In Silico Analysis of the Apolipoprotein E and the Amyloid β Peptide Interaction: Misfolding Induced by Frustration of the Salt Bridge Network

The relationship between Apolipoprotein E (ApoE) and the aggregation processes of the amyloid β (Aβ) peptide has been shown to be crucial for Alzheimer's disease (AD). The presence of the ApoE4 isoform is considered to be a contributing risk factor for AD. However, the detailed molecular properties of ApoE4 interacting with the Aβ peptide are unknown, although various mechanisms have been proposed to explain the physiological and pathological role of this relationship. Here, computer simulations have been used to investigate the process of Aβ interaction with the N-terminal domain of the human ApoE isoforms (ApoE2, ApoE3 and ApoE4). Molecular docking combined with molecular dynamics simulations have been undertaken to determine the Aβ peptide binding sites and the relative stability of binding to each of the ApoE isoforms. Our results show that from the several ApoE isoforms investigated, only ApoE4 presents a misfolded intermediate when bound to Aβ. Moreover, the initial α-helix used as the Aβ peptide model structure also becomes unstructured due to the interaction with ApoE4. These structural changes appear to be related to a rearrangement of the salt bridge network in ApoE4, for which we propose a model. It seems plausible that ApoE4 in its partially unfolded state is incapable of performing the clearance of Aβ, thereby promoting amyloid forming processes. Hence, the proposed model can be used to identify potential drug binding sites in the ApoE4-Aβ complex, where the interaction between the two molecules can be inhibited

Detection of secondary structures in 17-mer Ru(II)-labeled single-stranded oligonucleotides from luminescence lifetime studies.

The emission properties of a non intercalating complex, [Ru(TAP)2(dip)]2+ (TAP = 1,4,5,8-tetraazaphenanthrene; dip = 4,7-diphenyl-1,10-phenanthroline), tethered to 17-mer single-stranded oligodeoxyribonucleotides (ODNs) either in the middle or at the 5'-end of the sequence, are determined. The results highlight the fact that the luminescence of this metallic compound is sufficiently sensitive to its microenvironment to probe self-structuration of these short single-stranded ODNs. It is shown that the weighted averaged emission lifetimes (tau(M)) along with the quenching rate constants of luminescence by oxygen reflect particularly well different structures adopted by the different ODNs sequences. The determination of these parameters thus offers an elegant way to examine possible structurations of synthetic single-stranded ODNs that play important roles in biological applications.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Infections à mycobactéries atypiques liées à des soins esthétiques en France, 2001-2010

International audienceAbstractNon-tuberculous mycobacteria (NTM) infections usually occur in immunocompromised patients but also in immunocompetent patients following invasive procedures, especially for esthetic purposes. Since 2001, 20 episodes (57 cases) of NTM infections, seven of which (43 cases) were related to esthetic care, have been reported to the regional infection control coordinating centers (RICCC), the local health authorities (LHA), and the national institute for public health surveillance. Four notifications (40 cases) were related to non-surgical procedures performed by general practitioners in private settings: mesotherapy, carboxytherapy, and sclerosis of microvaricosities. The three other notifications (three cases) concerned surgical procedures-lifting and mammary prosthesis. Practice evaluations performed by the RICCC and LHA for five notifications showed deficiency of standard hygiene precautions and tap water misuse for injection equipment cleaning, or skin disinfection. Microbiological investigations (national reference center for mycobacteria) demonstrated the similarity of patient and environmental strains: in one episode (16 cases after mesotherapy), M. chelonae isolated from tap water was similar to those isolated from 11 cases. Healthcare-associated NTM infections are rare but have a potentially severe outcome. These cases stress the need of healthcare-associated infection notifications in outpatient settings.Les infections à mycobactéries atypiques (MA) surviennent généralement chez des patients immunodéprimés, mais elles sont également observées chez des patients immunocompétents, secondairement à des soins invasifs, notamment à visée esthétique. Depuis 2001, 20 signalements (57 cas) d’infections à MA, dont sept (43 cas) étaient liés à des soins esthétiques, ont été reçus par les centres de coordination de la lutte contre les infections nosocomiales (CClin), les directions départementales des affaires sanitaires et sociales (Ddass) et l’institut de veille sanitaire. Des procédures non chirurgicales, réalisées en ville, étaient en cause dans quatre signalements (40 cas) : mésothérapie, carboxythérapie et scléroses de microvaricosités. Les trois autres signalements (trois cas) concernaient des actes chirurgicaux - lifting et pose de prothèse mammaire. Des évaluations de pratique, réalisées par les CClin et les Ddass pour cinq signalements, ont montré le non-respect des précautions standard et un usage inapproprié de l’eau du robinet pour le nettoyage des appareils d’injection ou la désinfection de la peau. Les investigations microbiologiques (centre national de référence) ont permis d’identifier et de comparer les souches des patients et de l’environnement : dans un signalement (16 cas après mésothérapie), la souche de M. chelonae isolée de l’eau du robinet était similaire à celles isolées chez 11 cas. Les infections à MA associées aux soins sont rares mais parfois graves. Ces cas montrent l’intérêt du signalement des infections associées aux soins et aux pratiques invasives en médecine libérale

