Biomedical subjects

X Kong

Publications and source records attributed to X Kong.

At least 19 recordsLinked to original sources

PubMed2006

The rapid formation of a large rotating disk galaxy three billion years after the Big Bang.

Observations and theoretical simulations have established a framework for galaxy formation and evolution in the young Universe. Galaxies formed as baryonic gas cooled at the centres of collapsing dark-matter haloes; mergers of haloes and galaxies then led to the hierarchical build-up of galaxy mass. It remains unclear, however, over what timescales galaxies were assembled and when and how bulges and disks--the primary components of present-day galaxies--were formed. It is also puzzling that the most massive galaxies were more abundant and were forming stars more rapidly at early epochs than expected from models. Here we report high-angular-resolution observations of a representative luminous star-forming galaxy when the Universe was only 20% of its current age. A large and massive rotating protodisk is channelling gas towards a growing central stellar bulge hosting an accreting massive black hole. The high surface densities of gas, the high rate of star formation and the moderately young stellar ages suggest rapid assembly, fragmentation and conversion to stars of an initially very gas-rich protodisk, with no obvious evidence for a major merger.

Journal Article↗

PubMed2006

Relationships among genotypes, virulence and clinical forms of Sporothrix schenckii infection.

This study explored the relationships among genotypes, virulence and clinical forms of Sporothrix schenckii. Genomic DNA from isolates of S. schenckii, collected from different clinical forms of sporotrichosis, was amplified by randomly amplified polymorphic DNA (RAPD). Suspensions of different isolates of S. schenckii were inoculated into healthy BALB/c mice to compare their virulence, and the numbers and distribution of spores were determined by histological analysis. RAPD analysis indicated that the isolates from different clinical forms of sporotrichosis belonged to different genotypes. The mice inoculated with isolates from disseminated sporotrichosis showed an earlier onset of illness and more severe lesions than those inoculated with isolates from lymphocutaneous sporotrichosis, which, in turn, showed an earlier onset of illness and more severe lesions than those inoculated with isolates from fixed cutaneous sporotrichosis. Healthy BALB/c mice injected with isolates from disseminated sporotrichosis died within 10 days, whereas isolates from lymphocutaneous sporotrichosis and fixed cutaneous sporotrichosis failed to cause death. Histologically, mice inoculated with isolates from disseminated sporotrichosis had more spores than those inoculated with isolates from lymphocutaneous sporotrichosis and fixed cutaneous sporotrichosis. Thus, different genotypes may be associated closely with the virulence of different clinical forms of S. schenckii infection.

Animals↗

PubMed2005

Composition fluctuations in dilute nitride (Ga,In)(N,As)/GaAs heterostructures measured by low-loss electron energy-loss spectroscopy.

We report on the investigation of composition fluctuations in epitaxially grown (Ga,In)(N,As) epilayers on GaAs(001) substrates by using electron energy-loss spectroscopy (EELS). The N and In concentrations are determined locally with a probe size of about 8 nm from the low-loss EELS measurements. We demonstrate that the small amount of N incorporating in dilute nitride alloys can be measured quantitatively by the plasmon energy shift with respect to a GaAs reference, and that the In content is analyzed simultaneously from the In 4d transitions, which have been isolated from the overlapping Ga 3d transitions. Our spatially resolved EELS results are utilized to discuss the origin of the inherent composition fluctuations and their influences on the morphological instabilities during epitaxial growth.

Journal Article↗

PubMed2005

Effect of cardiac lymph flow obstruction on cardiac collagen synthesis and interstitial fibrosis.

The effect of chronic cardiac lymphatic obstruction on the myocardial synthesis of collagen type I and III was investigated in a rabbit model. In the lymphatic obstruction group (n=16), plasma C-terminal propeptide type I procollagen (PICP) and N-terminal propeptide type III procollagen (PIIINP) were elevated at 7, 14 and 30 days after the operation (p<0.05). The elevated PICP and PIIINP returned to the pre-operation values 60 days after the operation. The myocardial expression of collagen type I and III mRNA were also enhanced in the lymphatic flow obstruction group. Plasma PICP, PIIINP and myocardial collagen type I and III mRNA remained unchanged in the control group (n=16). We concluded that chronic obstruction of cardiac lymph flow leads to enhanced myocardial collagen synthesis in rabbits. The enhanced collagen synthesis starts within seven days after lymphatic obstruction and subsides after 60 days.

Animals↗

PubMed2004

A combined linkage-physical map of the human genome.

