26 research outputs found
LIPH Expression in Skin and Hair Follicles of Normal Coat and Rex Rabbits
Natural mutations in the LIPH gene were shown to be responsible for hair growth defects in humans and for the rex short hair phenotype in rabbits. In this species, we identified a single nucleotide deletion in LIPH (1362delA) introducing a stop codon in the C-terminal region of the protein. We investigated the expression of LIPH between normal coat and rex rabbits during critical fetal stages of hair follicle genesis, in adults and during hair follicle cycles. Transcripts were three times less expressed in both fetal and adult stages of the rex rabbits than in normal rabbits. In addition, the hair growth cycle phases affected the regulation of the transcription level in the normal and mutant phenotypes differently. LIPH mRNA and protein levels were higher in the outer root sheath (ORS) than in the inner root sheath (IRS), with a very weak signal in the IRS of rex rabbits. In vitro transfection shows that the mutant protein has a reduced lipase activity compared to the wild type form. Our results contribute to the characterization of the LIPH mode of action and confirm the crucial role of LIPH in hair production
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
Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study
Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation
Ultra Wide Micro Bumps Interconnection Matrix for High Energy Particle Detection: Process and Assembly
International audienceMicro pillars and micro bumps interconnections are considered as mature technology for 3-D integration and chip stacking. However, in the framework of high-energy particles detection as ATLAS Large Hadron Collider new tracker project at CERN, very large area array of dense interconnections with an aggressive specification of total thickness variation (TTV) of +/-2μm are required to grant successful detectors assembly process. This paper will first describe the test vehicle that has been designed on purpose for this study. The studies undertaken including lithography mapping, seed layer and electrochemical deposition (ECD) process will then be detailed introducing a model of anode intensity contribution to the overall TTV. To conclude, daisy chain electrical test results and yields after stacking using dieto-wafer approaches will be discussed with respects to process parameters
Un jardin de naturaliste — Histoire (s) d'un jardin-exposition au Muséum
This paper retraces the conception and the establishment of an exhibit-garden, and the preparation of an accompanying book with a preliminary account on the combined work of the authors. Located in the vicinity of the Evolution Gallery, the garden offers the visitor a portrait of both the scientist and his work. Beyond the personality of the scientist, the professional styles of 20th century naturalists of our century are thus revealed : the development of knowledge of nature, the research tools used, and the relationships that exist with other living beings.Ce texte retrace l'histoire de la conception et la réalisation d'un jardin- exposition, et en livre une première analyse, à partir d'une enquête effectuée auprès de ses différents acteurs. Hors les murs de la Grande Galerie de l'Évolution, au fil d'un parcours au travers des plantes et des carrés bordés de buis, le Jardin d'un naturaliste propose au visiteur le portrait de Paul Jovet - l'homme et son œuvre. Au-delà de la personnalité du savant, c'est la culture professionnelle des naturalistes de ce siècle qui est ici dévoilée : l'élaboration du savoir sur la nature, les outils d'investigation, les relations aux êtres vivants.Lizet Bernadette, Allain Yves-Marie, Brasz Jean-Pierre, Deligne Claire, Duhamel Hervé, Galangau-Quérat Fabienne, Morel Gaud, Riffet Xavier, Vitale Dominique, Wolf Anne-Elisabeth. Un jardin de naturaliste — Histoire (s) d'un jardin-exposition au Muséum. In: Journal d'agriculture traditionnelle et de botanique appliquée, 39ᵉ année, bulletin n°2,1997. Sauvages dans la ville. De l'inventaire naturaliste à l'écologie urbaine, sous la direction de Bernadette Lizet, Anne-Elizabeth Wolf et John Celecia. pp. 177-197
Why should the meningococcal B vaccine be recommended, and therefore reimbursed, for infants in France?
International audienc
Investigation of eating and deviant behaviors in bodybuilders according to their competitive engagement
Lipase activity of wild-type <i>LIPH</i> and 1362delA <i>LIPH</i> mutant constructs.
<p>Values obtained are shown as a percentage of that observed in cells transfected with the empty vector (pcDNA3.1+, control).</p
Primer pairs used for PCR amplification, qPCR and ISH.
<p>Primer pairs used for PCR amplification, qPCR and ISH.</p
<i>LIPH</i> expression at three different fetal stages (days 19, 25 and 29) corresponding respectively to the formation of the central primary, lateral primary and secondary hair follicles.
<p>(Bars = 20 µm). (A) Q-PCR expression of <i>LIPH</i> mRNA in the <i>orylag®</i> rabbit skin (light blue bars) and in the normal rabbit skin (dark blue bars). The Y axis represents the relative expression level of <i>LIPH</i>. (B) Histology (ROAN staining) of <i>orylag®</i> (B1) and normal rabbit skins (B2). (C) Immunohistochemistry of <i>orylag®</i> (C1) and normal rabbit skins (C2).</p