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Biomedical subjects

Gang Feng

Publications and source records attributed to Gang Feng.

17 recordsLinked to original sources

Characterization of oncohistone H2B variants in Schizosaccharomyces pombe reveals a key role of H2B monoubiquitination deficiency in genomic instability by altering gene expression.

Various amino acid substitutions commonly occur at one residue of a histone in human cancers, but it remains unclear whether these histone variants have distinct oncogenic effects and mechanisms. Our previous modeling study in the fission yeast Schizosaccharomyces pombe demonstrated that the oncohistone mutants H2BG52D, H2BD67N, and H2BP102L cause the homologous recombination defects and genomic instability by compromising H2B monoubiquitination (H2Bub). However, it is unknown whether other amino acid changes at the H2B-Gly52/Asp67/Pro102 residues influence H2Bub levels and whether they cause genomic instability by altering H2Bub-regulated gene expression. Here, we construct diverse oncomutants at the sole H2B gene htb1-Gly52/Asp67/Pro102 sites in S. pombe and study their impacts on genotoxic response, H2Bub levels, and gene expression. Interestingly, the oncomutants htb1-G52D, htb1-D67N, and htb1-P102L exclusively exhibit significant genotoxic sensitivity, reduced H2Bub levels, and altered gene expression. These defects can be rescued by restoring H2Bub levels with the deletion of the H2B deubiquitinase ubp8+. These strong genetic correlations suggest that H2Bub deficiency plays a determinant role in the genomic instability of htb1-Gly52/Asp67/Pro102 oncomutants and that the alteration of gene expression due to reduced H2Bub levels is a novel mechanism underlying the genomic instability caused by htb1-G52D, htb1-D67N, and htb1-P102L oncomutations.

Schizosaccharomyces↗

Identification of genes expressed differentially in an in vitro human lung carcinogenesis model.

Lung cancer is the deadliest among all cancers in the US for both men and women. Early detection of premalignant lesions or tumors appears to be a promising approach to reducing the morbidity and mortality from lung cancer because the survival of early stage lung cancer patients is better than that of patients with advanced cancers. We approached the identification of early biomarkers of human lung carcinogenesis, by combining the use of cDNA array and an in vitro human lung carcinogenesis model that consists of normal (NHBE), immortalized (BEAS-2B and 1799), transformed (1198) and tumorigenic (1170-I) human bronchial epithelial (HBE) cells. We hypothesized that certain genes that are expressed differentially among these cells can serve as both biomarkers for early detection and targets for intervention. Nineteen genes were downregulated and six were upregulated in tumorigenic 1170-I HBE cells compared to normal HBE cells (NHBE) using cDNA array. Downregulated genes encode cell-to-cell and cell-to-matrix adhesion-related proteins, calcium-binding proteins and some enzymes or growth factor-related proteins. The functions of upregulated gene were more variable. Similar expression of selected genes was found in different nonsmall cell lung cancer cell lines analyzed by Northern blotting. Furthermore, the differential expression of some genes was also observed by in silico analysis of database of human lung tumors. The differentially expressed genes encode calcium-binding proteins and cell-cell and cell-matrix adhesion proteins. Furthermore, Northern blotting analysis of RNA from different cell lines comprising an in vitro carcinogenesis model including normal, immortalized, transformed, and tumorigenic cells indicated that the expression of subsets of the identified genes changed at different stages of carcinogenesis. These data show that the in vitro carcinogenesis cell system could be useful for discovering potential biomarkers of early and late stages of lung carcinogenesis and targets for chemoprevention.

Carcinoma, Non-Small-Cell Lung↗

CD25+CD4+ regulatory T cells generated by exposure to a model protein antigen prevent allograft rejection: antigen-specific reactivation in vivo is critical for bystander regulation.

The importance of CD25(+)CD4(+) regulatory T (Treg) cells in the control of immune responses is established, but their antigen specificity in vivo remains unclear. Understanding Treg-cell specificity requirements will be important if their potential is to be developed for immunotherapy. Pretreatment of recipient mice with donor alloantigen plus anti-CD4 antibody generates CD25(+)CD4(+) Treg cells with the capacity to prevent skin allograft rejection in adoptive transfer recipients. Here we demonstrate that, although this regulation can be antigen-specific, reactivation with the original tolerizing alloantigen allows the Treg cells to suppress rejection of third-party allografts. Aware of the limitations of alloantigen pretreatment, we asked whether graft-protective Treg cells could be generated against unrelated, nongraft antigens. We demonstrate that bystander regulation also extends to CD25(+)CD4(+) Treg cells generated in vivo by exposure to nominal antigens under anti-CD4 antibody cover. Providing these Treg cells are reexposed to the tolerizing antigens before adoptive transfer, they prevent the rejection of fully allogeneic skin grafts. That this might form the basis of a clinically relevant tolerance induction strategy is demonstrated by the fact that, when combined with subtherapeutic anti-CD8 antibody, Treg cells generated in response to nongraft antigens facilitate the acceptance of cardiac allografts in primary recipients.

Adoptive Transfer↗

Exponential epsilon-regulation for multi-input nonlinear systems using neural networks.

This paper considers the problem of robust exponential epsilon-regulation for a class of multi-input nonlinear systems with uncertainties. The uncertainties appear not only in the feedback channel but also in the control channel. Under some mild assumptions, an adaptive neural network control scheme is developed such that all the signals of the closed-loop system are semiglobally uniformly ultimately bounded and, under the control scheme with initial data starting in some compact set, the states of the closed-loop system is guaranteed to exponentially converge to an arbitrarily specified epsilon-neighborhood about the origin. The important contributions of the present work are that a new exponential uniformly ultimately bounded performance is proposed and that the design parameters and initial condition set can be determined easily. The development generalizes and improves earlier results for the single-input case.

Algorithms↗

A primal-dual neural network for online resolving constrained kinematic redundancy in robot motion control.

This paper proposes a primal-dual neural network with a one-layer structure for online resolution of constrained kinematic redundancy in robot motion control. Unlike the Lagrangian network, the proposed neural network can handle physical constraints, such as joint limits and joint velocity limits. Compared with the existing primal-dual neural network, the proposed neural network has a low complexity for implementation. Compared with the existing dual neural network, the proposed neural network has no computation of matrix inversion. More importantly, the proposed neural network is theoretically proved to have not only a finite time convergence, but also an exponential convergence rate without any additional assumption. Simulation results show that the proposed neural network has a faster convergence rate than the dual neural network in effectively tracking for the motion control of kinematically redundant manipulators.

Algorithms↗

On convergence conditions of an extended projection neural network.

The output trajectory convergence of an extended projection neural network was developed under the positive definiteness condition of the Jacobian matrix of nonlinear mapping. This note offers several new convergence results. The state trajectory convergence and the output trajectory convergence of the extended projection neural network are obtained under the positive semidefiniteness condition of the Jacobian matrix. Comparison and illustrative examples demonstrate applied significance of these new results.

Algorithms↗

[Comparative study on physical parameters and biological effects of blast wave on plateau and on plain].

OBJECTIVE: To compare the physical parameters and biological effects of blast wave on plateau and on plain. METHODS: Twenty-five pigs were divided into two groups: plateau group (n=15) and plain group (n=10). They were placed either 5 meters or 6 meters away from the site of explosion. Ten kilogram of TNT was detonated to produce blast injury. Physical parameters were measured with pressure transducers. The survival rate and gross morphological changes were carefully observed 28 hours later. RESULTS: There was no significant difference in propagation speed of blast wave between the two groups. Compared with plain group, the over-pressure value measured in plateau group was a slightly lower, however, the duration of positive pressure was more lengthy and impulse stronger compared with that of plain group. The survival rate was 12/15 and 8/10 respectively for plateau and plain groups 28 hours after injury. The morphological changes were mainly lung hemorrhage and edema. Intestinal subserosal hemorrhage and subendocardial hemorrhage were found in some animals. The lung injury severity in plateau group was one scale severer than that of plain group. CONCLUSION: Plateau blast wave is characterized by slightly higher impulse, longer duration, and lower over-pressure value, although the propagation speed of the wave is not different from that of plain environment. The blast injury in plateau environment is also severer, its underlying mechanisms need to be further explored.

Altitude↗

[Cloning and screening of retina damage related genes in experimental rabbit chronic ocular hypertension].

