De novo epileptic confusional status in a patient with cobalamin deficiency

A 80-year-old man with cobalamin deficiency and no history of epilepsy developed a partial complex epileptic confusional status (ECS) unresponsive to acute i.v. diazepam. Brain CT scan and MRI investigation ruled out a focal cerebral lesion. Therapy with high doses (10,000 micrograms i.m. daily) of cobalamin alone was started, and the patient fully recovered in the following 72-hour. Control EEGs repeatedly performed days and weeks later showed progressive disappearance of the frontal interictal spiking, while the patient was on monotherapy with cobalamin (5,000 micrograms i.m. weekly). A month later the patient unfortunately discontinued replacement therapy and 13 weeks later he developed a fatal convulsive epileptic status. To our knowledge the association of ECS and cobalamin deficiency has not been previously reported.     

Structural Investigation and Molecular Modeling Studies of Strobilurin-Based Fungicides Active against the Rice Blast Pathogen Pyricularia oryzae

The increasing emergence of fungicide-resistant pathogens requires urgent solutions for crop disease management. Here, we describe a structural investigation of new fungicides obtained by combining strobilurin and succinate dehydrogenase inhibitor pharmacophores. We identified compounds endowed with very good activity against wild-type Pyricularia oryzae, combined in some cases with promising activity against strobilurin-resistant strains. The first three-dimensional model of P. oryzae cytochrome bc1 complex containing azoxystrobin as a ligand was developed. The model was validated with a set of commercially available strobilurins, and it well explains both the resistance mechanism to strobilurins mediated by the mutation G143A and the activity of metyltetraprole against strobilurin-resistant strains. The obtained results shed light on the key recognition determinants of strobilurin-like derivatives in the cytochrome bc1 active site and will guide the further rational design of new fungicides able to overcome resistance caused by G143A mutation in the rice blast pathogen.     

Electrochemical Behavior of Single CuO Nanoparticles: Implications for the Assessment of their Environmental Fate

The electrochemical behavior of copper oxide nanoparticles is investigated at both the single particle and at the ensemble level in neutral aqueous solutions through the electrode‐particle collision method and cyclic voltammetry, respectively. The influence of Cl^? and NO₃^? anions on the electrochemical processes occurring at the nanoparticles is further evaluated. The electroactivity of CuO nanoparticles is found to differ between the two types of experiments. At the single‐particle scale, the reduction of the CuO nanoparticles proceeds to a higher extent in the presence of chloride ion than of nitrate ion containing solutions. However, at the multiparticle scale the CuO reduction proceeds to the same extent regardless of the type of anions present in solution. The implications for assessing realistically the environmental fate and therefore the toxicity of metal‐based nanoparticles in general, and copper‐based nanoparticles in particular, are discussed.     

A hybrid particle swarm optimization approach for the sequential ordering problem

The sequential ordering problem is a version of the asymmetric travelling salesman problem where precedence constraints on vertices are imposed. A tour is feasible if these constraints are fulfilled, and the objective is to find a feasible solution with minimum cost.     

Oxidation of proteins: Basic principles and perspectives for blood proteomics

Protein oxidation mechanisms result in a wide array of modifications, from backbone cleavage or protein crosslinking to more subtle modifications such as side chain oxidations. Protein oxidation occurs as part of normal regulatory processes, as a defence mechanism against oxidative stress, or as a deleterious processes when antioxidant defences are overcome. Because blood is continually exposed to reactive oxygen and nitrogen species, blood proteomics should inherently adopt redox proteomic strategies. In this review, we recall the biochemical basis of protein oxidation, review the proteomic methodologies applied to analyse redox modifications, and highlight some physiological and in vitro responses to oxidative stress of various blood components.     

A signal theory approach to the space and frequency variant filtering performed by the human visual system

A mathematical representation is given of the processing performed by the peripheral nervous cells of the human visual system. This representation consists essentially of a set of shift-variant convolutions, implying non-uniform resolutions in both the space and frequency domains. A remarkable property of such “convolutions” is the form-invariance of their outputs with respect to (size) linear scalings of the inputs. It is shown that this latter property is a necessary support of the hypothesis according to which the visual system translates linear scalings of the (retinal) inputs into shifts of the (cortical) outputs.     

Intrinsic Fluorescence of the Active and the Inactive Functional Forms of Human Thymidylate Synthase

The observables associated with protein intrinsic fluorescence – spectra, time decays, anisotropies – offer opportunities to monitor in real time and non-invasively a protein‘s functional form and its interchange with other forms with different functions. We employed these observables to sketch the fluorometric profiles of two functional forms of human thymidylate synthase (hTS), a homodimeric enzyme crucial for cell proliferation and thus targeted by anticancer drugs. The protein takes an active and an inactive form. Stabilization of the latter by peptides that, unlike classical hTS inhibitors, bind it at the monomer/monomer interface offers an alternative inhibition mechanism that promises to avoid the onset of drug resistance in anticancer therapy. The fluorescence features depicted herein can be used as tools to identify and quantify each of the two protein forms in solution, thus making it possible to investigate the kinetic and thermodynamic aspects of the active/inactive conformational interchange. Two examples of fluorometrically monitored interconversion kinetics are provided.