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Biomedical subjects

Xin Lu

Publications and source records attributed to Xin Lu.

121 records · Page 7Linked to original sources
PubMed2003

A novel, repeated fed-batch, ethanol production system with extremely long term stability achieved by fully recycling fermented supernatants.

Using Saccharomyces cerevisiae, a novel, repeated fed-batch ethanol production system from corn flour by fully recycling fermented supernatants is demonstrated. With recovery of ethanol by evaporation coupled with consecutive removal of the insoluble and soluble inhibitory substances accumulated, either completely or partially by filtration, the concentrations of the soluble inhibitors in the system could be maintained at their equilibria. As a result, a sustained high concentration of ethanol (up to 15% v/v) and significant pollution control performance were obtained.

Bioreactors↗
PubMed2003

Haplotype information and linkage disequilibrium mapping for single nucleotide polymorphisms.

Single nucleotide polymorphisms in the human genome have become an increasingly popular topic in that their analyses promise to be a key step toward personalized medicine. We investigate two related questions, how much the haplotype information contributes to linkage disequilibrium (LD) mapping and whether an in silico haplotype construction preceding the LD analysis can help. For disease gene mapping, using both simulated and real data sets on cystic fibrosis and the Alzheimer disease, we reached the following conclusions: (1) for simple Mendelian diseases, in which case a tractable full statistical model can be developed, the loss of haplotype information for either control or disease data do not have a great impact on LD fine mapping, and haplotype inference should be carried out jointly with LD mapping; (2) for complex diseases, inferring haplotype phases for individuals prior to LD mapping helps achieve a better accuracy. An improved version of the linkage disequilibrium mapping program, BLADE v2, is available at http://www.fas.harvard.edu/junliu/TechRept/03folder/bladev2.tgz.

Algorithms↗
PubMed2003

[A new culture method for cerebral cortex neurons--application of Sertoli cells].

In the present study, cerebral cortex neurons were cultured with (named as co-culture group) or without (named as control group) Sertoli cells in vitro, in order to examine the trophic effect of Sertoli cells on the neurons. Our results demonstrated that the growth of the neurons and the viability was enhanced significantly. The increases in the cellular area and number of neurite of the neurons were observed (174.85 +/- 105.18 vs 96.59 +/- 41.63, 2.53 +/- 1.79 vs 1.36 +/- 0.54: P < 0.01). Our study suggests neurons culturing with Sertoli cells is a new and convenient method of obtaining a large number of neurons.

Animals↗
PubMed2003

Down-regulation of thiamine transporter THTR2 gene expression in breast cancer and its association with resistance to apoptosis.

The recent molecular identification of two thiamine transporters, SLC19A2 (THTR1) and SLC19A3 (THTR2), has provided the opportunity to study thiamine transporter gene expression in human malignancies. We compared RNA levels of both THTR1 and THTR2 in a panel of human breast tumors and corresponding normal tissues. THTR2 RNA levels were down-regulated in breast cancer to 14% of the level found in corresponding normal tissues, while THTR1 levels were unchanged. Both thiamine transport genes were cloned and expressed in a breast cancer cell line to examine the impact of reconstituted thiamine transport gene expression on drug and radiation sensitivity and on resistance to apoptosis. THTR2-transfected breast cancer cells showed a 2.5-fold increase in specific THTR2 activity and a 3-fold increase in cytotoxicity against a bromoacetyl ester derivative of thiamine. Surprisingly, these cells also showed a 3-fold increase in sensitivity to doxorubicin and an increase in sensitivity to ionizing radiation, but no change in sensitivity to methotrexate or paclitaxel. TUNEL assays demonstrate an increase in apoptosis in THTR2-transfected cells exposed to doxorubicin and radiation, and Western blot analysis suggests that apoptosis associated with these cytotoxic stresses is mediated at least in part by a caspase-3-dependent pathway. Therefore, thiamine transporter THTR2 gene expression is down-regulated in breast cancer, which may contribute to resistance to apoptosis in these tumors.

Apoptosis↗
PubMed2003

[Analysis on patial amino acid sequence of a novel glycoprotein binding to antiherpes simplex virus monoclonal antibody CHA9].

AIM: To acquire the characteristic amino acid sequence of a novel glycoprotein of herpes simplex virus (HSV), so as to localize gene encoding the novel glycoprotein accurately. METHODS: A 12-mer phage peptide library was screened for 3 rounds by using biotinylated mAb CHA9 against new glycoprotein g30k of HSV-2. Positive phage clones were detected by ELISA. 10 positive clones were selected randomly for sequencing. Sequence alignment and hydrophobic cluster analysis were carried out. RESULTS: Most of the sequences of 10 positive phage clones were highly homologous with a core-PH/KHXHXGS-. Phages containing this motif could react specifically with the mAb CHA9 and not cross-react with other IgG. Hydrophobic cluster analysis showed that the peptide was likely to form an epitope. CONCLUSION: We obtained a characteristic short peptide which shows some characters of g30K amino acid sequence. It provides valuable clue for prediction of the open reading frame of g30K gene and will be useful to explore biological characteristics of the new glycoprotein.

