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L Jiang

Publications and source records attributed to L Jiang.

At least 19 recordsLinked to original sources
PubMed2007

MODEL-molecular descriptor lab: a web-based server for computing structural and physicochemical features of compounds.

Molecular descriptors represent structural and physicochemical features of compounds. They have been extensively used for developing statistical models, such as quantitative structure activity relationship (QSAR) and artificial neural networks (NN), for computer prediction of the pharmacodynamic, pharmacokinetic, or toxicological properties of compounds from their structure. While computer programs have been developed for computing molecular descriptors, there is a lack of a freely accessible one. We have developed a web-based server, MODEL (Molecular Descriptor Lab), for computing a comprehensive set of 3,778 molecular descriptors, which is significantly more than the approximately 1,600 molecular descriptors computed by other software. Our computational algorithms have been extensively tested and the computed molecular descriptors have been used in a number of published works of statistical models for predicting variety of pharmacodynamic, pharmacokinetic, and toxicological properties of compounds. Several testing studies on the computed molecular descriptors are discussed. MODEL is accessible at http://jing.cz3.nus.edu.sg/cgi-bin/model/model.cgi free of charge for academic use.

Amino Acids↗
PubMed2006

PharmGED: Pharmacogenetic Effect Database.

Prediction and elucidation of pharmacogenetic effects is important for facilitating the development of personalized medicines. Knowledge of polymorphism-induced and other types of drug-response variations is needed for facilitating such studies. Although databases of pharmacogenetic knowledge, polymorphism and toxicogenomic information have appeared, some of the relevant data are provided in separate web-pages and in terms of relatively long descriptions quoted from literatures. To facilitate easy and quick assessment of the relevant information, it is helpful to develop databases that provide all of the information related to a pharmacogenetic effect in the same web-page and in brief descriptions. We developed a database, Pharmacogenetic Effect Database (PharmGED), for providing sequence, function, polymorphism, affected drugs and pharmacogenetic effects. PharmGED can be accessed at http://bidd.cz3.nus.edu.sg/phg/ free of charge for academic use. It currently contains 1825 entries covering 108 disease conditions, 266 distinct proteins, 693 polymorphisms, 414 drugs/ligands cited from 856 references.

Animals↗
PubMed2006

Increased glycophorin A somatic cell variant frequency in arsenic-exposed patients of Guizhou, China.

Exposure to arsenic through domestic burning arsenic-containing coal causes various tumors in a population of Guizhou, China. The glycophorin A (GPA) assay is a human mutation assay detecting somatic variation in erythrocytes expressing the MN blood type, and was used to assess genotoxicity of arsenic-exposed patients. Peripheral blood was collected from 18 adult healthy subjects and 40 arsenic-exposed patients in heparin-treated tubes. Erythrocytes were isolated, fixed in formalin and immuno-labeled with fluorescent antibodies against GPA, followed by flow cytometry analysis. Arsenic exposure increased the variant frequency (expressed as the number of variant red cells per 10(6) erythrocytes): NN, 3.7 in healthy subjects versus 21.2 in arsenic-exposed patients; N phi, 12.6 versus 33.1; MM, 13.1 versus 110; and M phi, 5.2 versus 20.3. The total GPA variant frequency was increased about five-fold (34.7 in healthy subjects versus 185 in arsenosis patients). Furthermore, the variant frequency was significantly higher in skin tumor-bearing patients: NN, 19.4 in arsenic-exposed non-tumor patients versus 31.5 in tumor-bearing patients; N phi, 29.5 versus 54.5; MM, 102 versus 159; M phi, 15.9 versus 45.1. Total GPA variant frequency in arsenic-exposed patients bearing skin tumors was significantly increased compared to patients without skin tumors (167 versus 290). The relationship between arsenic exposure history and GPA variant frequency was less evident. These data demonstrate that arsenic exposure is associated with mutations at the GPA locus, an effect exaggerated in patients bearing arsenic-induced skin tumors. The variant frequency of GPA could be a useful biomarker for arsenic exposure and arsenic carcinogenesis.

Adult↗
PubMed2006

Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene.

