Modeling the effect of a genetic factor for a complex trait in a simulated population

Genetic Analysis Workshop 14 simulated data have been analyzed with MASC(marker association segregation chi-squares) in which we implemented a bootstrap procedure to provide the variation intervals of parameter estimates. We model here the effect of a genetic factor, S, for Kofendrerd Personality Disorder in the region of the marker C03R0281 for the Aipotu population. The goodness of fit of several genetic models with two alleles for one locus has been tested. The data are not compatible with a direct effect of a single-nucleotide polymorphism (SNP) (SNP 16, 17, 18, 19 of pack 153) in the region. Therefore, we can conclude that the functional polymorphism has not been typed and is in linkage disequilibrium with the four studied SNPs. We obtained very large variation intervals both of the disease allele frequency and the degree of dominance. The uncertainty of the model parameters can be explained first, by the method used, which models marginal effects when the disease is due to complex interactions, second, by the presence of different sub-criteria used for the diagnosis that are not determined by S in the same way, and third, by the fact that the segregation of the disease in the families was not taken into account. However, we could not find any model that could explain the familial segregation of the trait, namely the higher proportion of affected parents than affected sibs

Misdiagnosed Tooth Aspiration in a Young Handicapped Boy: Case Report and Recommendations

Tooth inhalation remains a rare incident but it may occur during dental care, especially in children. We report here the case of a four-year-old boy with Down syndrome who came to the hospital after a dental trauma. During the extraction procedure, he aspired his maxillary incisor without presenting any signs of respiratory distress and was discharged by the surgical team, who thought that he had swallowed the tooth. Three weeks later, he was admitted to the emergency service because of a pulmonary infection. Two endoscopy interventions under general anesthesia were necessary to recover the foreign body inside the left lung. Because of the multiple symptoms associated with the trisomy 21 syndrome (general hypotonia, impaired immunity, etc.), practitioners should be very mindful of aspiration risks and complications during dental care. The systematic prescription of lung radiography would prevent the onset of pulmonary infections and enable an earlier intervention

Genome sequencing of Xanthomonas axonopodis pv. phaseoli CFBP4834-R reveals that flagellar motility is not a general feature of xanthomonads.

Xanthomonads are plant-associated bacteria that establish neutral, commensal or pathogenic relationships with plants. The list of common characteristics shared by all members of the genus Xanthomonas is now well established based on the entire genome sequences that are currently available and that represent various species, numerous pathovars of X. axonopodis (sensu Vauterin et al., 2000), X. oryzae and X. campestris, and many strains within some pathovars. These ?-proteobacteria are motile by a single polar flagellum. Motility is an important feature involved in biofilm formation, plant colonization and hence considered as a pathogenicity factor. X. axonopodis pv. phaseoli var. fuscans (Xapf) is one of the causal agents of common bacterial blight of bean and 4834-R is a highly aggressive strain of this pathogen that was isolated from a seed-borne epidemic in France in 1998. We obtained a high quality assembled sequence of the genome of this strain with 454-Solexa and 2X Sanger sequencing. Housekeeping functions are conserved in this genome that shares core characteristics with genomes of other xanthomonads: the six secretion systems which have been described so far in Gram negative bacteria are all present, as well as their ubiquitous substrates or effectors and a rather usual number of mobile elements. Elements devoted to the adaptation to the environment constitute an important part of the genome with a chemotaxis island and dispersed MCPs, numerous two-component systems, and numerous TonB dependent transporters. Furthermore, numerous multidrug efflux systems and functions dedicated to biofilm formation that confer resistance to stresses are also present. An intriguing feature revealed by genome analysis is a long deletion of 35 genes (33 kbp) involved in flagellar biosynthesis. This deletion is replaced by an insertion sequence called ISXapf2. Genes such as flgB to flgL and fliC to fleQ which are involved in the flagellar structure (rod, P- and L-ring, hook, cap and filament) are absent in the genome of strain 4834-R that is not motile. Primers were designed to detect this deletion by PCR in a collection of more than 300 strains representing different species and pathovars of Xanthomonas, and less than 5% of the tested xanthomonads strains were found nonmotile because of a deletion in the flagellum gene cluster. We observed that half of the Xapf strains isolated from the same epidemic than strain 4834-R was non-motile and that this ratio was conserved in the strains colonizing the next bean seed generation. Isolation of such variants in a natural epidemic reveals that either flagellar motility is not a key function for fitness or that some complementation occurs within the bacterial population. (Résumé d'auteur

