[Analysis of genetic variant in a child with Aspartylglucosaminuria].

OBJECTIVE: To explore the genetic basis for a child with Aspartylglucosaminuria (AGU). METHODS: Clinical data of the patient was analyzed. The child was subjected to trio-whole exome sequencing (WES) and copy number variation sequencing (CNV-seq), and candidate variant was verified by Sanger sequencing. RESULTS: The child was found to harbor homozygous c.319C>T (p.Arg107*) nonsense variant of the AGA gene, for which both of his parents were heterozygous carriers. No abnormality was found by CNV-seq analysis. The c.319C>T (p.Arg107*) variant was not found in population database, HGMD and other databases. Based on guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PM2+PP3). CONCLUSION: The c.319C>T variant of the AGA gene probably underlay the autosomal recessive AGU in this child. Above finding has enabled genetic counseling and prenatal diagnosis for his parents.

[Influence of Nitrogen Flow Rate on the Structure and Luminescence Properties of Silicon-Rich Silicon Nitride Film Materials in a High Hydrogen Atmosphere].

High hydrogenated silicon-rich silicon nitride(SiNx∶H)thin films are deposited on the glass and monocrystalline silicon(110) substrates by plasma enhanced chemical vapor deposition using SiH4 and H2 as the main reaction gas with doping the N2. The ultraviolet-visible absorption spectrum, Fourier transform infrared absorption spectroscopy, Raman spectroscopy and photoluminescence spectrum are applied to characterize the changes of the band gap, the microstructure and related photoluminescence properties of the nitrogen-doped silicon film. It shows that hydrogen atoms can suppress the defects in the film and make film present silicon-rich under the low SiH4/H2 flow ratio, but they are not beneficial to the formation of silicon clusters in a hydrogen atmosphere. With the incorporation of nitrogen atoms, all the content of Si-N bonds, band gap and the degree of disorder in the microstructure of the films increase, films produce light emission related to the defect states. While the content of doped nitrogen atoms are further increased, it appears the band tail emission. Then the relationships between several light emissions and microstructure to be discussed. These results are useful for the optimization of light emission and microstructure for the silicon-rich silicon nitride film material prepared by PECVD.

Optimization of CCR4 antagonists: side-chain exploration.

The design, synthesis, and activity of novel and selective small molecule antagonists of the CC chemokine receptor-4 (CCR4) are presented. Compound 8c was efficacious in a murine allergic inflammation model (ED(50) 30 mg/kg).

Identification of chemokine receptor CCR4 antagonist.

The present study reports the identification and hits to leads optimization of chemokine receptor CCR4 antagonists. Compound 12 is a high affinity, non-cytotoxic antagonist of CCR4 that blocks the functional activity mediated by the receptor.

Aminotriazine 5-HT7 antagonists.

The present studies have identified a series of aminotriazines as novel 5-HT(7) receptor antagonists. Compounds 10 and 17 have high affinity for the 5-HT(7) receptor and do not bind to either the 5-HT(2C) or 5-HT(6) receptors. These compounds produce no agonist effects by themselves, and shift the dose-response curve of 5-CT to the right in the manner of an antagonist.

Diaminopyrimidine and diaminopyridine 5-HT7 ligands.

The present studies have identified a series of diaminopyrimidines and diaminopyridines as novel 5-HT(7) receptor ligands. Three regiosiomeric classes of pyrimidines and four regioisomeric classes of pyridines were synthesized and analyzed for binding to the 5-HT(7) receptor. The 5-HT(7) binding affinities of different regioisomers show clearly the structure-activity relationship with position of ring nitrogens.