Cardiolipin vesicles can accommodate cholesterol up to 0.80 mole fraction, i.e. one molecule per cardiolipin fatty acid chain

AbstractCardiolipin-cholesterol interactions were studied by time-resolved fluorescence spectroscopy with 1,6-diphenyl-1, 3,5-hexatriene as probe. The residual anisotropy parameter, r∞ (reflecting the fatty acid chain packing), was measured in the liquid crystalline phase as a function of cholesterol addition. Two main results are reported: (i) a slight increase of the order parameter, S, computed from the r∞ value as S = (r∞/r0)12, in the physiological concentration range of cholesterol; (ii) a sharp enhancement of S from a cholesterol mole fraction (X̄chl) of 0.20 and up to X̄chl of 0.80. This is in contrast to unsaturated kcithin systems for which a continuous increase of the order parameter was monitored, culminating at X̄chl = 0.50, the wellknown maximum level of incorporation of cholesterol into lecithin model membranes

Bactericidal/Permeability-Increasing Protein Inhibits Induction of Macrophage Nitric Oxide Production by Lipopolysaccharide

A recombinant (r) NH2-terminal fragment of bactericidal/permeability-increasing protein, rBPI23, was shown to inhibit murine macrophage nitric oxide (NO) production elicited by lipopolysaccharide (LPS) plus interferon-β (IFN-β). Normal mouse plasma amplified NO synthesis (measured as NO-2 release) at LPS concentrations of 1-10 ng/mL, and antibody to the plasma LPS-binding protein (LBP) partially inhibited N02 release in the presence of normal mouse plasma. rBPI23 (1 µg/mL) effectively inhibited LPS-dependent NO-2 release in the presence or absence of normal mouse plasma. Fifty percent inhibition of IFN-β/LPS-elicited NO-2 production or of binding of fluoresceinated LPS was obtained with ∼0.2 µg/mL rBPI23. These results provide a basis for studies of rBPI23 effects on NO synthase activity in murine models of gramnegative sepsi

Annexin A5 D226K structure and dynamics: identification of a molecular switch for the large-scale conformational change of domain III

AbstractThe domain III of annexin 5 undergoes a Ca2+- and a pH-dependent conformational transition of large amplitude. Modeling of the transition pathway by computer simulations suggested that the interactions between D226 and T229 in the IIID–IIIE loop on the one hand and the H-bond interactions between W187 and T224 on the other hand, are important in this process [Sopkova et al. (2000) Biochemistry 39, 14065–14074]. In agreement with the modeling, we demonstrate in this work that the D226K mutation behaves as a molecular switch of the pH- and Ca2+-mediated conformational transition. In contrast, the hydrogen bonds between W187 and T224 seem marginal

Evf, a virulence factor produced by the Drosophila pathogen Erwinia carotovora, is an S-palmitoylated protein with a new fold that binds to lipid vesicles

Erwinia carotovora are phytopathogenic Gram-negative bacteria of agronomic interest as these bacteria are responsible for fruit soft rot and use insects as dissemination vectors. The Erwinia carotovora carotovora strain 15 (Ecc15) is capable of persisting in the Drosophila gut by the sole action of one protein, Erwinia virulence factor (Evf). However, the precise function of Evf is elusive, and its sequence does not provide any indication as to its biochemical function. We have solved the 2.0-angstroms crystal structure of Evf and found a protein with a complex topology and a novel fold. The structure of Evf confirms that Evf is unlike any virulence factors known to date. Most remarkably, we identified palmitoic acid covalently bound to the totally conserved Cys209, which provides important clues as to the function of Evf. Mutation of the palmitoic binding cysteine leads to a loss of virulence, proving that palmitoylation is at the heart of Evf infectivity and may be a membrane anchoring signal. Fluorescence studies of the sole tryptophan residue (Trp94) demonstrated that Evf was indeed able to bind to model membranes containing negatively charged phospholipids and to promote their aggregation

A search for small noncoding RNAs in Staphylococcus aureus reveals a conserved sequence motif for regulation