Amino Acid Sequence↗
PubMed2002

Organic functionalization of the sidewalls of carbon nanotubes by diels-alder reactions: a theoretical prediction.

[structure: see text] The viability of the Diels-Alder (DA) cycloaddition of conjugated dienes onto the sidewalls of single-wall carbon nanotubes is assessed by means of a two-layered ONIOM(B3LYP/6-31G:AM1) approach. Whereas the DA reaction of 1,3-butadiene on the sidewall of an armchair (5,5) nanotube is found to be unfavorable, the cycloaddition of quinodimethane is predicted to be viable due to the aromaticity stabilization at the corresponding transition states and products.

Journal Article↗
PubMed2002

Pathological shear stress stimulates the tyrosine phosphorylation of alpha-actinin associated with the glycoprotein Ib-IX complex.

Shear-induced platelet responses are triggered by VWF binding to the platelet GpIb-IX complex, and there is evidence that this ligand-receptor coupling stimulates transmembranous signaling through the cytoplasmic tail of glycoprotein (Gp) Ib alpha. To investigate the mechanism by which signaling is effected, new molecular interactions involving GpIb-IX that develop in response to pathological shearing stress were examined in intact human platelets. Exposure to shear, but not alpha-thrombin, results in the co-immunoprecipitation of the actin cross-linking protein alpha-actinin with the GpIb-IX complex. Blockers of VWF binding to GpIb alpha or actin polymerization inhibit the association of alpha-actinin with the GpIb-IX complex, but the association of alpha-actinin with the GpIb-IX complex is not affected by inhibiting VWF binding to platelet integrin alpha IIb beta 3 (GpIIb-IIIa). alpha-Actinin becomes tyrosine phosphorylated in response to pathological shear stress, and phosphorylated alpha-actinin associates with GpIb-IX. In resting platelets, class IA heterodimeric phosphatidylinositol 3-kinase (PI 3-K) and protein kinase N (PKN) associate with nonphosphorylated alpha-actinin. Shear stress causes PI 3-K to disassociate from alpha-actinin, while it stimulates PKN binding to alpha-actinin. These results demonstrate that shear-induced VWF binding to GpIb alpha causes enhanced binding of cytoskeletal alpha-actinin to GpIb-IX and suggest that alpha-actinin, perhaps through tyrosine phosphorylation, serves as an adapter for a signaling complex that could regulate VWF-induced platelet aggregation.

Actinin↗
PubMed2002

A DFT study of the 1,3-dipolar cycloadditions on the C(100)-2 x 1 surface.

The 1,3-dipolar cycloadditions (1,3-DCs) of a series of 1,3-dipolar molecules onto the C(100)-2 x 1 surface have been investigated by means of hybrid density functional B3LYP method in combination with cluster model approach. It was found that 1,3-DCs on the C(100)-2 x 1 surface are more favorable over their molecular analogues both thermodynamically and kinetically. The enhancement of the reactivity on the surface due to the reduced overlap between the p(pi) orbitals of the surface C=C dimer should be important for the semiconductor industry because it might lead to a breakthrough in the fabrication of diamond films at low temperature.

Journal Article↗
PubMed2002

Identification of OCT6 as a novel organic cation transporter preferentially expressed in hematopoietic cells and leukemias.

OBJECTIVE: Human organic cation transporters (OCTs) play a critical role in the cellular uptake and efflux of endogenous cationic substrates and hydrophilic exogenous xenobiotics. We sought to identify OCT genes preferentially expressed in hematopoietic cells. MATERIALS AND METHODS: We isolated a novel OCT, named OCT6, by data-mining human expressed sequence tag databases for sequences homologous to known OCT genes. We developed a quantitative reverse transcriptase polymerase chain reaction assay to determine the relative expression of this gene in 50 cancer cell lines and in tissues. RESULTS: The two highest expressing cell lines were the leukemia cell lines HL-60 and MOLT4. Quantitative reverse transcriptase polymerase chain reaction analysis using a normal tissue cDNA panel demonstrated that this transport gene is highly expressed in testis and fetal liver, with detectable RNA levels in bone marrow and peripheral blood leukocytes. Unlike other OCT genes, RNA levels were not detectable in placenta, liver, or kidney. To further define the expression of OCT6 in hematopoietic tissues, we measured OCT6 RNA levels in sorted peripheral blood cell populations and found a clear enrichment of OCT6-expressing cells in purified CD34(+) cells. To determine if OCT6 was highly expressed in leukemias, we examined circulating leukemia cells from 25 patients and found high levels of OCT6 RNA in all specimens in comparison with liver, kidney, and placenta. CONCLUSIONS: The results demonstrate the existence of a novel OCT preferentially expressed in human hematopoietic tissues, including CD34(+) cells and leukemia cells. Its narrow tissue distribution, potential for substrate specificity, and close homology to other cell membrane transporters make OCT6 an attractive target for the treatment of leukemia.

