Kyung Soon Kim

Upregulation of Daxx mediates apoptosis in response to oxidative stress

Oxidative stress induces apoptosis in a variety of cell types by as yet unclear signaling mechanisms. The Daxx protein is reportedly involved in apoptosis through its interactions with Fas, transforming growth factor‐β receptor, and promyelocytic leukemia protein (PML). Here, we explored the possible roles of Daxx in oxidative stress‐induced apoptosis. We found that both the mRNA and protein levels of Daxx markedly increased when cells underwent apoptosis after H2O2 treatment. Pretreatment with the cell‐permeable antioxidant, N‐acetyl cysteine, prevented cells from H2O2‐induced Daxx upregulation and subsequent apoptosis, indicating that the endogenous oxidant regulated Daxx expression. Furthermore, suppression of endogenous Daxx expression by antisense oligonucleotide technology inhibited oxidative stress‐induced apoptosis in HeLa cells. Taken together, these results suggest that Daxx acts as an intermediary messenger of pro‐apoptotic signals triggered by oxidative stress.

Analysis of the canine brain transcriptome with an emphasis on the hypothalamus and cerebral cortex

The diversity of dog breeds make the domestic dog a valuable model for identifying genes responsible for many phenotypic and behavioral traits. The brain, in particular, is a region of interest for the analysis of molecular changes that are involved in dog-specific behavioral phenotypes. However, such studies are handicapped due to incomplete annotation of the dog genome. We present a high-coverage transcriptome of the dog brain using RNA-Seq. Two areas of the brain, hypothalamus and cerebral cortex, were selected for their roles in cognition, emotion, and neuroendocrine functions. We detected many novel features of the dog transcriptome, including 13,799 novel exons, 51,357 exons with unique 5′ or 3′ modifications, and many novel alternative splicing events. We provide some examples of novel features in genes that are related to domestication, including ADCY8, SMOC2, and PRNP. We also found 247 novel protein-coding genes and 328 noncoding RNAs, including 57 long noncoding RNAs that represent the first empirical evidence for a large fraction of noncoding RNAs in the dog. In addition, we analyze both gene expression and alternative splicing differences between the hypothalamus and cerebral cortex and find that there is very little overlap between genes that are differentially alternatively spliced and genes that are differentially expressed. We thereby suggest that researchers who want to pinpoint the genetic causes for dog breed-specific traits and diseases should not confine their studies to gene expression alone, but should consider other factors such as alternative splicing and changes in untranslated regions.

Synthesis of 4‐Alkyl‐1(2H)‐phthalazinones and 4‐Alkyl‐2,3‐benzoxazin‐1‐ones via Ring Cleavage of 3‐Substituted N‐Alkylated‐3‐hydroxyisoindolin‐1‐ones

Abstract N‐Alkyl (Me, Et, i‐Pr, t‐Bu)‐substituted phthalimdes 5a–d were easily transformed to 1(2H)‐phthalazinones 8d–i and 2,3‐benzoxazin‐1‐ones 9d, f, and j via a one‐pot addition–decyclization–cyclocondensation process.

Synthesis of Multi-substituted Pyrazoles Utilizing the N-Alkylated 3-Hydroxy-3-propargyl- or allenylisoindolines

N-Alkyl-substituted phthalimides (1) were easily converted to di-, tri-, and tetra-substituted pyrazoles (10) via a one-pot addition-decyclization-cyclocondensation process. Then, the structure and the position of N1-substitution of the 1,3-pyrazole ring were determined by X-Ray crystallographic analysis and 1 H-nOe experiments.

Corrigendum to “Novel 3,5-diaryl pyrazolines as human acyl-CoA:cholesterol acyltransferase inhibitors” [Bioorg. Med. Chem. Lett. 14 (2004) 3109–3112]

Corrigendum Corrigendum to ‘‘Novel 3,5-diaryl pyrazolines as human acyl-CoA:cholesterol acyltransferase inhibitors” [Bioorg. Med. Chem. Lett. 14 (2004) 3109–3112] Tae-Sook Jeong , Kyung Soon Kim , Sojin An, Kyung-Hyun Cho, Sangku Lee, Woo Song Lee * National Research Laboratory of Lipid Metabolism and Atherosclerosis, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, South Korea