Chao Dai - Academia.edu (original) (raw)
Papers by Chao Dai
F1000Research, 2015
Anti-dsDNA antibodies are the most studied antibodies of the lupus-related autoantibodies. The do... more Anti-dsDNA antibodies are the most studied antibodies of the lupus-related autoantibodies. The dogma is that these are the most important autoantibodies in systemic lupus erythematosus. In this review, evidence is presented to show that these antibodies (as measured by modern clinical laboratories) are not the most important autoantibodies in the diagnosis of systemic lupus erythematosus, and are of limited value in clinical correlation and in predicting disease flares. In addition, they are not likely to be the initiating autoantibodies in lupus nephritis. Thus, several pervasively held beliefs on anti-dsDNA antibodies are not valid. We suggest that anti-dsDNA antibodies should be considered as just one of the many autoantibodies associated with systemic lupus erythematosus.
2010 Asia-Pacific Power and Energy Engineering Conference, 2010
ABSTRACT CO2 capture processes by carbonation-calcination cycles of CaO/CaCO3 were limited by the... more ABSTRACT CO2 capture processes by carbonation-calcination cycles of CaO/CaCO3 were limited by the carbonation conversion and sorbents reutilization with the number of carbonation/calcinations cycles. In order to optimizing the CaO/CaCO3 cycles, BP neural network model and PID temperature control system were established based on the simulation of the process parameters and dynamic characteristics. The carbonization/calcination temperature, the mass fraction of additives for sorbents and calcination time were selected for the input conditions, while the output conditions were capture capacity and the reutilization of sorbents. Genetic algorithm(GA) model is established to optimize the PID controller's proportional coefficient kp, integral coefficient k1, and differential coefficient kD. The results indicated that BPNN coupled with PID model could form a complete optimization strategy for CO2 capture process by CaO/CaCO3 cycles.
2011 IEEE Vehicular Technology Conference (VTC Fall), 2011
ABSTRACT To cope with the too much energy consumption of base station (BS), this paper firstly gi... more ABSTRACT To cope with the too much energy consumption of base station (BS), this paper firstly gives a green heterogeneous network architecture, in which some BSs could be switched off or set as sleep mode when its local traffic is low, while the resident users rely on the mobile relay network composed by intelligent mobile nodes to connect to one of its neighboring BSs. Moreover, in order to achieve better performance, a mathematical model for relay selection is proposed by considering multiple factors, such as secrecy capacity (SC) for selected channels, remained energy¿iRE¿j for relays and location information. Accordingly, a novel dynamic relay selection approach based on Principal Component Analysis (PCA) is brought forward. Using this approach,the related factors which affect the quality of service (QoS) provisioning most could be found out by processing the observation data, and the their weights could be computed in a real-time way as well. The significant property of this approach is to reduce the useless energy loss by removing the redundant parameters. Finally, simulation results prove that the proposed approach outweights the existing ones in terms of system rewards, average throughput, and network lifetime.
5th International Conference on Pervasive Computing and Applications, 2010
Opportunistic networking-forwarding messages in a disconnected mobile ad hoc network via any enco... more Opportunistic networking-forwarding messages in a disconnected mobile ad hoc network via any encountered nodes-offers a new mechanism for exploiting the mobile devices that many users already carry. However, forwarding messages in such a network is trapped by many particular challenges, and some protocols have contributed to solve them partly. In this paper, we propose heterogeneous content-aware routing protocol (HCR) for opportunistic network, an approach containing basic cognitive thoughts, that focuses on optimal efficiency, based on the distinct significance of content renders distinguish priorities, including the quantity of copy, TTL and so on, in the process of transmission. Simulation results reflect that compared with the Spray-and-wait and Prophet, the HCR improves the performance of the delivery ratio and delay of the network.
