A5087097572- Metabolism and Genetic Disorders
- Folate and B Vitamins Research
- Mitochondrial Function and Pathology
- Animal Virus Infections Studies
- Immune Cell Function and Interaction
- Advanced MRI Techniques and Applications
- Epilepsy research and treatment
- Aquaculture disease management and microbiota
- Lysosomal Storage Disorders Research
- T-cell and B-cell Immunology
- Neuroscience and Neuropharmacology Research
- Immune Response and Inflammation
- Sperm and Testicular Function
- Cellular transport and secretion
- Birth, Development, and Health
- Advanced Neuroimaging Techniques and Applications
- Lipid Membrane Structure and Behavior
- Genomics and Rare Diseases
- Reproductive Biology and Fertility
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cancer-related Molecular Pathways
- Reproductive System and Pregnancy
- Functional Brain Connectivity Studies
- Atomic and Subatomic Physics Research
- Erythrocyte Function and Pathophysiology
National Human Genome Research Institute
1999-2024
National Institutes of Health
1999-2022
Virologie et Immunologie Moléculaires
2004-2010
Maison des Sciences de l’Homme de Dijon
1994-1996
CHU Dijon Bourgogne
1994-1996
Hôpital d'Enfants
1996
Hôpital de la Timone
1993
Yale University
1984-1987
Phosphatidylinositol 3,4,5-trisphosphate is a phospholipid signaling molecule involved in many cellular functions including growth factor receptor signaling, cytoskeletal organization, chemotaxis, apoptosis, and protein trafficking. Phosphorylation at the 3 position of inositol ring catalyzed by different 3-kinases (classified as types IA, IB, II, III), but physiological roles played each 3-kinase isozymes during embryonic development homeostasis animals incompletely understood. Mammalian...
The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked human genetic disorder characterized by mental retardation, congenital cataracts, and renal tubular dysfunction. gene, OCRL1, encodes a phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi complex. pathogenesis due to deficiency complex unknown. We have used targeted disruption embryonic stem cells make mice deficient Ocrl1, mouse homologue for as animal model disease. Surprisingly, Ocrl1 do not develop Fanconi...
α-Synuclein ( SNCA) gene has been implicated in the development of rare forms familial Parkinson disease (PD). Recently, it was shown that an increase SNCA copy numbers leads to elevated levels wild-type SNCA- mRNA and protein is sufficient cause early-onset, PD. A critical question concerning molecular pathogenesis PD what contributory role, if any, played by sporadic The expansion -Rep1, upstream, polymorphic microsatellite gene, associated with risk for However, whether -Rep1 causal...
Folic acid supplementation reduces the risk of neural tube defects and congenital heart defects. The biological mechanisms through which folate prevents birth are not well understood. We explore use zebrafish as a model system to investigate role metabolism during development.We first identified orthologs 12 human metabolic genes. RT-PCR in situ analysis indicated maternal transcripts supply embryo with mRNA so that has an intact pathway. To perturb we exposed embryos methotrexate (MTX),...
Abstract T cell activation requires both specific recognition of the peptide-MHC complex by TCR and additional signals delivered costimulatory receptors. We have identified rainbow trout sequences similar to CD28 (rbtCD28) CTLA4 (rbtCTLA4). rbtCD28 rbtCTLA4 are composed an extracellular Ig-superfamily V domain, a transmembrane region, cytoplasmic tail. The presence conserved ligand binding site within domain molecules suggests that these receptors likely recognize fish homologues B7 family....
Galactokinase (GK; EC 2.7.1.6) is the first enzyme in metabolism of galactose. In humans, GK deficiency results congenital cataracts due to an accumulation galactitol within lens. attempt make a galactosemic animal model, we cloned mouse gene (Glk1) and disrupted it by targeting. As expected, galactose was very poorly metabolized GK-deficient mice. addition, both accumulated tissues Surprisingly, animals did not form even when fed high diet. However, introduction human aldose reductase...
T-cell responses to viruses are still poorly investigated in lower vertebrates. In rainbow trout, a specific clonal expansion of T cells response infection with viral haemorrhagic septicaemia virus (VHSV) was recently identified. Expanded clones expressed unique 8 aa V β 4-J 1 junction (SSGDSYSE) different individuals, reminiscent typical public response. To get further insight into the nature this modifications repertoire following immunization plasmid expressing VHSV external glycoprotein...
