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Li Jin

Publications and source records attributed to Li Jin.

At least 55 records · Page 3Linked to original sources
PubMed2005

Accelerated evolution of the pituitary adenylate cyclase-activating polypeptide precursor gene during human origin.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide abundantly expressed in the central nervous system and involved in regulating neurogenesis and neuronal signal transduction. The amino acid sequence of PACAP is extremely conserved across vertebrate species, indicating a strong functional constraint during the course of evolution. However, through comparative sequence analysis, we demonstrated that the PACAP precursor gene underwent an accelerated evolution in the human lineage since the divergence from chimpanzees, and the amino acid substitution rate in humans is at least seven times faster than that in other mammal species resulting from strong Darwinian positive selection. Eleven human-specific amino acid changes were identified in the PACAP precursors, which are conserved from murine to African apes. Protein structural analysis suggested that a putative novel neuropeptide might have originated during human evolution and functioned in the human brain. Our data suggested that the PACAP precursor gene underwent adaptive changes during human origin and may have contributed to the formation of human cognition.

Amino Acid Motifs↗
PubMed2005

Identification of mouse SLC39A8 as the transporter responsible for cadmium-induced toxicity in the testis.

Testicular necrosis is a sensitive endpoint for cadmium (Cd(2+), Cd) toxicity across all species tested. Resistance to Cd-induced testicular damage is a recessive trait assigned to the Cdm locus on mouse chromosome 3. We first narrowed the Cdm-gene-containing region to 880 kb. SNP analysis of this region from two sensitive and two resistant inbred strains demonstrated a 400-kb haplotype block consistent with the Cd-induced toxicity phenotype; in this region is the Slc39a8 gene encoding a member of the solute-carrier superfamily. Slc39a8 encodes SLC39A8 (ZIP8), whose homologs in plant and yeast are putative zinc transporters. We show here that ZRT-, IRT-like protein (ZIP)8 expression in cultured mouse fetal fibroblasts leads to a >10-fold increase in the rate of intracellular Cd influx and accumulation and 30-fold increase in sensitivity to Cd-induced cell death. The complete ZIP8 mRNA and intron-exon splice junctions have no nucleotide differences between two sensitive and two resistant strains of mice; by using situ hybridization, we found that ZIP8 mRNA is prominent in the vascular endothelial cells of the testis of the sensitive strains of mice but absent in these cells of resistant strains. Slc39a8 is therefore the Cdm gene, defining sensitivity to Cd toxicity specifically in vascular endothelial cells of the testis.

Alternative Splicing↗
PubMed2005

The involvement of survival signaling pathways in rubella-virus induced apoptosis.

Rubella virus (RV) causes severe congenital defects when acquired during the first trimester of pregnancy. RV cytopathic effect has been shown to be due to caspase-dependent apoptosis in a number of susceptible cell lines, and it has been suggested that this apoptotic induction could be a causal factor in the development of such defects. Often the outcome of apoptotic stimuli is dependent on apoptotic, proliferative and survival signaling mechanisms in the cell. Therefore we investigated the role of phosphoinositide 3-kinase (PI3K)-Akt survival signaling and Ras-Raf-MEK-ERK proliferative signaling during RV-induced apoptosis in RK13 cells. Increasing levels of phosphorylated ERK, Akt and GSK3beta were detected from 24-96 hours post-infection, concomitant with RV-induced apoptotic signals. Inhibition of PI3K-Akt signaling reduced cell viability, and increased the speed and magnitude of RV-induced apoptosis, suggesting that this pathway contributes to cell survival during RV infection. In contrast, inhibition of the Ras-Raf-MEK-ERK pathway impaired RV replication and growth and reduced RV-induced apoptosis, suggesting that the normal cellular growth is required for efficient virus production.

Animals↗
PubMed2005

A locus on chromosome 9p predisposes to a specific disease manifestation, acute anterior uveitis, in ankylosing spondylitis, a genetically complex, multisystem, inflammatory disease.