Le gisement paléolithique multistratifié « les Bossats » à Ormesson (Seine-et-Marne, France) : palethnographie ou pâle ethnographie ? Une synthèse des huit premières années de fouille (2009-2016)

editorial reviewedÀ l'évidence, ces vingt dernières années ont vu en France, notamment, se développer en parallèle deux nouvelles façons de traiter le Paléolithique supérieur ancien qui ne sont pas antagonistes d'ailleurs. L'une consiste en une reprise des stratigraphies anciennes dans le Centre et le Sud-Ouest de la France plus spécifiquement et est associée à une meilleure redéfinition des entités culturelles par l'analyse détaillée des différentes composantes des systèmes techniques. L'autre s'efforce d'appliquer à cette période la démarche palethnographique, inféodée historiquement au Magdalénien du Bassin parisien. Il est vrai que peu de gisements autorisaient ce type d'approche, en raison d'une surface fouillée insuffisante ou d'un état de conservation médiocre, mais même lorsque les découvertes s'y prêtaient, le manque de temps et d'investissement freinait également toute velléité d'une étude approfondie des sites en question, qui aurait alors débouché sur une lecture palethnographique des lieux et des artefacts. À l'issue d'un PCR mené entre 1999 et 2005, nous pouvions ainsi légitimement nous demander si nous étions capables de jouer les ethnologues du passé pour le Paléolithique supérieur ancien dans le Bassin parisien. Les sites identifiés dans le cadre de ce programme de recherche étaient certes nombreux mais représentés surtout par des découvertes de surface, ils ne garantissaient pas un niveau d'analyse digne de ce qui a pu se faire depuis plus de 50 ans à Pincevent ou à Étiolles par exemple (Bodu et al., 2013). Il aura fallu attendre la découverte fortuite du gisement de plein-air d'Ormesson « les Bossats » (Seine-et-Marne, près de Nemours) au début des années 2000 pour que cette question trouve une réponse positive. Concernant, au départ, presqu'exclusivement des vestiges lithiques et osseux attribués au Gravettien, les premières fouilles menées en 2009 permirent d'identifier rapidement un second niveau d'occupation, d'attribution moustérienne. Les campagnes suivantes amenèrent à la découverte de cinq autres niveaux d'occupation paléolithiques, inégaux tant pour la surface couverte que pour l'état de conservation : un second niveau moustérien résultant vraisemblablement de palimpsestes, un ensemble châtelperronien, un autre solutréen, un quatrième badegoulien et enfin entre Châtelperronien et Gravettien, un foyer isolé sans vestiges archéologiques associés. Cette stratigraphie paléolithique de plein-air dilatée est le témoignage d'une forte occupation du lieu pendant près de 30 000 ans, ce qui s'explique notamment par la configuration particulière de la vallée à cet endroit. À la diversité chronologique des occupations préhistoriques répond une diversité des comportements économiques et techniques au sein des différentes sphères d'activités mais également des habitudes spatiales différentes. À l'issue des huit premières années de fouille (2009-2016), le site d'Ormesson « les Bossats » permet ainsi de développer une approche détaillée des comportements techniques, économiques, spatiaux de groupes culturels distincts ayant vécu durant 30 000 ans dans un cadre géomorphologique et plus globalement naturel, relativement identique. Dépassant le jeu de mot facile « palethnographie ou pâle ethnographie ? » à Ormesson « les Bossats », nous proposons ici quelques éléments de réponse

Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)

Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4–20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance.Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group—patients with current MDD (n = 20), (ii) remitted depressed group—patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups.Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice.Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&cond=depression&cntry=FR&rank=

The ANTENATAL multicentre study to predict postnatal renal outcome in fetuses with posterior urethral valves: objectives and design

Abstract Background Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature. Methods Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in >30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1–β = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature. Results In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment. Conclusions Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV

LIF-Dependent Signaling: New Pieces in the Lego

LIF, a member of the IL6 family of cytokine, displays pleiotropic effects on various cell types and organs. Its critical role in stem cell models (e.g.: murine ES, human mesenchymal cells) and its essential non redundant function during the implantation process of embryos, in eutherian mammals, put this cytokine at the core of many studies aiming to understand its mechanisms of action, which could benefit to medical applications. In addition, its conservation upon evolution raised the challenging question concerning the function of LIF in species in which there is no implantation. We present the recent knowledge about the established and potential functions of LIF in different stem cell models, (embryonic, hematopoietic, mesenchymal, muscle, neural stem cells and iPSC). We will also discuss EVO-DEVO aspects of this multifaceted cytokine

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon