Biomedical subjects

Meng Wang

Publications and source records attributed to Meng Wang.

52 records · Page 3Linked to original sources

PubMed2004

Weighted-support vector machines for predicting membrane protein types based on pseudo-amino acid composition.

Membrane proteins are generally classified into the following five types: (1) type I membrane proteins, (2) type II membrane proteins, (3) multipass transmembrane proteins, (4) lipid chain-anchored membrane proteins and (5) GPI-anchored membrane proteins. Prediction of membrane protein types has become one of the growing hot topics in bioinformatics. Currently, we are facing two critical challenges in this area: first, how to take into account the extremely complicated sequence-order effects, and second, how to deal with the highly uneven sizes of the subsets in a training dataset. In this paper, stimulated by the concept of using the pseudo-amino acid composition to incorporate the sequence-order effects, the spectral analysis technique is introduced to represent the statistical sample of a protein. Based on such a framework, the weighted support vector machine (SVM) algorithm is applied. The new approach has remarkable power in dealing with the bias caused by the situation when one subset in the training dataset contains many more samples than the other. The new method is particularly useful when our focus is aimed at proteins belonging to small subsets. The results obtained by the self-consistency test, jackknife test and independent dataset test are encouraging, indicating that the current approach may serve as a powerful complementary tool to other existing methods for predicting the types of membrane proteins.

Algorithms↗

PubMed2004

Persistent electrical coupling and locomotory dysfunction in the zebrafish mutant shocked.

On initial formation of neuromuscular junctions, slow synaptic signals interact through an electrically coupled network of muscle cells. After the developmental onset of muscle excitability and the transition to fast synaptic responses, electrical coupling diminishes. No studies have revealed the functional importance of the electrical coupling or its precisely timed loss during development. In the mutant zebrafish shocked (sho) electrical coupling between fast muscle cells persists beyond the time that it would normally disappear in wild-type fish. Recordings from sho indicate that muscle depolarization in response to motor neuron stimulation remains slow due to the low-pass filter characteristics of the coupled network of muscle cells. Our findings suggest that the resultant prolonged muscle depolarizations contribute to the premature termination of swimming in sho and the delayed acquisition of the normally rapid touch-triggered movements. Thus the benefits of gap junctions during early synapse development likely become a liability if not inactivated by the time that muscle would normally achieve fast autonomous function.

Animals↗

PubMed2004

Cyclophilin A is a proinflammatory cytokine that activates endothelial cells.

OBJECTIVE: Cyclophilin A (CyPA) is an abundant intracellular protein that is considered to be the main target of the immunosuppressive drug cyclosporine A. We and others showed that CyPA is secreted from smooth muscle cells and macrophages in response to oxidative stress and lipopolysaccharide, suggesting a role for CyPA in inflammation. We therefore studied the proinflammatory effects of CyPA on vascular endothelium. METHODS AND RESULTS: Because atherosclerosis is an inflammatory disease, we studied expression of CyPA in atherosclerotic plaques from the ApoE-/- mouse. Using immunohistochemistry, we showed that CyPA was highly expressed in these plaques. Because endothelial cells (EC) are important mediators of inflammation, we next studied the ability of CyPA to activate EC. Human recombinant CyPA activated mitogen-activated protein kinases, including ERK1/2, JNK, and p38 in cultured human umbilical vein EC. CyPA also stimulated IkappaB-alpha phosphorylation and NF-kappaB activation, and induced expression of adhesion molecules including E-selectin and vascular cell adhesion molecule-1. Furthermore, the combination of CyPA and cycloheximide induced EC apoptosis similar to the proapoptotic effect of tumor necrosis factor-alpha. CONCLUSIONS: Our data indicate that CyPA has proinflammatory effects on EC and may play an important role in the pathogenesis of inflammatory diseases, such as atherosclerosis.

Animals↗

PubMed2004

Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies.

Broadly neutralizing monoclonal antibodies (MAbs) are potentially important tools in human immunodeficiency virus type 1 (HIV-1) vaccine design. A few rare MAbs have been intensively studied, but we still have a limited appreciation of their neutralization breadth. Using a pseudovirus assay, we evaluated MAbs from clade B-infected donors and a clade B HIV(+) plasma against 93 viruses from diverse backgrounds. Anti-gp120 MAbs exhibited greater activity against clade B than non-B viruses, whereas anti-gp41 MAbs exhibited broad interclade activity. Unexpectedly, MAb 4E10 (directed against the C terminus of the gp41 ectodomain) neutralized all 90 viruses with moderate potency. MAb 2F5 (directed against an epitope adjacent to that of 4E10) neutralized 67% of isolates, but none from clade C. Anti-gp120 MAb b12 (directed against an epitope overlapping the CD4 binding site) neutralized 50% of viruses, including some from almost every clade. 2G12 (directed against a high-mannose epitope on gp120) neutralized 41% of the viruses, but none from clades C or E. MAbs to the gp120 V3 loop, including 447-52D, neutralized a subset of clade B viruses (up to 45%) but infrequently neutralized other clades (</=7%). MAbs b6 (directed against the CD4 binding site) and X5 (directed against a CD4-induced epitope of gp120) neutralized only sensitive primary clade B viruses. The HIV(+) plasma neutralized 70% of the viruses, including some from all major clades. Further analysis revealed five neutralizing immunotypes that were somewhat associated with clades. As well as the significance for vaccine design, our data have implications for passive-immunization studies in countries where clade C viruses are common, given that only MAbs b12 and 4E10 were effective against viruses from this clade.

AIDS Vaccines↗

PubMed2004

The long third complementarity-determining region of the heavy chain is important in the activity of the broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2F5.

The human monoclonal antibody 2F5 neutralizes primary human immunodeficiency virus type 1 (HIV-1) with rare breadth and potency. A crystal structure of a complex of 2F5 and a peptide corresponding to its core epitope on gp41, ELDKWAS, revealed that the peptide interacts with residues at the base of the unusually long (22-residue) third complementarity-determining region of the heavy chain (CDR H3) but not the apex. Here, we perform alanine-scanning mutagenesis across CDR H3 and make additional substitutions of selected residues to map the paratope of Fab 2F5. Substitution of residues from the base of the H3 loop or from CDRs H1, H2, and L3, which are proximal to the peptide, significantly diminished the affinity of Fab 2F5 for gp41 and a short peptide containing the 2F5 core motif. However, nonconservative substitutions to a phenylalanine residue at the apex of the H3 loop also markedly decreased 2F5 binding to both gp41 and the peptide, suggesting that recognition of the core epitope is crucially dependent on features at the apex of the H3 loop. Furthermore, substitution at the apex of the H3 loop had an even more pronounced effect on the neutralizing activity of 2F5 against three sensitive HIV-1. These observations present a challenge to vaccine strategies based on peptide mimics of the linear epitope.

Amino Acid Sequence↗

PubMed2004

Comparison of linear growth patterns in the first three years of life across two generations in Guatemala.

OBJECTIVE: The secular increase in height is assumed to result from long-term improvements in nutritional intakes and reductions in infectious disease burdens. Nutritional supplementation in early life reduces stunting in chronically undernourished populations. It is not known whether these improvements have an impact on the growth of subsequent generations. Our objective was to estimate the intergenerational effect on offspring length of improved nutrition in the mother's early childhood. METHODS: We studied 283 mother-child pairs (mothers born 1969-1977; children born 1996-1999). The mothers had received nutritional supplementation--either atole (enhanced protein-energy) or fresco (moderate energy, no protein), with both containing vitamins and minerals--prenatally and up to age 7 y as part of a community trial conducted in 4 villages in Guatemala. Length was measured on repeated occasions to 36 months of age in both mothers and children. Growth was modeled as a fractional polynomial. RESULTS: Children grew faster than their mothers. Children of mothers who received atole grew faster than children of women who received fresco. In both groups, lengths of individual children were positively correlated with lengths of their own mothers at the same ages. Correlations were generally stronger when the mothers had received atole in early life. CONCLUSION: We have confirmed a secular trend in growth of children in a developing country setting. The rate of child growth reflects, in part, the growth pattern of the mother, including improvements to that pattern resulting from nutritional supplementation.

Child, Preschool↗

PubMed2004

[Inhibition of Longzhi extracts on tumor growth of transplanted H22 and S180 in mice].

OBJECTIVE: To study the inhibitory effect of Longzhi extracts (extracts from a Chinese herbal compound) on the growth of transplanted hepatoma H22 and sarcoma S180 in mice. METHODS: Certain dosage of Longzhi extracts was dissolved into distilled water to obtain the suspension of definite concentration. The suspension of 0.2 ml was planted on the right forefoot of each mouse. The mice were randomly divided into groups 24 hours later and treated for 7 days. One day after the treatment stopped, the mice were sacrificed and the tumor masses were taken out and weighed. RESULTS: The inhibition rates of Longzhi extracts on the tumor of transplanted H22 and S180 were 63% and 41% respectively. CONCLUSION: Longzhi extracts has antitumor action.