TELKOMNIKA Indonesian Journal of Electrical Engineering, 2012
Since malwares contain stalling codes, malicious behaviors can’t be detected in emulated analysis... more Since malwares contain stalling codes, malicious behaviors can’t be detected in emulated analysis environment. This paper proposes an approach to detect malicious behaviors by evade stalling codes. First, we executed a malware in the emulated analysis environment, and saved every executed instruction in a trace file; Second, we began to detect stalling codes with the trace file, and constructed stalling code evasive points; At last, we executed the malware again and evade stalling codes with the evasive points, and then the malicious behaviors detected. It has been proven by experiments that the approach can evade stalling codes to detect the later malware behaviors effectively, and improve the performance of detecting the malicious behaviors in the emulated analysis environment. DOI: http://dx.doi.org/10.11591/telkomnika.v10i7.1573 Full Text: PDF
2011 7th International Conference on Wireless Communications, Networking and Mobile Computing, 2011
Fusion decision plays an important part in the cooperation sensing of cognitive radio. In this pa... more Fusion decision plays an important part in the cooperation sensing of cognitive radio. In this paper, a fusion decision algorithm based on channel estimation (FD_CE) is proposed in the architecture of central cooperative sensing in cognitive radio. Instead of the traditional hard decision methods such as AND, OR, Most, we consult to a soft decision algorithm which combines all the detected information of different secondary user (SU) by a linear weight of their channel gains. The algorithm proposed has evaluated the reliability about each secondary user's radio environment, so it brings a better sensing performance. Simulation results show that a higher probability of detection can be achieved using the proposed algorithm comparing with single node sensing, cooperative sensing by AND and OR rules; meanwhile, it decrease the detection threshold effectively at the same time, which means saving single node's hardware cost in other words.
PLoS genetics, 2013
Nucleosome occupancy controls the accessibility of the transcription machinery to DNA regulatory ... more Nucleosome occupancy controls the accessibility of the transcription machinery to DNA regulatory regions and serves an instructive role for gene expression. Chromatin remodelers, such as the BAF complexes, are responsible for establishing nucleosome occupancy patterns, which are key to epigenetic regulation along with DNA methylation and histone modifications. Some reports have assessed the roles of the BAF complex subunits and stemness in murine embryonic stem cells. However, the details of the relationships between remodelers and transcription factors in altering chromatin configuration, which ultimately affects gene expression during cell differentiation, remain unclear. Here for the first time we demonstrate that SNF5, a core subunit of the BAF complex, negatively regulates OCT4 levels in pluripotent cells and is essential for cell survival during differentiation. SNF5 is responsible for generating nucleosome-depleted regions (NDRs) at the regulatory sites of OCT4 repressed targ...
Journal of Proteome Research, 2007
Potassium channels show a huge variability in the affinity when recognizing enormous bioactive pe... more Potassium channels show a huge variability in the affinity when recognizing enormous bioactive peptides, and the elucidation of their recognition mechanism remains a great challenge due to an undetermined peptide-channel complex structure. Here, we employed combined computation methods to study the specific binding of BeKm-1 peptide to the hERG potassium channel, which is an essential determinant of the long-QT syndrome. By the use of a segment-assembly homology modeling method, the closed-state hERG structure containing unusual longer S5P linker was successfully constructed. It has a "petunia" shape, while four "petals" of symmetrically distributed S5P segments always decentralize. Starting from the hERG and BeKm-1 structures, a considerably reasonable BeKm-1-hERG complex structure was then screened out and identified by protein-protein docking, molecular dynamics (MD) simulations, and calculation of relative binding free energies. The validity of this predicted complex was further assessed by computational alanine-scanning, with the results correlating reasonably well with experimental data. In the novel complex structure, four considerably flexible S5P linkers are far from the BeKm-1 peptide. The BeKm-1 mainly uses its helical region to associate the channel outer vestibule, except for the S5P linker region; however, structural analysis further implies this neutral pore region with wiggling S5P linker is highly beneficial to the binding of BeKm-1 with lower positive charges. The most critical Lys18 of BeKm-1 plugs its side chain into the channel selectivity filter, while the secondarily important Arg20 forms three hydrogen bonds with spatially neighboring residues in the hERG channel. Different from the classical peptide-K + channel interaction mainly induced by electrostatic interaction, a synergetic effect of the electrostatic and van der Waals interactions was found to mediate the molecular recognition between BeKm-1 and the hERG channel. And this specific binding process is revealed to be a dynamic change of reduction of binding free energy and conformational rearrangement mainly in the interface of both BeKm-1 and the hERG channel. All these structural and energy features yield deep insights on the high selective binding mechanism of hERGspecific peptides, present a diversity of peptide-K + channel interactions, and also provide important clues to further study structure-function relationships of the hERG channel.
