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Biomedical subjects

J Yoon

Publications and source records attributed to J Yoon.

At least 37 records · Page 2Linked to original sources
PubMed2000

The DNA replication-related element (DRE)-DRE-binding factor (DREF) system may be involved in the expression of the Drosophila melanogaster TBP gene.

The TATA box binding protein (TBP) is a general transcription factor required for initiation by all three eukaryotic RNA polymerases. Previously, we found that the promoter region of the Drosophila melanogaster TBP gene contains three sequences similar to the DNA replication-related element (DRE) (5'-TATCGATA). In the present study, we found that the DRE-like sequences are also present in the promoter of the Drosophila virilis TBP gene, suggesting a role for these sequences in TBP expression. Band mobility shift assays revealed that oligonucleotides containing sequences similar to the DRE of D. melanogaster TBP gene promoter form specific complexes with a factor in a Kc cell nuclear extract and with recombinant DRE-binding factor (DREF). Furthermore, these complexes were either supershifted or diminished by monoclonal antibodies to DREF. Transient luciferase assays demonstrated that induction of mutations in two DRE-related sequences at positions -223 and -63 resulted in an extensive reduction of promoter activity. Thus, the DRE-DREF system appears to be involved in the expression of the D. melanogaster TBP gene.

Animals↗
PubMed2000

Structure, chromosomal localization, and expression of the Drosophila melanogaster gene encoding sepiapterin reductase.

We have isolated and characterized a Drosophila melanogaster gene encoding the sepiapterin reductase (SR). The gene does not have introns. The 5'- and 3'-RACE analysis, which determined the transcription start point (tsp) and polyadenylation site, respectively, showed that the gene produces single mRNA species. The potential promoter region lacks distinct TATAAA or CCAAT box consensus sequences. RNA blot analysis revealed that the gene encodes a 1.4kb transcript that could be detected throughout development and in both heads and bodies of adults. The Drosophila SR gene maps to 15A on the X chromosome.

Alcohol Oxidoreductases↗
PubMed2000

Parallel solid-phase synthesis of vitronectin receptor (alphavbeta3) inhibitors.

A combinatorial approach for rapid optimization of a vitronectin receptor (alphavbeta3) inhibitor lead was accomplished by solid-phase synthesis. Orthogonally bis protected 2,3-diaminopropionic acid was used to immobilize the C-terminus of the molecule. Selective deprotection and functionalization of the alpha-amino group followed by acyl resorcinol scaffold attachment and N-terminus diversification was used to explore structure activity relationship (SAR).

Receptors, Vitronectin↗
PubMed2000

NMR studies on novel antitumor drug candidates, deoxoartemisinin and carboxypropyldeoxoartemisinin.

Artemisinin and its derivatives, which have been known as antimalarial drugs, have also demonstrated their cytotoxicity against tumor cells. It has been proposed that antitumor activity depends on the lipophilicity of functional group on artemisinin derivatives. Solution structures of two artemisinin derivatives as antitumor drug candidates, deoxoartemisinin and carboxypropyldeoxoartemisinin, were determined by NMR spectroscopy to elucidate structure-activity relationship. According to biological assay, antitumor efficiencies are not dependent upon lipophilicity. Instead, these compounds demonstrated their distinctive structural features of boat/chair conformation and capability to interact with receptors, as they have different efficiencies on antitumor activity. Especially, carboxypropyl moiety or carbonyl moiety in artemisinin derivatives influences the conformation and stability of ring structure. Although the detailed mechanism of antitumor activity by artemisinin derivatives has not been addressed, we suggest that antitumor activity is not determined only with lipophilicity and that artemisinin derivatives have specific target proteins in each type of cancer.

Animals↗
PubMed2000

Efficient syntheses and ring-opening reactions of trans- and cis-oxazoline-5-carboxylates

[formula: see text] cis- and trans-Oxazoline-5-carboxylates were synthesized efficiently from isopropyl trans-cinnamate utilizing the Sharpless AA reaction. trans-Oxazoline was much more reactive than the cis-isomer toward ring opening reactions. From ab initio molecular calculations, the cis-isomer was predicted to be less reactive than the trans-isomer by 2.7 kcal/mol. Both syn and anti acetylthio esters and anti diamino esters were synthesized from these cis- and trans-oxazoline-5-carboxylates.

Journal Article↗
PubMed2000

Novel mechanism of massive photoreceptor degeneration caused by mutations in the trp gene of Drosophila.

