a certain point of the sample and simultaneously collecting the current itself at different points on the half space opposite the point of current injection. After that, the injection is shifted to another point and collected as above and so on.

Bond energies and attachments sites of sodium and potassium cations to DNA and RNA nucleic acid bases in the gas phase.

Gas-phase metal affinities of DNA and RNA bases for the Na(+) and K(+) ions were determined at density functional level employing the hybrid B3LYP exchange correlation potential in connection with the 6-311+G(2df,2p) basis set. All the molecular complexes, obtained by the interaction between several low-lying tautomers of nucleic acid bases and the alkali ions on the different binding sites, were considered. Structural features of the sodium and potassium complexes were found to be similar except in some uracil and thymine compounds in which the tendency of potassium ion toward monocoordination appeared evident.