Journal of Computational Biology, 2012
Current network analysis methods all focus on one or multiple networks of the same type. However,... more Current network analysis methods all focus on one or multiple networks of the same type. However, cells are organized by multi-layer networks (e.g., transcriptional regulatory networks, splicing regulatory networks, protein-protein interaction networks), which interact and influence each other. Elucidating the coupling mechanisms among those different types of networks is essential in understanding the functions and mechanisms of cellular activities. In this article, we developed the first computational method for pattern mining across many two-layered graphs, with the two layers representing different types yet coupled biological networks. We formulated the problem of identifying frequent coupled clusters between the two layers of networks into a tensor-based computation problem, and proposed an efficient solution to solve the problem. We applied the method to 38 two-layered co-transcription and co-splicing networks, derived from 38 RNA-seq datasets. With the identified atlas of coupled transcription-splicing modules, we explored to what extent, for which cellular functions, and by what mechanisms transcription-splicing coupling takes place.
IUBMB Life (International Union of Biochemistry and Molecular Biology: Life), 2005
A series of isoforms of a-KT 6 14 (short chain potassium channel scorpion toxins) were isolated f... more A series of isoforms of a-KT 6 14 (short chain potassium channel scorpion toxins) were isolated from the venom of Buthus martensii Karsch by RACE and screening cDNA library methods. These isoforms adding BmKK 1-3 and BmSKTx 1-2 together shared high homology (more than 97%) with each other. The result of genomic sequence analysis showed that a length 79bp intron is inserted Ala codes between the first and the second base at the 17th amino acid of signal peptide. The introns of these isoforms also share high homology with those of BmKK 2 and BmSKT 6 1 reported previously. Sequence analysis of many clones of cDNA and genomic DNA showed that a species population or individual polymorphism of a-KT 6 14 genes took place in scorpion Buthus martensii Karsch and accelerated evolution played an important role in the forming process of a-KT 6 14 scorpion toxins subfamily. The result of southern hybridization indicated that a-KT 6 14 toxin genes existed in scorpion chromosome with multicopies. All findings maybe provided an important evidence for an extensive evolutionary process of the scorpion ''pharmacological factory'': at the early course of evolution, the ancestor toxic gene duplicated into a series of multicopy genes integrated at the different chromosome; at the late course of evolution, subsequent functional divergence of duplicate genes was generated by mutations, deletions and insertion.
International Immunopharmacology, 2006
Vascular endothelial cells (ECs) that initiate tumor angiogenesis may acquire distinct properties... more Vascular endothelial cells (ECs) that initiate tumor angiogenesis may acquire distinct properties after conditioning in tumor microenvironment as compared to ECs in non-malignant tissues. Thus far, most in vitro studies of angiogenesis used ECs isolated from normal tissues, which may not fully represent the nature of ECs in tumor vasculature. In this study, glioma-derived microvascular ECs (GDMEC) were purified from human glioma tissues by incubating with magnetic beads coated with anti-CD105 antibody and highly pure (98%) preparations of GDMEC were obtained. These cells exhibited typical EC phenotype, and proliferated rapidly in culture. Interestingly, GDMEC expressed higher levels of VEGF receptors, flt-1 and flk-1, as compared to an established human EC cell line ECV304 and primary human umbilical vascular EC (HUVEC). Functionally, GDMEC were capable of forming intercellular junctions and tubule-like structures (TLS) of various sizes. Stimulation by VEGF further promoted TLS formation with diverse tubular walls by GDMEC. In contrast, TLS formed by ECV304 and HUVEC showed significantly different features. We further observed that Nordy, a synthetic lipoxygenase inhibitor, potently inhibited TLS formation by GDMEC. The results suggest that isolation of highly pure ECs derived from tumor tissues is more appropriate for studies of tumor angiogenesis and for test of potential anti-cancer therapeutic targets.
Glia, 2012
Increased intraocular pressure (IOP) damages the retinal ganglion cell axons as they pass through... more Increased intraocular pressure (IOP) damages the retinal ganglion cell axons as they pass through the optic nerve head (ONH). The massive connective tissue structure of the human lamina cribrosa is generally assumed to be the pressure transducer responsible for the damage. The rat, however, with no lamina cribrosa, suffers the same glaucomatous response to raised IOP. Here, we show that the astrocytes of the rat ONH are "fortified" by extraordinarily dense cytoskeletal filaments that would make them ideal transducers of distorting mechanical forces. The ONH astrocytes are arranged as a fan-like radial array, firmly attached ventrally to the sheath of the ONH by thick basal processes, but dividing dorsally into progressively more slender processes with only delicate attachments to the sheath. At 1 week after raising the IOP by an injection of magnetic microspheres into the anterior eye chamber, the fine dorsal processes of the ONH astrocytes are torn away from the surroundi...
