Biomedical subjects

Lili Wang

Publications and source records attributed to Lili Wang.

At least 37 records · Page 2Linked to original sources

PubMed2006

Differential glycosylation of rhLf expressed in the mammary gland of transgenic mice.

Differential glycosylation of natural hLf and rhLf from hLf-transgenic mice, which harbored a 146 Kb BAC insert that includes the intact hLf gene sequence, was studied in the present report. There were significant differences between the immunoblotting results of rhLf and natural hLf, which were denatured with nonreducing SDS sample buffer. The differences disappeared after rhLf and natural hLf samples were digested with N-glycosidase F, respectively. The results showed that there were significant differences (P<0.01) between the glycosylation of natural hLf and rhLf that were purified, respectively, from milk samples of seven hLf-transgenic mouse lines.

Animals↗

PubMed2006

Family-based association analysis validates chromosome 3p21 as a putative nasopharyngeal carcinoma susceptibility locus.

PURPOSE: Nasopharyngeal carcinoma (NPC) poses one of the serious health problems in southern Chinese, with an incidence rate ranging from 15 to 50/100,000. In our previously linkage analysis, a locus on 3p21 was identified to link to NPC. In this study, family-based association analysis was performed to test the transmission disequilibrium of chromosome 3p in 18 high-risk nasopharyngeal carcinoma families of Hunan province in southern China. METHODS: Single locus and multi-point of transmission disequilibrium test was performed by Genehunter program package with 15 microsatellite markers on chromosome 3p in 18 nasopharyngeal carcinoma pedigrees. RESULTS: A major transmission disequilibrium peak was observed near D3S1568, which possessed 20 alleles or haplotypes of 6 loci, spanning a 12.4 cM region from D3S1298 to D3S1289 on chromosome 3p21.31-3p21.2, and 3 alleles or haplotypes reached high significantly difference (P < 0.01). CONCLUSION: These results reflected a link disequilibrium between this chromosome region and a nasopharyngeal carcinoma susceptibility locus, and provided further evidence that a novel nasopharyngeal carcinoma susceptibility gene may be located in this chromosome region. These alleles or haplotypes transmitting disequilibrium in nasopharyngeal carcinoma pedigrees may act as the highly risk molecular markers after verified in large population.

Alleles↗

PubMed2006

Cholesterol distribution, not total levels, correlate with altered amyloid precursor protein processing in statin-treated mice.

There are now a number of studies that suggest that cholesterol might regulate the processing of the amyloid precursor protein to form the neurotoxic peptide Abeta. This research has opened the possibility that cholesterol-lowering drugs might be efficacious as anti-Abeta drugs for use in Alzheimer's disease. The use of HMG-CoA reductase inhibitors (commonly called statins) in vitro and in vivo has proven them to be Abeta-lowering agents, however, the mechanism of action of these drugs is not yet known. One possible mechanism is that they reduce Abeta levels indirectly by reducing cholesterol in the central nervous system (CNS). In this study, we administered three different statins (simvastatin, lovastatin, and atorvastatin) to nontransgenic mice. We found that all three compounds had similar effects on Abeta, reducing both Abeta40 and Abeta42. The statins decreased beta-cleaved C-terminal fragment (CTF) although having no effect on alpha-CTF levels. However, the drugs did not have a similar effect on cholesterol in the CNS. Only lovastatin significantly reduced total cholesterol in isolated plasma membranes. As cholesterol is not distributed evenly in the plasma membrane, we examined bilayer distribution of cholesterol and found that all three statins caused CNS cholesterol to translocate from the cytofacial leaflet to the exofacial leaflet. This data suggests that cholesterol distribution and not total cholesterol levels may be important to Abeta production in the CNS.

Amyloid beta-Peptides↗

PubMed2006

Fate of centrosomes following somatic cell nuclear transfer (SCNT) in bovine oocytes.