The Drosophila trp gene encodes a light-activated Ca(2+) channel subunit, which is a prototypical member of a novel class of channel proteins. Previously identified trp mutants are all recessive, loss-of-function mutants characterized by a transient receptor potential and the total or near-total loss of functional TRP protein. Although retinal degeneration does occur in these mutants, it is relatively mild and slow in onset. We report herein a new mutant, Trp(P365), that does not display the transient receptor potential phenotype and is characterized by a substantial level of the TRP protein and rapid, semi-dominant degeneration of photoreceptors. We show that, in spite of its unusual phenotypes, Trp(P365) is a trp allele because a Trp(P365) transgene induces the mutant phenotype in a wild-type background, and a wild-type trp transgene in a Trp(P365) background suppresses the mutant phenotype. Moreover, amino acid alterations that could cause the Trp(P365) phenotype are found in the transmembrane segment region of the mutant channel protein. Whole-cell recordings clarified the mechanism underlying the retinal degeneration by showing that the TRP channels of Trp(P365) are constitutively active. Although several genes, when mutated, have been shown to cause retinal degeneration in Drosophila, the underlying mechanism has not been identified for any of them. The present studies provide evidence for a specific mechanism for massive degeneration of photoreceptors in Drosophila. Insofar as some human homologs of TRP are highly expressed in the brain, a similar mechanism could be a major contributor to degenerative disorders of the brain.

Amino Acid Sequence↗
PubMed2000

Nodal and bone morphogenetic protein 5 interact in murine mesoderm formation and implantation.

Mice mutant for the TGF-beta family member, nodal, lack mesoderm and die between E8.5 and E9.5. The short ear-lethal (se(l) ) mutation, a deletion that eliminates Bmp-5, causes a strikingly similar gastrulation defect. Here we analyze se(l);nodal compound mutants and find a dosage effect. Embryos homozygous for one mutation show distinct gastrulation stage defects that depend on whether they are heterozygous or homozygous for the other mutation. Embryos mutant for nodal or se(l);nodal compound mutants fail to execute an antigenic shift indicative of mesoderm differentiation and ectoderm cells are shunted into an apoptotic pathway. Furthermore, we find a novel phenotype in se(l);nodal double mutant litters, in which two to four genetically different embryos are contained within the same deciduum. Both the gastrulation and implantation phenotypes can also arise in short ear-viable (se(v) ) and se(v); nodal mutant mice. These data indicate that loss of Bmp-5 may underlie the se(l) gastrulation phenotype and suggest that nodal and Bmp-5 interact during murine mesoderm formation. Our data also reveal an unsuspected role for Bmp-5 in implantation and the decidual response in the mouse.

Animals↗
PubMed2000

ENVIRONMENTAL AUDITING: Economic Values of Recreational Power Boating Resources in Pennsylvania.

/ The travel cost method was used to estimate the economic value of seven major power boating resources in Pennsylvania. A significant relationship between number of visitor trips and cost per visitor trip existed for five of the seven water bodies. The annual total value for those five resources was $396 million, which was 2.5 times greater than the total out-of-pocket expenditures of approximately $157 million visitors spent to visit them. Research results can help resource managers plan and craft programs and policies that are founded on economic values of the natural resources involved.

Journal Article↗
PubMed2000

Effects of electric stimulation on bovine oocyte activation and embryo development in intracytoplasmic sperm injection procedure.

PURPOSE: This study was carried out to investigate the efficacy of electric stimulation before and/or after intracytoplasmic sperm injection (ICSI) on bovine oocyte activation and embryo development. METHODS: The oocytes were treated with electric shock before (B), before and after (B&A), and after (A) sperm injection. In each group, sham ICSI (ICSI-s) was performed to exclude the effect of parthenogenesis (B ICSI-s, B&A ICSI-s, and A ICSI-s). An electric pulse was applied with a single direct current (DC) pulse (0.8 kV/cm, 70 microseconds). RESULTS: One pronucleus (PN) formation in the B&A ICSI-s group was slightly higher than that found in B and B&A ICSI group; however, the difference was not significant. Two PN formation in B&A ICSI group was higher than that found in sham ICSI groups (P < 0.05). There were no differences among treatment groups in the cleavage rate; however, morulae and blastocyst formation in the B&A embryos was significantly higher than that of other groups (P < 0.05) and got pregnant. CONCLUSIONS: Electric stimulation before and after injection was an effective method in inducing bovine oocyte activation and in sustaining embryo development to the morulae and blastocyst stage.

Animals↗
PubMed2000

Supervisor support in the work place: legitimacy and positive affectivity.

The authors tested 3 hypotheses regarding supervisor support in the work place. The validation hypothesis predicts that when employees are supported by their coworkers and the larger organization, they also receive more support from their supervisors. The positive affectivity hypothesis predicts that employees with positive dispositions receive more supervisor support because they are more socially oriented and likable. The moderation hypothesis predicts a joint multiplicative effect between validation and positive affectivity. An assessment of the hypotheses among a sample of 1,882 hospital employees in Korea provided strong support for the validation and moderation hypotheses.

Adult↗
PubMed2000

Identification, characterization, and mapping of expressed sequence tags from an embryonic zebrafish heart cDNA library.