We have constructed de novo a high-resolution genetic map that includes the largest set, to our knowledge, of polymorphic markers (N=14,759) for which genotype data are publicly available; that combines genotype data from both the Centre d'Etude du Polymorphisme Humain (CEPH) and deCODE pedigrees; that incorporates single-nucleotide polymorphisms; and that also incorporates sequence-based positional information. The position of all markers on our map is corroborated by both genomic sequence and recombination-based data. This specific combination of features maximizes marker inclusion, coverage, and resolution, making this map uniquely suitable as a comprehensive resource for determining genetic map information (order and distances) for any large set of polymorphic markers.

Chromosome Mapping↗

PubMed2004

MAP-O-MAT: internet-based linkage mapping.

UNLABELLED: MAP-O-MAT is a web-based server for automated linkage mapping of human polymorphic DNA markers. MAP-O-MAT facilitates the verification of order and map distances for custom mapping sets using genotype data from the CEPH database, and from the Marshfield, SNP Consortium and Rutgers linkage maps (exclusive to the deCODE genotyping data). The CRI-MAP program is used for likelihood calculations and some mapping algorithms, and physical map positions are provided from the human genome assembly. AVAILABILITY: MAP-O-MAT is located at http://compgen.rutgers.edu/mapomat/ CONTACT: matise@biology.rutgers.edu.

Chromosome Mapping↗

PubMed2004

Scd1ab-Xyk: a new asebia allele characterized by a CCC trinucleotide insertion in exon 5 of the stearoyl-CoA desaturase 1 gene in mouse.

We describe here a spontaneous, autosomal recessive mutant mouse suffering from skin and hair defects, which arose in the outbred Kunming strain. By haplotype analysis and direct sequencing of PCR products, we show that this mutation is a new allele of the asebia locus with a naturally occurring mutation in the Scd1 gene (a CCC insertion at nucleotide position 835 in exon 5), which codes for stearoyl-CoA desaturase 1. This mutation introduces an extra proline residue at position 279 in the Scd1 protein. The mutant mice, originally designated km/km but now assigned the name Scd1ab-Xyk (hereafter abbreviated as abXyk/abXyk), have a similar gross and histological phenotype to that reported for previously characterized allelic asebia mutations (Scd1ab, Scd1abJ, Scd1ab2J, and Scd1tm1Ntam). Histological analysis showed they were also characterized by hypoplasic sebaceous glands and abnormal hair follicles. In a cross between Kunming- abXyk/abXyk and ABJ/Le-abJ/abJ mice, all the progeny showed the same phenotype, indicating that the two mutations were non-complementing and therefore allelic. Comparisons with the other four allelic mutants indicate that the Scd1ab-Xyk mutation causes the mildest change in Scd1 function. This new mouse mutant is a good model not only for the study of scarring alopecias in humans, which are characterized by hypoplasic sebaceous glands, but also for studying the structure and function of the Scd1 protein.

Alleles↗

PubMed2004

Association between apolipoprotein CI HpaI polymorphism and sporadic Alzheimer's disease in Chinese.

OBJECTIVE: To investigate into the relationship of apolipoprotein CI (ApoCI) polymorphism with sporadic Alzheimer's disease (AD) in Chinese. SUBJECTS AND METHODS: A total of 257 AD patients and 242 age-matched elderly individuals were genotyped for the ApoCI HpaI and apolipoprotein E (ApoE) HhaI polymorphisms. RESULTS: The ApoCI A allele was associated with AD of moderate to severe dementia when patients were divided into two subgroups according to Clinical Dementia Rating scale, and the AA genotype was strongly associated with moderate to severe AD in ApoE epsilon4 allele carriers [odds ratio (OR) = 8.19, 95% confidential interval: 1.28-52.30, after adjusting for age and gender by logistic regression analysis], although in total no significant differences of allele or genotype frequency between patients and controls were found. CONCLUSION: The present study partially confirmed the previous findings, suggesting that the ApoCI A allele might contribute to the susceptibility to moderate to severe sporadic AD in Chinese.

Aged↗

PubMed2004

Cationic silica nanoparticles as gene carriers: synthesis, characterization and transfection efficiency in vitro and in vivo.