OBJECTIVE: To construct the subtractive differentially expressed genes cDNA library of retina in rabbits with chronic ocular hypertension then to clone and screen the genes that related with retina damage. METHODS: Rabbit chronic ocular hypertension model was Established by injecting 1% methylcellulose into anterior chamber once a week for 5 weeks. Total RNA was extracted from retina of experimental and control rabbit eyes. Differentially expressed cDNAs libraries between chronic ocular hypertension eyes and control eyes were constructed using suppression subtraction hybridization (SSH) and then the preliminary data was screened for gene expression. One of upregulation expressed sequence tags (ESTs) was labeled with biotin as a probe. Cellular location of the interested genes in retina was identified by in situ hybridization. RESULTS: The constructed subtractive cDNA library that related to retina damage of chronic ocular hypertension was established and sixteen effective sequences were obtained. Two known expressed sequence tags (similarity over 98%) were found by BLAST Analyze in NCBI. The EST(number F9) was 99% similar to Ras genes family. Through ISH cellular location it was found the gene highly expressed in retina ganglion cells and inner nuclear layer of experimental retina but not in controls. CONCLUSIONS: There was abnormal gene expression in rabbit retina in response to chronic ocular hypertension. Our result suggests EST F9 may play an important role in retina damage under chronic ocular hypertension. The subtractive differentially expressed genes cDNA library could provide valuable information in the research of optical neuro damage and protection in glaucoma.

Animals↗

Chemistry on a single protein, vascular cell adhesion molecule-1, during forced unfolding.

Proteins of many types experience tensile forces in their normal function, and vascular cell adhesion molecule-1 (VCAM-1) is typical in this. VCAM has seven Ig domains, and each has a disulfide bond (-S-S-) buried in its core that covalently stabilizes about half of each domain against unfolding. VCAM is extended here by single molecule atomic force microscopy in the presence or absence of reducing agents. In the absence of reducing agent, a sawtooth pattern of forced unfolding reveals an average period and total length consistent with disulfide locations in VCAM. With increasing reducing agent, accessible disulfides are specifically reduced (to SH); the average period for unfolding increases up to saturation together with additional metrics of unfolding. Steered molecular dynamics simulations of unfolding indeed show that the core disulfide bond is solvent-exposed in the very earliest stages of protein extension. Michaelis-Menten kinetics emerge with reduction catalyzed by force (tau(reduction) approximately 10(-4) s). The results establish single molecule reduction, one bond at a time, and show that mechanical forces can play a key role in modulating the redox state of cell adhesion proteins that are invariably stressed in cell adhesion.

Disulfides↗

A recurrent neural network with exponential convergence for solving convex quadratic program and related linear piecewise equations.

This paper presents a recurrent neural network for solving strict convex quadratic programming problems and related linear piecewise equations. Compared with the existing neural networks for quadratic program, the proposed neural network has a one-layer structure with a low model complexity. Moreover, the proposed neural network is shown to have a finite-time convergence and exponential convergence. Illustrative examples further show the good performance of the proposed neural network in real-time applications.

Artificial Intelligence↗

Piecewise H infinity: controller design of discrete time fuzzy systems.

This paper presents a new H infinity controller design method for the discrete time fuzzy systems based on the piecewise Lyapunov functions. The basic idea of the proposed approach is to construct the controller for the fuzzy systems in such a way that a discrete time piecewise Lyapunov function can be used to establish the global stability with H infinity-disturbance attenuation performance of the resulting close loop fuzzy control systems. It is shown that the control laws can be obtained by solving a set of linear matrix inequalities (LMIs) that is numerically tractable with commercially available software. Numerical example is given to demonstrate the advantage of the proposed method.

Journal Article↗

Hinfinity controller design of fuzzy dynamic systems based on piecewise Lyapunov functions.

This paper presents a controller design method for fuzzy dynamic systems based on a piecewise smooth Lyapunov function. The basic idea of the proposed approach is to construct controllers for the fuzzy dynamic systems in such a way that a piecewise continuous Lyapunov function can be used to establish the global stability with Hinfinity performance of the resulting closed loop fuzzy control systems. It is shown that the control law can be obtained by solving a set of Linear Matrix Inequalities (LMI) that is numerically feasible with commercially available software. An example is given to illustrate the application of the proposed method.

