Antibacterial Resistance, Wayampis Amerindians, French Guyana

Drug resistance in fecal bacteria was high in Wayampis Amerindians who did not take antibacterial agents and were not hospitalized for 1 year. In the Wayampis Amerindians, an isolated traditional community in French Guyana, antibacterial use was 0.64 treatments per person per year. Hospitalization rate was 6.1% per year. Antibacterial drug–resistant bacteria can spread in persons who are not taking antibacterial agents

Minimum energy conformations of DNA dimeric subunits: Potential energy calculations for dGpdC, dApdA, dCpdC, dGpdG, and dTpdT

Minimum energy conformations have been calculated for the deoxydinucleoside phosphates dGpdC, dApdA, dCpdC, dGpdG, and dTpdT. In these potential energy calculations the eight diheldral angles and the sugar pucker were flexible parameters. A substantial survey of conformation space was made in which all staggred combination of the dihedral angles ω′,ω, and ψ, in conjunction with C(2′)-endo pucker, were used as starting conformers for the energy minimization. The most important conformations in the C(3′)-endo-puckering domain have ψ = g+; ω′,ω = g−,g−(A-form),g+, g+, and g−,t. With C(2′)-endo-type pucker the most important conformations have ψ = g+; ω′,ω =g-,g-(B-form) and g+,t; and ψ =t; ω′,ω =g-,t(Watson-Crick from) and t,g+ (skewed). Stacked bases are a persistent feature of the low-energy conformations, the g+ conformer being an exception. Freeing the suger pucker allowed this conformation to become low energy, with C(3′)-exo pucker. It also caused other low-energy forms, such and the Waston-Crick conformation, to become more favourable. Conformation flexibility in the sugar pucker and in ψ, as well as the ω′,ω angle pair, is indicated for the dimeric subunits of DNA

Non-Metabolic Membrane Tubulation and Permeability Induced by Bioactive Peptides

BACKGROUND: Basic cell-penetrating peptides are potential vectors for therapeutic molecules and display antimicrobial activity. The peptide-membrane contact is the first step of the sequential processes leading to peptide internalization and cell activity. However, the molecular mechanisms involved in peptide-membrane interaction are not well understood and are frequently controversial. Herein, we compared the membrane activities of six basic peptides with different size, charge density and amphipaticity: Two cell-penetrating peptides (penetratin and R9), three amphipathic peptides and the neuromodulator substance P. METHODOLOGY/PRINCIPAL FINDINGS: Experiments of X ray diffraction, video-microscopy of giant vesicles, fluorescence spectroscopy, turbidimetry and calcein leakage from large vesicles are reported. Permeability and toxicity experiments were performed on cultured cells. The peptides showed differences in bilayer thickness perturbations, vesicles aggregation and local bending properties which form lipidic tubular structures. These structures invade the vesicle lumen in the absence of exogenous energy. CONCLUSIONS/SIGNIFICANCE: We showed that the degree of membrane permeabilization with amphipathic peptides is dependent on both peptide size and hydrophobic nature of the residues. We propose a model for peptide-induced membrane perturbations that explains the differences in peptide membrane activities and suggests the existence of a facilitated “physical endocytosis,” which represents a new pathway for peptide cellular internalization

Development and Validation of an Internationally-Standardized, High-Resolution Capillary Gel-Based Electrophoresis PCR-Ribotyping Protocol for Clostridium difficile

PCR-ribotyping has been adopted in many laboratories as the method of choice for C. difficile typing and surveillance. However, issues with the conventional agarose gel-based technique, including inter-laboratory variation and interpretation of banding patterns have impeded progress. The method has recently been adapted to incorporate high-resolution capillary gel-based electrophoresis (CE-ribotyping), so improving discrimination, accuracy and reproducibility. However, reports to date have all represented single-centre studies and inter-laboratory variability has not been formally measured or assessed. Here, we achieved in a multi-centre setting a high level of reproducibility, accuracy and portability associated with a consensus CE-ribotyping protocol. Local databases were built at four participating laboratories using a distributed set of 70 known PCR-ribotypes. A panel of 50 isolates and 60 electronic profiles (blinded and randomized) were distributed to each testing centre for PCR-ribotype identification based on local databases generated using the standard set of 70 PCR-ribotypes, and the performance of the consensus protocol assessed. A maximum standard deviation of only ±3.8bp was recorded in individual fragment sizes, and PCR-ribotypes from 98.2% of anonymised strains were successfully discriminated across four ribotyping centres spanning Europe and North America (98.8% after analysing discrepancies). Consensus CE-ribotyping increases comparability of typing data between centres and thereby facilitates the rapid and accurate transfer of standardized typing data to support future national and international C. difficile surveillance programs

Simulations de spectres de résonance magnétique appliquées à la dynamique moléculaire en milieu anisotrope

On décrit deux programmes interactifs rédigés en APL destinés respectivement à la simulation de spectres de RMN et de RPE ainsi qu'aux calculs des temps de relaxation T, et T2 et des largeurs de raies. Ces programmes sont particulièrement adaptés à l'étude de l'ordre et de la dynamique moléculaire dans les cristaux liquides et l'on donne plusieurs exemples de leurs applications

Dynamique à basses températures d’une sonde adicalaire nitroxyde en milieux poreux

La dynamique du radical nitroxyde TEMPO dans l'ethanol adsorbé dans des matériaux poreux est étudiée par RPE en bande X entre 100 et 250 K. Au dessus du point de transition vitreuse de l'éthanol, le radical se répartit entre les parois des pores et le solvant libre. On a déterminé les proportions de ces sites et leur vitesse d'échange qui se situe entre 106 et 108s-1 lorsqu'il n'y a pas de liaison hydrogène entre le radical et les parois. Lorsque celle-ci existe, dans la silice par exemple, l'échange n'est plus observé. Ce comportement est corrélé avec le couplage hyperfin de l'azote qui augmente avec la polarité locale. Des expériences analogues sur des résines de polymère, confirment une large distribution de tailles de pores mise en évidence par relaxation nucléaire