In this study we focused on detecting schizophrenia related changes of plasma proteins using proteomic technology and examining the relation between schizophrenia and haptoglobin (Hp) genotype. We investigated plasma proteins from schizophrenic subjects (n = 42) and healthy controls (n = 46) by two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry. To further reveal the genetic relationship between acute phase proteins (APPs) and schizophrenia disease, we tested Hp alpha1/Hp alpha2 (Hp 1/2) polymorphism and two single nucleotide polymorphisms (SNPs) of Hp, rs2070937 and rs5473, for associations with schizophrenia in the Chinese Han population. With the relatively high number of samples for 2-DE work, we found that four proteins in the family of positive APPs were all up-regulated in patients. In genetic association study, we found significant associations existing between schizophrenia and Hp polymorphisms, Hp 1/2 and rs2070937 variants. Schizophrenia is accompanied by both an altered expression of Hp protein and a different genotype distribution of Hp gene, demonstrating that Hp is associated with schizophrenia. The results from proteomic and genomic aspects both indicate that acute phase reaction is likely to be an aetiological agent in the pathophysiology of schizophrenia, but not just an accompanying symptom. The positive APPs are schizophrenic related proteins, with the highly concordant results on four positive APPs.

Acute-Phase Proteins↗
PubMed2006

Cyclops: new modular software suite for cryo-EM.

Cyclops is a new computer program designed as a graphical front-end that allows easy control and interaction with tasks and programs for 3D reconstruction of biological complexes using cryo-electron microscopy. Cyclops' current plug-ins are designed for automated particle picking and include two new algorithms, automated carbon masking and quaternion based rotation space sampling, which are also presented here. Additional plug-ins are in the pipeline. Cyclops allows straightforward organization and visualization of all data and tasks and allows both interactive and batch-wise processing. Furthermore, it was designed for straightforward implementation in grid architectures. As a front-end to a collection of programs it provides a common interface to these programs, thus enhancing the usability of the suite and the productivity of the user.

Algorithms↗
PubMed2006

PROFEAT: a web server for computing structural and physicochemical features of proteins and peptides from amino acid sequence.

Sequence-derived structural and physicochemical features have frequently been used in the development of statistical learning models for predicting proteins and peptides of different structural, functional and interaction profiles. PROFEAT (Protein Features) is a web server for computing commonly-used structural and physicochemical features of proteins and peptides from amino acid sequence. It computes six feature groups composed of ten features that include 51 descriptors and 1447 descriptor values. The computed features include amino acid composition, dipeptide composition, normalized Moreau-Broto autocorrelation, Moran autocorrelation, Geary autocorrelation, sequence-order-coupling number, quasi-sequence-order descriptors and the composition, transition and distribution of various structural and physicochemical properties. In addition, it can also compute previous autocorrelations descriptors based on user-defined properties. Our computational algorithms were extensively tested and the computed protein features have been used in a number of published works for predicting proteins of functional classes, protein-protein interactions and MHC-binding peptides. PROFEAT is accessible at http://jing.cz3.nus.edu.sg/cgi-bin/prof/prof.cgi.

Algorithms↗
PubMed2006

QTL analysis for rice grain length and fine mapping of an identified QTL with stable and major effects.

Grain length in rice plays an important role in determining rice appearance, milling, cooking and eating quality. In this study, the genetic basis of grain length was dissected into six main-effect quantitative trait loci (QTLs) and twelve pairs of epistatic QTLs. The stability of these QTLs was evaluated in four environments using an F7 recombinant inbred line (RIL) population derived from the cross between a Japonica variety, Asominori, and an Indica variety, IR24. Moreover, chromosome segment substitution lines (CSSLs) harboring each of the six main-effect QTLs were used to evaluate gene action of QTLs across eight environments. A major QTL denoted as qGL-3a, was found to express stably not only in the isogenic background of Asominori but also in the recombinant background of Asominori and IR24 under multiple environments. The IR24 allele at qGL-3a has a positive effect on grain length. Based on the test of advanced backcross progenies, qGL-3a was dissected as a single Mendelian factor, i.e., long rice grain was controlled by a recessive gene gl-3. High-resolution genetic and physical maps were further constructed for fine mapping gl-3 by using 11 simple sequence repeat (SSR) markers designed using sequence information from seven BAC/PAC clones and a BC4F2 population consisting of 2,068 individuals. Consequently, the gl-3 gene was narrowed down to a candidate genomic region of 87.5 kb long defined by SSR markers RMw357 and RMw353 on chromosome 3, which provides a basis for map-based cloning of this gene and for marker-aided QTL pyramiding in rice quality breeding.

Alleles↗
PubMed2006

Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus.