Animals↗

PubMed2004

[Development of coated electrode of immobilized denitrifying bacteria and bio-electrochemical denitrifying reactor].

OBJECTIVE: A coated electrode of immobilized denitrifying bacteria was developed to study the feasibility of electrochemical denitrification. METHODS: The coated electrode of denitrifying bacteria was made by batch cultivation and PVA immobilization using activated carbon fiber (ACF). The coated ACF electrode was used as cathode, while graphite as anode in bioelectrochemical reactor. RESULTS: After having been acclimated in two stages, mixotrophic and autotrophic denitrification stages, the denitrifying bacteria could use hydrogen as electron donor to reduce nitrate. When the initial nitrate concentration was 30.7mg NO3- -N/L, the denitrification rate was 38.4% at an applied electric current of 10mA and a hydraulic retention time of 12 hours. CONCLUSION: With great surface area and a rough surface, it was very easy to develop a biofilm on ACF. The membrane of PVA gel could adhere to the surface of ACF firmly. After having been acclimated, the denitrifying bacteria could use hydrogen generated by the electrolysis of water to be treated as electron donor to reduce nitrate.

Ammonia↗

PubMed2004

[Factors affecting denitrification by denitrificans coated electrode].

OBJECTIVE: To optimize the efficiency of coated electrode denitrifying reactor. METHODS: Synthetic groundwater was treated by coated electrode denitrifying reactor submitted to different operational parameters, such as electric current intensity (CI), oxidation reduction potential (ORP), hydraulic retention time (HRT) and temperature. RESULTS: Denitrification efficiencies of the reactor was found to be related with the applied electric current. The denitrification efficiency was 57.3% with a HRT of 12 hours and the optimum applied electric current intensity was 15 mA. Nitrate removal rate of the reactor was calculated to be 34.4 g NO3(-)-N/m3 x d. Denitrification efficiencies were also found to be related to HRT. The average denitrification velocity was 0.183 mg NO3(-)-N/h within 12 hours. The denitrification rates increased when the temperature of synthetic water raised from 5-35 degrees C. After the electrodes had been connected to the power supply for 1 hour, the concentration of dissolved oxygen (DO) and ORP decreased sharply to 1.08 mg/L and -40 mV, respectively. CONCLUSION: An adaptable reduction environment could be set up in the reactor for autotrophic denitrification shortly after the bio-electrochemical reaction began. The optimum electrode potential and current density were 2.5 V and 0.083 mA/cm2 . As the bio-electrochemical reaction went on, the pH volume decreased sharply, and nitrite accumulation was found corresponsively, which leads to the inhibition of denitrification. HRT should be controlled within 12 hours. Anode oxidation reaction could offer inorganic carbon sources for autotrophic denitrifying bacteria, but might lead to pH increase, should be paid attention in the practical operation.

Bioreactors↗

PubMed2003

Lack of association between the G protein beta3 subunit gene and essential hypertension in Chinese: a case-control and a family-based study.

A C825T polymorphism of the gene encoding the G protein beta3 subunit (GNB3) is associated with enhanced G protein activity and increased intracellular signal transduction. The 825T allele has been implicated in the development of hypertension in some ethnic groups, especially in whites. Studies in Asians and blacks are more controversial, and little information is available on this polymorphism in the susceptibility to hypertension in the Chinese population. Furthermore, the inconsistency between studies may be due to genetic heterogeneity of the population selected and/or the lack of statistical power. We investigated the relationship of this polymorphism with hypertension in two independent northern Chinese populations using both a case-control and a family-based study design. The GNB3 C825T polymorphism was determined by polymerase chain reaction and restriction enzyme digestion. In the case-control study which included 585 hypertensive case subjects and 580 normotensive control subjects there was no significant association between the polymorphism and hypertension status or blood pressure levels. The lack of association was confirmed by the results obtained in 181 hypertensive families using both transmission disequilibrium test and sib transmission disequilibrium test. No preferential transmission was observed for the GNB3 825T allele to the affected subjects. Furthermore, there was no significant association between the polymorphism and body mass index in the case-control study. Therefore our work does not provide evidence in favor of GNB3 C825T being a candidate gene for conferring genetic susceptibility to hypertension or obesity in northern Chinese population.

