Unveiling Novel RecO Distant Orthologues Involved in Homologous Recombination

The generation of a RecA filament on single-stranded DNA is a critical step in homologous recombination. Two main pathways leading to the formation of the nucleofilament have been identified in bacteria, based on the protein complexes mediating RecA loading: RecBCD (AddAB) and RecFOR. Many bacterial species seem to lack some of the components involved in these complexes. The current annotation of the Helicobacter pylori genome suggests that this highly diverse bacterial pathogen has a reduced set of recombination mediator proteins. While it is now clear that homologous recombination plays a critical role in generating H. pylori diversity by allowing genomic DNA rearrangements and integration through transformation of exogenous DNA into the chromosome, no complete mediator complex is deduced from the sequence of its genome. Here we show by bioinformatics analysis the presence of a RecO remote orthologue that allowed the identification of a new set of RecO proteins present in all bacterial species where a RecR but not RecO was previously identified. HpRecO shares less than 15% identity with previously characterized homologues. Genetic dissection of recombination pathways shows that this novel RecO and the remote RecB homologue present in H. pylori are functional in repair and in RecA-dependent intrachromosomal recombination, defining two initiation pathways with little overlap. We found, however, that neither RecOR nor RecB contributes to transformation, suggesting the presence of a third, specialized, RecA-dependent pathway responsible for the integration of transforming DNA into the chromosome of this naturally competent bacteria. These results provide insight into the mechanisms that this successful pathogen uses to generate genetic diversity and adapt to changing environments and new hosts

Stabilization of HIV-1 Envelope in the CD4-bound Conformation through Specific Cross-linking of a CD4 Mimetic*

CD4 binding on gp120 leads to the exposure of highly conserved regions recognized by the HIV co-receptor CCR5 and by CD4-induced (CD4i) antibodies. A covalent gp120-CD4 complex was shown to elicit CD4i antibody responses in monkeys, which was correlated with control of the HIV virus infection (DeVico, A., Fouts, T., Lewis, G. K., Gallo, R. C., Godfrey, K., Charurat, M., Harris, I., Galmin, L., and Pal, R. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 17477–17482). Because the inclusion of CD4 in a vaccine formulation should be avoided, due to potential autoimmune reactions, we engineered small sized CD4 mimetics (miniCD4s) that are poorly immunogenic and do not induce anti-CD4 antibodies. We made covalent complexes between such an engineered miniCD4 and gp120 or gp140, through a site-directed coupling reaction. These complexes were recognized by CD4i antibodies as well as by the HIV co-receptor CCR5. In addition, they elicit CD4i antibody responses in rabbits and therefore represent potential vaccine candidates that mimic an important HIV fusion intermediate, without autoimmune hazard

Compétences d'adaptation à la maladie du patient : une proposition

International audienceIntroduction: The 2007 recommendations of the HAS-INPES (Haute Autorité de Santé-Institut National de Prévention et d’Éducation pour la Santé) on therapeutic patient education (TPE) differentiate two classifications of the skills patients should acquire through educational programs in order to cope with their disease: self-care and life skills (the latter are inspired by the psychosocial skills suggested by the WHO). Being their formulation very general, a working group of IPCEM (association for developing TPE) suggests to formalize the definition of eight additional skills that we explain in this article. Description: These are contextualized skills, that is to say, characteristic of the life situations most frequently encountered by the patients. Therefore, their use can make therapeutic education programs closer to the real life of people. They borrow some teaching methods to the field of communication and justify to imagine new assessment techniques. Conclusion: The interest of formulating these psychosocial skills is to provide the caregivers and their partners the possibility of planning the future educational programs and share their fields of intervention. Conceptual changes which bring these new competences in the management of chronic diseases are discussed.Introduction : Les recommandations 2007 de la HAS-INPES (Haute Autorité de Santé-Institut National de Prévention et d’Éducation pour la Santé) sur l’éducation thérapeutique différencient deux registres de compétences du patient : compétences d’auto-soins et compétences d’adaptation à la maladie, ces dernières étant inspirées de l’OMS. Devant le constat que leur formulation est de nature très générale, un groupe de travail de l’IPCEM (association pour le développement de l’ETP) a proposé la formalisation de huit nouvelles compétences d’adaptation à la maladie que nous explicitons dans cet article. Description : ces compétences sont caractéristiques des situations de vie le plus fréquemment rencontrées par les patients. En ce sens, leur utilisation permet de rendre les programmes d’éducation thérapeutique plus proches de la réalité des personnes. Elles font appel à certaines méthodes pédagogiques du domaine du savoir-être et justifient d’imaginer de nouvelles techniques d’évaluation. Conclusions : L’intérêt de formuler ces compétences d’adaptation à la maladie est d’offrir aux soignants et à leurs partenaires la possibilité de concevoir les futurs programmes éducatifs et de s’en répartir les champs d’intervention. Les changements conceptuels qu’apportent ces nouvelles compétences dans la prise en charge des maladies chroniques sont discutés

