Biomedical subjects

Boqin Qiang

Publications and source records attributed to Boqin Qiang.

11 recordsLinked to original sources

PubMed2003

Translocation and phosphorylation of calcyclin binding protein during retinoic acid-induced neuronal differentiation of neuroblastoma SH-SY5Y cells.

For better understanding of functions of the Calcyclin Binding Protein (CacyBP) and exploring its possible roles in neuronal differentiation, the subcellular localization of human CacyBP was examined in retinoic acid(RA)-induced and uninduced neuroblastoma SH-SY5Y cells. Immunostaining indicated that CacyBP was present in the cytoplasm of uninduced SH-SY5Y cells, in which the resting Ca(2+) concentration was relatively lower than that of RA-induced cells. After the RA induction, immunostaining was seen in both the nucleus and cytoplasm. In the RA-induced differentiated SH-SY5Y cells, CacyBP was phosphorylated on serine residue(s), while it existed in a dephosphorylated form in normal (uninduced) cells. Thus, the phosphorylation of CacyBP occurs when it is translocated to the nuclear region. The translocation of CacyBP during the RA-induced differentiation of SH-SY5Y cells suggested that this protein might play a role in neuronal differentiation.

Active Transport, Cell Nucleus↗

PubMed2003

Extensive association analysis between polymorphisms of PON gene cluster with coronary heart disease in Chinese Han population.

OBJECTIVE: An extensive association analysis of PON gene cluster (PONs) with coronary heart disease (CHD) was performed in Chinese Han population. METHODS AND RESULTS: Thirty polymorphisms of PON1, PON2, and PON3 gene were identified by direct sequencing of genomic DNA derived from 48 randomly selected patients. Twelve polymorphisms were additionally investigated for association with CHD in 474 male patients and 475 controls. Univariate analyses showed the cases had significantly higher frequencies of PON1 192Q allele, 160R allele, -162A allele, and PON2 311C allele than were seen in the controls. Logistic regression analyses revealed only the PON1 R160G and -162G/A polymorphisms remained significantly associated with CHD (P=0.0054 and P=0.0002). Haplotype analyses for various polymorphism combinations additionally confirmed the results of individual polymorphism analyses. Only the frequencies of haplotypes containing -162A allele were significantly higher, whereas only the frequencies of haplotypes containing 160G allele were significantly lower in cases than in controls in various polymorphism combinations. CONCLUSIONS: This extensive association study has identified the PON1 -162G/A and R160G polymorphisms to be independently associated with CHD in Chinese Han population and warrants additional study to elucidate the biological mechanism.

Alleles↗

PubMed2003

Association between genetic variation of CACNA1H and childhood absence epilepsy.

Direct sequencing of exons 3 to 35 and the exon-intron boundaries of the CACNA1H gene was conducted in 118 childhood absence epilepsy patients of Han ethnicity recruited from North China. Sixty-eight variations have been detected in the CACNA1H gene, and, among the variations identified, 12 were missense mutations and only found in 14 of the 118 patients in a heterozygous state, but not in any of 230 unrelated controls. The identified missense mutations occurred in the highly conserved residues of the T-type calcium channel gene. Our results suggest that CACNA1H might be an important susceptibility gene involved in the pathogenesis of childhood absence epilepsy.

Age of Onset↗

PubMed2003

Linkage analysis of 2q14-q23 and 5q32 with blood pressure quantitative traits in Chinese sib pairs.

OBJECTIVES: Several genome-wide scans recently accomplished in the ethnic Chinese revealed a number of candidate loci possibly contributing to essential hypertension, and some appeared to be replicable in 2q14-q23 and 5q32. The current study aimed to examine the linkage of qualitative and blood pressure quantitative traits in essential hypertension with these genomic regions in a large sample of Chinese hypertensive families. METHODS: We performed a genetic analysis on 148 randomly ascertained families containing 328 affected sib pairs, grouped into two geographically distinct subsets. Five highly informative microsatellite markers (D2S151, D2S142, D5S2090, D5S413 and D5S2013) were genotyped, and linkage analyses were performed with different genetic models. RESULTS: We did not observe consistent evidence for excess allele sharing identity by descent in either of the qualitative or the quantitative test. However, higher LOD scores were found at D5S2013 in North Group subset with Haseman-Elston and maximum likelihood (ML) variance (no dominance variance, NDV) algorithms. With the ML (NDV) algorithm, the LOD was 1.410 for diastolic blood pressure at this locus, although this was not statistically significant. CONCLUSIONS: These findings provide no evidence to support a significant linkage of 2q14-q23 or 5q32 with essential hypertension or blood pressure quantitative traits in the ethnic Chinese, and indicate the aetiologic diversity and complexity of hypertension. Previous reports implied 2q14-q23 or beta 2- adrenergic receptor gene potentially linked to essential hypertension in the ethnic Chinese. To replicate these results and perform quantitative linkage analysis, we genotyped members of 148 hypertensive families with five highly informative microsatellite markers. We observed no evidence of excess allele sharing identity by descent in sib pairs, revealing a lack of linkage between 2q14-q23 or 5q32 (chromosome region harboring the gene encoding beta 2 adrenergic receptor) and hypertension in our study sample.

