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Biomedical subjects

X Ye

Publications and source records attributed to X Ye.

At least 19 recordsLinked to original sources

Reentrant wetting transition on surfactant solution surfaces.

The wetting of polydimethylsiloxane oil drops on the surfaces of anionic surfactant sodium dodecylsulfate solutions is studied systematically by changing the bulk surfactant concentration. The wetting state changes from complete wetting to pseudopartial wetting at 0.3 cmc (critical micelle concentration) surfactant concentration and there is a reentrant transition back to complete wetting at 1.4 cmc. The measured free energy is consistent with the prediction of the wetting theory. The interaction potential minimum of the two surfaces of the oil film disappears at the reentrant point, which is speculated to be an effect of micelle formation in the solution.

Journal Article↗

Analysis of candidate genes on chromosome 2 in oral cleft case-parent trios from three populations.

Isolated oral clefts, including cleft lip with/without cleft palate (CL/P) and cleft palate (CP), have a complex and heterogeneous etiology. Case-parent trios from three populations were used to study genes spanning chromosome 2, where single nucleotide polymorphic (SNP) markers were analyzed individually and as haplotypes. Case-parent trios from three populations (74 from Maryland, 64 from Singapore and 95 from Taiwan) were genotyped for 962 SNPs in 104 genes on chromosome 2, including two well-recognized candidate genes: TGFA and SATB2. Individual SNPs and haplotypes (in sliding windows of 2-5 SNPs) were used to test for linkage and disequilibrium separately in CL/P and CP trios. A novel candidate gene (ZNF533) showed consistent evidence of linkage and disequilibrium in all three populations for both CL/P and CP. SNPs in key regions of ZNF533 showed considerable variability in estimated genotypic odds ratios and their significance, suggesting allelic heterogeneity. Haplotype frequencies for regions of ZNF533 were estimated and used to partition genetic variance into among-and within-population components. Wright's fixation index, a measure of genetic diversity, showed little difference between Singapore and Taiwan compared with Maryland. The tensin-1 gene (TNS1) also showed evidence of linkage and disequilibrium among both CL/P and CP trios in all three populations, albeit at a lower level of significance. Additional genes (VAX2, GLI2, ZHFX1B on 2p; WNT6-WNT10A and COL4A3-COL4A4 on 2q) showed consistent evidence of linkage and disequilibrium only among CL/P trios in all three populations, and TGFA showed significant evidence in two of three populations.

Chromosome Mapping↗

Computer-assisted detection for CT colonography: external validation.

AIM: To externally validate a computer-assisted detection (CAD) system for computed tomography (CT) colonography, using data from a single centre uninvolved with the software development. MATERIALS AND METHODS: Twenty-five multi-detector CT colonography examinations of patients with validated polyps accumulated at a single centre were examined by two readers who used endoscopic and histopathological data to identify polyp coordinates. A CAD system that had been developed using data from elsewhere, and had not previously encountered the present data, was then applied to the data at sphericity filter settings of 0.75 and 0.50 and identified potential polyps. True-positive, false-negative, and false-positive counts were determined by comparison with the known polyp coordinates. RESULTS: Twenty-five patients had 57 polyps, median size 6mm (range 1-15mm). Per-patient sensitivity for the CAD system was 96% (24 of 25). The CAD system detected 44 (77%) polyps at sphericity setting 0.75 and 49 (86%) polyps at sphericity 0.50: the additional five polyps detected all measured 5mm or less. Sphericity of 0.75 resulted in a median of 10 (one to 34) easily dismissed false-positive prompts per patient and a median of 4 (zero to 15) that needed three-dimensional rendering before dismissal. This rose to 32 (16 to 99) and 11 (three to 35), respectively, at sphericity 0.5. CONCLUSIONS: A per-patient sensitivity of 96% was found for the CAD system (in patients with a median polyp diameter of 6mm) using external validation, a more stringent test than either internal cross-validation or temporal validation. Decreasing sphericity increases sensitivity for small polyps at the expense of decreased specificity.

Colonic Polyps↗

A tumor-specific conditionally replicative adenovirus vector expressing TRAIL for gene therapy of hepatocellular carcinoma.