In humans, poor nutrition, malabsorption and variation in cobalamin (vitamin B12) metabolic genes are associated with hematological, neurological developmental pathologies. Cobalamin is transported from blood into tissues via the transcobalamin (TC) receptor encoded by CD320 gene. We created mice carrying a targeted deletion of mouse ortholog, Cd320. Knockout (KO) lacking this TC have elevated levels plasma methylmalonic acid homocysteine but otherwise healthy, viable, fertile not anemic. To...
The dynamic nature of cellular interactions during differentiation germ cells and their translocation from the basement membrane to lumen seminiferous tubules requires existence complex well-regulated adhesion mechanisms in testis. Successful migration developing is characterized by breakage reformation cadherin-containing adherens junctions between Sertoli cells, polarized somatic testis that support nourish gametes. Here, we demonstrate accumulation abnormally swollen, actin-coated,...
The analysis of somatic variation in the mitochondrial genome requires deep sequencing DNA. This is ordinarily achieved by selective enrichment methods, such as PCR amplification or probe hybridization. These methods can introduce bias and are prone to contamination nuclear-mitochondrial sequences (NUMTs), elements that artefacts into heteroplasmy analysis. We isolated intact mitochondria using differential centrifugation alkaline lysis subjected purified DNA a sequence-independent PCR-free...
We performed proton magnetic resonance spectroscopy (1H-MRS) in three patients with amyotrophic lateral sclerosis (ALS) to evaluate the distribution and extent of cortical neuronal damage as demonstrated by decreased N-acetyl-aspartate (NAA) levels. examined primary motor (precentral gyrus) parietal neocortical (superior regions. ALS was defined lower upper neuron signs. Compared matched healthy controls, had a significant decrease NAA levels cortex (p < 0.001) compared regions homologous...
Audiogenic seizure (AGS)-susceptible DBA/2 (D2) mice have a significant reduction in brain Ca2+-ATPase activity compared to AGS-resistant C57BL/6 (B6) mice. This is inherited together with AGS susceptibility B6 X D2 recombinant inbred strains. The occurs microsomes and synaptosomes, but not mitochondria. enzyme measured at high Ca2+ concentration (2 mM) no added Mg2+ or EGTA. We further studied this Mg2+-dependent (Ca2+ + Mg2+)-ATPase synaptic plasma membranes (SPM) from the Using EGTA CDTA...
To determine a possible asymmetric metabolic profile in right- handed and non-right-handed healthy subjects by comparing proton spectra from temporal lobes.Twenty-eight adults (17 right-handers, 11 non-right-handers) underwent magnetic resonance (MR) imaging single-voxel MR spectroscopy. N-acetylaspartate (NAA), choline (Cho), creatine (Cr) peak areas were measured.Volume of hippocampal formations was larger on the right right-handers (right volume: 4.04 cm3 +/- 0.67 vs left 3.84 0.62; P =...
Mutations in the human OCRL gene, which encodes a phosphatidylinositol(4,5)bisphosphate 5-phosphatase, result X-linked oculocerebrorenal syndrome of Lowe. Mice with targeted disruption Ocrl have no phenotypic abnormalities. Targeted its closest paralog, Inpp5b, causes male infertility 129S6 background. disruptions both genes are lost utero prior to 9.5-10.5 dpc, indicating that there is functional overlap between two paralogs early development. We analyzed pattern X-inactivation four tissues...
The biological and clinical significance of the p.E88del variant in transcobalamin receptor, CD320, is unknown. This allele annotated ClinVar as likely benign, pathogenic, uncertain significance. To determine functional consequence relevance this allele, we employed cell culture genetic association studies. Fibroblasts from 16 CD320 homozygotes exhibited reduced binding uptake cobalamin. Complete ascertainment newborns with transiently elevated C3 (propionylcarnitine) New York State...
In order to investigate the possible molecular regulatory mechanisms that repress classical HLA class I and stimulate nonclassical HLA-G E-class gene transcription in human trophoblast cells, we searched for nuclear expression of enhancer A DNA-binding proteins KBF1/NF-KB/rel family. Using both purified extravillous cytotrophoblast villous syncytiotrophoblast from first trimester placenta, it appeared members this family were present absent syncytiotrophoblast. First, using double stranded...