Alzheimer disease (AD) is a progressive neurodegenerative disorder of later life with a complex etiology and a strong genetic component. Several genomic screens have suggested that a region between chromosome 12p13 and 12q22 contains at least one additional locus underlying the susceptibility of AD. However, localization of this locus has been difficult. We performed a 5 cM microsatellite marker screen across 74 cM on chromosome 12 with 15 markers in 585 multiplex families consisting of 994 affected sibpairs and 213 other affected relative pairs. Analyses across the entire data set did not reveal significant evidence of linkage. However, suggestive linkage was observed in several subsets. In the 91 families where no affected individuals carry an ApoE varepsilon4 allele, an HLOD score of 1.55 was generated at D12S1042. We further examined the linkage data considering the proposed linkages to chromosome 9 (D9S741) and chromosome 10 (alpha-catenin gene). There was a modest (P=0.20) increase in the LOD score for D12S368 (MLOD=1.70) when using the D9S741 LOD scores as a covariate and a highly significant (P<0.001) increase in the MLOD score (4.19) for D12S1701 in autopsy-confirmed families (n=228) when using alpha-catenin LOD scores as a covariate. In both cases, families with no evidence of linkage to D9S741 or alpha-catenin demonstrated most of the evidence of linkage to chromosome 12, suggesting locus heterogeneity. Taken together, our data suggest that the 16 cM region between D12S1042 and D12S368 should be the subject of further detailed genomic efforts for the disease.

Age of Onset↗
PubMed2006

Two novel mutations and evidence for haploinsufficiency of the ADAR gene in dyschromatosis symmetrica hereditaria.

BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH, MIM 127400) is a dominantly inherited skin disease associated with mutations in ADAR, the gene that encodes a double-stranded RNA-specific adenosine deaminase. We previously reported two novel ADAR mutations (p.Q513X and p.R916W) and confirmed the role of ADAR in Chinese patients with DSH. Both haploinsufficiency and a dominant-negative effect have been suggested as the potential mechanism by which ADAR mutations cause DSH. OBJECTIVES: To identify ADAR mutations in two additional Chinese DSH families and to obtain insight into the pathogenic mechanism of heterozygous ADAR mutations. METHODS: For mutation detection, all ADAR exons and their flanking intronic sequences were amplified and sequenced. Mutations were further confirmed by restriction analysis. Direct sequencing of cDNA fragments produced by reverse transcription-polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR were used to examine the expression of ADAR in peripheral lymphocytes isolated from affected individuals. RESULTS: A small deletion, c.1555delT (p.C519fs), and a missense mutation, c.3116A>G (p.K1039R), were found in families A and B, respectively. In individuals carrying p.Q513X or p.C519fs, sequencing of cDNA fragments indicated almost total loss of mRNA expression from the mutant alleles, and real-time quantitative RT-PCR showed an approximately 50% reduction of ADAR expression. However, equal abundance of the wild-type and mutant cDNA sequences without reduction of ADAR expression was found in a patient with the missense p.R916W mutation. These results suggest that both the nonsense p.Q513X and frameshift p.C519fs mutations have generated null alleles probably by nonsense-mediated mRNA decay. CONCLUSIONS: Two novel ADAR mutations were found in Chinese patients with DSH. Evidence for ADAR haploinsufficiency as a mechanism underlying the molecular pathogenesis of DSH was obtained.

Adenosine Deaminase↗
PubMed2006

Patterns of genetic variation in the hypertension candidate gene GRK4: ethnic variation and haplotype structure.

Association studies using single nucleotide polymorphisms (SNPs) have the potential to help unravel the genetic basis of hypertension. Nevertheless, to date, association studies of hypertension have yielded ambiguous results. It is becoming clear that such association studies must be interpreted within the context of the genetic structure of the populations being studied, and patterns of variation within specific genomic regions. With this in mind we analyzed genetic variation in the G protein-coupled receptor kinase 4 (GRK4) gene, a gene whose product has recently been shown to inhibit the dopamine receptor D1 (DRD1) from increasing sodium excretion. We genotyped three previously identified GRK4 SNPs, as well as ten additional SNPs, over 71.6 kb of the GRK4 locus in four populations: African Americans, Asians, Hispanics and Caucasians. Haplotype structure varied among populations, with Hispanics and Caucasians having the most linkage disequilibrium (LD) among SNPs. African Americans had three shorter haplotype blocks, while patterns of markers in the Asian populations demonstrated less LD among markers, a pattern inconsistent with block structure. We observed limited haplotype diversity in each of the four populations, with differing haplotype frequencies among the ethnic groups. We also found substantial evidence for population differentiation, with the largest differences between the African-American and Asian samples with F(ST) values in the upper 90(th) percentile when compared to a genome-wide distribution. However, for all population comparisons, F(ST) values decreased sharply in the 3' region of the gene. This pattern of differentiation among populations is consistent with selection in this part of the gene maintaining similar patterns of variation among otherwise divergent populations. Our results document not only different allele frequencies between populations, but differences in haplotype structure that may be important in evaluating association studies between hypertension and GRK4.