We constructed a novel hepatocellular carcinoma-specific conditionally replicative adenovirus (CRAd). This adenovirus, designated Ad.HS4.AFP.E1A/TRAIL, expresses E1A to mediate viral replication and TRAIL to enhance HCC-killing efficacy under the control of a modified AFP promoter. An insulator HS-4 was placed in front of the AFP promoter to enhance the fidelity of the heterologous promoter. This virus was shown to have specific cytolytic activity in AFP-expressing HCC cells in vitro. Furthermore, the replication efficiency of Ad.HS4.AFP.E1A/TRAIL correlated well with AFP expression of the host cells, showing a 100-fold and 1 000 000-fold decrease in the low-and non-AFP-expressing HCC cells, respectively, compared to the high AFP-expressing HCC cells. An increase in mRNA of TRAIL and the elevated Caspase-3 activity were also observed in Ad.HS4.AFP.E1A/TRAIL-infected HCC cells. These results indicated that TRAIL expression from the viral vector activated the Caspase-3 enzymatic capacity and the HCC cells were sensitive to TRAIL. In vivo, Ad.HS4.AFP.E1A/TRAIL effectively prevented the growth of low AFP-expressing BEL-7404 xenografts. These results indicate that Ad.HS4.AFP.E1A/TRAIL could provide a new strategy of gene therapy for HCC.

Adenoviridae↗

Rapid identification of single nucleotide polymorphisms and estimation of allele frequencies using sequence traces from DNA pools.

Millions of single nucleotide polymorphisms (SNP) are now known in the chicken, but the ones that segregate may differ among populations. The current study characterized a simple method to simultaneously identify SNP in populations and to estimate allele frequencies by using relative peak heights of nucleotides in sequencing traces from DNA pools. In the first experiment, known concentration gradients of alleles were produced by measured admixture of DNA from highly inbred individual chickens. In the second experiment, pools of DNA from 100 individuals of each of 3 populations were produced, and the estimated frequencies were compared with those from genotyping of individuals sampled from the same populations. Linear relationships (slope = 0.93 to 1.02) were demonstrated between relative peak heights of nucleotide sequence traces and allelic frequency from both types of experimental samples. The correlation of frequency estimates from pools and individual genotyping was 0.917 to 0.997. Therefore, relative peak heights of nucleotides in sequence traces from DNA isolated from blood pools provide accurate estimates of SNP frequencies of the population from which the pool individuals were sampled and can, therefore, increase efficiency of selecting SNP to genotype in specific populations.

Alleles↗

Association of twelve immune-related genes with performance of three broiler lines in two different hygiene environments.

Elite populations of farm animals under genetic selection are often maintained in high hygiene conditions, yet the commercial populations may be raised in, and are expected to perform well in, environments of varied hygiene levels. This presents special challenges to genetically improve those traits for which genotype by environment interactions are important. Twelve immune-related genes were studied for associations with general mortality and other performance traits in 3 elite commercial broiler chicken lines raised in high and low hygiene environments. The genes were toll-like receptor 4, MD-2 (accessory' protein of TLR4), interferon-gamma, transforming growth factor-beta3, inducible nitric oxide synthase, macrophage migration inhibitory factor, interleukin-2, caspase-1, inhibitor of apoptosis protein-1, tumor necrosis factor-related apoptosis-inducing ligand, chicken B-cell marker, and bone morphogenetic protein-7. From a total of 56 identified single-nucleotide polymorphisms (SNP) in 12 genes, 14 SNP that had moderate allelic frequencies in at least 2 of the 3 lines were typed in about 100 progeny-tested sires from each of 3 elite commercial broiler chicken lines using restriction fragment length polymorphism techniques and then used in association analysis. The traits measured on the progeny (total progeny = 145,467) were: mortality from hatching to 14 d and from 14 to 40 d of age, BW at 7 and 40 d of age, feed conversion, ultrasound breast depth, percentage of breast, eviscerated carcass weight, twisted legs or evident tibial dyschondroplasia, x-ray-inspection-based subclinical or incipient development of tibial dyschondroplasia, curly or crooked toes or bowed legs, oxygen content of blood, and female's antibody titer to infectious bursal disease virus at 27 wk. Association analyses were conducted with allele and haplotype substitution effect models using progeny mean data adjusted for fixed and mate effects as sire trait records. Ten of the 12 genes had SNP associations with at least 1 trait. Most detected effects were with mortality and growth traits. Most gene-SNP trait associations varied by genetic line or with environment. These results indicate that associations of candidate genes with important broiler traits can be identified in multiple environments, and they offer a potential for the implementation of marker-assisted selection for traits expressed in the environment in which the commercial broiler needs to perform. The effects of these immune-related candidate genes, however, are complex and affected by genetic background and environment.