Adult↗

PubMed2003

Variation near the region of the lipoprotein lipase gene and hypertension or blood pressure levels in Chinese.

Essential hypertension (EH) is a common late-onset disease that exhibits complex genetic heterogeneity. Human lipoprotein lipase (LPL) is a rate-limiting enzyme that regulates the catabolism of triglycerides (TG) and chylomicrons (CM). Since dyslipidemia is a common finding in hypertensive patients, the LPL gene is a logical candidate gene that could contribute to the development of hypertension. Using linkage analysis in 148 Chinese hypertensive families, we identified a region of linkage with systolic blood pressure (SBP) and diastolic blood pressure (DBP) that consisted of a 10.6-cM interval defined by markers D8S1145, D8S261, and D8S282 on chromosome 8, which maps between 31 to 41.6 cM from the 8p-telomere contained LPL gene, with statistically significant p values for the marker D8S261 (p = 0.0021 for SBP, and p = 0.0395 for DBP). In the qualitative-trait linkage analysis, evidence for linkage between the marker D8S1145 and EH was found (p = 0.0286). The transmission/disequilibrium test (TDT/S-TDT) also supported a significant linkage-disequilibrium of the allele 3 of D8S261 with EH (chi2 = 8.643, p < 0.01). Furthermore, the marker neurofilament light polypeptide (NEFL) (11 cM centromeric to the LPL gene) appeared to be in linkage with SBP and DBP (p = 0.0329 for SBP; p = 0.0319 for DBP). Additionally, two flanking markers for LPL, D8S511 (9.5 cM telomeric to the LPL gene) and D8S560 (3.2 cM centromeric to the LPL gene), also showed significant linkage with EH (p = 0.0036 for D8S511; p = 0.0115 for D8S560). Previous knowledge about the physiological involvement of LPL in blood pressure regulation and the present findings of variation near the LPL gene support the proposition that a region near the LPL gene or the LPL gene itself might contribute to the individual blood pressure variation in Chinese.

Adult↗

PubMed2002

Expression, crystallization and preliminary X-ray studies of the recombinant PTB domain of human dok-5 protein.

The human dok-5 PTB domain fusion protein has been overexpressed in Escherichia coli and crystallized in a form suitable for X-ray crystallographic study. Crystals were obtained by the vapour-diffusion method. The crystal has unit-cell parameters a = b = 75.9, c = 108.0 A, alpha = beta = 90, gamma = 120 degrees and belongs to space group P3(2)21. Diffraction data were collected to 2.8 A resolution in-house. Furthermore, a selenomethionine (SeMet) derivative of dok-5 PTB domain fusion protein was overexpressed using the same expression system and was purified in a reductive environment. The derivative crystals were obtained under similar conditions. Subsequently, three different wavelength data sets were collected to 2.3 A resolution from the derivative crystal at the Advanced Photon Source, Argonne National Laboratory.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Gene expression profiling in developing human hippocampus.

The gene expression profile of developing human hippocampus is of particular interest and importance to neurobiologists devoted to development of the human brain and related diseases. To gain further molecular insight into the developmental and functional characteristics, we analyzed the expression profile of active genes in developing human hippocampus. Expressed sequence tags (ESTs) were selected by sequencing randomly selected clones from an original 3'-directed cDNA library of 150-day human fetal hippocampus, and a digital expression profile of 946 known genes that could be divided into 16 categories was generated. We also used for comparison 14 other expression profiles of related human neural cells/tissues, including human adult hippocampus. To yield more confidence regarding differential expression, a method was applied to attach normalized expression data to genes with a low false-positive rate (<0.05). Finally, hierarchical cluster analysis was used to exhibit related gene expression patterns. Our results are in accordance with anatomical and physiological observations made during the developmental process of the human hippocampus. Furthermore, some novel findings appeared to be unique to our results. The abundant expression of genes for cell surface components and disease-related genes drew our attention. Twenty-four genes are significantly different from adult, and 13 genes might be developing hippocampus-specific candidate genes, including wnt2b and some Alzheimer's disease-related genes. Our results could provide useful information on the ontogeny, development, and function of cells in the human hippocampus at the molecular level and underscore the utility of large-scale, parallel gene expression analyses in the study of complex biological phenomena.