OBJECTIVE: Uveitis or intraocular inflammation is a major cause of visual loss. Acute anterior uveitis (AAU) affects approximately 40% of patients with ankylosing spondylitis (AS) but also affects patients with no evidence of spondylarthritis. We sought to determine whether a unique genetic region could be implicated in a specific manifestation-AAU-of a multisystem, inflammatory, genetically complex disease, AS. METHODS: Individuals from families multiplex for AAU were genotyped at 400 markers representing the ABI PRISM linkage map MD-10, and at the HLA-B, DRB1, DQA1, DQB1, and DPB1 alleles. Among the family members with AAU, 76 affected sibpairs were analyzed (6 without concomitant AS, 12 discordant for AS, and 58 concordant for AS). Two-point and multipoint nonparametric linkage analyses were performed, and 1-parameter allele-sharing model logarithm of odds (LOD) scores were determined. RESULTS: As previously reported for AS, linkage at the major histocompatibility complex region (chromosome 6p21) was evident, exhibiting the highest multipoint LOD score (4.96 at marker HLA-B). Strong linkage was seen at a region on chromosome 9p21-9p24, with a LOD score of 3.72 at marker D9S157. When compared with a companion cohort of AS families, the linkage at this region was found in association with AAU but not with AS. A third region on chromosome 1q23-1q31 was observed to have suggestive linkage (LOD 2.05 at marker D1S238), which overlaps with a region associated with AS. CONCLUSION: This is the first study in which a genetic region for AAU has been identified by genome-wide scan. Even though AS was highly prevalent in this cohort of families, a locus at chromosome 9p21-9p24 was identified that uniquely associates with AAU. Identifying the genetic perturbation at this region may advance our understanding of the mechanisms involved in tissue-specific pathology of complex inflammatory diseases.

Acute Disease↗
PubMed2005

Classification analysis of the transcriptosome of nonlesional cultured dermal fibroblasts from systemic sclerosis patients with early disease.

OBJECTIVE: To compare the transcriptosome of early-passage nonlesional dermal fibroblasts from systemic sclerosis (SSc) patients with diffuse disease and matched normal controls in order to gain further understanding of the gene activation patterns that occur in early disease. METHODS: Total RNA was isolated from early-passage fibroblasts obtained from nonlesional skin biopsy specimens from 21 patients with diffuse SSc (disease duration <5 years in all but 1) and 18 healthy controls who were matched to the cases by age (+/-5 years), sex, and race. Array experiments were performed on a 16,659-oligonucleotide microarray utilizing a reference experimental design. Supervised methods were used to select differentially expressed genes. Quantitative polymerase chain reaction (PCR) was used to independently validate the array results. RESULTS: Of the 8,324 genes that passed filtering criteria, classification analysis revealed that <5% were differentially expressed between SSc and normal fibroblasts. Individually, differentially expressed genes included COL7A1, COL18A1 (endostatin), DAF, COMP, and VEGFB. Using the panel of genes discovered through classification analysis, a set of model predictors that achieved reasonably high predictive accuracy was developed. Analysis of 1,297 gene ontology (GO) classes revealed 35 classes that were significantly dysregulated in SSc fibroblasts. These GO classes included anchoring collagen (30934), extracellular matrix structural constituent (5201), and complement activation (6958, 6956). Validation by quantitative PCR demonstrated that 7 of 7 genes selected were concordant with the array results. CONCLUSION: Fibroblasts cultured from nonlesional skin of patients with SSc already have detectable abnormalities in a variety of genes and cellular processes, including those involved in extracellular matrix formation, fibrillogenesis, complement activation, and angiogenesis.

Dermis↗
PubMed2005

Toward the evaluation of function in genetic variability: characterizing human SNP frequencies and establishing BAC-transgenic mice carrying the human CYP1A1_CYP1A2 locus.