Animal Husbandry↗

HIV and syphilis in migrant workers in eastern China.

OBJECTIVE: To measure the prevalence of HIV and syphilis in migrant and urban workers in eastern China, and to determine their knowledge and attitudes towards HIV. METHODS: A cross sectional survey involving dried blood spot testing and self completion questionnaires. Migrants and urban workers in 39 work units in two districts of Hangzhou, Zhejiang Province, were recruited. Respondents completed a questionnaire about knowledge and attitudes towards HIV. Testing for antibodies to HIV-1 and syphilis was carried out on dried blood spots using a gelatin particle agglutination technique. RESULTS: Data were obtained from 4148 migrants and 2197 urban workers. There were no HIV infections detected in either the migrant or urban populations. Syphilis was detected, but the prevalence was not significantly different between urban workers (0.68%, 95% CI: 0.35 to 1.02) and migrant workers (0.48%, 95% CI 0.26 to 0.66, p = 0.07). 36% of the migrants had migrated with a partner, and 7% had also migrated with children. Urban workers were consistently more knowledgeable than migrants about HIV, but knowledge of the major modes of transmission was good in both groups. Traditional attitudes to sexual behaviour were still pervasive in both groups and attitudes towards individuals with HIV were generally intolerant. The use of sex workers appears rare and no more common in migrants than urban workers. CONCLUSION: At present HIV is probably not spreading in the internal migrant population in eastern China. Syphilis is a problem in both the migrant and urban populations. The tendency to migrate with partners makes migrants relatively low risk for engaging in casual sex.

Adolescent↗

Association of a single nucleotide polymorphism in the calpastatin gene with carcass and meat quality traits of beef cattle.

Calpastatin (CAST) is a naturally occurring protein that inhibits the normal tenderization of meat as it ages postmortem. A SNP was identified in the CAST gene (a G to C substitution) and genotyped on crossbred commercially fed heifers (n = 163), steers (n = 226), and bulls (n = 61) from beef feedlots, and steers (n = 178) from a University of Guelph feeding trial. The association of the CAST SNP with carcass and meat quality traits was studied. Carcass traits included fat, lean, and bone yield; grade fat; LM area; and HCW. Meat quality traits included marbling grade; i.m. fat content of LM; tenderness evaluation of LM (Warner-Bratzler shear force) at 2, 7, 14, and 21 d of postmortem aging; and tenderness evaluation of semitendinosus muscle at 7 d of postmortem aging. The mixed model used in the analyses included fixed effects of CAST genotype, sex, slaughter group, and breed composition (linear covariate); sire was a random effect. For the analysis of shear force, i.m. fat content of LM was also included in the model as a linear covariate. Shear force measures were analyzed within days of postmortem aging and by repeated measures analysis. The CAST SNP allele C was more frequent (63%) in the crossbred population than allele G. The CAST SNP was associated with shear force across days of postmortem aging (P = 0.005); genotype CC yielded beef that was more tender than GG (-0.32 kg +/- 0.13), and CG had intermediate tenderness. The corresponding average allele substitution effect (G to C substitution) was also highly significant (-0.15 +/- 0.05 kg, P = 0.002). A lower percentage of unacceptably tough steaks (shear force > 5.7 kg) at 2 and 7 d postmortem was associated with an increasing number of C alleles (P < or = 0.05). At 7 d postmortem, the percentage of unacceptably tough steaks decreased by 24 and 35%, respectively, for animals carrying 1 and 2 copies of the C allele relative to animals with no C alleles. However, genotype CC had a greater fat yield (+1.44 +/- 0.56%; P = 0.037) than genotype GG, with a corresponding allele substitution effect of 0.67 +/- 0.27% (P = 0.015). Therefore, the CAST SNP allele C was associated with increased LM tenderness across days of postmortem aging and, importantly for the beef industry, had a significant reduction in the percentage of steaks rated unacceptably tough by consumers based on an assumed threshold level.