Blood Pressure↗

PubMed2003

Heterogeneity of envelope molecules expressed on primary human immunodeficiency virus type 1 particles as probed by the binding of neutralizing and nonneutralizing antibodies.

Virion capture assays, in which immobilized antibodies (Abs) capture virus particles, have been used to suggest that nonneutralizing Abs bind effectively to human immunodeficiency virus type 1 (HIV-1) primary viruses. Here, we show that virion capture assays, under conditions commonly reported in the literature, give a poor indication of epitope expression on the surface of infectious primary HIV-1. First, estimation of primary HIV-1 capture by p24 measurements shows a very poor correlation with an estimation based on infectivity measurements. Second, virion capture appears to require relatively low Ab affinity for the virion, as shown by the ability of a monoclonal Ab to capture a wild-type and a neutralization escape variant virus equally well. Nevertheless, in a more interpretable competition format, it is shown that nonneutralizing anti-CD4 binding site (CD4bs) Abs compete with a neutralizing anti-CD4bs Ab (b12) for virus capture, suggesting that the nonneutralizing anti-CD4bs Abs are able to bind to the envelope species that is involved in virion capture in these experiments. However, the nonneutralizing anti-CD4bs Abs do not inhibit neutralization by b12 even at considerable excess. This suggests that the nonneutralizing Abs are unable to bind effectively to the envelope species required for virus infectivity. The results were obtained for three different primary virus envelopes. The explanation that we favor is that infectious HIV-1 primary virions can express two forms of gp120, an accessible nonfunctional form and a functional form with limited access. Binding to the nonfunctional form, which needs only to be present at relatively low density on the virion, permits capture but does not lead to neutralization. The expression of a nonfunctional but accessible form of gp120 on virions may contribute to the general failure of HIV-1 infection to elicit cross-neutralizing Abs and may represent a significant problem for vaccines based on viruses or virus-like particles.

CD4 Antigens↗

PubMed2003

Molecular features of the broadly neutralizing immunoglobulin G1 b12 required for recognition of human immunodeficiency virus type 1 gp120.

IgG1 b12 is a broadly neutralizing antibody against human immunodeficiency virus type 1 (HIV-1). The epitope recognized by b12 overlaps the CD4 receptor-binding site (CD4bs) on gp120 and has been a target for vaccine design. Determination of the three-dimensional structure of immunoglobulin G1 (IgG1) b12 allowed modeling of the b12-gp120 interaction in which the protruding third complementarity-determining region (CDR) of the heavy chain (H3) was crucial for antibody binding. In the present study, extensive mutational analysis of the antigen-binding site of Fab b12 was carried out to investigate the validity of the model and to identify residues important for gp120 recognition and, by inference, key to the anti-HIV-1 activity of IgG1 b12. In all, 50 mutations were tested: 40 in H3, 4 each in H2 and L1, and 2 in L3. The results suggest that the interaction of gp120 with H3 of b12 is crucially dependent not only on a Trp residue at the apex of the H3 loop but also on a number of residues at the base of the loop. The arrangement of these residues, including aromatic side chains and side chains that hydrogen bond across the base of the loop, may rigidify H3 for penetration of the recessed CD4-binding cavity. The results further emphasize the importance to gp120 binding of a Tyr residue at the apex of the H2 loop that forms a second finger-like structure and a number of Arg residues in L1 that form a positively charged, shelf-like structure. In general, the data are consistent with the b12-gp120 interaction model previously proposed. At the gene level, somatic mutation is seen to be crucial for the generation of many of the structural features described. The Fab b12 mutants were also tested against the b12 epitope-mimic peptide B2.1, and the reactivity profile had many similarities but also significant differences from that observed for gp120. The paratope map of b12 may facilitate the design of molecules that are able to elicit b12-like activities.

Amino Acid Sequence↗

PubMed2003

A novel human antibody against human immunodeficiency virus type 1 gp120 is V1, V2, and V3 loop dependent and helps delimit the epitope of the broadly neutralizing antibody immunoglobulin G1 b12.