Cancer Letters, 2010
Malignant gliomas are the most common primary brain tumors associated with significant morbidity ... more Malignant gliomas are the most common primary brain tumors associated with significant morbidity and mortality. How to target the tumor in situ, and inhibit tumor cell proliferation and invasion is the key for therapy. Gliomas express a glioma-specific chloride ion channel that is sensitive to toxins including BmKCT. In the current study, the inhibitory effect of BmKCT on glioma growth was observed in vivo using the glioma/SD rat model. Furthermore, BmKCT prevented the metastasis of glioma cells in vivo. Moreover, biodistribution experiments with (l3l)I-labeled or Cy5.5-conjugated BmKCT revealed that BmKCT selectively targeted the glioma in situ. Our data suggest that BmKCT could be exploited as a potential therapeutic for glioma diagnosis and therapy.
Brain Research, 2010
Transplants of olfactory ensheathing cells (OECs) cultured from the olfactory bulb are able to in... more Transplants of olfactory ensheathing cells (OECs) cultured from the olfactory bulb are able to induce structural regeneration of severed central axons and return of function in rat models. For clinical purposes it would be preferable to obtain the cells from the more accessible olfactory mucosa in the nasal lining. However, in our laboratory preparations cultures from mucosal samples yielded around 5% of OECs compared with the 50% obtained from samples cultured from the bulb, and when transplanted these mucosal cell preparations were less effective at repair. There are a number of manipulations which may increase the OEC content and the effectiveness of mucosal preparations, but in vivo transplantation would be a highly labour intensive method for evaluating them. As a candidate for a high throughput assay to screen for beneficial effects of modifications to mucosal cells we here report the effects of co-culture of the cells with retinal explants. Both bulbar and mucosal cell preparations prolong the survival of the explants. Counts of the surviving retinal ganglion cells, identified by β-III-tubulin immunohistochemistry and by their axon trajectory, show that the bulbar cell preparations have around twice the potency of those from the mucosa. This in vitro system, therefore, provides a bioassay that discriminates bulbar and mucosal cell preparations, and a useful tool for evaluating the functional effects of manipulations of cultured mucosal preparations.
Antimicrobial Agents and Chemotherapy, 2009
The pace of resistance against antibiotics almost exceeds that of the development of new drugs. A... more The pace of resistance against antibiotics almost exceeds that of the development of new drugs. As many bacteria have become resistant to conventional antibiotics, new drugs or drug resources are badly needed to combat antibiotic-resistant pathogens, like methicillin-resistant Staphylococcus aureus (MRSA). Antimicrobial peptides, rich sources existing in nature, are able to effectively kill multidrug-resistant pathogens. Here, imcroporin, a new antimicrobial peptide, was screened and isolated from the cDNA library of the venomous gland of Isometrus maculates . The MIC of imcroporin against MRSA was 50 μg/ml, 8-fold lower than that of cefotaxime and 40-fold lower than that of penicillin. Imcroporin killed bacteria rapidly in vitro, inhibited bacterial growth, and cured infected mice. These results revealed that imcroporin could be considered a potential anti-infective drug or lead compound, especially for treating antibiotic-resistant pathogens.
Amino Acids, 2011
Identification of cytotoxic T lymphocyte (CTL) epitopes from tumor antigens is essential for the ... more Identification of cytotoxic T lymphocyte (CTL) epitopes from tumor antigens is essential for the development of peptide vaccines against tumor immunotherapy. Among all the tumor antigens, the caner-testis (CT) antigens are the most widely studied and promising targets. PLAC1 (placenta-specific 1, CT92) was considered as a novel member of caner-testis antigen, which expressed in a wide range of human malignancies, most frequently in breast cancer. In this study, three native peptides and their analogues derived from PLAC1 were predicted by T cell epitope prediction programs including SYFPEITHI, BI-MAS and NetCTL 1.2. Binding affinity and stability assays in T2 cells showed that two native peptides, p28 and p31, and their analogues (p28-1Y9 V, p31-1Y2L) had more potent binding activity towards HLA-A*0201 molecule. In ELISPOT assay, the CTLs induced by these four peptides could release IFN-c. The CTLs induced by these four peptides from the peripheral blood mononuclear cells (PBMCs) of HLA-A*02 ? healthy donor could lyse MCF-7 breast cancer cells (HLA-A*0201 ? , PLAC1 ?) in vitro. When immunized in HLA-A2.1/K b transgenic mice, the peptide p28 could induce the most potent peptide-specific CTLs among these peptides. Therefore, our results indicated that the peptide p28 (VLCSIDWFM) could serve as a novel candidate epitope for the development of peptide vaccines against PLAC1-positive breast cancer.