Animals↗

A novel locus for autosomal dominant hereditary gingival fibromatosis, GINGF3, maps to chromosome 2p22.3-p23.3.

Hereditary gingival fibromatosis (HGF) is a rare, benign disorder characterized by slowly progressive fibrous overgrowth of the gingiva. To date, two loci have been mapped in familial cases with autosomal dominant non-syndromic HGF: GINGF (MIM 135300) on chromosome 2p21-p22 and GINGF2 (MIM 605544) on chromosome 5q13-q22. Of the two loci, only SOS1 (son of sevenless one, MIM 182530) gene underlying GINGF locus has been identified. Ascertainment of a large Chinese family has allowed the mapping of a novel locus to 2p22.3-p23.3, GINGF3. Haplotype construction and analysis localized the new locus to an 11.4-cM interval between markers D2S2221 (telomeric) and D2S1788 (centromeric). The maximum two-point limit of detection (LOD) score of 3.45 (theta=0) and multipoint LOD score of 5.00 for marker D2S390 strongly supported linkage to this region. Thus, this genetic interval is distal to and does not overlap with the previously described locus, GINGF, on 2p21-p22.

Asian People↗

Association of single nucleotide polymorphisms in the leptin gene with carcass and meat quality traits of beef cattle.

Studies with different populations are required to properly characterize the robustness of associations of polymorphisms in candidate genes with economically important traits across beef cattle populations before this sort of genetic information can be used efficiently in breeding and management decisions. The objective of this study was to evaluate the association of previously reported SNP in the bovine leptin gene with carcass and meat quality traits from a large sample of crossbred beef cattle. Five SNP (UASMS1, UASMS2, UASMS3, E2JW, and E2FB) were genotyped on 1,111 crossbred bulls, heifers, and steers. The measured traits included fat, lean, and bone yield (%) by partial rib dissection, grade fat, LM area, HCW, quality grade, LM i.m. fat, and tenderness evaluation of LM and semitendinosus muscle. Only four SNP were analyzed (UASMS1, UASMS2, E2JW, and E2FB), because UASMS1 and UASMS3 were completely linked. A uni-variate mixed-inheritance animal model was used to evaluate the association of either genotypes or haplo-types with the traits. The two leptin exon 2 SNP were associated with fat and lean yield and grade fat (E2JW, P < 0.01; E2FB, P < 0.05), and they interacted in their effect on LM tenderness (P < 0.01). The leptin promoter SNP were either not associated with any of the traits (UASMS2) or with fat yield only (UASMS1). Three haplotypes (TCAC, CCAT, TTAC) were at high frequency in the population (88%) and had similar effects on all the traits. Compared with the common haplotypes, one haplotype (CCTT) showed a significantly different effect on fat and lean yield and grade fat (P < 0.01), and one haplotype (TTTT) had a different effect on LM tenderness (P < 0.03). Therefore, important associations between SNP within the leptin gene with lean yield, fatness (fat yield and subcutaneous fat), and tenderness were detected. Results confirm some of the previously reported associations, but diverge with respect to others, showing that further efforts are required to validate some prospective associations.

Adipose Tissue↗

Genetics and cell biology of lysophosphatidic acid receptor-mediated signaling during cortical neurogenesis.

Lysophosphatidic acid (LPA) is a small lysophospholipid that signals through G-protein coupled receptors (GPCRs) to mediate diverse cellular responses. Two LPA receptors, LPA(1) and LPA(2), show gene expression profiles in mouse embryonic cerebral cortex, suggesting roles for LPA signaling in cerebral cortical development. Here, we review loss-of-function and gain-of-function models that have been used to examine LPA signaling. Genetic deletion of lpa(1) or both lpa(1) and lpa(2) in mice results in 50-65% neonatal lethality, but not obvious cortical phenotypes in survivors, suggesting that compensatory signaling systems exist for regulating cortical development. A gain-of-function model, approached by increasing receptor activation through exogenous delivery of LPA, shows that LPA signaling regulates cerebral cortical growth and anatomy by affecting proliferation, differentiation and cell survival during embryonic development.

