A5101849771- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Genetics and Neurodevelopmental Disorders
- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neurogenesis and neuroplasticity mechanisms
- Receptor Mechanisms and Signaling
- Genomics and Rare Diseases
- Wastewater Treatment and Nitrogen Removal
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic Neurodegenerative Diseases
- Fungal and yeast genetics research
- Bacterial Genetics and Biotechnology
- Protist diversity and phylogeny
- Retinal Development and Disorders
- Genomic variations and chromosomal abnormalities
- Microbial Metabolic Engineering and Bioproduction
- Autism Spectrum Disorder Research
- MicroRNA in disease regulation
- Genomics and Phylogenetic Studies
- Diet and metabolism studies
- Plant nutrient uptake and metabolism
- Mitochondrial Function and Pathology
- Amyotrophic Lateral Sclerosis Research
- Metalloenzymes and iron-sulfur proteins
State Key Laboratory of Medical Neurobiology
2012-2023
Fudan University
2012-2023
University of California, San Francisco
2002-2021
Institute of Neurobiology
2021
Allen Institute for Brain Science
2017
Chinese Institute for Brain Research
2016
Institut de Neurobiologie de la Méditerranée
2012
Inserm
2012
Hôpitaux Universitaires de Strasbourg
2012
Aix-Marseille Université
2012
Andersen syndrome (AS) is a rare, inherited disorder characterized by periodic paralysis, long QT (LQT) with ventricular arrhythmias, and skeletal developmental abnormalities. We recently established that AS caused mutations in KCNJ2, which encodes the inward rectifier K+ channel Kir2.1. In this report, we functional consequences of three novel seven previously described KCNJ2 using two-microelectrode voltage-clamp technique correlated findings clinical phenotype. All resulted loss function...
The nit-2 major nitrogen regulatory gene of Neurospora crassa turns on the expression various unlinked structural genes that specify nitrogen-catabolic enzymes under nitrogen-limitation conditions. encodes a protein 1036 amino acid residues with single zinc finger and downstream basic region may make up DNA-binding domain. zinc-finger domain NIT2 was synthesized in two ways to examine its activity gel-band-mobility shift DNA-footprint experiments. binds specific DNA recognition elements are...
The nitrogen regulatory circuit of Neurospora crassa consists a set unlinked structural genes which specify various catabolic enzymes plus control and metabolic effectors regulate their expression. positive-acting nit-2 gene is required to turn on the expression during conditions limitation. complete nucleotide sequence was determined. mRNA 4.3 kilobases long has nontranslated at both its 5' 3' ends. can be translated yield protein containing 1,036 amino acid residues with molecular weight...
Mutations in KCNJ2, the gene encoding inward-rectifying K+ channel Kir2.1, cause cardiac, skeletal muscle, and developmental phenotypes of Andersen-Tawil syndrome (ATS; also known as Andersen syndrome). Although pathogenic mechanisms have been proposed for select mutations, a common mechanism has not identified.Seventeen probands presenting with symptoms characteristic ATS were evaluated clinically screened mutations KCNJ2. The results mutation analysis combined those from previously studied...
Andersen-Tawil syndrome is a skeletal and cardiac muscle disease with developmental features caused by mutations in the inward rectifier K+ channel gene KCNJ2. Patients harboring these exhibit extremely variable expressivities. To explore whether can be correlated specific patient phenotype, we expressed both wild-type (WT) mutant genes cloned into bi-cistronic vector. Functional expression human embryonic kidney 293 cells showed that none of channels express current when present alone. When...
Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial intrafamilial variability patients may have IC or PKD. Association hemiplegic migraine (HM) has also been reported. In order explore mutational clinical spectra, we analyzed 34 additional either typical PKD/IC migraine.We...
nit-4, a pathway-specific regulatory gene in the nitrogen circuit of Neurospora crassa, is required for expression nit-3 and nit-6, structural genes which encode nitrate nitrite reductase, respectively. The complete nucleotide sequence nit-4 has been determined. predicted NIT4 protein contains 1,090 amino acids appears to possess single Zn(II)2Cys6 binuclear-type zinc finger, may mediate DNA binding. Site-directed mutagenesis studies demonstrated that cysteine other conserved acid residues...
Eye opening, a natural and timed event during animal development, influences cortical circuit assembly maturation; yet, little is known about its precise effect on inhibitory synaptic connections. Here, we show that coinciding with eye the strength of unitary postsynaptic currents (uIPSCs) from somatostatin-expressing interneurons (Sst-INs) to nearby excitatory neurons, but not interneurons, sharply decreases in layer 2/3 mouse visual cortex. In contrast, uIPSCs fast-spiking (FS-INs) neurons...