Oligonucleotide duplexes with tethered photoreactive ruthenium (II) complexes :influence of the ligands and their linker on the photoinduced electron transfer and crosslinking processes of the two strands

FLWINinfo:eu-repo/semantics/publishe

Ru(II) complexes and light :molecular tools for biomolecules

FLWINinfo:eu-repo/semantics/publishe

Oxidizing Ru(II) complexes as irreversible and specific photo-cross-linking agents of oligonucleotide duplexes.

Oxidizing polyazaaromatic Ru(II) complexes containing two TAP ligands (TAP = 1,4,5,8-tetraazaphenanthrene) are able under illumination to cross-link irreversibly the two strands of an oligonucleotide (ODN) duplex by covalent bond formation. The cross-linking proceeds by two successive absorptions of a photon. An adduct of the metallic complex on a guanine (G) base of one ODN strand is first photoproduced, followed by a second photoaddition of the same Ru species to a G base of the complementary strand, provided that the two G moieties are separated by 0 or 1 base pair. These two processes lead to the cross-linking of the two strands. Such a photo-cross-linking is easily detected with [Ru(TAP)(2)(phen)](2+) (1; phen = 1,10-phenanthroline) and [Ru(HAT)(2)(phen)](2+) (2; HAT = 1,4,5,8,9,12-hexaazatriphenylene), whereas it is not observed with [Ru(TAP)(2)TPAC](2+) (3; TPAC = tetrapyridoacridine) at the same level of loading of the duplex by 3. With a concentration of 3 similar to that of 1 and 2, when the loading of the duplex by 3 is much more important than with 1 and 2, the photo-cross-linking with 3 can thus also be observed. As 3 intercalates its TPAC ligand into the base pairs stack, its mobility is restricted in the duplex. In contrast, 1 and 2 can adopt different geometries of interaction, which probably facilitate the photo-cross-linking.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Triazacyclohexane (tach) complexes of high-valent rhenium: syntheses of [(R(3)tach)ReO(3)](+) (R = -CH(3), -CH(2)C(6)H(5)) and its substitution reactions

N-Alkylated derivatives of 1,3,5-triazacyclohexane (tach) are versatile, facially coordinating ligands. We present the syntheses and full characterization of two new complexes of the (R(3)tach)ReO3](+) type. In these complexes, the tach ligand is readily substituted by bi- and tridentate ligands; hence, they can be considered as sources of the ReO3](+) motif for Re-VII complexes

Site-Selective DNA Photocleavage Involving Unusual Photoinitiated Tautomerization of Chiral Tridentate Vanadyl(V) Complexes Derived from N-Salicylidene α-Amino Acids

[[abstract]]The titled vanadyl(V) complexes serve as efficient reagents for cleaving supercoiled plasmid DNA by photoinitiation. Complex 3d, derived from 2-hydroxy-1-naphthaldehyde and l-phenylalanine, exhibits a unique wedge feature, inducing a site-selective photocleavage at the C22-T23 of the bulge backbone for a HIV-27 DNA system at 0.1−5 μM. Transient absorption experiments for 3d indicate the involvement of LMCT with concomitant tautomerization, leading to an o-quinone-methide V-bound hydroxyl species responsible for the cleavage profiles.[[notice]]補正完畢[[journaltype]]國外[[incitationindex]]SC