Animals↗

Pathological changes in the liver of a senescence accelerated mouse strain (SAMP8): a mouse model for the study of liver diseases.

Liver disease is characterized by fatty liver, hepatitis, fibrosis and cirrhosis and is a major cause of illness and death worldwide. The prevalence of liver diseases highlights the need for animal models for research on the mechanism of disease pathogenesis and efficient and cost-effective treatments. Here we show that a senescence-accelerated mouse strain (SAMP8 mice), displays severe liver pathology, which is not seen in senescence-resistant mice (SAMR1). The livers of SAMP8 mice show fatty degeneration, hepatocyte death, fibrosis, cirrhotic changes, inflammatory mononuclear cell infiltration and sporadic neoplastic changes. SAMP8 mice also show abnormal liver function tests: significantly increased levels of alanine amino-transferase (ALT) and aspartate aminotransferase (AST). Furthermore, titers of murine leukemia virus are higher in livers of SAMP8 than in those of SAMR1 mice. Our observations suggest that SAMP8 mouse strain is a valuable animal model for the study of liver diseases. The possible mechanisms of liver damage in SAMP8 mice are also discussed.

Alanine Transaminase↗

Complete and sustained phenotypic correction of hemophilia B in mice following hepatic gene transfer of a high-expressing human factor IX plasmid.

Therapeutic correction of hemophilia B was achieved by rapid infusion of a large-volume solution containing a high-expressing human factor IX (hFIX) plasmid into the tail vein of hemophilia B mice. hFIX circulated at therapeutic levels (1-5 micro g mL-1) in all animals for more than 1 year as determined by both species-specific antigen assay and an activated partial thromboplastin time (APTT)-based clotting assay. There was acute, transient hepatic tissue damage by the infusion procedure and no significant inhibitory anti-hFIX antibodies developed. No bleeding episode was observed during or after treatment. Immunohistochemical studies indicated that the hFIX gene was exclusively expressed in hepatocytes, and that transduced cells had readily detectable hFIX protein at 4 h postinfusion, and stainable protein persisted for up to 1 year. Repeated infusions of hFIX plasmids boosted the hFIX expression to higher levels. These results demonstrate that hemophilia B can be treated by gene transfer of naked hFIX plasmids.

Animals↗

Increased c-Fos protein in the brains of scrapie-infected SAMP8, SAMR1, AKR and C57BL mice.

Scrapie is a neurodegenerative disease that occurs naturally in sheep and goats. The histopathological changes include vacuolation, neuronal apoptosis and astrocytosis. The mechanisms involved in neuronal apoptosis are still unknown. Recently, we observed that activated p38 immunohistostaining was increased in scrapie-infected mice. In many neurodegenerative diseases, activation of the p38 pathway and of the immediate-early gene termed c-Fos appears to be required for the initiation of apoptosis. There are similarities in histopathological changes seen in scrapie-infected mice and in an uninfected senescence-accelerated mouse strain (SAMP8). This led us to investigate c-Fos protein levels in the brains of both uninfected and scrapie-infected SAMP8, SAMR1, AKR and C57BL mice using immunohistochemical methods. The SAMR1 strain served as a control in that it is a mouse strain that does not show accelerated ageing, but has a background that is similar to the SAMP8 strain. AKR was used because it is one of the progenitor strains of both SAM strains and, finally, C57BL is a completely unrelated strain. The results showed a low basal c-Fos expression in controls and a marked increase in c-Fos staining in scrapie-infected mice. In scrapie-positive mice, c-Fos immunoreactivity was observed in neurones in the cortex, hippocampus, thalamus, hypothalamus, medulla, midbrain, brainstem, paraterminal body, internal capsule and cerebellar Purkinje cells. Immunoreactivity of c-Fos was also observed in astrocytes in many brain areas of scrapie-infected mice, particularly in the hippocampus and cortex. Our results show that normal mouse brain (NMB)-injected AKR and SAMP8 mice had more c-Fos production than NMB-injected SAMR1 or C57BL mice; scrapie-infection induces significant increases in c-Fos immunoreactivity in all four mouse strains. Our study suggests that the increase in c-Fos levels may play a role in the neuronal apoptosis observed in scrapie-infected mice.