Adult↗

PubMed2002

Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157.

We have sequenced the genome of Shigella flexneri serotype 2a, the most prevalent species and serotype that causes bacillary dysentery or shigellosis in man. The whole genome is composed of a 4 607 203 bp chromosome and a 221 618 bp virulence plasmid, designated pCP301. While the plasmid shows minor divergence from that sequenced in serotype 5a, striking characteristics of the chromosome have been revealed. The S.flexneri chromosome has, astonishingly, 314 IS elements, more than 7-fold over those possessed by its close relatives, the non-pathogenic K12 strain and enterohemorrhagic O157:H7 strain of Escherichia coli. There are 13 translocations and inversions compared with the E.coli sequences, all involve a segment larger than 5 kb, and most are associated with deletions or acquired DNA sequences, of which several are likely to be bacteriophage-transmitted pathogenicity islands. Furthermore, S.flexneri, resembling another human-restricted enteric pathogen, Salmonella typhi, also has hundreds of pseudogenes compared with the E.coli strains. All of these could be subjected to investigations towards novel preventative and treatment strategies against shigellosis.

Amino Acid Sequence↗

PubMed2002

cDNA cloning, chromosomal localization and expression pattern analysis of human LIM-homeobox gene LHX4.

LHX4 gene is a member of the LIM-homeobox gene family and plays a critical role in the development of motor neurons. We have isolated a cDNA of human LHX4 from a library of the adult human spinal cord. Its sequence is 92% homologous to that of the mouse Lhx4. The genomic structure of the LHX4 gene and its chromosomal localization were determined. The gene was mapped on human chromosome 1q 24.1-1q 24.3 and composed of six exons. The homeodomain was encoded by two exons, exons 4 and 5. The first LIM domain was coded by exon 2, and the second by exon 3. Human MTE Array was used to study the expression profile of LHX4 in 72 human tissues. The expression was specific in the CNS including the fetal brain, the spinal cord, and the cerebral cortex. In situ hybridization of the adult rodent CNS showed the abundant expression of LHX4 in the cerebral cortex and motor neurons of the spinal cord. Our results suggest that LHX4 may play a role in the CNS, especially the neocortex and the spinal cord, and provide a basis to investigate potential involvement of the LHX4 gene in human diseases.

Animals↗

PubMed2002

Crystal structure of the catalytic domain of a human thioredoxin-like protein.

Thioredoxin is a ubiquitous dithiol oxidoreductase found in many organisms and involved in numerous biochemical processes. Human thioredoxin-like protein (hTRXL) is differentially expressed at different development stages of human fetal cerebrum and belongs to an expanding family of thioredoxins. We have solved the crystal structure of the recombinant N-terminal catalytic domain (hTRXL-N) of hTRXL in its oxidized form at 2.2-A resolution. Although this domain shares a similar three-dimensional structure with human thioredoxin (hTRX), a unique feature of hTRXL-N is the large number of positively charged residues distributed around the active site, which has been implicated in substrate specificity. Furthermore, the hTRXL-N crystal structure is monomeric while hTRX is dimeric in its four crystal structures (reduced, oxidized, C73S and C32S/C35S mutants) reported to date. As dimerization is the key regulatory factor in hTRX, the positive charge and lack of dimer formation of hTRXL-N suggest that it could interact with the acidic amino-acid rich C-terminal region, thereby suggesting a novel regulation mechanism.

Catalytic Domain↗

PubMed2002

Cloning and characterization of human ubiquitin binding enzyme 2 cDNA.

OBJECTIVE: To clone and identify the gene encoding human ubiquitin binding enzyme 2 and study its expression pattern. METHODS: According to the sequence of human EST, which is highly homologous to the mouse ubiquitin binding/conjugating enzyme (E2), primers were synthesized to screen the human fetal brain cDNA library. The gene was analyzed by bioinformatics technique and its expression pattern was studied by using multiple-tissue Northern blot. RESULTS: Two cDNA clones encoding human ubiquitin conjugating enzyme have been isolated and identified. Both containing the ubiquitin conjugating domain, the 2 cDNA clones are 88% identical in amino acid sequences and splicing isoforms to each other only with an exon excised to form the short sequence. They belong to a highly conserved and widely expressed E2 enzyme family. Northern blot shows that they are expressed exclusively in adult human heart, placenta, and pancreas but no transcripts can be detected in brain, lung, liver, skeletal muscle or kidney. CONCLUSIONS: The gene encoding human ubiquitin binding enzyme is expressed under temporal control. As a key enzyme in the degradation of proteins, ubiquitin conjugating enzymes play a central role in the expression regulation on the level of post-translation.

Amino Acid Sequence↗