Biomedical subjects

Xu Ling

Publications and source records attributed to Xu Ling.

8 recordsLinked to original sources

PubMed2006

Functional CpG methylation system in a social insect.

DNA methylation systems are well characterized in vertebrates, but methylation in Drosophila melanogaster and other invertebrates remains controversial. Using the recently sequenced honey bee genome, we present a bioinformatic, molecular, and biochemical characterization of a functional DNA methylation system in an insect. We report on catalytically active orthologs of the vertebrate DNA methyltransferases Dnmt1 and Dnmt3a and b, two isoforms that contain a methyl-DNA binding domain, genomic 5-methyl-deoxycytosine, and CpG-methylated genes. The honey bee provides an opportunity to study the roles of methylation in social contexts.

Amino Acid Sequence↗

PubMed2006

Genome scan for cis-regulatory DNA motifs associated with social behavior in honey bees.

Honey bees (Apis mellifera) undergo an age-related, socially regulated transition from working in the hive to foraging, which is associated with changes in the expression of thousands of genes in the brain. To begin to study the cis-regulatory code underlying this massive social regulation of gene expression, we used the newly sequenced honey bee genome to scan the promoter regions of eight sets of behaviorally related genes differentially expressed in the brain in the context of division of labor among worker bees, for 41 cis-regulatory motifs previously characterized in Drosophila melanogaster. Binding sites for the transcription factors Hairy, GAGA, Adf1, Cf1, Snail, and Dri, known to function in nervous system development, olfactory learning, or hormone binding in Drosophila, were significantly associated with one or more gene sets. The presence of some binding sites also predicted expression patterns for as many as 71% of the genes in some gene sets. These results suggest that there is a robust relationship between cis and social regulation of brain gene expression, especially considering that we studied <15% of all known transcription factors. These results also suggest that transcriptional networks involved in the regulation of development in Drosophila are used to regulate behavioral development in adult honey bees. However, differences in gene regulation between these two processes are suggested by the finding that the promoter regions for the behaviorally related bee genes differed in both motif occurrence and G/C content relative to their Drosophila orthologs.

Animals↗

PubMed2006

Automatically generating gene summaries from biomedical literature.

Biologists often need to find information about genes whose function is not described in the genome databases. Currently they must try to search disparate biomedical literature to locate relevant articles, and spend considerable efforts reading the retrieved articles in order to locate the most relevant knowledge about the gene. We describe our software, the first that automatically generates gene summaries from biomedical literature. We present a two-stage summarization method, which involves first retrieving relevant articles and then extracting the most informative sentences from the retrieved articles to generate a structured gene summary. The generated summary explicitly covers multiple aspects of a gene, such as the sequence information, mutant phenotypes, and molecular interaction with other genes. We propose several heuristic approaches to improve the accuracy in both stages. The proposed methods are evaluated using 10 randomly chosen genes from FlyBase and a subset of Medline abstracts about Drosophila. The results show that the precision of the top selected sentences in the 6 aspects is typically about 50-70%, and the generated summaries are quite informative, indicating that our approaches are effective in automatically summarizing literature information about genes. The generated summaries not only are directly useful to biologists but also serve as useful entry points to enable them to quickly digest the retrieved literature articles.

Animals↗

PubMed2005

Expanded breadth of virus neutralization after immunization with a multiclade envelope HIV vaccine candidate.

Although the V3 loop of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) effectively elicits potent neutralizing antibody responses, the specificity of the antibody response is often restricted to T cell line adapted (TCLA) strains and a small subset of primary isolates, limiting its utility for an AIDS vaccine. In this study, we have compared Env immunogens with substituted V3 regions to combinations of strains from different clades and evaluated their ability to expand the breadth of the neutralizing antibody response. When the V3 region from HIV BaL was substituted for HIV HXB2, an effective neutralizing antibody response against several clade B primary isolates was elicited, but it remained restricted to neutralization of most clade B isolates. In an attempt to expand this response further, a linear epitope recognized by the broadly neutralizing 2F5 antibody was inserted into V3. A V3 2F5 epitope was identified that bound to 2F5 and elicited a potent 2F5 antibody response as an immunogen, but the antisera neutralized only a lab-adapted strain and not primary isolates. In contrast, combinations of Envs from clades A, B, and C, elicited neutralizing antibodies to a more diverse group of primary HIV-1 isolates. These studies suggest that combinations of Env immunogens, despite the limited reactivity of the V3 from each component, can be used to expand the breadth of the neutralizing antibody response.

AIDS Vaccines↗

PubMed2003

Enhanced mucosal immunoglobulin A response of intranasal adenoviral vector human immunodeficiency virus vaccine and localization in the central nervous system.

