Accumulation of organochlorine pesticides in marine fishes from coast of Taoyuan in Taiwan.
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Biomedical subjects
Publications and source records attributed to Y C Yuan.
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The MILDOS-AREA code was developed to estimate radiological doses and risks from uranium milling activities. The code has been used for demonstrating radiological compliance regarding the U.S. Nuclear Regulatory Commission's licensing requirements for uranium milling activities. The code was recently updated with an enhanced software package to address the following four areas: regulatory changes, in-situ leaching extraction technologies, software user interfaces, and software distribution technologies via the internet. Users can now specify in-situ leaching processes through a Windows object-based Geographic information System interface with incorporated updated regulation methodologies. The code and documentation are freely distributed through the Internet.
Ubiquitination plays important roles in a variety of biological processes, such as DNA repair, cell cycle regulation, and p53-dependent processes. Despite intensive studies in ubiquitination, the mechanism of substrate recognition is still not well understood. Each E2 has its own substrate specificity, yet substrate proteins recognized by each E2 are highly diverse. To better understand how E2 proteins confer both substrate specificity and diversity, we have studied conformational flexibility of an E2, UBC9, using nuclear magnetic resonance 15N relaxation and hydrogen-deuterium exchange measurements. Two regions in human UBC9 show higher mobility over a wide range of time scales. Combined with previous biochemical studies, both regions are likely to be important for protein-protein recognition in the ubiquitin pathway. The region near the N-terminus may be important for interactions with the E1-UBL1 conjugate. The region near the C-terminus, which undergoes conformational exchange may be important for substrate binding and catalytic activity. Since E2 enzymes share high homology in primary sequences and three-dimensional structures, the conformational flexibility of UBC9 may represent a general feature of E2 enzymes. This study provides a new perspective for further studies of protein-protein recognition in ubiquitination.
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A novel class of DNA-binding domains has been established from at least sixteen recently identified DNA-binding proteins. The three-dimensional structure of one of these domains, Mrf-2, has been solved using NMR methods. This structure is significantly different from known DNA-binding domain structures. The mechanism of DNA recognition by this motif has been suggested based on conserved residues, surface electrostatic potentials and chemical shift changes. This new DNA-binding motif shares structural homology with T4 RNase H, E. coli endonuclease III and Bacillus subtilis DNA polymerase I. The structural homology suggests a mechanism for substrate recognition by these enzymes.
Human immunodeficiency virus, type 1, (HIV-1) encodes a transactivating regulatory protein, called Tat, which is required for efficient transcription of the viral genome. Tat acts by binding to a specific RNA stem-loop element, called TAR, on nascent viral transcripts. The specificity of binding is principally determined by residues in a short, highly basic domain of Tat. The structure in aqueous solution of a biologically active peptide, comprised of the ten-amino acid HIV-1 Tat basic domain linked to a 15-amino acid segment of the core regulatory domain of another lentiviral Tat, i.e., that from equine infectious anemia virus (EIAV), has been determined. The restraint data set includes interproton distance bounds determined from two-dimensional nuclear Overhauser effect (2D NOE) spectra via a complete relaxation matrix analysis. Thirty structures consistent with the experimental data were generated via the distance geometry program DIANA. Subsequent restrained molecular mechanics calculations were used to define the conformational space subtended by the peptide. A large fraction of the 25-mer peptide assumes a structure in aqueous solution with the lysine- and arginine-rich HIV-1 basic domain being separated from the basic domain by a turn and characterized by a nascent helix as well. The Tat peptide/TAR complex could be modeled with the basic alpha-helix lying in the major groove of TAR such that important interactions of a putative specificity-endowing arginine are maintained and very slight widening of the major groove is entailed.
HL-60 cell lines and AML fresh bone marrow cells were incubated with rhTNF-alpha and rhIFN-gamma in suspension culture system. Then total RNA was prepared for dot blot with 32P nick-translated c-myc DNA probe. The expression changes of c-myc oncogene when the HL-60 cell lines were treated with rhTNF-alpha and IFN-gamma and the AML fresh bone marrow cells treated with rhTNF-alpha alone were observed. The results showed that when the HL-60 cells were treated with 100U/ml or 500U/ml IFN-gamma and 50U/ml rhTNF-alpha for 8 hours, the expression of c-myc oncogene can be inhibited remarkably. The combination of rhIFN-gamma and rhTNF-alpha shows synergistic effect on inhibition of c-myc expression. High expression of c-myc was found in 8 patients with AML; c-myc mRNA level decreased remarkably after treatment of fresh bone marrow cells with 50U/ml rhTNF-alpha for 12 hours in 6 cases, while the remaining 2 cases showed minimal changes. The results demonstrate that rhTNF-alpha have inhibitive effect on c-myc expression in HL-60 cells and AML fresh leukemic cells. It also indicates the possibility of treating AML with low-dose rhTNF-alpha.
The promyelocytic leukemic cell line HL-60 with 20-200U/ml of low-dose rhTNF-a cultured in liquid culture system in vitro was used to observe the effect on HL-60 by TNF. TNF within dose of 50-200 U/ml can induce HL-60 cell differentiation along the monocytic-macrophage pathway, and inhibit HL-60 cell proliferation. The total RNA of HL-60 cell was used to hybrize to v-myc or v-fos probe by dot blot. We detected the expression changes of c-myc or c-fos proto-oncogene by 1-100U/ml of TNF inducing HL-60 cell for 1-12 hours. TNF could regulate the level of c-myc or c-fos mRNA, the transcription of c-myc was inhibited remarkdly, and the expression of c-fos was increased early. The results indicated that TNF in low-dose have effect on inducing HL-60 cell differentiation and regulating expression of multioncogene.
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The clustering of cases of a rare disease is considered. The number of events observed for each unit is assumed to have a Poisson distribution, the mean of which depends upon the population size and the cluster membership of that unit. Here a cluster consists of those units that are homogeneous in their rate of occurrence of the rare events under study. A sample of units is modeled by a mixture of Poisson distributions, one for each cluster, the mixing parameters being the proportions of all units represented by the components of the mixture. Maximum likelihood and Bayes approaches are employed to determine criteria for separating a sample into groups of units with homogeneous rates. A likelihood ratio test for the significance of a two-component mixture is presented as an example. The performance of the criteria is illustrated with data on the spatial occurrence of sudden infant deaths (SIDs) in North Carolina counties over a four-year period. The results suggest that the practice of dividing the counties into high- and low-risk categories on the basis of the ordered rates alone should be questioned. Tests based upon combinatorial methods are also presented to examine the significance of the number of contiguous counties among those with high rates.