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Biomedical subjects

Yi Sun

Publications and source records attributed to Yi Sun.

98 records · Page 6Linked to original sources
PubMed2002

[Sequence variation of the chloroplast gene ndh D region in cytoplasmic male sterile sorghum].

A fragment SAAU-02(700) was amplified specifically from total DNA of seven sorghun varieties with male-fertile cytoplasm (N-cytoplasm). PCR assays indicated that it was amplified from chloroplast (cp) DNA. Sequence analysis revealed this newly cloned fragment contained a portion of chloroplast gene psa C (88 bp) and part of ndh D gene (192 bp). Total DNA, mitochondrial (mt) DNA, and cpDNA were digested with EcoR I + Hind III and probed with fragment SAAU-02(700). The Southern hybridization patterns displayed a 0.74 kb band both in total DNA and cpDNA, but an additional faint band 0.45 kb in size was found only in the latter. No polymorphic hybridization signal between the N-cytoplasm and male-sterile cytoplasm (S-cytoplasm) was observed. Southern hybridization of total DNA of CMS line A1 Tx623 and fertile line Tx623 digested with Hae III gave a band 4.9 kb in size in the former and a 4.45 kb band in the latter. This revealed that the sequence of ndh D from CMS line was likely altered. Further studies designed to determine whether or not the variation has some effect on the metabolism of mitochondria and chloroplast, even on the occurrence of male sterility in sorghum are underway.

Amino Acid Sequence↗
PubMedDate not supplied

Measurements of NO2, SO2, O3, benzene and toluene using differential optical absorption spectroscopy (DOAS) in Shanghai, China.

NO2, SO2, O3, benzene, and toluene were measured in Taopu industry park of Shanghai during the period June to August 2003 by differential optical absorption spectroscopy (DOAS) technique. The daily average concentrations of SO2, NO2, and O3 ranged from 5.7 ppb to 40 ppb, 22 ppb to 123 ppb, and 10.6 ppb to 23 ppb respectively. SO2 and NO2 concentrations were found to depend on wind direction. The diurnal variation of NO2 concentrations had two peaks due to traffic emission. Our DOAS measurements of NO2, SO2 and O3 were compared with the conventional measurement instruments (API automatic monitoring instrument). The concept of a percent difference (PD) and linear regression methods were employed to study the difference between DOAS and API instruments. The correlation analysis between PD values and meteorological parameters and analysis of abnormal higher absolute PD values indicated that the lower visibility induced the bad compatibility between the two systems. The results showed that both systems exhibited strong compatibility with good correlation, therefore the DOAS system is able to provide reliable information on distribution patterns of major air pollutants. Average benzene and toluene concentrations were 1.4 and 8.0 ppb respectively.

Air Pollutants↗
PubMedDate not supplied

Nonlinear prediction of quantitative structure-activity relationships.

Predicting the log of the partition coefficient P is a long-standing benchmark problem in Quantitative Structure-Activity Relationships (QSAR). In this paper we show that a relatively simple molecular representation (using 14 variables) can be combined with leading edge machine learning algorithms to predict logP on new compounds more accurately than existing benchmark algorithms which use complex molecular representations.

Journal Article↗
PubMedDate not supplied

Expression of a fusion protein of human ciliary neurotrophic factor and soluble CNTF-receptor and identification of its activity.

Ciliary neurotrophic factor (CNTF) has pleiotropic actions on many neuronal populations as well as on glia. Signal transduction by CNTF requires that it bind first to CNTF-R, permitting the recruitment of gp130 and LIF-R, forming a tripartite receptor complex. Cells that only express gp130 and LIF-R, but not CNTF-R are refractory to stimulation by CNTF. On many target cells CNTF only acts in the presence of its specific agonistic soluble receptors. We engineered a soluble fusion protein by linking the COOH-terminus of sCNTF-R to the NH2-terminus of CNTF. Recombinant CNTF/sCNTF-R fusion protein (Hyper-CNTF) was successfully expressed in COS-7 cells. The apparent molecular mass of the Hyper-CNTF protein was estimated from western blots to be 75 kDa. Proliferation assays of transfected BAF/3 cells in response to CNTF and Hyper-CNTF were used to verify the activity of the cytokines. The proliferative results confirmed that CNTF required homodimerization of the gp130, CNTF-R and LIF-R receptor subunit whereas Hyper-CNTF required heterodimerization of the gp130 and LIF-R receptor subunit. We concluded that the fusion protein Hyper-CNTF had superagonistic activity on target cells expressing gp130 and LIF-R, but lacking membrane-bound CNTF-R.

Animals↗
PubMedDate not supplied

Global genechip profiling to identify genes responsive to p53-induced growth arrest and apoptosis in human lung carcinoma cells.