F1000Research, 2015
Anti-dsDNA antibodies are the most studied antibodies of the lupus-related autoantibodies. The do... more Anti-dsDNA antibodies are the most studied antibodies of the lupus-related autoantibodies. The dogma is that these are the most important autoantibodies in systemic lupus erythematosus. In this review, evidence is presented to show that these antibodies (as measured by modern clinical laboratories) are not the most important autoantibodies in the diagnosis of systemic lupus erythematosus, and are of limited value in clinical correlation and in predicting disease flares. In addition, they are not likely to be the initiating autoantibodies in lupus nephritis. Thus, several pervasively held beliefs on anti-dsDNA antibodies are not valid. We suggest that anti-dsDNA antibodies should be considered as just one of the many autoantibodies associated with systemic lupus erythematosus.
2010 Asia-Pacific Power and Energy Engineering Conference, 2010
ABSTRACT CO2 capture processes by carbonation-calcination cycles of CaO/CaCO3 were limited by the... more ABSTRACT CO2 capture processes by carbonation-calcination cycles of CaO/CaCO3 were limited by the carbonation conversion and sorbents reutilization with the number of carbonation/calcinations cycles. In order to optimizing the CaO/CaCO3 cycles, BP neural network model and PID temperature control system were established based on the simulation of the process parameters and dynamic characteristics. The carbonization/calcination temperature, the mass fraction of additives for sorbents and calcination time were selected for the input conditions, while the output conditions were capture capacity and the reutilization of sorbents. Genetic algorithm(GA) model is established to optimize the PID controller's proportional coefficient kp, integral coefficient k1, and differential coefficient kD. The results indicated that BPNN coupled with PID model could form a complete optimization strategy for CO2 capture process by CaO/CaCO3 cycles.
2011 IEEE Vehicular Technology Conference (VTC Fall), 2011
ABSTRACT To cope with the too much energy consumption of base station (BS), this paper firstly gi... more ABSTRACT To cope with the too much energy consumption of base station (BS), this paper firstly gives a green heterogeneous network architecture, in which some BSs could be switched off or set as sleep mode when its local traffic is low, while the resident users rely on the mobile relay network composed by intelligent mobile nodes to connect to one of its neighboring BSs. Moreover, in order to achieve better performance, a mathematical model for relay selection is proposed by considering multiple factors, such as secrecy capacity (SC) for selected channels, remained energy¿iRE¿j for relays and location information. Accordingly, a novel dynamic relay selection approach based on Principal Component Analysis (PCA) is brought forward. Using this approach,the related factors which affect the quality of service (QoS) provisioning most could be found out by processing the observation data, and the their weights could be computed in a real-time way as well. The significant property of this approach is to reduce the useless energy loss by removing the redundant parameters. Finally, simulation results prove that the proposed approach outweights the existing ones in terms of system rewards, average throughput, and network lifetime.
5th International Conference on Pervasive Computing and Applications, 2010
Opportunistic networking-forwarding messages in a disconnected mobile ad hoc network via any enco... more Opportunistic networking-forwarding messages in a disconnected mobile ad hoc network via any encountered nodes-offers a new mechanism for exploiting the mobile devices that many users already carry. However, forwarding messages in such a network is trapped by many particular challenges, and some protocols have contributed to solve them partly. In this paper, we propose heterogeneous content-aware routing protocol (HCR) for opportunistic network, an approach containing basic cognitive thoughts, that focuses on optimal efficiency, based on the distinct significance of content renders distinguish priorities, including the quantity of copy, TTL and so on, in the process of transmission. Simulation results reflect that compared with the Spray-and-wait and Prophet, the HCR improves the performance of the delivery ratio and delay of the network.