Black or African American↗
PubMed2006

Identification of Bruton tyrosine kinase mutations in 12 Chinese patients with X-linked agammaglobulinaemia by long PCR-direct sequencing.

X-linked agammaglobulinaemia (XLA) is an immunodeficiency caused by Bruton tyrosine kinase (BTK) gene mutations. The disease is characterized by recurrent bacterial infections and profound hypogammaglobulinemia with marked reduction or lack of mature B-cells in the peripheral blood. Molecular characterization of BTK gene provides an opportunity for definitive diagnosis of XLA patients, especially for those with atypical phenotype resulting in a milder or late-onset form of the disease. The diagnosis allows accurate carrier detection with subsequent genetic counselling and prenatal diagnosis. In this study, long polymerase chain reaction (PCR)-direct sequencing analysis of the BTK gene in 12 unrelated Chinese XLA patients had been performed. Eight recurrent mutations and four novel mutations were identified. This is the first report of Chinese cases from three different East Asia regions together, including Hong Kong, Singapore and mainland China. Future clinical and genetic information from the undiagnosed Chinese XLA patients may provide insight into the genotype-phenotype correlations of BTK gene.

Adolescent↗
PubMed2005

Stability of QTLs for rice grain dimension and endosperm chalkiness characteristics across eight environments.

Rice appearance quality, including traits specifying grain dimension and endosperm chalkiness, represents a major problem in many rice-producing areas of the world. In this study, the genetic basis of six appearance quality traits of milled rice was dissected into quantitative trait loci (QTL) main effects, and the stability of these QTLs was assessed in a population of 66 chromosome segment substitution lines (CSSLs) across eight environments. The CSSLs showed transgressive segregation for many of the traits, and significant correlations were detected among most of the traits. Twenty-two QTLs were identified on eight chromosomes, and numerous QTLs affecting related traits were mapped in the same regions, probably reflecting pleiotropic effects. Nine QTLs, namely qGL-1,qGL-3, qGW-5,qLWR-3, qLWR-5,qPGWC-8, qPGWC-9, qACE-8, and qDEC-8, were consistently detected across the eight environments. The additive main effect and multiplicative interaction (AMMI) analysis showed that genotype (G) x environment (E) interaction was significant for all six traits, with the first three iPCA terms accounting for over 80% of the G x E variance. Both D(I) values and the iPCA1-iPCA2 biplots showed that the CSSLs harboring the nine QTL alleles were more stable than those carrying any of the additional 13 QTL alleles, thereby confirming their environmental stability and pointing to their appropriateness as targets for marker-assisted selection for high-quality rice varieties.

Analysis of Variance↗
PubMed2005

Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder.

Major depressive disorder is one of the most common and devastating psychiatric disorders. To identify candidate mechanisms for major depressive disorder, we compared gene expression in the temporal cortex from 12 patients with major depressive disorder and 14 matched controls using Affymetrix HgU95A microarrays. Significant expression changes were revealed in families of genes involved in neurodevelopment, signal transduction and cell communication. Among these, the expression of 17 genes related to oligodendrocyte function was significantly (P < 0.05, fold change > 1.4) decreased in patients with major depressive disorder. Eight of these 17 genes encode structural components of myelin (CNP, MAG, MAL, MOG, MOBP, PMP22, PLLP, PLP1). Five other genes encode enzymes involved in the synthesis of myelin constituents (ASPA, UGT8), or are essential in regulation of myelin formation (ENPP2, EDG2, TF, KLK6). One gene, that is, SOX10, encodes a transcription factor regulating other myelination-related genes. OLIG2 is a transcription factor present exclusively in oligodendrocytes and oligodendrocyte precursors. Another gene, ERBB3, is involved in oligodendrocyte differentiation. In addition to myelination-related genes, there were significant changes in multiple genes involved in axonal growth/synaptic function. These findings suggest that major depressive disorder may be associated with changes in cell communication and signal transduction mechanisms that contribute to abnormalities in oligodendroglia and synaptic function. Taken together with other studies, these findings indicate that major depressive disorder may share common oligodendroglial abnormalities with schizophrenia and bipolar disorder.

Adult↗
PubMed2005

Morphological alteration and biological properties of hepatocytes not related to tumorigenesis following transfection with HCV core protein.