The generation of expressed sequence tags (ESTs) has proven to be a rapid and economical approach by which to identify and characterize expressed genes. We generated 5102 ESTs from a 3-d-old embryonic zebrafish heart cDNA library. Of these, 57.6% matched to known genes, 14.2% matched only to other ESTs, and 27.8% showed no match to any ESTs or known genes. Clustering of all ESTs identified 359 unique clusters comprising 1771 ESTs, whereas the remaining 3331 ESTs did not cluster. This estimates the number of unique genes identified in the data set to be approximately 3690. A total of 1242 unique known genes were used to analyze the gene expression patterns in the zebrafish embryonic heart. These were categorized into seven categories on the basis of gene function. The largest class of genes represented those involved in gene/protein expression (25.9% of known transcripts). This class was followed by genes involved in metabolism (18.7%), cell structure/motility (16.4%), cell signaling and communication (9.6%), cell/organism defense (7.1%), and cell division (4.4%). Unclassified genes constituted the remaining 17.91%. Radiation hybrid mapping was performed for 102 ESTs and comparison of map positions between zebrafish and human identified new synteny groups. Continued comparative analysis will be useful in defining the boundaries of conserved chromosome segments between zebrafish and humans, which will facilitate the transfer of genetic information between the two organisms and improve our understanding of vertebrate evolution.

Animals↗
PubMed2000

Structural and functional dissection of human cytomegalovirus US3 in binding major histocompatibility complex class I molecules.

The human cytomegalovirus US3, an endoplasmic reticulum (ER)-resident transmembrane glycoprotein, forms a complex with major histocompatibility complex (MHC) class I molecules and retains them in the ER, thereby preventing cytolysis by cytotoxic T lymphocytes. To identify which parts of US3 confine the protein to the ER and which parts are responsible for the association with MHC class I molecules, we constructed truncated mutant and chimeric forms in which US3 domains were exchanged with corresponding domains of CD4 and analyzed them for their intracellular localization and the ability to associate with MHC class I molecules. All of the truncated mutant and chimeric proteins containing the luminal domain of US3 were retained in the ER, while replacement of the US3 luminal domain with that of CD4 led to cell surface expression of the chimera. Thus, the luminal domain of US3 was sufficient for ER retention. Immunolocalization of the US3 glycoprotein after nocodazole treatment and the observation that the carbohydrate moiety of the US3 glycoprotein was not modified by Golgi enzymes indicated that the ER localization of US3 involved true retention, without recycling through the Golgi. Unlike the ER retention signal, the ability to associate with MHC class I molecules required the transmembrane domain in addition to the luminal domain of US3. Direct interaction between US3 and MHC class I molecules could be demonstrated after in vitro translation by coimmunoprecipitation. Together, the present data indicate that the properties that allow US3 to be localized in the ER and bind MHC class I molecules are located in different parts of the molecule.

Endoplasmic Reticulum↗
PubMed1999

An element with palindromic structure is required for the expression of TBP (TATA box-binding protein) gene in Drosophila melanogaster.

Previously we showed that the 5'-flanking regions between -261 and -207 of the Drosophila melanogaster TBP (TATA box binding protein) gene is important for its expression. We further made serial deletion mutants in this region and analyzed their promoter activities using the transient transfection assay. We found that the 16 bp deletion from -261 to -245 greatly reduces the promoter activity of the Drosophila TBP gene. The 16 bp DNA element contains half of a 11 bp long palindromic sequence, CTTTT-GAAAAG. Disruption of the palindromic sequence by site-directed mutagenesis severely affected promoter activity. In addition, the electrophoretic mobility shift assay showed that the oligonucleotide containing the palindromic sequence can make specific DNA/protein complexes when it was mixed with the Drosophila nuclear extract, suggesting that it interacts with nuclear protein(s). Our data suggest that the palindromic sequence has a critical role in the expression of the Drosophila TBP gene.

Animals↗
PubMed1999

The Ets factors PU.1 and Spi-B regulate the transcription in vivo of P2Y10, a lymphoid restricted heptahelical receptor.

To investigate the in vivo functions of PU.1 and Spi-B, two highly related Ets transcription factors, we previously generated PU. 1(+/+)Spi-B(-/-) and PU.1(+/-)Spi-B(-/-) mice and demonstrated a significant decrease in B-cell receptor (BCR) signaling in mutants. Major components of BCR signaling appear to be expressed at normal levels in these mice, implying that PU.1 and Spi-B cooperate in the transcription of additional target genes important for antigen receptor signaling. We used subtractive hybridization to identify novel in vivo PU.1/Spi-B target genes and determined that the expression of a heptahelical receptor, P2Y10, is dramatically reduced in PU.1(+/-)Spi-B(-/-) B-cells. Further analysis shows that P2Y10 expression is restricted to lymphoid cells and parallels that of Spi-B in B-lymphocytes. Lastly, the P2Y10 promoter contains a PU. 1/Spi-B binding site functionally required for efficient transcription in B-cells. Thus, P2Y10 is likely to be a direct in vivo transcriptional target for PU.1 and Spi-B and provides a unique model to explore transcriptional regulation by this Ets factor subfamily. Furthermore, P2Y10 suggests an intriguing connection between heterotrimeric G-proteins and BCR signaling.

3T3 Cells↗