TELKOMNIKA Indonesian Journal of Electrical Engineering, 2012
Since malwares contain stalling codes, malicious behaviors can’t be detected in emulated analysis... more Since malwares contain stalling codes, malicious behaviors can’t be detected in emulated analysis environment. This paper proposes an approach to detect malicious behaviors by evade stalling codes. First, we executed a malware in the emulated analysis environment, and saved every executed instruction in a trace file; Second, we began to detect stalling codes with the trace file, and constructed stalling code evasive points; At last, we executed the malware again and evade stalling codes with the evasive points, and then the malicious behaviors detected. It has been proven by experiments that the approach can evade stalling codes to detect the later malware behaviors effectively, and improve the performance of detecting the malicious behaviors in the emulated analysis environment. DOI: http://dx.doi.org/10.11591/telkomnika.v10i7.1573 Full Text: PDF
2011 7th International Conference on Wireless Communications, Networking and Mobile Computing, 2011
Fusion decision plays an important part in the cooperation sensing of cognitive radio. In this pa... more Fusion decision plays an important part in the cooperation sensing of cognitive radio. In this paper, a fusion decision algorithm based on channel estimation (FD_CE) is proposed in the architecture of central cooperative sensing in cognitive radio. Instead of the traditional hard decision methods such as AND, OR, Most, we consult to a soft decision algorithm which combines all the detected information of different secondary user (SU) by a linear weight of their channel gains. The algorithm proposed has evaluated the reliability about each secondary user's radio environment, so it brings a better sensing performance. Simulation results show that a higher probability of detection can be achieved using the proposed algorithm comparing with single node sensing, cooperative sensing by AND and OR rules; meanwhile, it decrease the detection threshold effectively at the same time, which means saving single node's hardware cost in other words.
PLoS genetics, 2013
Nucleosome occupancy controls the accessibility of the transcription machinery to DNA regulatory ... more Nucleosome occupancy controls the accessibility of the transcription machinery to DNA regulatory regions and serves an instructive role for gene expression. Chromatin remodelers, such as the BAF complexes, are responsible for establishing nucleosome occupancy patterns, which are key to epigenetic regulation along with DNA methylation and histone modifications. Some reports have assessed the roles of the BAF complex subunits and stemness in murine embryonic stem cells. However, the details of the relationships between remodelers and transcription factors in altering chromatin configuration, which ultimately affects gene expression during cell differentiation, remain unclear. Here for the first time we demonstrate that SNF5, a core subunit of the BAF complex, negatively regulates OCT4 levels in pluripotent cells and is essential for cell survival during differentiation. SNF5 is responsible for generating nucleosome-depleted regions (NDRs) at the regulatory sites of OCT4 repressed targ...
Journal of Proteome Research, 2007
Potassium channels show a huge variability in the affinity when recognizing enormous bioactive pe... more Potassium channels show a huge variability in the affinity when recognizing enormous bioactive peptides, and the elucidation of their recognition mechanism remains a great challenge due to an undetermined peptide-channel complex structure. Here, we employed combined computation methods to study the specific binding of BeKm-1 peptide to the hERG potassium channel, which is an essential determinant of the long-QT syndrome. By the use of a segment-assembly homology modeling method, the closed-state hERG structure containing unusual longer S5P linker was successfully constructed. It has a "petunia" shape, while four "petals" of symmetrically distributed S5P segments always decentralize. Starting from the hERG and BeKm-1 structures, a considerably reasonable BeKm-1-hERG complex structure was then screened out and identified by protein-protein docking, molecular dynamics (MD) simulations, and calculation of relative binding free energies. The validity of this predicted complex was further assessed by computational alanine-scanning, with the results correlating reasonably well with experimental data. In the novel complex structure, four considerably flexible S5P linkers are far from the BeKm-1 peptide. The BeKm-1 mainly uses its helical region to associate the channel outer vestibule, except for the S5P linker region; however, structural analysis further implies this neutral pore region with wiggling S5P linker is highly beneficial to the binding of BeKm-1 with lower positive charges. The most critical Lys18 of BeKm-1 plugs its side chain into the channel selectivity filter, while the secondarily important Arg20 forms three hydrogen bonds with spatially neighboring residues in the hERG channel. Different from the classical peptide-K + channel interaction mainly induced by electrostatic interaction, a synergetic effect of the electrostatic and van der Waals interactions was found to mediate the molecular recognition between BeKm-1 and the hERG channel. And this specific binding process is revealed to be a dynamic change of reduction of binding free energy and conformational rearrangement mainly in the interface of both BeKm-1 and the hERG channel. All these structural and energy features yield deep insights on the high selective binding mechanism of hERGspecific peptides, present a diversity of peptide-K + channel interactions, and also provide important clues to further study structure-function relationships of the hERG channel.
Journal of Computational Biology, 2012
Current network analysis methods all focus on one or multiple networks of the same type. However,... more Current network analysis methods all focus on one or multiple networks of the same type. However, cells are organized by multi-layer networks (e.g., transcriptional regulatory networks, splicing regulatory networks, protein-protein interaction networks), which interact and influence each other. Elucidating the coupling mechanisms among those different types of networks is essential in understanding the functions and mechanisms of cellular activities. In this article, we developed the first computational method for pattern mining across many two-layered graphs, with the two layers representing different types yet coupled biological networks. We formulated the problem of identifying frequent coupled clusters between the two layers of networks into a tensor-based computation problem, and proposed an efficient solution to solve the problem. We applied the method to 38 two-layered co-transcription and co-splicing networks, derived from 38 RNA-seq datasets. With the identified atlas of coupled transcription-splicing modules, we explored to what extent, for which cellular functions, and by what mechanisms transcription-splicing coupling takes place.