The sulfur-regulatory circuit of Neurospora crassa consists a set unlinked structural genes which encode sulfur-catabolic enzymes and two major regulatory govern their expression. positive-acting cys-3 gene is required to turn on the expression sulfur-related enzymes, whereas other gene, scon, acts in negative fashion repress synthesis same enzymes. Expression was found be controlled by scon sulfur availability. nucleotide sequence determined can translated yield protein molecular weight...
Layer 1 of the neocortex harbors a unique group neurons that play crucial roles in synaptic integration and information processing. Although extensive studies have characterized properties layer mature neocortex, it remains unclear how these progressively acquire their distinct morphological, neurochemical, physiological traits. In this study, we systematically examined dynamic development Cajal-Retzius cells γ-aminobutyric acid (GABA)-ergic interneurons during first 2 postnatal weeks....
Paroxysmal non-kinesigenic dyskinesia (PNKD) is a rare autosomal dominant movement disorder triggered by stress, fatigue or consumption of either alcohol caffeine. Attacks last 1–4 h and consist dramatic dystonia choreoathetosis in the limbs, trunk face. The disease associated with single amino acid changes (A7V A9V) PNKD, protein unknown function. Here we studied stability, cellular localization enzymatic activity PNKD cultured cells transgenic animals. N-terminus wild-type (WT) long...
The nit-3 gene of Neurospora crassa encodes the enzyme nitrate reductase and is regulated by nitrogen catabolite repression specific induction with nitrate. was isolated from a cosmid-based genomic library dual selection for benomyl resistance ability to complement mutant strain using sibling-selection procedure. subcloned as 3.8-kilobase DNA fragment cosmid that carried an approximately 40-kilobase N. insert. A restriction length polymorphism analysis revealed cloned segment displayed tight...
Triplet repeats are the sites of mutation in three human heritable disorders, spinal and bulbar muscular atrophy (SBMA), fragile X syndrome, myotonic dystrophy (DM). These GC-rich highly polymorphic normal population. Fragile syndrome DM examples diseases which premutation alleles cause little or no disease individual, but give rise to significantly amplified affected progeny. This newly identified mechanism has, so far, been two most common DM, one rare disease, SBMA.
In Neurospora crassa, the expression of nit-3, structural gene which encodes nitrate reductase, is highly regulated and requires both induction nitrogen catabolite derepression. The major regulatory gene, nit-2, acts in a positive fashion to turn on nit-3 other nitrogen-related genes during A second designated nmr, negative repress reductase related enzymes, nmr mutants are partially insensitive repression. Using cloned as specific hybridization probes, we demonstrated that does not affect...
Andersen syndrome (AS) is a rare, inherited disorder characterized by periodic paralysis, long QT (LQT) with ventricular arrhythmias, and skeletal developmental abnormalities. We recently established that AS caused mutations in KCNJ2, which encodes the inward rectifier K+ channel Kir2.1. In this report, we functional consequences of three novel seven previously described KCNJ2 using two-microelectrode voltage-clamp technique correlated findings clinical phenotype. All resulted loss function...
A small subset of interneurons that are generated earliest as pioneer neurons the first cohort enter neocortex. However, it remains largely unclear whether these early-generated (EGIns) predominantly regulate neocortical circuit formation. Using inducible genetic fate mapping to selectively label EGIns and pseudo-random (pRIns), we found exhibited more mature electrophysiological morphological properties higher synaptic connectivity than pRIns in somatosensory cortex at early postnatal...
Next-generation sequencing technologies both boost the discovery of variants in human genome and exacerbate challenges pathogenic variant identification. In this study, we developed Pathogenicity Prediction Tool for missense (mvPPT), a highly sensitive accurate classifier based on gradient boosting. mvPPT adopts high-confidence training sets with wide spectrum profiles, extracts three categories features, including scores from existing prediction tools, frequencies (allele frequencies, amino...
Abstract Neocortical vasoactive intestinal polypeptide-expressing (VIP+) interneurons display highly diverse morpho-electrophysiological and molecular properties. To begin to understand the function of VIP+ in cortical circuits, they must be clearly comprehensively classified into distinct subpopulations based on specific markers. Here, we utilized patch-clamp RT-PCR (Patch-PCR) simultaneously obtain morpho-electric properties mRNA profiles 155 layers 2 3 (L2/3) mouse somatosensory cortex....