Housing (In)Equity and the Spatial Dynamics of Homeownership in France: A Research Agenda

First published: 11 August 2020 (online)Print: Februray 2021International audienceThis paper advances a research agenda on how asset-based welfare policies, residential marketvolatility, stratified accumulation and vulnerability impinge upon the geography of inequality inproperty markets. Since the mid-1990s, housing prices have increased faster than the incomeof buyers, becoming a driver of social polarisation and household vulnerability. Few studieshave however explicitly linked socio-spatial inequality to asset capitalisation, instability andvulnerability in residential housing markets. We employ an empirically-grounded investigationof the factors driving and reinforcing these dynamics, what we conceptualise as a feedback loopmediating particular housing finance regimes. Drawing on three French cities (Paris, Lyon,and Avignon) our study develops a comparative framework to interpret the relational effectsof price, equity and homeowner vulnerability on the production of inequality across differentgeographical scales. Our approach puts into conversation debates concerning housing markets,social inequality, and ordinary financialisation in the period since the Global Financial Crisis.Cet article développe un agenda de recherche portant sur la la géographie des inégalités sur les marchés immobiliers, influencée par les politiques de protection sociale fondées sur les actifs, la volatilité du marché résidentiel, les logiques d’accumulation socialement et spatialement stratifiées, et la vulnérabilité induite des ménages. Depuis le milieu des années 1990, les prix des logements ont augmenté plus rapidement que les revenus des acheteurs, devenant un facteur de polarisation sociale et de vulnérabilité des ménages devant l’accès au logement. Peu d'études ont cependant explicitement établi un lien entre l'inégalité socio-spatiale et la capitalisation des actifs d’une part, l'instabilité et la vulnérabilité des marchés immobiliers résidentiels d’autre part. Partant d’un étude empirique des facteurs qui entraînent et renforcent ces dynamiques, notre cadre conceptuel est celui d’une boucle de rétroaction entre des régimes particuliers de financement du logement. En s'appuyant sur trois villes françaises (Paris, Lyon et Avignon), notre étude développe un cadre comparatif pour interpréter les effets du prix, de la valeur nette et de la vulnérabilité des propriétaires sur la production d'inégalités à différentes échelles géographiques. Notre approche met en débat les analyses du marchés du logement, l'inégalité sociale et la financiarisation ordinaire dans la période qui a suivi la crise financière mondiale

Mutations in the netrin-1 gene cause congenital mirror movements

Netrin-1 is a secreted protein that was first identified 20 years ago as an axon guidance molecule that regulates midline crossing in the CNS. It plays critical roles in various tissues throughout development and is implicated in tumorigenesis and inflammation in adulthood. Despite extensive studies, no inherited human disease has been directly associated with mutations in NTN1, the gene coding for netrin-1. Here, we have identified 3 mutations in exon 7 of NTN1 in 2 unrelated families and 1 sporadic case with isolated congenital mirror movements (CMM), a disorder characterized by involuntary movements of one hand that mirror intentional movements of the opposite hand. Given the diverse roles of netrin-1, the absence of manifestations other than CMM in NTN1 mutation carriers was unexpected. Using multimodal approaches, we discovered that the anatomy of the corticospinal tract (CST) is abnormal in patients with NTN1-mutant CMM. When expressed in HEK293 or stable HeLa cells, the 3 mutated netrin-1 proteins were almost exclusively detected in the intracellular compartment, contrary to WT netrin-1, which is detected in both intracellular and extracellular compartments. Since netrin-1 is a diffusible extracellular cue, the pathophysiology likely involves its loss of function and subsequent disruption of axon guidance, resulting in abnormal decussation of the CST