Cloning mammalians by somatic cell nuclear transfer (SCNT) remains inefficient. A majority of clones produced by SCNT fail to develop properly and of those which do survive, some exhibit early aging, premature death, tumors, and other pathologies associated with aneuploidy. Alterations of centrosomes are linked to aberrant cell cycle progression, aneuploidy, and tumorigenesis in many cell types. It remains to be determined how centrosomes are remodeled in cloned bovine embryos. We show that abnormalities in either distribution and/or number of centrosomes were evident in approximately 50% of reconstructed embryos following SCNT. Moreover, centrosome abnormalities and failed 'pronuclear' migration which manifested during the first cell cycle coincided with errors in spindle morphogenesis, chromosome alignment, and cytokinesis. By contrast, nuclear mitotic apparatus protein (NuMA) exhibited normal expression patterns at metaphase spindle poles and in 'pronucleus' during interphase. The defects in centrosome remodeling and 'pronuclear' migration could lead to chromosome instability and developmental failures associated with embryo production by SCNT. Addressing these fundamental problems may enhance production of normal clones.

Animals↗

PubMed2006

Streptococcus suis sequence type 7 outbreak, Sichuan, China.

An outbreak of Streptococcus suis serotype 2 emerged in the summer of 2005 in Sichuan Province, and sporadic infections occurred in 4 additional provinces of China. In total, 99 S. suis strains were isolated and analyzed in this study: 88 isolates from human patients and 11 from diseased pigs. We defined 98 of 99 isolates as pulse type I by using pulsed-field gel electrophoresis analysis of SmaI-digested chromosomal DNA. Furthermore, multilocus sequence typing classified 97 of 98 members of the pulse type I in the same sequence type (ST), ST-7. Isolates of ST-7 were more toxic to peripheral blood mononuclear cells than ST-1 strains. S. suis ST-7, the causative agent, was a single-locus variant of ST-1 with increased virulence. These findings strongly suggest that ST-7 is an emerging, highly virulent S. suis clone that caused the largest S. suis outbreak ever described.

Animals↗

PubMed2006

Vignettes: Diverse library staff offering diverse bioinformatics services.

OBJECTIVES: The paper gives examples of the bioinformatics services provided in a variety of different libraries by librarians with a broad range of educational background and training. METHODS: Two investigators sent an email inquiry to attendees of the "National Center for Biotechnology Information's (NCBI) Introduction to Molecular Biology Information Resources" or "NCBI Advanced Workshop for Bioinformatics Information Specialists (NAWBIS)" courses. The thirty-five-item questionnaire addressed areas such as educational background, library setting, types and numbers of users served, and bioinformatics training and support services provided. Answers were compiled into program vignettes. DISCUSSION: The bioinformatics support services addressed in the paper are based in libraries with academic and clinical settings. Services have been established through different means: in collaboration with biology faculty as part of formal courses, through teaching workshops in the library, through one-on-one consultations, and by other methods. Librarians with backgrounds from art history to doctoral degrees in genetics have worked to establish these programs. CONCLUSION: Successful bioinformatics support programs can be established in libraries in a variety of different settings and by staff with a variety of different backgrounds and approaches.

Computational Biology↗

PubMed2006

[Determination of puerarin in Kangshen granule by reversed-phase high performance liquid chromatography].

Kangshen granule, containing 12 kinds of traditional Chinese medicine, has complex composition. A new method for the determination of puerarin in Kangshen granule was developed using reversed-phase high performance liquid chromatography coupled with matrix assisted laser desorption ionization time of flight mass spectrometry and ultraviolet detection (RP-HPLC/MALDI-TOF MS/UV). The sample was separated by RP-HPLC with a non-linear gradient elution, and then was qualitatively detected by mass spectrometry to identify the puerarin peak. The chromatographic process was performed on a YMC-ODS column under the optimized conditions with a mobile phase consisting of methanol, water and 0.1% TFA, and detected at 250 nm. The linear range of puerarin was from 0. 132 to 1.32 microg (r = 0.9997). The recovery was higher than 103% and the relative standard deviation was lower than 2.0% (n=6). The puerarin content in Kangshen granule sample was determined and the puerarin content was 3.09 mg/g. The method is simple and feasible for the determination of puerarin with a good repeatability. The method can be used for quality control of Kangshen granule.

Chromatography, High Pressure Liquid↗

PubMed2006

[The temperature control for cancer thermotherapy using interstitial microwave antenna].