Interindividual differences in human CYP1A1 and CYP1A2 expression appear to be associated with variability in risk toward various types of environmental toxicity and cancer. These two genes are oriented head-to-head on human chromosome 15; the 23.3-kb spacer region might contain distinct regulatory regions for CYP1A1 and distinct regulatory regions for CYP1A2, or the regulatory regions for the two genes might overlap one another. From 24 unrelated subjects of five major, geographically-isolated subgroups, we resequenced both genes (all exons and all introns) plus some 3' flanking sequences and the entire spacer region (39.6 kb total); 85 SNPs were found, 49 of which were not currently in the National Center for Biotechnology Information (NCBI) database. Of the 57 double-hit SNPs, we carried out SNP-typing in 94 Africans, 96 Asians, and 83 Caucasians and found striking ethnic differences in SNP frequencies and haplotype evolution; the two CYP1A1 SNPs and the one CYP1A2 SNP that are most commonly used in epidemiological studies were shown not to be representative haplotype tag SNPs across these three human subgroups. Four BAC-transgenic mouse lines, carrying the human CYP1A2 and 15,190 bp of 5' flank, expressed only negligible basal or inducible CYP1A2 mRNA. A fifth BAC-transgenic mouse line, carrying both the human CYP1A1 and CYP1A2 genes and ample amounts of 3' flanking sequences, plus all of the spacer region--in the absence of the mouse Cyp1a1 or Cyp1a2 genes--expressed the human CYP1A1 and CYP1A2 mRNA, protein and enzyme activities in liver and nonhepatic tissues very similar to that of the mouse. Comparison of this hCYP1A1_1A2 transgenic line with hCYP1A1_1A2 lines carrying other common human haplotypes will enable us to evaluate function in human CYP1A1_CYP1A2 locus variability, with regard to toxicity and cancer caused by combustion products.

Animals↗
PubMed2005

Whole-genome amplification: relative efficiencies of the current methods.

Whole genome amplification (WGA) has emerged as a fundamental method for DNA analysis from limited quantities of genomic DNA in forensic analysis and disease gene discovery. Several strategies for WGA have been developed during the past decade, each with variable fidelity, yield and coverage of the amplified genome. In the search for a reliable and robust WGA method for genotyping short tandem repeat (STR) loci and single nucleotide polymorphic (SNP) markers, we initially tested four common methods, viz., degenerate oligonucleotide primed PCR (DOP), primer extension preamplification (PEP), improved-PEP (I-PEP) and multiple displacement amplification (MDA), typing the 13 CODIS tetranucleotide repeat loci. The results showed among all methods, I-PEP and MDA have higher genomic coverage. DOP and PEP produced locus and allelic dropouts. Therefore, we emphasized on the evaluation of I-PEP and MDA protocols, which shows that the two methods have their relative strengths and weaknesses. In general, the product yield of MDA is higher than that of I-PEP. However, the specificity of the I-PEP products appears to be higher, particularly in the analysis of STR loci. In the analysis of SNP markers, some loci amplify better using products obtained from I-PEP whereas some worked better with MDA. Our analyses also demonstrate that blood spots on FTA cards are a more efficient source of DNA for I-PEP as compared to MDA, especially for STR analysis.

Allelic Imbalance↗
PubMed2005

Therapeutic effects of Lycium barbarum polysaccharide (LBP) on irradiation or chemotherapy-induced myelosuppressive mice.