The V1/V2 and V3 loops are proximal to the CD4 binding site (CD4bs) of human immunodeficiency virus type 1 (HIV-1) gp120 and undergo conformational change upon CD4 receptor engagement by the HIV-1 envelope spike. Nearly all of the reported monoclonal antibodies (MAbs) against the CD4bs exhibit a very limited capacity to neutralize HIV-1. However, one such human MAb, immunoglobulin G1 (IgG1) b12, is uniquely able to neutralize primary isolates across subtypes with considerable potency. The molecular basis for the anti-HIV-1 activity of b12 is not fully understood but is relevant to vaccine design. Here we describe a novel human MAb, 4KG5, whose binding to monomeric gp120 is moderately enhanced by IgG1 b12. In sharp contrast, 4KG5 binding to gp120 is inhibited by soluble CD4 (sCD4) and by all other (n = 14) anti-CD4bs MAbs tested. 4KG5 is unable to recognize gp120 in which either V1, V2, or V3 has been deleted, and MAbs against the V2 or V3 loops inhibit the binding of 4KG5 to gp120. Moreover, 4KG5 is able to inhibit the binding of the CD4-induced MAbs 17b and X5 in the absence of sCD4, whereas 17b and X5 only weakly inhibit the binding of 4KG5 to gp120. Mutagenesis of gp120 provides further evidence of a discontinuous epitope of 4KG5 that is formed by the V1/V2 loop, the V3 loop, and a portion of the bridging sheet (C4). 4KG5 was isolated as a single-chain Fv from a phage display library constructed from the bone marrow of an HIV-1-seropositive subject (FDA2) whose serum neutralizes HIV-1 across subtypes. Despite its source, we observed no significant neutralization with 4KG5 against the autologous (R2) virus and several other strains of HIV-1. The results suggest a model in which antibody access to the CD4bs on the envelope spike of HIV-1 is restricted by the orientation and/or dynamics of the V1/V2 and V3 loops, and b12 avoids these restrictions.

Amino Acid Sequence↗

PubMed2003

[Clinical analysis of 20 cases of carcinoma of the middle ear].

OBJECTIVE: In order to deeply realized the cancer of middle ear, a retrospective analysis of 20 cases was done. METHOD: The combined treatment (operation plus radiation) were adopted for all of them. The surgical procedures included sleeve resection for 14 cases, temporal bone resection for 3 cases, subtotal temporal bone resection for 3 cases. There patients with cervical metastases were treated by postoperative radiotherapy. RESULT: The survival rates for three years, five years, ten years were 50.0% (11/20), 45.0% (9/20) and 30.1% (6/20), respectively. CONCLUSION: Patients of cancer middle ear located mastoid process who were treated by sleeve resection or temporal bone resection were suitable for radiation therapy and clearing the cancer and reducing infection. If the can cer exceeded mastoid process, patients must undergo subtotal temporal bone resection. However, there were dysfunction included hearing, vestibular and facial nerve.

Adult↗

PubMed2002

[The experimental study of bone marrow mesenchymal stem cells on the repair of skin wound combined with local radiation injury].

OBJECTIVE: To explore the effects of swine bone marrow derived mesenchymal stem cells (MSC) on the repair of skin wound combined local irradiation injury and theirs mechanism. METHODS: MSC were isolated from the adult swine bone marrow and autologous MSC were directly transplanted into the local site full thickness skin incision round wounds combined with 20 Gy irradiation. By means of laser confocal microscopy, quantitative collagen measurement, ELSIA, fibroblasts scrap test, RT-PCR technology and so on in order to observe the effects of MSC promote the repair of wound and theirs mechanism. RESULTS: Transplanted autologous MSC into local skin wound combined with 20 Gy irradiation could accelerate the speed of wound healing, the healing time moved up 3 - 4 days. The granule tissues were abundant in the wounds and the content of collagen was increased in MSC groups. On one hand, MSC attracted the inflammatory cells and repaired cells to immigrate into wounds by themselves or secretion of IL-6, IL-8 and G-CSF and thus initiated the repairing processes. On the other hand, the wound microenviroment induced the proliferation and changes of I collagen mRNA expression of MSC showed that MSC could secrete extracellular matrix or differentiate into fibroblast. CONCLUSION: Local transplanted MSC promoted the repair of skin wounds combined with irradiation injury. The promotion effects were achieved by the interaction between MSC and wound microenviroment.

Animals↗

PubMed2002

Addition of organozinc species to cyclic 1,3-diene monoepoxide.

[reaction: see text] The reaction of organozinc reagents (ZnEt(2), ZnPh(2)) with cyclic 1,3-diene monoepoxides in the presence of CF(3)COOH gave the cis-addition products. Lewis acids such as (CF(3)CO(2))(2)Zn and ZnCl(2) mediated the nucleophilic addition of ZnEt(2) to cyclooctadiene monoepoxide with high stereoselectivity.

Journal Article↗