The basic objective of microwave hyperthermia is to raise the temperature in the tumor tissue without overheating point for a long time. It's difficult to achieve uniform temperature distribution using the continuous heating without changing the antenna shape and inserting position. In this paper, the interstitial antenna worked in the frequency of 2450 MHz inserted into an infinite muscle model is studied. The Finite Difference Time Domoin (FDTD) method was used to calculate the electromagnetic field, while the finite difference method (FDM) was used to analyze the temperature distribution in tumor tissue. The simulation results show that the long-time evenly heating can be achieved by using the alternately heating process and the treatment area can be changed by adjusting input power.

Electromagnetic Phenomena↗

PubMed2005

Organ messenger ribonucleic acid and plasma proteome changes in the adjuvant-induced arthritis model: responses to disease induction and therapy with the estrogen receptor-beta selective agonist ERB-041.

Two receptors [estrogen receptor (ER)alpha and ERbeta] mediate the manifold effects of estrogens throughout the body. Although a clear role has been established for ERalpha in the classical effects of estrogen activity, the physiological role of ERbeta is less well understood. A small-molecule ERbeta selective agonist, ERB-041, has potent antiinflammatory activity in the Lewis rat model of adjuvant-induced arthritis. To characterize the response of target organs and pathways responsible for this antiinflammatory effect, mRNA expression profiling of the spleen, lymph node, and liver was performed, in conjunction with a global analysis of the plasma proteome. We find that the expression of a large number of genes and proteins are altered in the disease model and the majority of these are partially or fully reversed by ERB-041 treatment. Regulated pathways include the acute-phase response, eicosanoid synthesis, fatty acid metabolism, and iron metabolism. In addition, many of the regulated genes and proteins are known to be dysregulated in human rheumatoid arthritis, providing further evidence that the manifestations of the Lewis rat adjuvant-induced arthritis model bear similarity to the human disease.

Animals↗

PubMed2005

The positional effect of Ebeta on Vbeta genes of TCRbeta chain in the ordered rearrangement and allelic exclusion.

In the TCRbeta gene locus, the Vbeta, Dbeta and Jbeta gene segments are assembled in a tightly ordered manner. To investigate the positional effects of TCRbeta enhancer (Ebeta) on the recombination processes of the Vbeta genes, we utilized beta(LD) mice lacking 70% of the TCRbeta locus, leaving four Vbeta genes at the 5' side and, consequently, the Vbeta10 gene moves into the Ebeta regulatory region. In this mutant mouse, the Vbeta10 gene showed direct Vbeta-to-Dbeta and Vbeta-to-Jbeta recombination, although the Dbeta-to-Jbeta joining was still predominant. Interestingly, these two aberrant recombination processes were barely suppressed when beta(LD) mice were crossed with TCRbeta transgenic mice, whereas V(D)J recombination of the Vbeta10 gene was sufficiently suppressed. These results suggest that the positional effects of Ebeta on the Vbeta genes may enable the recombination potential to increase prior to Dbeta-to-Jbeta joining and that such aberrant recombination may be free from allelic suppression.

Animals↗

PubMed2005

Biology of AAV serotype vectors in liver-directed gene transfer to nonhuman primates.

Vectors based on adeno-associated viruses (AAVs) show promise for the treatment of genetic diseases. This study evaluates the biology of AAV-mediated gene transfer to liver in nonhuman primates (NHPs) using vectors based on AAV serotypes 2, 7, and 8. Transgenes encoding self-proteins were selected to minimize the confounding development of transgene-specific immune responses. These included the beta subunit of choriogonadotropic hormone (bCG) and erythropoietin (Epo), both derived from cDNAs from rhesus macaques. Experiments were performed with bCG in rhesus macaques and Epo in cynomolgus macaques. We demonstrated the previously untested hypothesis that preexisting immunity to a natural infection does substantially diminish the efficacy of gene transfer with a vector derived from an endogenous virus. Route of vector administration clearly has an impact on the development of immune responses to self-antigens. In general, efficiency of gene transfer to liver with AAV7 and 8 vectors was higher than what was achieved with AAV2, although a variety of host factors may influence this important parameter, such as preexisting immunity, gender, and transgene immunity.