Journal Article↗

[Pathomorphological changes in abdominal viscerae in dogs subjected to underwater blast wave injury].

OBJECTIVE: To explore the pathomorphological changes in abdominal viscerae injuries produced by underwater blast waves. METHODS: Sixty-one adult mongrel dogs were used in this study. Underwater explosions in different intensity were produced by detonating 200 g, 500 g and 1,000 g TNT, respectively. The physical parameters of blast wave were measured by PCB dynamic pressure transducers specially designed for underwater explosion. The pathomorphological changes in abdominal viscerae were observed at 6 hours after injury. RESULTS: The physical features of underwater blast wave were characterized by high peak pressure, short positive action duration, and higher intensity of impulse. The pathomorphological observation revealed high incidence of injuries of gastrointestinal tract (62.30 percent), manifesting mainly various degrees of subserosal and submucous bleeding in gastrointestinal tract. Rupture of seromuscular layer, subserosal hematoma, and even, perforations of gastrointestinal tract occurred in some animals. Injuries of the liver, spleen, pancreas and other parenchymatous organs injuries, such as subcapsular bleeding, hematoma, and ruptures, appeared with low incidence. No obvious injuries were found in the gallbladder or urinary bladder and other fluid containing organs. CONCLUSION: Underwater blast wave can induce injuries to many abdominal viscerae. Gastrointestinal tract injuries, occurring in high incidence are usually severe, and they should be given early treatment in underwater blast injuries.

Animals↗

[Human peripheral blood monocyte derived dendritic cell culture and mature regulation].

Mature dendritic cells are potent antigen-presenting cells that initiate primary immune responses, while immature dendritic cells have quite different properties from mature dendritic cells and are tolerance inducer actually. Here we describe the method of using monocyte condition medium to generate dendritic cells of different maturation phases from nonproliferating progenitors in human peripheral blood. The procedure involves two steps. The first step(or priming phase) is to work on a 6-7-day culture of plastic-adherent blood monocyte in medium supplement with GM-CSF and IL-4. The second step (or differentiation phase) requires the exposure to monocyte conditioned medium. Only the dendritic cells generated by the first step are actually immature, with strong immature dendritic cell features such as active endocytosis, the same expression of monocyte marker CD14, and much of the MHC class II still lies within intracellular compartments (MIIC). The second stage dendritic cells have all the features of mature dendritic cell, including a stellate shape, nonadherence to plastic, the expression of dendritic cells restricted marker CD83, and very strong T cell stimulatory function. All of these dendritic cell properties are retained for at least 3 days when the cytokines are removed, suggesting that these populations are stable and terminally differentiated. Since progression from immature to mature dendritic cell is entirely dependent on exogenously added growth factor such as monocyte condition medium, the peripheral blood monocyte may help to harness synchronized population of mature and immature dendritic cells for studies or therapies.

Cell Culture Techniques↗

[Antisense inhibition of gene expression in human dendritic cells by peptide nucleic acid against CD86].

OBJECTIVE: Dendritic cells (DCs) are the most potent antigen presenting cells (APCs) of the immune system. We intent to block the expression of CD86 in DCs using antisense peptide nucleic acids (PNA), a novel synthetic structural DNA mimic, and interrupt the second signal transmission so that a suppression of corresponding T cell function can be achieved. METHODS: Human DCs grown up from peripheral blood monocytes in GM-CSF and IL-4 were collected. We investigated antisense PNA internalization with laser scan confocal microscope (LSCM). Fluorescence immunocytochemistry, flow cytometry and RT-PCR were used to determine the expression of CD86 protein and mRNA in DCs. RESULTS: LSCM proved that cultured immature DCs could internalized PNA efficiently, according to the specific internalization property of the immature DCs. Antisense PNA DC exhibited striking reductions in cell surface staining for CD86, but not MHC class II, and were poor stimulators of T cell proliferation. RT-PCR found that PNA depressed the amounts of CD86 mRNA in DCs. CONCLUSION: Antisense PNA against CD86 could inhibit the expression of CD86 mRNA and protein in DCs. The blockade of B7/CD28 pathway may increase the potential of costimulatory molecule-deficient antisense PNA DCs of donor origin to induce long-lasting allograft survival.

Antigens, CD↗