Aging↗

Lipopolysaccharide regulates constitutive and inducible transcription factor activities differentially in vivo in the rat.

The pathophysiology of septic shock is characterized by the induction of multiple proinflammatory genes and their products. Transcription factors play key roles in the transcription of these genes. Transcription factors may play important roles in the pathophysiology of septic shock. However, little information is available regarding the in vivo transcription factor activities during sepsis. We have studied the in vivo effects of LPS on the DNA binding activities of transcription factors Sp1 (promoter selective transcription factor), AP-2 (activating protein-2), AP-1 (activating protein-1), NF-kappaB (nuclear factor kappa B), and CREB (cAMP response element binding protein). We found that LPS up-regulated the DNA binding activity of inducible transcription factors AP-1, NF-kappaB, and CREB in a time-dependent manner, but down-regulated the DNA binding activity of constitutive transcription factors Sp1 and AP-2. Thus, LPS regulates the inducible and constitutive transcription factors differentially under in vivo conditions.

Animals↗

Sequence-dependent interactions of two forms of UvrC with DNA helix-stabilizing CC-1065-N3-adenine adducts.

The uvrA, uvrB, and uvrC genes of Escherichia coli control the initial steps of nucleotide excision repair. The uvrC gene product is involved in at least one of the dual incisions produced by the UvrABC complex. Using single-stranded (ss) DNA affinity chromatography, we have separated two forms of UvrC from both wild-type E. coli cells and overproducing cells. UvrCI elutes at 0.4 M KCl, and UvrCII elutes at 0.6 M KCl. In general, both forms, in the presence of UvrA and UvrB, actively incise UV-irradiated and CC-1065-modified DNA in the same fashion; i.e., they incise six to eight nucleotides 5' to and three to five nucleotides 3' to a photoproduct or a CC-1065-N3-adenine adduct. They produce different incisions, however, at a CC-1065-N3-adenine adduct in the sequence 5'-GATTACG- present in the MspI-BstNI 117 bp fragment of M13mp1. UvrABCI incises at both the 5' and 3' sides of the adduct (UvrABCI cut), while UvrABCII incises only at the 5' side (UvrABCII cut). Mixing UvrCI and UvrCII results in both UvrABCI and UvrABCII cuts, and the levels of these two types of cutting are proportional to the amount of UvrCI and UvrCII. DNase I footprints of the MspI-BstNI 117 bp DNA fragment containing a site-directed CC-1065-adenine adduct at the 5'-GATTACG- site show that UvrCII, but not UvrCI, binds to the adduct site. Furthermore, the pattern of DNase I footprints induced by UvrCII binding differs from the pattern of the footprints induced by UvrA, UvrAB, and UvrABCI binding. Interestingly, while the presence of unirradiated DNA enhances the efficiency of UvrABCII in incising UV-irradiated DNA, it does not enhance UvrABCII incision of the CC-1065-N3-adenine adduct formed at 5'-GATTACG-. These results show that two different forms of UvrC differ in DNA binding properties as well as incision modes at some kinds of DNA damage.

Adenine↗

Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase.

Cyclin E binds and activates the cyclin-dependent kinase Cdk2 and catalyzes the transition from the G1 phase to the S phase of the cell cycle. The amount of cyclin E protein present in the cell is tightly controlled by ubiquitin-mediated proteolysis. Here we identify the ubiquitin ligase responsible for cyclin E ubiquitination as SCFFbw7 and demonstrate that it is functionally conserved in yeast, flies, and mammals. Fbw7 associates specifically with phosphorylated cyclin E, and SCFFbw7 catalyzes cyclin E ubiquitination in vitro. Depletion of Fbw7 leads to accumulation and stabilization of cyclin E in vivo in human and Drosophila melanogaster cells. Multiple F-box proteins contribute to cyclin E stability in yeast, suggesting an overlap in SCF E3 ligase specificity that allows combinatorial control of cyclin E degradation.

Amino Acid Motifs↗