To identify critical genes that mediate p53-induced growth arrest and apoptosis at a global level, we profiled a human lung carcinoma cell model in which cells undergo growth arrest and apoptosis in a p53 and DNA damage-dependent manner. Profiling of the Affymetrix human HG-U1333 GeneChip, covering the entire human transcriptome, revealed about 3, 000 unique genes either induced or repressed during p53-induced growth arrest or apoptosis, respectively. A total of 1, 057 genes, including many well-known p53 targets, responded to both conditions. A mini apoptotic protein database was generated from 3, 033 unique apoptosis responsive genes. Analysis of this database yielded 23 proteins with a pro-apoptotic BH3 domain and three with anti-apoptotic BIR2/BIR3 domains, including well-known p53 targets: Bax, Puma, Noxa and survivin. In addition, 14 mitochondrial proteins were identified that contain a pro-apoptotic AVPI-like motif, and 15 proteins were identified that contain a DAVPI-like domain with the potential of being cleaved by caspases during apoptosis to release the AVPI motif. Many of the genes we identified with these domains do contain p53-binding sites either in the promoter or in the first three introns, suggesting a high probability of being direct p53 targets. Pathway analysis revealed that p53 might control the Wnt pathway through transcriptional regulation of some of its components. Thus, global chip profiling coupled with bioinformatics analysis is a powerful tool in identification of genes critical for p53-induced apoptosis. Further characterization of these genes will lead to a better understanding of the mechanism of p53 action and p53 regulation of other signaling pathways. It will also provide novel cancer drug targets for further validation.

Apoptosis↗
PubMedDate not supplied

Mdm2 ligase dead mutants did not act in a dominant negative manner to re-activate p53, but promoted tumor cell growth.

Mdm2 (murine double minute 2) is an oncogene, first identified in BALB/c 3T3 cells. Over-expression and gene amplification of Mdm2 were found in a variety of human cancers. Recently, Mdm2 was found to be an E3 ubiquitin ligase that promotes degradation of p53, which contributes significantly to its oncogenic activity. In this study, we test a hypothesis that Mdm2 ligase dead mutants, which retained p53 binding activity but lost degradation activity, would act in a dominant negative manner to re-activate p53, especially upon stressed conditions. Five Mdm2 constructs expressing wild-type and E3 ligase-dead Mdm2 proteins were generated in a Tet-Off system and transfected into MCF-7 breast cancer cells (p53+/+ with Mdm2 overexpression) as well as MCF10A immortalized breast cells (p53+/+ without Mdm2 overexpression) as a normal control. We found that expression of Mdm2 mutants were tightly regulated by doxycycline. Withdrawal of doxycycline in culture medium triggered overexpression of Mdm2 mutants. However, expression of ligase dead mutants in MCF7 and MCF10A cells did not reactivate p53 as shown by a luciferase-reporter transcription assay and Western blot of p53 and its downstream target p21 under either unstressed condition or after exposure to DNA damaging agents. Biologically, over-expression of Mdm2 mutants had no effect on p53-induced apoptosis following DNA damage. Interestingly, over-expression of Mdm2 mutants promoted growth of MCF7 tumor cells probably via a p53-independent mechanism. Over-expression of Mdm2 mutants, however, had no effect on the growth of normal MCF10A cells and did not cause their transformation. Thus, ligase dead mutants of Mdm2 did not act in a dominant negative manner to reactivate p53 and they are not oncogenes in MCF10A cells.

Apoptosis↗
PubMedDate not supplied

Targeting E3 ubiquitin ligases for cancer therapy.

E3 ubiquitin ligases are a large family of proteins that can be classified into three major structurally distinct types: N-end rule E3s, E3s containing the HECT (Homology to E6AP C-Terminus) domain, and E3s with the RING (Really Interesting New Gene) finger, including its derivatives, the U- Box and the PHD (Plant Homeo-Domain). E3 ubiquitin ligases exist as single polypeptide or multimeric complexes. Together with ubiquitin activating enzyme E1 and ubiquitin conjugating enzyme E2, E3 ubiquitin ligases catalyze the ubiquitination of a variety of protein substrates for targeted degradation via the 26S proteasome. E3 ubiqutin ligases, therefore, play an essential role in regulation of many biological processes. Furthermore, E3s are enzymes that determine the specificity of protein substrates; they represent a class of "drugable" targets for pharmaceutical intervention. In this review, I will mainly focus on E3 ubiquitin ligases as potential cancer targets and discuss three of the most promising E3s, Mdm2/Hdm2, IAPs, and SCF, for their target rationales, target validation, and critical issues associated with them. These E3 ligases or their components are overexpressed in many human cancers and their inhibition leads to growth suppression or apoptosis. In addition, I will evaluate two current methodologies available for the high throughput screening for small molecular weight chemical inhibitors of the E3 ubiquitin ligases. Although targeting E3 ubiquitin ligases is still in its infancy, speedy approval of the general proteasome inhibitor, Velcade (bortezomib) by the FDA for the treatment of relapsed and refractory multiple myeloma suggests the promise of specific E3 inhibitors in anti-cancer therapy. Emerging technologies, such as siRNA, will provide a better validation of many E3s. It is anticipated that E3 ubiquitin ligases will represent an important new target platform for future mechanism-driven drug discovery.

Animals↗