IUBMB Life (International Union of Biochemistry and Molecular Biology: Life), 2005
A series of isoforms of a-KT 6 14 (short chain potassium channel scorpion toxins) were isolated f... more A series of isoforms of a-KT 6 14 (short chain potassium channel scorpion toxins) were isolated from the venom of Buthus martensii Karsch by RACE and screening cDNA library methods. These isoforms adding BmKK 1-3 and BmSKTx 1-2 together shared high homology (more than 97%) with each other. The result of genomic sequence analysis showed that a length 79bp intron is inserted Ala codes between the first and the second base at the 17th amino acid of signal peptide. The introns of these isoforms also share high homology with those of BmKK 2 and BmSKT 6 1 reported previously. Sequence analysis of many clones of cDNA and genomic DNA showed that a species population or individual polymorphism of a-KT 6 14 genes took place in scorpion Buthus martensii Karsch and accelerated evolution played an important role in the forming process of a-KT 6 14 scorpion toxins subfamily. The result of southern hybridization indicated that a-KT 6 14 toxin genes existed in scorpion chromosome with multicopies. All findings maybe provided an important evidence for an extensive evolutionary process of the scorpion ''pharmacological factory'': at the early course of evolution, the ancestor toxic gene duplicated into a series of multicopy genes integrated at the different chromosome; at the late course of evolution, subsequent functional divergence of duplicate genes was generated by mutations, deletions and insertion.
International Immunopharmacology, 2006
Vascular endothelial cells (ECs) that initiate tumor angiogenesis may acquire distinct properties... more Vascular endothelial cells (ECs) that initiate tumor angiogenesis may acquire distinct properties after conditioning in tumor microenvironment as compared to ECs in non-malignant tissues. Thus far, most in vitro studies of angiogenesis used ECs isolated from normal tissues, which may not fully represent the nature of ECs in tumor vasculature. In this study, glioma-derived microvascular ECs (GDMEC) were purified from human glioma tissues by incubating with magnetic beads coated with anti-CD105 antibody and highly pure (98%) preparations of GDMEC were obtained. These cells exhibited typical EC phenotype, and proliferated rapidly in culture. Interestingly, GDMEC expressed higher levels of VEGF receptors, flt-1 and flk-1, as compared to an established human EC cell line ECV304 and primary human umbilical vascular EC (HUVEC). Functionally, GDMEC were capable of forming intercellular junctions and tubule-like structures (TLS) of various sizes. Stimulation by VEGF further promoted TLS formation with diverse tubular walls by GDMEC. In contrast, TLS formed by ECV304 and HUVEC showed significantly different features. We further observed that Nordy, a synthetic lipoxygenase inhibitor, potently inhibited TLS formation by GDMEC. The results suggest that isolation of highly pure ECs derived from tumor tissues is more appropriate for studies of tumor angiogenesis and for test of potential anti-cancer therapeutic targets.
Glia, 2012
Increased intraocular pressure (IOP) damages the retinal ganglion cell axons as they pass through... more Increased intraocular pressure (IOP) damages the retinal ganglion cell axons as they pass through the optic nerve head (ONH). The massive connective tissue structure of the human lamina cribrosa is generally assumed to be the pressure transducer responsible for the damage. The rat, however, with no lamina cribrosa, suffers the same glaucomatous response to raised IOP. Here, we show that the astrocytes of the rat ONH are "fortified" by extraordinarily dense cytoskeletal filaments that would make them ideal transducers of distorting mechanical forces. The ONH astrocytes are arranged as a fan-like radial array, firmly attached ventrally to the sheath of the ONH by thick basal processes, but dividing dorsally into progressively more slender processes with only delicate attachments to the sheath. At 1 week after raising the IOP by an injection of magnetic microspheres into the anterior eye chamber, the fine dorsal processes of the ONH astrocytes are torn away from the surroundi...