AIM: The aim of this study was to investigate the effects of Lycium barbarum polysaccharide (LBP) on irradiation- or chemotherapy-induced myelosuppressive mice and cultured peripheral blood mononuclear cells (PBMCs). METHODS: In an in vivo experiment, mice were irradiated with a sublethal dose of 550 cGy X-ray or intraperitoneally (i.p.) injected with carboplatin (CB) 125 mg/kg to produce severe myelosuppression. Four to 6 hours after the irradiation or injection, mice were subcutaneously (s.c.) injected with LBP (50, 100, and 200 mg/kg) daily from day 0 to day 6. Blood samples were collected from the tail veins of mice at different time points, and peripheral white blood cells (WBC), red blood cells (RBC), and platelet (PLT) counts were monitored. In an in vitro experiment, human PBMCs were incubated with LBP at different concentrations in combination with phytohemagglutinin (PHA), and the production of granulocyte colony-stimulating factor (G-CSF) was tested. RESULTS: Compared to the control, 50 mg/kg LBP (LBP-L) significantly ameliorated the decrease of peripheral WBC of irradiated myelosuppressive mice on day 13, and 100 mg/kg LBP (LBP-M) did the same on days 17 and 21. All dosages of LBP significantly ameliorated the decrease of peripheral RBC of irradiated myelosuppressive mice on days 17 and 25. Two-hundred mg/kg LBP (LBP-H) and LBP-M significantly enhanced peripheral PLT counts of irradiated myelosuppressive mice on days 10, 13, 17, and 21, as did LBP-L on days 13 and 17. All dosages of LBP increased peripheral WBC counts of chemotherapy-induced myelosuppressive mice to some extent, but there was no statistic difference when compared to the control. LBP-H significantly ameliorated the decrease of peripheral RBC of chemotherapy-induced myelosuppressive mice on days 13, 15, 17, and 20, and LBP-M and LBP-L did the same on days 15 and 17. All dosages of LBP significantly enhanced peripheral PLT counts of chemotherapy-induced myelosuppressive mice on days 7 and 10, as did LBP-H on days 13, 15, and 17, and LBP-M on days 13 and 15. Also, LBP could obviously stimulate human PBMCs to produce G-CSF. CONCLUSIONS: LBP promoted the peripheral blood recovery of irradiation or chemotherapy-induced myelosuppressive mice, and the effects may be the result of the stimulation of PBMCs to produce G-CSF.

Animals↗
PubMed2005

Laparoscopic Roux-en-Y gastric bypass: differences in outcome between attendings and assistants of different training backgrounds.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is associated with a significant learning curve. We hypothesize that differences in surgeon and assistant training backgrounds may significantly impact outcomes during the learning curve. METHODS: Retrospective analysis was performed on patients undergoing LRYGBP at an academic medical center between January 1998 and August 2003. Operations were performed by surgeons with different training backgrounds: without formal laparoscopic fellowship (S1, n=95); immediately following laparoscopic fellowship (S2, n=100); and with extensive laparoscopic experience post fellowship (S3, n=88). First assistants were attendings, fellows, or residents. The variables analyzed included demographics, operative times, estimated blood loss (EBL), rate of conversion, length of stay (LOS), ICU stay, re-operation/re-admission rate, and complications. Results were analyzed by ANOVA and Fisher's exact test. RESULTS: There were significant differences among surgeons of different training backgrounds in EBL, LOS, rate of ICU admission, and intraoperative and late complications rates. Among assistants of different training levels, there were significant differences in operative time, EBL, intraoperative complication rates and re-admission rates. CONCLUSIONS: Differences in training background of the surgeons resulted in significant differences in outcome, including EBL, LOS, ICU admission and intraoperative and late complication rates. Lower assistant training levels significantly impacted efficiency through lengthened operative times and increased EBL, as well as increased intraoperative complication rates and re-admission rates. Our results suggested that participating in a laparoscopic fellowship and operating with a more experienced assistant may improve outcomes during the learning curve.

Adult↗
PubMed2005

[Polymorphism in insulin receptor gene exon 17 in women with polycystic ovary syndrome].

OBJECTIVE: To investigate insulin receptor (INSR) genotype exon 17 frequencies in women with polycystic ovary syndrome (PCOS) and to elucidate its role in the pathogenesis of PCOS. METHODS: The study involved 33 women with PCOS and 28 healthy control women who were genotyped for polymorphism of INSR gene exon 17 by single strand conformation polymorphism (SSCP) analysis. Body mass index (BMI), insulin sensitive index (ISI), the expression of INSR beta subunit, and serum concentration of luteinizing hormone (LH), total testosterone between the genotypes were compared. RESULTS: (1) The T-to-C mutation was observed in the INSR gene exon 17 (1008 bp). The frequency of the C/C genotype was significantly higher in patients (39%) than in the controls (11%) (P < 0.05). There was no significant difference in the distribution of genotypes between obese PCOS and non-obese PCOS, and between PCOS with insulin resistance (IR) and PCOS without IR. (2) In comparison of mutation genotype groups with wild genotype (T/T), ISI was significantly decreased (C/C genotype, P < 0.01; C/T genotype, P < 0.05), and no significant difference was observed in the other indices. CONCLUSIONS: There is polymorphism in INSR gene exon 17 in patients with PCOS. This variant leads to increased risk of IR in women with PCOS. It does not influence the expression of INSR beta subunit.