Bioinformatic analysis of the intergenic regions of Staphylococcus aureus predicted multiple regulatory regions. From this analysis, we characterized 11 novel noncoding RNAs (RsaA‐K) that are expressed in several S. aureus strains under different experimental conditions. Many of them accumulate in the late-exponential phase of growth. All ncRNAs are stable and their expression is Hfq-independent. The transcription of several of them is regulated by the alternative sigma B factor (RsaA, D and F) while the expression of RsaE is agrA-dependent. Six of these ncRNAs are specific to S. aureus, four are conserved in other Staphylococci, and RsaE is also present in Bacillaceae. Transcriptomic and proteomic analysis indicated that RsaE regulates the synthesis of proteins involved in various metabolic pathways. Phylogenetic analysis combined with RNA structure probing, searches for RsaE‐mRNA base pairing, and toeprinting assays indicate that a conserved and unpaired UCCC sequence motif of RsaE binds to target mRNAs and prevents the formation of the ribosomal initiation complex. This study unexpectedly shows that most of the novel ncRNAs carry the conserved C−rich motif, suggesting that they are members of a class of ncRNAs that target mRNAs by a shared mechanism

Etude descriptive du projet du futur lieu d'exercice professionnel des internes de médecine générale des promotions 2006 et 2007 formés à la faculté d'Amiens

Objectif : Le but de cette étude était de décrire le projet du futur lieu d exercice professionnel des internes de médecine générale (IMG) des promotions 2006 et 2007 formés à Amiens et ainsi de savoir si former plus d IMG à la faculté d Amiens suite à la réforme du 3ème cycle des études médicales de 2004 aurait un impact significatif sur le nombre de médecins exerçant en Picardie. Matériels et méthodes : Il s agissait d une enquête observationnelle transversale descriptive effectuée par l intermédiaire d un questionnaire auto administré envoyé de manière électronique à 118 IMG ayant débuté leur 3ème cycle des études médicales en Picardie en 2006 et 2007. L étude portait sur l analyse des réponses de 37 internes. Résultats : Le taux de réponse était de 31%. Il s agissait de 24 femmes et 13 hommes, avec une médiane d âge de 30 ans. La majorité (57%) des IMG de l étude provenait de la faculté de médecine d Amiens et 35% de régions limitrophes. 70% des IMG étaient classés au-delà de la 4001ème place à l Examen Classant National (ECN). 75% des IMG considéraient avoir reçu une bonne formation théorique et 97% une bonne formation pratique durant leur 3ème cycle des études médicales. 80% des IMG avaient débuté une activité professionnelle en post internat immédiat en Picardie mais seuls 57% envisageaient d y travailler à long terme. Si on recoupe cette valeur avec celle des 57% d IMG originaires de la faculté d Amiens, on remarque que le flux migratoire est nul. La moitié des IMG ayant effectué un SASPAS fût incitée à s installer en Picardie mais peu d IMG en ont bénéficié (22%) du fait d un manque d enseignants. Conclusion : L analyse des flux migratoires dans notre étude montrait que malgré l augmentation du nombre d IMG formés en Picardie suite à la réforme du 3ème cycle des études médicales de 2004, le bilan entrée-sortie sur le long terme serait nul.Objective: The purpose of this study was to describe the project of the future professional practice place of residents from the 2006 and 2007 promotions after completing their general medicine internship in Amiens and to analyse whether training more residents at the faculty of Amiens following the reform of postgraduate medical studies in 2004 would have a significant impact on the number of physicians practicing in Picardie. Materials and methods: This was a descriptive cross-sectional observational survey conducted via a self-administered questionnaire sent electronically to 118 general medicine residents who had started their third cycle of medical studies in Picardie in 2006 and 2007. The study focused on the analysis of the responses from 37 residents. Results: The response rate was 31%. There were 24 women and 13 men, median age 30 years old. The majority (57%) of the residents came from the faculty of medicine of Amiens, 35% came from neighboring regions. 70% were classified beyond the 4,001th place at the national ranking exam. 75% of the residents thought that they received a good theoretical education and 97% a good practical training during their third cycle of medical studies. 80% of the residents had started a job right after their internship in Picardie but only 57% planned to work in Picardie for a long term. If we consider that 57% of the residents originally came from the faculty of Amiens, we note that the migration flow is zero. Half the of residents who performed SASPAS were encouraged to settle in Picardie but few of them had benefited (22%) due to a lack of teachers. Conclusion: The analysis of migration flow in our study showed that despite the increase in the number of residents training in Picardie following the reform of postgraduate medical studies in 2004, the final balance in the long term would be zero.AMIENS-BU Santé (800212102) / SudocSudocFranceF

REPORTE CORTO / SHORT REPORT - CONFORMATIONAL SUBSTATES IN PROTEINS: TWO-DIMENSIONAL ANALYSIS OF THE POLARIZED INTENSITY DECAYS OF THE TRYPTOPHAN FLUORESCENCE EMISSION BYTHE MAXIMUM ENTROPY METHOD

no abstrac