Animals↗

PubMed2005

Schizosaccharomyces pombe adenylate cyclase suppressor mutations suggest a role for cAMP phosphodiesterase regulation in feedback control of glucose/cAMP signaling.

Mutations affecting the Schizosaccharomyces pombe cAMP phosphodiesterase (PDE) gene cgs2+ were identified in a screen for suppressors of mutant alleles of the adenylate cyclase gene (git2+/cyr1+), which encode catalytically active forms of the enzyme that cannot be stimulated by extracellular glucose signaling. These mutations suppress both the git2(-) mutant alleles used in the suppressor selection and mutations in git1+, git3+, git5+, git7+, git10+, and git11+, which are all required for adenylate cyclase activation. Notably, these cgs2 mutant alleles fail to suppress mutations in gpa2+, which encodes the Galpha subunit of a heterotrimeric G protein required for adenylate cyclase activation, although the previously identified cgs2-2 allele does suppress loss of gpa2+. Further analysis of the cgs2-s1 allele reveals a synthetic interaction with the gpa2(R176H)-activated allele, with respect to derepression of fbp1-lacZ transcription in glucose-starved cells. In addition, direct measurements of cAMP levels show that cgs2-s1 cells maintain normal basal cAMP levels, but are severely defective in feedback regulation upon glucose detection. These results suggest that PDE activity in S. pombe may be coordinately regulated with adenylate cyclase activity as part of the feedback regulation mechanism to limit the cAMP response to glucose detection.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2005

A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays.

We have developed a robust algorithm for copy number analysis of the human genome using high-density oligonucleotide microarrays containing 116,204 single-nucleotide polymorphisms. The advantages of this algorithm include the improvement of signal-to-noise (S/N) ratios and the use of an optimized reference. The raw S/N ratios were improved by accounting for the length and GC content of the PCR products using quadratic regressions. The use of constitutional DNA, when available, gives the lowest SD values (0.16 +/- 0.03) and also enables allele-based copy number detection in cancer genomes, which can unmask otherwise concealed allelic imbalances. In the absence of constitutional DNA, optimized selection of multiple normal references with the highest S/N ratios, in combination with the data regressions, dramatically improves SD values from 0.67 +/- 0.12 to 0.18 +/- 0.03. These improvements allow for highly reliable comparison of data across different experimental conditions, detection of allele-based copy number changes, and more accurate estimations of the range and magnitude of copy number aberrations. This algorithm has been implemented in a software package called Copy Number Analyzer for Affymetrix GeneChip Mapping 100K arrays (CNAG). Overall, these enhancements make CNAG a useful tool for high-resolution detection of copy number alterations which can help in the understanding of the pathogenesis of cancers and other diseases as well as in exploring the complexities of the human genome.

Algorithms↗

PubMed2005

Expression and functional characterization of LRRC4, a novel brain-specific member of the LRR superfamily.

LRRC4, a novel member of LRR superfamily thought to be involved in development and tumorigenesis of the nervous tissue, has the potential to suppress tumorigenesis and cell proliferation of U251MG cells. This study aimed at revealing the correlation between expression of LRRC4 and the maintenance of normal function and tumorigenesis suppression within the central nervous system. We systematically analyzed the expression and tissue distributions of the gene in tissues. Results showed that LRRC4 expression was limited to normal adult brain, both in human and in mouse, and exhibited a development-regulated pattern, but was down-regulated in brain tumor tissues and U251MG cell line. Furthermore, dynamic alterations in gene expression associated with cell cycle progression were investigated by using Tet-on system. Results showed that LRRC4 induced a cell cycle delay at the late G1 phase, probably through the alteration of the expression of different cell cycle regulating proteins responsible for mediating G1-S progression, such as p21(Waf1/Cip1) and p27(Kip1), Cdk2 and PCNA, p-ERK1/2. These findings suggest that LRRC4 may play an important role in maintaining normal function and suppressing tumorigenesis in the central nervous system.

Animals↗

PubMed2005

Synthesis and biological activity of nitronyl nitroxide containing peptides.