Adult↗
PubMed2004

Genetic structure of Hmong-Mien speaking populations in East Asia as revealed by mtDNA lineages.

Hmong-Mien (H-M) is a major language family in East Asia, and its speakers distribute primarily in southern China and Southeast Asia. To date, genetic studies on H-M speaking populations are virtually absent in the literature. In this report, we present the results of an analysis of genetic variations in the mitochondrial DNA (mtDNA) hypervariable segment 1 (HVS1) region and diagnostic variants in the coding regions in 537 individuals sampled from 17 H-M populations across East Asia. The analysis showed that the haplogroups that are predominant in southern East Asia, including B, R9, N9a, and M7, account for 63% (ranging from 45% to 90%) of mtDNAs in H-M populations. Furthermore, analysis of molecular variance (AMOVA), phylogenetic tree analysis, and principal component (PC) analysis demonstrate closer relatedness between H-M and other southern East Asians, suggesting a general southern origin of maternal lineages in the H-M populations. The estimated ages of the mtDNA lineages that are specific to H-M coincide with those based on archeological cultures that have been associated with H-M. Analysis of genetic distance and phylogenetic tree indicated some extent of difference between the Hmong and the Mien populations. Together with the higher frequency of north-dominating lineages observed in the Hmong people, our results indicate that the Hmong populations had experienced more contact with the northern East Asians, a finding consistent with historical evidence. Moreover, our data defined some new (sub-)haplogroups (A6, B4e, B4f, C5, F1a1, F1a1a, and R9c), which will direct further efforts to improve the phylogeny of East Asian mtDNAs.

Asia, Southeastern↗
PubMed2004

Genetic evidence supports demic diffusion of Han culture.

The spread of culture and language in human populations is explained by two alternative models: the demic diffusion model, which involves mass movement of people; and the cultural diffusion model, which refers to cultural impact between populations and involves limited genetic exchange between them. The mechanism of the peopling of Europe has long been debated, a key issue being whether the diffusion of agriculture and language from the Near East was concomitant with a large movement of farmers. Here we show, by systematically analysing Y-chromosome and mitochondrial DNA variation in Han populations, that the pattern of the southward expansion of Han culture is consistent with the demic diffusion model, and that males played a larger role than females in this expansion. The Han people, who all share the same culture and language, exceed 1.16 billion (2000 census), and are by far the largest ethnic group in the world. The expansion process of Han culture is thus of great interest to researchers in many fields.

Agriculture↗
PubMed2004

Steroid effects on osteogenesis through mesenchymal cell gene expression.

We have studied the mechanism of steroid-induced osteonecrosis by examining the effect of dexamethasone on a multipotential cell line, D1, which is derived from bone marrow and is capable of differentiating into either the osteoblast or the adipocyte lineage. The expression of bone cell and fat cell transcription factors Cbfa1/Runx2 and PPARgamma2, were determined. Osteocalcin promoter activity was measured by co-transfecting the cells with the phOC-luc and pSV beta-Gal plasmids. Dexamethasone increased PPARgamma2 gene expression 2-fold, while Cbfa1/Runx2 gene expression and osteocalcin promoter activity decreased by 50-60%, and VEGF protein, measured by ELISA, decreased by 55%. These changes indicate enhanced adipogenesis and decreased osteogenesis by mesenchymal cells in vitro, together with a decrease in VEGF, a potent angiogeneic factor, suggesting that dexamethasone may shunt uncommitted osteoprogenitor cells in marrow from osteoblastic differentiation into the adipocytic pathway, leading to diminished vascularization and eventual osteonecrosis.

Adipocytes↗
PubMed2004

Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells.