Replication-defective adenovirus (ADV) vectors represent a promising potential platform for the development of a vaccine for AIDS. Although this vector is typically administered intramuscularly, it would be desirable to induce mucosal immunity by delivery through alternative routes. In this study, the immune response and biodistribution of ADV vectors delivered by different routes were evaluated. ADV vectors expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pol, and Env were delivered intramuscularly or intranasally into mice. Intranasal immunization induced greater HIV-specific immunoglobulin A (IgA) responses in mucosal secretions and sera than in animals with intramuscular injection, which showed stronger systemic cellular and IgG responses. Administration of the vaccine through an intranasal route failed to overcome prior ADV immunity. Animals exposed to ADV prior to vaccination displayed substantially reduced cellular and humoral immune responses to HIV antigens in both groups, though the reduction was greater in animals immunized intranasally. This inhibition was partially overcome by priming with a DNA expression vector expressing HIV-1 Gag, Pol, and Env before boosting with the viral vector. Biodistribution of recombinant adenovirus (rADV) vectors administered intranasally revealed infection of the central nervous system, specifically in the olfactory bulb, possibly via retrograde transport by olfactory neurons in the nasal epithelium, which may limit the utility of this route of delivery of ADV vector-based vaccines.

AIDS Vaccines↗

PubMed2003

Dynamic investigation of leukocyte-endothelial cell adhesion interaction under fluid shear stress in vitro.

To establish a method to investigate the dynamic adhesion between leukocytes and human umbilical vein endothelial cells (HUVECs) under definite shear stress. A parallel plate flow chamber system was developed to produce the definite shear stress in vitro. After the cultured HUVECs were loaded in the flow chamber, the circulation solution containing acridine orange (AO)-labeled leukocytes was perfused to flow through chamber at 0.71 dynes/cm(2). In this case, leukocyte-endothelial cell adhesion process was induced. Lipopolysaccharide(LPS) was used as the chemical stimulus and dexamethasone(DXM) was used as the anti-inflammatory reagent. The adhesion process was recorded in videotape by Olympus IX70 fluorescence microscope and CCD-camera. Then the number of adhesion leukocyte, slow and fast rolling velocities of leukocytes on the surface of HUVECs were measured based on the captured images. The number of static adhering and slow rolling leukocytes on the HUVECs treated with LPS was significantly increased by 23.7-fold and 4.1-fold compared with that of the control group. Meanwhile, both the slow and fast rolling velocities of the leukocytes on HUVECs treated with LPS were significantly decreased by 25.6% and 26.1%. When HUVECs were treated with both LPS and DXM, the effect of LPS was inhibited obviously. This developed method can be used in studying ECs adhesion function affected by different chemical and physical stimulus and evaluating the various compounds interfering with cell adhesion.

Animals↗

PubMed2003

Bone mineral analysis of whole body in 292 normal subjects assessed by dual X-ray absorptiometry.

OBJECTIVE: To study the whole body bone mineral changes in normal subjects. METHODS: Bone mineral was measured by dual X-ray absorptiometry (DXA) in 292 normal subjects aged 10-79 years, including 152 females and 140 males. They were divided into age-groups by decade. RESULTS: In males, the ages with peak value of total bone mineral content (TBMC), total bone mineral density (TBMD), anteroposterior spine BMD (L2-4 BMD) were in the 30-39, 20-39, 20-29 age-groups respectively. In females, they were all in the 30-39 age-group. Peak values of TBMC, TBMD, L2-4 BMD were higher in males than those in females. Loss of bone mineral for females was more pronounced than that for males. Loss of L2-4 BMD was more pronounced than TBMD. CONCLUSION: This study provides the normal bone mineral data of whole body for males and females, and the characteristic of changes.

Absorptiometry, Photon↗

PubMed2002

Modifications of the human immunodeficiency virus envelope glycoprotein enhance immunogenicity for genetic immunization.

In this study, we have investigated the effect of specific mutations in human immunodeficiency virus type 1 (HIV-1) envelope (Env) on antibody production in an effort to improve humoral immune responses to this glycoprotein by DNA vaccination. Mice were injected with plasmid expression vectors encoding HIV Env with modifications in regions that might affect this response. Elimination of conserved glycosylation sites did not substantially enhance humoral or cytotoxic-T-lymphocyte (CTL) immunity. In contrast, a modified gp140 with different COOH-terminal mutations intended to mimic a fusion intermediate and stabilize trimer formation enhanced humoral immunity without reducing the efficacy of the CTL response. This mutant, with deletions in the cleavage site, fusogenic domain, and spacing of heptad repeats 1 and 2, retained native antigenic conformational determinants as defined by binding to known monoclonal antibodies or CD4, oligomer formation, and virus neutralization in vitro. Importantly, this modified Env, gp140 Delta CFI, stimulated the antibody response to native gp160 while it retained its ability to induce a CTL response, a desirable feature for an AIDS vaccine.

AIDS Vaccines↗