PloS one

The HIV-1 nucleocapsid protein (NC) is a small basic protein containing two zinc fingers (ZF) separated by a short linker. It is involved in several steps of the replication cycle and acts as a nucleic acid chaperone protein in facilitating nucleic acid strand transfers occurring during reverse transcription. Recent analysis of three-dimensional structures of NC-nucleic acids complexes established a new property: the unpaired guanines targeted by NC are more often inserted in the C-terminal zinc finger (ZF2) than in the N-terminal zinc finger (ZF1). Although previous NMR dynamic studies were performed with NC, the dynamic behavior of the linker residues connecting the two ZF domains remains unclear. This prompted us to investigate the dynamic behavior of the linker residues. Here, we collected 15N NMR relaxation data and used for the first time data at several fields to probe the protein dynamics. The analysis at two fields allows us to detect a slow motion occurring between the two domains around a hinge located in the linker at the G35 position. However, the amplitude of motion appears limited in our conditions. In addition, we showed that the neighboring linker residues R29, A30, P31, R32, K33 displayed restricted motion and numerous contacts with residues of ZF1. Our results are fully consistent with a model in which the ZF1-linker contacts prevent the ZF1 domain to interact with unpaired guanines, whereas the ZF2 domain is more accessible and competent to interact with unpaired guanines. In contrast, ZF1 with its large hydrophobic plateau is able to destabilize the double-stranded regions adjacent to the guanines bound by ZF2. The linker residues and the internal dynamics of NC regulate therefore the different functions of the two zinc fingers that are required for an optimal chaperone activity

Variabilité régionale de l’incidence des bactéries multirésistantes aux antibiotiques (BMR) En France : réseau de surveillance BMR-Raisin

National audienc

A Spatial Distribution Study of Faunal Remains from Two Lower Magdalenian Occupation Levels in El Mirón Cave, Cantabria, Spain

Abstract: Human behaviour can be reconstructed by analysing specific activities and campsite organization using spatial analysis. The dense occupation layers of the Lower Cantabrian Magdalenian in the Northern Spain reveal varied aspects of Upper Palaeolithic lifeways, including evidence of specific localized activities. The outer vestibule of El Mirón cave has a particularly rich and intact Lower Magdalenian occupation horizon, Levels 15–17. The excavations in the outer vestibule “Cabin” area of the site revealed excellent bone preservation. Artefacts and faunal remains were individually recorded and sediments water-screened to yield a large sample of archaeological finds and spatial data. Zooarchaeological analysis provided the taxonomic, anatomic and taphonomic determination of the faunal individual finds. Smaller animal remains were categorized and counted; special attention was given to the identification of anthropogenic modifications such as burnt bones or bone flakes. These small refuse items are considered to be useful, in situ indicators of localized activities. The spatial distribution analysis of this dense and complex palimpsest of El Mirón Lower Cantabrian Magdalenian layers required GIS based methods including density analysis, heatmaps and cluster analysis. Based on the spatial distribution of Level 15 and 16 faunal remains, different activity areas were identified comprising hearth, working and dropping zones. These results imply the deliberately segregated use of space within the Lower Cantabrian Magdalenian site area, in which bone-processing activities played a central rol

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29–39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance

Disorganized attachment and genetics in the development of borderline personality disorder

International audienc

Surveillance des bactéries multirésistantes aux antibiotiques (BMR) : Réseau BMR-Raisin, 2002 – 2008