Cancer Letters, 2010
Malignant gliomas are the most common primary brain tumors associated with significant morbidity ... more Malignant gliomas are the most common primary brain tumors associated with significant morbidity and mortality. How to target the tumor in situ, and inhibit tumor cell proliferation and invasion is the key for therapy. Gliomas express a glioma-specific chloride ion channel that is sensitive to toxins including BmKCT. In the current study, the inhibitory effect of BmKCT on glioma growth was observed in vivo using the glioma/SD rat model. Furthermore, BmKCT prevented the metastasis of glioma cells in vivo. Moreover, biodistribution experiments with (l3l)I-labeled or Cy5.5-conjugated BmKCT revealed that BmKCT selectively targeted the glioma in situ. Our data suggest that BmKCT could be exploited as a potential therapeutic for glioma diagnosis and therapy.
Brain Research, 2010
Transplants of olfactory ensheathing cells (OECs) cultured from the olfactory bulb are able to in... more Transplants of olfactory ensheathing cells (OECs) cultured from the olfactory bulb are able to induce structural regeneration of severed central axons and return of function in rat models. For clinical purposes it would be preferable to obtain the cells from the more accessible olfactory mucosa in the nasal lining. However, in our laboratory preparations cultures from mucosal samples yielded around 5% of OECs compared with the 50% obtained from samples cultured from the bulb, and when transplanted these mucosal cell preparations were less effective at repair. There are a number of manipulations which may increase the OEC content and the effectiveness of mucosal preparations, but in vivo transplantation would be a highly labour intensive method for evaluating them. As a candidate for a high throughput assay to screen for beneficial effects of modifications to mucosal cells we here report the effects of co-culture of the cells with retinal explants. Both bulbar and mucosal cell preparations prolong the survival of the explants. Counts of the surviving retinal ganglion cells, identified by β-III-tubulin immunohistochemistry and by their axon trajectory, show that the bulbar cell preparations have around twice the potency of those from the mucosa. This in vitro system, therefore, provides a bioassay that discriminates bulbar and mucosal cell preparations, and a useful tool for evaluating the functional effects of manipulations of cultured mucosal preparations.
Antimicrobial Agents and Chemotherapy, 2009
The pace of resistance against antibiotics almost exceeds that of the development of new drugs. A... more The pace of resistance against antibiotics almost exceeds that of the development of new drugs. As many bacteria have become resistant to conventional antibiotics, new drugs or drug resources are badly needed to combat antibiotic-resistant pathogens, like methicillin-resistant Staphylococcus aureus (MRSA). Antimicrobial peptides, rich sources existing in nature, are able to effectively kill multidrug-resistant pathogens. Here, imcroporin, a new antimicrobial peptide, was screened and isolated from the cDNA library of the venomous gland of Isometrus maculates . The MIC of imcroporin against MRSA was 50 μg/ml, 8-fold lower than that of cefotaxime and 40-fold lower than that of penicillin. Imcroporin killed bacteria rapidly in vitro, inhibited bacterial growth, and cured infected mice. These results revealed that imcroporin could be considered a potential anti-infective drug or lead compound, especially for treating antibiotic-resistant pathogens.
Amino Acids, 2011
Identification of cytotoxic T lymphocyte (CTL) epitopes from tumor antigens is essential for the ... more Identification of cytotoxic T lymphocyte (CTL) epitopes from tumor antigens is essential for the development of peptide vaccines against tumor immunotherapy. Among all the tumor antigens, the caner-testis (CT) antigens are the most widely studied and promising targets. PLAC1 (placenta-specific 1, CT92) was considered as a novel member of caner-testis antigen, which expressed in a wide range of human malignancies, most frequently in breast cancer. In this study, three native peptides and their analogues derived from PLAC1 were predicted by T cell epitope prediction programs including SYFPEITHI, BI-MAS and NetCTL 1.2. Binding affinity and stability assays in T2 cells showed that two native peptides, p28 and p31, and their analogues (p28-1Y9 V, p31-1Y2L) had more potent binding activity towards HLA-A*0201 molecule. In ELISPOT assay, the CTLs induced by these four peptides could release IFN-c. The CTLs induced by these four peptides from the peripheral blood mononuclear cells (PBMCs) of HLA-A*02 ? healthy donor could lyse MCF-7 breast cancer cells (HLA-A*0201 ? , PLAC1 ?) in vitro. When immunized in HLA-A2.1/K b transgenic mice, the peptide p28 could induce the most potent peptide-specific CTLs among these peptides. Therefore, our results indicated that the peptide p28 (VLCSIDWFM) could serve as a novel candidate epitope for the development of peptide vaccines against PLAC1-positive breast cancer.