[1-(1',3'-Dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetic acid (4), a nitronyl nitroxide, and its peptide derivatives, N-[1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetyl-ARPAK (9a), -GRPAK (9b), and -QRPAK (9c), were synthesized and characterized. Judging from the results of electron spin resonance analysis, the newly synthesized nitronyl nitroxide containing peptides, 9a, 9b, and 9c, demonstrated the characteristics of free radicals. The free radical scavenging activities of 9a, 9b, and 9c were assessed using in vitro free radical scavenging tests. The thrombolysis effect of 9a, 9b, and 9cwas evaluated using an euglobulin clot lysis test, a fibrinolytic lysis test, and in vivo thrombolysis tests. Results indicated that these nitronyl nitroxide containing peptides possessed both free radical scavenging activity and thrombolytic activity.

Amino Acid Sequence↗

PubMed2005

T-cell specific enhancement of histone H3 acetylation in 5' flanking region of the IL-2 gene.

The IL-2 gene expression is highly T-cell specific in an activation-dependent manner. However, little is known about how T-cell specific expression is regulated, although related transcription factors have been identified. To address this issue, we examined the chromatin structure change of the IL-2 gene by analyzing histone acetylation status in the upstream of IL-2 gene transcription initiation site. Interestingly, the histone acetylation level was found to be higher in various sites on the widespread upstream region in resting T-cells than resting B-cells. After T-cell stimulation with PMA and ionomycin, the same regions were further acetylated on histone H3. Particularly, the distal enhancer region showed prompt enhancement of histone acetylation, followed by the IL-2 mRNA expression. These results suggest that the 5' flanking region including the distal enhancer region of the IL-2 gene is already accessible in T cells with constitutive acetylation of histone H3,which may serve for T-cell specific IL-2 expression.

5' Flanking Region↗

PubMed2005

Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo.

Neurofibrillary tangles composed of hyperphosphorylated, aggregated tau are a common pathological feature of tauopathies, including Alzheimer's disease. Abnormal phosphorylation of tau by kinases or phosphatases has been proposed as a pathogenic mechanism in tangle formation. To investigate whether kinase inhibition can reduce tauopathy and the degeneration associated with it in vivo, transgenic mice overexpressing mutant human tau were treated with the glycogen synthase kinase-3 (GSK-3) inhibitor lithium chloride. Treatment resulted in significant inhibition of GSK-3 activity. Lithium administration also resulted in significantly lower levels of phosphorylation at several epitopes of tau known to be hyperphosphorylated in Alzheimer's disease and significantly reduced levels of aggregated, insoluble tau. Administration of a second GSK-3 inhibitor also correlated with reduced insoluble tau levels, supporting the idea that lithium exerts its effect through GSK-3 inhibition. Levels of aggregated tau correlated strongly with degree of axonal degeneration, and lithium-chloride-treated mice showed less degeneration if administration was started during early stages of tangle development. These results support the idea that kinases are involved in tauopathy progression and that kinase inhibitors may be effective therapeutically.

Animals↗

PubMed2005

NGX6 gene inhibits cell proliferation and plays a negative role in EGFR pathway in nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC) is a common cancer in South China but is rare in other parts of the world. A novel NPC-related gene was isolated by location candidate cloning strategy, whose expression was down-regulated in NPC. This gene was designated human NGX6 (Genbank accession AF188239) and encoded a predicted protein of 338 amino acids that harbors an EGF-like domain. The effects of NGX6 on cells from human NPC cell line HNE1 were investigated. The cells transfected with NGX6 had a markedly high expression of NGX6, leading to significant decrease in cell proliferation and the capability to form colonies in soft agar, delaying the G0-G1 cell cycle progression. Flow cytometry assay indicated that the expression of cyclin D1 significantly decreased in NGX6-transfected HNE1 cells as well as cyclin A and E. There was a delay in tumor formation and a dramatic reduction in tumor size when cells transfected with NGX6 were injected into nude mice. In another way, we found NGX6 played a negative role in EGFR Ras/Mek/MAPK pathway. We propose that NGX6, as an EGF-like domain gene, could delay cell cycle G0-G1 progression and thus inhibit cell proliferation by negatively regulating EGFR pathway in NPC cells and down-regulating the expression of cyclin D1 and E.

Animals↗