National audienceIntroduction/objectif du travail : Les taux de prévalence des BMR dans les établissements de santé (ES) français sont parmi les plus élevés parmi les pays européens. Depuis le milieu des années 90, le contrôle de la transmission croisée est devenu une priorité nationale pour le programme de contrôle des infections nosocomiales. En 1998, les ES ont été avisés de renforcer la surveillance des BMR et d’en augmenter la prévention à l’aide d’un guide de recommandations nationales.Matériel et Méthodes :Afin d’étudier l’impact du programme, un réseau national de surveillance des BMR est mis en place en 2002. La surveillance s’effectue 3 mois par an à partir d’ES volontaires. Toutes les souches à visée diagnostique (dédoublonnées par patient) de S. aureus résistants à la méticilline (SARM) et d’entérobactéries productrices de bêta-lactamase à spectre étendu (EBLSE) sont prospectivement incluses. Les densités d’incidence pour 1000 journées d’hospitalisation (JH) sont calculées pour les SARM et les EBLSE. Les tendances d’incidence entre 2004 et 2008 ont été analysées en utilisant la régression de Poisson.Résultats :Le nombre d’ES participant a augmenté de 478 en 2002 à 930 en 2008, représentant 58% des lits d’hospitalisation français. En 2008, l’incidence des SARM est plus élevée dans les réanimations (1,72/1000 JH) qu’en court séjour (0,53) ou en SSR-SLD (0,34). L’incidence des EBLSE est la plus élevée en réanimation (1,35) par rapport aux services de court séjour (0,34) et de SSR-SLD (0,15). Les EBLSE les plus fréquentes sont Enterobacter aerogenes (36%) en 2002 et Escherichia coli (58%) en 2008. Les bactériémies représentent respectivement 9% des prélèvements à SARM et 8% des prélèvements à EBLSE. Les tendances d’incidence entre 2004 et 2008 ont été analysées sur une cohorte de 302 ES. L’incidence des SARM a significativement diminué de 0,66 en 2004 à 0,51/1000 JH en 2008 (p&lt;10-3). Cette diminution concerne tous les services des ES. En revanche l’incidence des EBLSE a significativement augmenté de 0,17 à 0,31/1000 JH. Cette augmentation est observée pour tous les services (p&lt;10-3).Conclusion :Ces résultats tendent à montrer l’impact positif du programme national de prévention sur l’incidence des SARM. Néanmoins, les incidences restent élevées et les efforts doivent être maintenus. Au contraire, les incidences des EBLSE augmentent, plus particulièrement Escherichia coli productrices de BLSE. La diffusion de ces souches est d’origine complexe impliquant les établissements de santé mais également la communauté. Sa maîtrise doit faire l’objet de recommandations nationales spécifiques.</p

Palindromic Sequence Plays a Critical Role in Human Foamy Virus Dimerization

The retroviral RNA genome is dimeric, consisting of two identical strands of RNA linked near their 5′ ends by a dimer linkage structure. Previously it was shown that human foamy virus (HFV) RNA transcribed in vitro contained three sites, designated SI, SII, and SIII, which contributed to the dimerization process (O. Erlwein, D. Cain, N. Fischer, A. Rethwilm, and M. O. McClure, Virology 229:251–258, 1997). To characterize these sites further, a series of mutants were designed and tested for their ability to dimerize in vitro. The primer binding site and a G tetrad in SI were dispensable for dimerization. However, a mutant that changed the 3′ end of SI migrated slower on nondenaturing gels than wild-type RNA dimers. The sequence composition of the SII palindrome, consisting of 10 nucleotides, proved to be critical for in vitro dimerization, since mutations within this sequence or replacement of the sequence with a different palindrome of equal length impaired in vitro dimerization. The length of the palindrome also seems to play an important role. A moderate extension to 12 nucleotides was tolerated, whereas an extension to 16 nucleotides or more impaired dimerization. When nucleotides flanking the palindrome were mutated in a random fashion, dimerization was unaffected. Changing the SIII sequence also led to decreased dimer formation, confirming its contribution to the dimerization process. Interesting mutants were cloned into the infectious molecular clone of HFV, HSRV-2, and were transfected into BHK-21 cells. Mutations in SII that reduced dimerization in vitro also abolished virus replication. In contrast, constructs containing mutations in SI and SIII replicated to some extent in cell culture after an initial drop in viral replication. Analysis of the SIM1 mutant revealed reversion to the wild type but with the insertion of an additional two nucleotides. Analysis of cell-free virions demonstrated that both replication-competent and replication-defective mutants packaged nucleic acid. Thus, efficient dimerization is a critical step for HFV to generate infectious virus, but HFV RNA dimerization is not a prerequisite for packaging