Amino Acid Sequence↗
PubMed2002

Novel function of the cyclin A binding site of E2F in regulating p53-induced apoptosis in response to DNA damage.

We demonstrate here that the E2F1 induced by DNA damage can bind to and promote the apoptotic function of p53 via the cyclin A binding site of E2F1. This function of E2F1 does not require its DP-1 binding, DNA binding, or transcriptional activity and is independent of mdm2. All the cyclin A binding E2F family members can interact and cooperate with p53 to induce apoptosis. This suggests a novel role for E2F in regulating apoptosis in response to DNA damage. Cyclin A, but not cyclin E, prevents E2F1 from interacting and cooperating with p53 to induce apoptosis. However, in response to DNA damage, cyclin A levels decrease, with a concomitant increase in E2F1-p53 complex formation. These results suggest that the binding of E2F1 to p53 can specifically stimulate the apoptotic function of p53 in response to DNA damage.

Apoptosis↗
PubMedDate not supplied

Mouse extrahepatic hepatoma detected on MicroPET using copper (II)-64 chloride uptake mediated by endogenous mouse copper transporter 1.

PURPOSE: This study was conducted to assess the positron-emitting copper (II)-64 chloride ((64)CuCl(2)) as a probe for imaging mouse extrahepatic hepatoma expressing mouse copper transporter 1 (mCtr1) with positron emission tomography (PET). PROCEDURES: Following the intravenous administration of (64)CuCl(2), athymic mice bearing extrahepatic hepatoma grafts were subjected to whole-body static PET imaging with a Concorde microPET R4 tomograph. Upon completion of the imaging study, immunohistochemistry (IHC) study of mCtr1 was performed with postmortem tissues. RESULTS: The mouse extrahepatic hepatoma grafts were well visualized on static microPET images. Quantitative analysis demonstrated that the tracer concentration in the hepatoma was significantly higher than those in the soft tissue of the right shoulder opposite to the tumor site and the brain (p < 0.001). mCtr1 immunoreactivity in the hepatoma graft was approximately 70% of that in liver, whereas (64)CuCl(2) concentration in the graft was approximately 11% of the liver concentration. CONCLUSIONS: The extrahepatic mouse hepatoma grafts may be visualized by Cu-64 PET, taking advantage of the (64)CuCl(2) uptake mediated by the functional endogenous mCtr1.

Animals↗
PubMedDate not supplied

Correlation of nucleoside and nucleobase transporter gene expression with antimetabolite drug cytotoxicity.

Antimetabolite drugs that inhibit nucleic acid metabolism are widely used in cancer chemotherapy. Nucleoside and nucleobase transporters are important for the cellular uptake of nucleic acids and their corresponding anticancer analogue drugs. Thus, these transporters may play a role both in antimetabolite drug sensitivity, by mediating the uptake of nucleoside analogues, and in antimetabolite drug resistance, by mediating the uptake of endogenous nucleosides that may rescue cells from toxicity. Therefore, we examined the relation of the expression of nucleoside and nucleobase transporters to antimetabolite cytotoxicity. We measured the RNA levels of all eight known nucleoside and nucleobase transporters in 50 cell lines included in the National Cancer Institute's Anticancer Drug Screen panel. RNA levels of concentrative nucleoside transporters (CNTs), equilibrative nucleoside transporters (ENTs) and nucleobase transporters (NCBTs) were determined by quantitative RT-PCR using real-time fluorescence acquisition. This method was validated by measuring the expression of the MDR1 gene, and correlating our results with independently determined measurements of MDR1 RNA levels and protein function in these cell lines. We then correlated the pattern of RNA levels to the pattern of cytotoxicity of anticancer drugs in the NCI drug screen database using the COMPARE analysis. Several hypothesized relations between transporter gene expression and cytotoxicity, based upon known interactions between certain nucleoside analogues and transporter proteins, were not observed, suggesting that expression of individual transporters may not be a significant determinant of the cytotoxicity of these drugs. The most closely correlated drug cytotoxicity patterns to transporter gene expression patterns (where increased expression corresponds to increase sensitivity) included those between CNT1 and O6-methylguanine and between ENT2 and hydroxyurea. We also observed that p53 status influenced correlations between ENT1 transporter gene RNA levels and sensitivity to the drugs tiazafurin, AZQ and 3-deazauridine. One of three drugs identified by correlation of cytotoxicity patterns with ENT1 RNA levels, 3-deazauridine, inhibited uptake of the classic ENT1 substrate uridine, demonstrating a physical interaction between an identified drug and the transporter. These studies demonstrate that it is possible to correlate genetic information to functional databases to determine the influence of transport gene expression on drug sensitivity and to identify transporter-drug interactions.

ATP Binding Cassette Transporter, Subfamily B, Mem↗