Neural stem cells are reported to lie in a vascular niche, but there is no direct evidence for a functional relationship between the stem cells and blood vessel component cells. We show that endothelial cells but not vascular smooth muscle cells release soluble factors that stimulate the self-renewal of neural stem cells, inhibit their differentiation, and enhance their neuron production. Both embryonic and adult neural stem cells respond, allowing extensive production of both projection neuron and interneuron types in vitro. Endothelial coculture stimulates neuroepithelial cell contact, activating Notch and Hes 1 to promote self-renewal. These findings identify endothelial cells as a critical component of the neural stem cell niche.

Animals↗
PubMed2004

Analyses of genetic structure of Tibeto-Burman populations reveals sex-biased admixture in southern Tibeto-Burmans.

An unequal contribution of male and female lineages from parental populations to admixed ones is not uncommon in the American continents, as a consequence of directional gene flow from European men into African and Hispanic Americans in the past several centuries. However, little is known about sex-biased admixture in East Asia, where substantial migrations are recorded. Tibeto-Burman (TB) populations were historically derived from ancient tribes of northwestern China and subsequently moved to the south, where they admixed with the southern natives during the past 2600 years. They are currently extensively distributed in China and Southeast Asia. In this study, we analyze the variations of 965 Y chromosomes and 754 mtDNAs in >20 TB populations from China. By examining the haplotype group distributions of Y-chromosome and mtDNA markers and their principal components, we show that the genetic structure of the extant southern Tibeto-Burman (STB) populations were primarily formed by two parental groups: northern immigrants and native southerners. Furthermore, the admixture has a bias between male and female lineages, with a stronger influence of northern immigrants on the male lineages (approximately 62%) and with the southern natives contributing more extensively to the female lineages (approximately 56%) in the extant STBs. This is the first genetic evidence revealing sex-biased admixture in STB populations, which has genetic, historical, and anthropological implications.

Chromosomes, Human, Y↗
PubMed2004

Lipid retention in the arterial wall of two mouse strains with different atherosclerosis susceptibility.

LDL deposition in the subendothelium of arterial walls is the initial event in the development of atherosclerosis. The deposited LDL undergoes oxidative modification by arterial wall cells to become oxidized LDL and consequently contributes to atherosclerotic formation. Using mouse strains C57BL/6J (B6) and C3H/HeJ (C3H), which differ markedly in susceptibility to atherosclerosis, we determined whether variation in subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins constitutes a genetic component in atherosclerosis. Lipoprotein retention was quantitated by Western blot analysis to detect the presence of apoB in aortic walls before foam cells developed. In both dietary and apoE-deficient models, B6 mice exhibited up to a 2-fold increase of apoB in the aortic wall compared with C3H mice. This increase could not be attributed to differences in plasma lipid levels of the two strains. In vitro, endothelial cells from C3H mice took up more acetylated and oxidized LDL but not native LDL and converted more native LDL to oxidized LDL than did endothelial cells from B6 mice. C3H mice expressed more scavenger receptor A in their aortic wall than B6 mice. Thus, variation in the subendothelial retention of apoB-containing lipoproteins cannot explain the dramatic difference in atherosclerosis susceptibility between B6 and C3H mice, and endothelial cells may play a role in alleviating lipid accumulation in arterial walls.

Acetylation↗
PubMed2004

Genetic diversity of mumps virus in oral fluid specimens: application to mumps epidemiological study.

Three hundred nine mumps virus (MuV) strains detected in the United Kingdom during 1995-2002 were characterized by partial sequencing of the small hydrophobic gene and were shown to belong to at least 6 different genotypes. A strain representing a new genotype was isolated from a seminal fluid specimen. Identical strains belonging to genotypes G and C were found to circulate for up to 3 years. One genotype H strain reappeared after an absence of 4 years. Distinct lineages (G1-G7) within genotype G were recognizable in the present study, and this level of characterization proved to be very useful for tracking MuV importations and subsequent transmission. We propose, here, a preliminary standardization of international nomenclature for genetic characterization of MuV strains, to facilitate future molecular epidemiological studies of mumps. Oral fluid (OF) specimens (n=1441) were used to detect both anti-MuV IgM and MuV genome, and the results indicate that OF specimens can be used successfully for diagnosis and have the potential to play a valuable role in diagnosis and surveillance of mumps.

Base Sequence↗