The hepatitis C virus (HCV) core protein is supposed to play a critical role in HCV-mediated human liver disease with its capabilities to regulate the growth rate of hepatocytes and to partially contribute to the pathogenesis of hepatocellular carcinoma in association with cellular oncogenes. In this study, to analyse the possible pathological mechanism of the HCV core protein, human primary embryo hepatocytes transfected with HCV core were monitored by immunofluorescence, reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. The morphological changes and biological properties of the transfected hepatocytes were also studied. The results showed that the HCV core gene integrated in the cellular genome and the protein expressed in the transfected hepatocyte, could be detected following serial passage at both the mRNA and protein level. The proliferation assays indicated that hepatocytes transfected with the HCV core gene alone did not exhibit any tumorigenic tendency. Meanwhile, the morphological alterations of these cells demonstrated obvious changes in size, and large vacuolar degeneration. In conclusion, the hepatocytes transfected with the HCV core gene revealed that the core protein expressed induced pathological changes of degeneration, probably related indirectly to tumorigenicity.

Carcinoma, Hepatocellular↗
PubMed2005

DNA vaccination using bacillus Calmette-Guerin-DNA as an adjuvant to enhance immune response to three kinds of swine diseases.

In order to enhance the immune efficacy of DNA vaccination, experiments were conducted to investigate the regulating effects of Bacillus Calmette-Guerin (BCG)-DNA as an adjuvant on immune responses of mice against foot-and-mouth disease (FMD), Aujeszky's disease (AjD) and classical swine fever (CSF). BCG-DNA was purified from BCG by ion-exchange chromatography. Three DNA vaccines (pVSG, pVgD and pVE2) against the respective infection were constructed, and BCG-DNA was coimmunized to mice by muscle injection. The results showed that titres of specific immunoglobulin (Ig)G to the vaccines mounted remarkably in the sera of the adjuvant covaccinated mice (P < 0.01). Antibody isotype IgG2a and IgG1 also increased, respectively, in mice coimmunized with BCG-DNA compared with those of the control groups (P < 0.01). Cellular immune cytokine interferon-gamma and cytotoxic T lymphocytes were detected in coimmunized BCG-DNA groups (P < 0.05). Whereas interleukin-4, humoral immune cytokine, was not significant (P > 0.05). These results suggest that codelivery of BCG-DNA with DNA vaccines against FMD, AjD and CSF can enhance the induction of antigen-specific, especially, cell-mediated immunity.

Adjuvants, Immunologic↗
PubMed2004

Depletion of the high-abundance plasma proteins.

Body fluids, like plasma and urine, are comparatively easy to obtain and are useful for the detection of novel diagnostic markers by applying new technologies, like proteomics. However, in plasma, several high-abundance proteins are dominant and repress the signals of the lower-abundance proteins, which then become undetectable either by two-dimensional gels or chromatography. Therefore, depletion of the abundant proteins is a prerequisite for the detection of the low-abundance components. We applied affinity chromatography on blue matrix and Protein G and removed the most abundant human plasma proteins, albumin and the immunoglobulin chains. The plasma proteins, prior to albumin and immunoglobulin depletion, as well the eluates from the two chromatography steps were analyzed by two-dimensional electrophoresis and the proteins were identified by MALDI-TOF-MS. The analysis resulted in the identification of 83 different gene products in the untreated plasma. Removal of the high-abundance proteins resulted in the visualization of new protein signals. In the eluate of the two affinity steps, mostly albumin and immunoglobulin spots were detected but also spots representing several other abundant plasma proteins. The methodology is easy to perform and is useful as a first step in the detection of diagnostic markers in body fluids by applying proteomics technologies.

Blood Proteins↗
PubMed2004

QTL detection for eating quality of cooked rice in a population of chromosome segment substitution lines.

The genetic mechanism underlying six palatability properties of cooked rice and three physico-chemical traits was dissected in 66 BC(3)F(2) chromosome segment substitution lines (CSSLs), using a complete linkage map in three successive years. The CSSLs showed transgressive segregation for all traits studied. Significant correlation was detected among most palatability traits. A total of 25 QTLs for the nine traits were identified on nine chromosomes, and many QTLs affecting different quality traits were mapped in the same regions. Six QTLs--qLT-8 for luster, qTD-6 and qTD-8 for tenderness, qIVOE-6 and qIVOE-8 for integrated value of organoleptic evaluation, and qAC-8 for amylose content--were repeatedly detected across the 3 years. Phenotypic values were significantly different between the recurrent parent, cultivar Asominori, and the CSSLs harboring any of the six QTL alleles across the three environments, indicating that these six QTLs were non-environment-specific and could be used for marker-assisted selection in rice quality improvement.

Chromosome Mapping↗