The potential of cationic SiO2 nanoparticles was investigated for in vivo gene transfer in this study. Cationic SiO2 nanoparticles with surface modification were generated using amino-hexyl-amino-propyltri-methoxysilane (AHAPS). The zeta potential of the nanoparticles at pH = 7.4 varied from -31.4 mV (unmodified particles; 10 nm) to +9.6 mV (modified by AHAPS). Complete immobilization of DNA at the nanoparticle surface was achieved at a particle ratio of 80 (w/w nanoparticle/DNA ratio). The surface modified nanoparticle had a size of 42 nm with a distribution from 10-100 nm. The ability of these particles to transfect pCMVbeta reporter gene was tested in Cos-1 cells, and optimum results were obtained in the presence of FCS and chloroquine at a particle ratio of 80. These nanoparticles were tested for their ability to transfer genes in vivo in the mouse lung, and a two-times increase in the expression levels was found with silica particles in comparison to EGFP alone. Very low or no cell toxicity was observed, suggesting silica nanoparticles as potential alternatives for gene transfection.

Animals↗

PubMed2004

Cationic poly(lactide-co-glycolide) nanoparticles as efficient in vivo gene transfection agents.

Poly(lactide-co-glycolide) (PLGA), a biocompatible and biodegradable polyester co-polymer of PLA and PGA, has been recognized for its ability to deliver genes. However, gene delivery by PLGA nanoparticles is limited by their negative charge and their poor transport through mucosal barriers. In this study, PLGA nanoparticles were surface modified with cationic chitosan in an effort to improve their gene delivery capability. PLGA nanoparticles were synthesized by emulsion-diffusion-evaporation technique using PVA-chitosan (PLGA1) or PVA-chitosan-PEG (PLGA2) blend as stabilizers. This method is reproducible and produces nanoparticles with hydrodynamic diameter <200 nm. The nanoparticles were characterized by zetasizer, photon correlation spectroscopy and atomic force microscopy. A549 epithelial cells were transfected in vitro with PLGA particles complexed with a reporter plasmid encoding green fluorescent protein. PLGA particles transferred EGFP gene, but were less efficient than the lipofectamine control. The nanoparticles were also tested for their ability to transport across the nasal mucosa in vivo in mice. The results show that both PLGA1 and PLGA2 facilitate gene delivery and expression in vivo with increased efficiency and without causing inflammation, as measured by IL-6. Together, these results indicate that chitosan-modified PLGA nanoparticles have greater potential as gene carriers.

Animals↗

PubMed2003

Construction and characterization of a half million clone BAC library of durum wheat ( Triticum turgidum ssp. durum).

Durum wheat ( Triticum turgidum ssp. durum, 2 n = 4 x = 28, genomes AB) is an economically important cereal used as the raw material to make pasta and semolina. In this paper we present the construction and characterization of a bacterial artificial chromosome (BAC) library of tetraploid durum wheat cv. Langdon. This variety was selected because of the availability of substitution lines that facilitate the assignment of BACs to the A and B genome. The selected Langdon line has a 30-cM segment of chromosome 6BS from T. turgidum ssp. dicoccoides carrying a gene for high grain protein content, the target of a positional cloning effort in our laboratory. A total of 516,096 clones were organized in 1,344 384-well plates and blotted on 28 high-density filters. Ninety-eight percent of these clones had wheat DNA inserts (0.3% chloroplast DNA, 1.4% empty clones and 0.3% empty wells). The average insert size of 500 randomly selected BAC clones was 131 kb, resulting in a coverage of 5.1-fold genome equivalents for each of the two genomes, and a 99.4% probability of recovering any gene from each of the two genomes of durum wheat. Six known copy-number probes were used to validate this theoretical coverage and gave an estimated coverage of 5.8-fold genome equivalents. Screening of the library with 11 probes related to grain storage proteins and starch biosynthesis showed that the library contains several clones for each of these genes, confirming the value of the library in characterizing the organization of these important gene families. In addition, characterization of fingerprints from colinear BACs from the A and B genomes showed a large differentiation between the A and B genomes. This library will be a useful tool for evolutionary studies in one of the best characterized polyploid systems and a source of valuable genes for wheat. Clones and high-density filters can be requested at http://agronomy.ucdavis.edu/Dubcovsky/BAC-library/BAC_Langdon.htm

Chromosomes, Artificial, Bacterial↗

PubMed2002

Interaction between alcohol dehydrogenase II gene, alcohol consumption, and risk for breast cancer.

MaeIII Restriction Fragment Length Polymorphism in exon 3 of the alcohol dehydrogenase II was assessed in serum from 467 randomly selected German women and 278 women with invasive breast cancer to evaluate the interaction between a polymorphism of the alcohol dehydrogenase II gene, alcohol consumption and risk for breast cancer. In both groups, usual consumption of different alcoholic beverages was asked for using semiquantitative food frequency questionnaires. We used multivariable logistic regression to separately estimate the association between alcohol consumption and alcohol dehydrogenase II polymorphism in the population sample and women with breast cancer. The alcohol dehydrogenase II polymorphism was detected in 14 women from the population sample (3.0%) and in 27 women with invasive breast cancer (9.7%). Frequency of alcohol consumption was independent of the genotype in the population sample. In women with breast cancer, there was a significant inverse association between the alcohol dehydrogenase II polymorphism and frequency of alcohol consumption (adjusted case-only odds ratio over increasing frequency of alcohol consumption=0.5; P for interaction=0.02). We observed a gene-environment interaction between the alcohol dehydrogenase II polymorphism, alcohol consumption, and risk for breast cancer. Breast cancer risk associated with alcohol consumption may vary according to the alcohol dehydrogenase II polymorphism, probably due to differences in alcohol metabolism.

Adult↗

PubMed2001

Directed evolution of alpha-aspartyl dipeptidase from Salmonella typhimurium.

Model-free approaches (error-prone PCR to introduce random mutations, DNA shuffling to combine positive mutations, and screening of the resultant mutant libraries) have been used to enhance the catalytic activity and thermostability of alpha-aspartyl dipeptidase from Salmonella typhimurium, which is uniquely able to hydrolyze Asp-X dipeptides (where X is any amino acid) and one tripeptide (Asp-Gly-Gly). Under double selective pressures of activity and thermostability, through two rounds of error-prone PCR and three sequential generations of DNA shuffling, coupled with screening, a mutant pepEM3074 with approximately 47-fold increased enzyme activity compared with its wild-type parent was obtained. Moreover, the stability of pepEM3074 is increased significantly. Three amino acid substitutions (Asn89His, Gln153Glu, and Leu205Arg), two of them are near the active site and substrate binding pocket, were identified by sequencing the genes encoding this evolved enzyme. The mechanism of the enhancement of activity and stability was analyzed in this paper.

Amino Acid Substitution↗

PubMed2001

A new locus for hereditary gingival fibromatosis (GINGF2) maps to 5q13-q22.

Gingival fibromatosis (GINGF) is an oral disorder characterized by enlargement of the gingiva. It occurs either as the sole phenotype or combined with other symptoms. Thus far, one GINGF locus has been mapped on chromosome 2, at 2p21, and a second possible locus has been mapped to 2p13. However, the genes responsible for this disorder have not been elucidated. We identified a four-generation Chinese GINGF family in which the disease manifests within 1 year after birth. After exclusion of the two known GINGF loci in this family, we performed a genome-wide search to map the chromosome location of the responsible gene. We identified a new locus, GINGF2, on chromosome 5q13-q22 with a maximum two-point lod score of 4.31 at D5S1721 (theta = 0.00). Haplotype analysis placed the critical region in the interval defined by D5S1491 and D5S1453. Within this region, calcium/calmodulin-dependent protein kinase IV (CAMK4) is a strong candidate.

Age of Onset↗

PubMed2001

[Keratin 17 gene mutation in patients with steatocystoma multiplex].

OBJECTIVE: To study the relationship between steatocystoma multiplex (SCM) and keratin 17 gene mutation. METHODS: The keratin 17 gene mutation in the cDNA of cystic tissue of 5 patients of SCM and in the DNA in peripheral blood of 25 patients with SCM from a SCM family was studied by direct sequencing of the RT-PCR products, nested PCR, and restricted fraction length polymorphism (RFLP) analysis. Thirty-nine blood specimens from the unaffected members of that family were collected and tested too. Ten DNA pool specimens and other 2000 DNA pool specimens of normal individuals outside that SCM family were used as controls. RESULTS: In the base 428, 94(th) codon in keratin 17 gene in the cDNA of patients' cystic tissue, R94C mutation, a G-->A mutation, was detected Nested PCR, and restricted enzyme Acil polymorphism analysis showed that in the DNA specimens of peripheral blood of patients a mutated allele lacking enzyme cutting locus was detected, thus causing an uncut band with 200 bp while the corresponding allele was cut and caused two bands with 108 bp and 92 bp. In the DNA pool specimens of normal controls only these two bands with 108 bp and 92 bp were observed. CONCLUSION: The R94C mutation in keratin 17 gene is one of the genetic bases of SCM in Chinese. The results of this study provide scientific data for genetic diagnosis and counseling of SCM.

Adolescent↗

PubMed2001

Directed evolution of operon of trehalose-6-phosphate synthase/phosphatase from Escherichia coli.

Trehalose is a nonspecific protective agent for biomacromolecules. Trehalose-6-phosphate synthase (OtsA)/phosphatase (OtsB), which is encoded by the gene operon otsBA located at -42 of the Escherichia coli genome, is the main enzyme system that catalyzes the synthesis of trehalose in E. coli. We cloned the operon and modified it by directed evolution. Unlike in the previously reported work, we modified the whole operon and screened the positive mutant simultaneously. Thus we believe that the gene complex solves the negative effects between two enzymes if one of them diversifies its structure or functions and finds the form most suitable for trehalose synthesis. It thus mimics the natural process, in which the functional improvement of organisms is related to alterations in coordinated enzymes. The evolution procedure was carried out in a sequence of error-prone PCR, shuffling PCR, and then strict screening of the mutants. After screening of a library of more than 4000 colonies, about 15 positive colonies were analyzed, resulting in a higher concentration of trehalose than control. One of them, E. coli TS7, shows 12.3-fold higher trehalose synthesis ability than E. coli DH5alpha. In contrast, we introduced the cDNA sequence of the tps1 gene from Saccharomyces cerevisiae, which has 54% identity with the gene otsA, as one of the templates in shuffling PCR. By hybrid evolution and screening, we obtained 10 positive colonies with higher concentrations of trehalose than control. E. coli TS22 appears to have 5.3-fold higher trehalose synthesis ability than E. coli DH5alpha and 1.6-fold more than E. coli DEF3(pOTS11). This result demonstrated that coevolution and hybrid evolution, as powerful protocols in protein engineering, are effective in modifying enzyme. It indicates that repeating the process of genomic evolution in nature is feasible.

Directed Molecular Evolution↗

PubMed2001

Blocking intercellular adhesion molecule-1 on human epithelial cells decreases respiratory syncytial virus infection.

The respiratory syncytial virus (RSV) causes potentially fatal lower respiratory tract infection in infants. The molecular mechanism of RSV infection is unknown. Our data show that RSV colocalizes with intercellular adhesion molecule-1 (ICAM-1) on the HEp-2 epithelial cell surface. Furthermore, a neutralizing anti-ICAM-1 mAb significantly inhibits RSV infection and infection-induced secretion of proinflammatory chemokine RANTES and mediator ET-1 in HEp-2 cells. Similar decrease in RSV infection is also observed in A549, a type-2 alveolar epithelial cell line, and NHBE, the normal human bronchial epithelial cell line when pretreated with anti-ICAM-1 mAb prior to RSV infection. Incubation of virus with soluble ICAM-1 also significantly decreases RSV infection of epithelial cells. Binding studies using ELISA indicate that RSV binds to ICAM-1, which can be inhibited by an antibody to the fusion F protein and also the recombinant F protein can bind to soluble ICAM-1, suggesting that RSV interaction with ICAM-1 involves the F protein. It is thus concluded that ICAM-1 facilitates RSV entry and infection of human epithelial cells by binding to its F protein, which is important to viral replication and infection and may lend itself as a therapeutic target.

Antibodies, Monoclonal↗

PubMed2001

Sarcolemmal and mitochondrial K(atp)channels mediate cardioprotection in chronically hypoxic hearts.

X. Kong, J. S. Tweddell, G. J. Gross and J. E. Baker. Sarcolemmal and Mitochondrial K(ATP)Channels Mediate Cardioprotection in Chronically Hypoxic Hearts. Journal of Molecular and Cellular Cardiology (2001) 33, 1041-1045. Hypoxia from birth increases the resistance of the isolated neonatal heart to ischemia. We determined if increased resistance to ischemia was due to activation of sarcolemmal or mitochondrial K(ATP)channels. Rabbits (n=8/group) were raised from birth in a normoxic (F(I)O(2)=0.21) or hypoxic (F(I)O(2)=0.12) environment for 8-10 days and the heart perfused with Krebs-Henseleit bicarbonate buffer. A mitochondrial-selective K(ATP)channel blocker 5-hydroxydecanoate (5-HD) (300 micromol/l) or a sarcolemmal-selective K(ATP)channel blocker HMR 1098 (30 micromol/l) were added alone or in combination for 20 min prior to a global ischemic period of 30 min, followed by 35 min reperfusion. Recovery of ventricular developed pressure was higher in chronically hypoxic than normoxic hearts. 5-HD and HMR 1098 partially reduced the cardioprotective effect of chronic hypoxia, but had no effect in normoxic hearts. The combination of 5-HD and HMR 1098 abolished the cardioprotective effect of chronic hypoxia. We conclude that both sarcolemmal and mitochondrial K(ATP)channels contribute to cardioprotection in the chronically hypoxic heart.

Animals↗