Giant cell arteritis(GCA)is a commonly occurring large vacuities characterized by angiopathy of medium and large-sized vessels.GCA granulomatous formation plays an important role in the pathogenesis of GCA.Analysis of...Giant cell arteritis(GCA)is a commonly occurring large vacuities characterized by angiopathy of medium and large-sized vessels.GCA granulomatous formation plays an important role in the pathogenesis of GCA.Analysis of T cell lineages and signaling pathways in GCA have revealed the essential role of T cells in the pathology of GCA.T cells are the dominant population present in GCA lesions.CD4+T cell subtypes that are present include Th1,Th2,Th9,Th17,follicular helper T(Tfh)cells,and regulatory T(Treg)cells.CD8 T cells can primarily differentiate into cytotoxic CD8+T lymphocytes and Treg cells.The instrumental part of GCA is the interplay between dendritic cells,macrophages and endothelial cells,which can result in the vascular injury and the characteristics granulomatous infiltrates formation.During the inflammatory loop of GCA,several signaling pathways have been reported to play an essential role in recruiting,activating and differentiating T cells,including T-cell receptor(TCR)signaling,vascular endothelial growth factor(VEGF)-Jagged-Notch signaling and the Janus kinase and signal transducer and activator of transcription(STAT)pathway(JAK-STAT)pathway.In this review,we have focused on the role of T cells and their potential signaling mechanism(s)that are involved in the pathogenesis of GCA.A better understanding of the role of T cells mediated complicated orchestration during the homeostasis and the changes could possibly favor developments of novel treatment strategies against immunological disorders associated with GCA.展开更多
The presence of hepatitis B virus (HBV) proteins leads to changes in the cellular gene expression. As a consequence, the cellular signaling processes are influenced by the actions of HBV proteins. It has been shown th...The presence of hepatitis B virus (HBV) proteins leads to changes in the cellular gene expression. As a consequence, the cellular signaling processes are influenced by the actions of HBV proteins. It has been shown that HBV nucleocapsid protein and the amino-terminal part of polymerase termed as terminal protein (TP) could inhibit interferon signaling. Further, the global gene expression profiles differ in hepatoma cells with and without HBV gene expression and replication. The expression of interferon (IFN) stimulated genes (ISGs) was differently regulated in cells with HBV replication and could be modulated by antiviral treatments. The HBV TP has been found to modulate the ISG expression and enhance the HBV replication. The modulation of the cellular signaling processes by HBV may have significant implications for pathogenesis.展开更多
The regulatory mechanisms in cellular signaling systems have been studied intensively from the viewpoint that the malfunction of the regulation is thought to be one of the substantial causes of cancer formation. On th...The regulatory mechanisms in cellular signaling systems have been studied intensively from the viewpoint that the malfunction of the regulation is thought to be one of the substantial causes of cancer formation. On the other hand, it is rather difficult to develop the theoretical framework for investigation of the regulatory mechanisms due to their complexity and nonlinearity. In this study, more general approach is proposed for elucidation of characteristics of the stability in cellular signaling systems by construction of mathematical models for a class of cellular signaling systems and stability analysis of the models over variation of the network architectures and the parameter values. The model system is formulated as regulatory network in which every node represents a phosphorylation-dephosphorylation cyclic reaction for respective constituent enzyme. The analysis is performed for all variations of the regulatory networks comprised of two nodes with multiple feedback regulation loops. It is revealed from the analysis that the regulatory networks become mono-stable, bi-stable, tri-stable, or oscillatory and that the negative mutual feedback or positive mutual feedback is favorable for multi-stability, which is augmented by a negatively regulated node with a positive auto-regulation. Furthermore, the multi-stability or the oscillation is more likely to emerge in the case of low value of the Michaelis constant than in the case of high value, implying that the condition of higher saturation levels induces stronger nonlinearity in the networks. The analysis for the parameter regions yielding the multi-stability and the oscillation clarified that the stronger regulation shifts the systems toward multi-stability.展开更多
In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to th...In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to the changes (emergency) of kinetic behaviors of signaling system compared with single molecule or pathway. Depending on the known experimental data, we have constructed a model for complex cellular signaling transduction system, which is derived from signaling transduction of epidermal growth factor receptor in neuron. By the computational simulating methods, the self-adaptive controls of this system have been investigated. We find that this model exhibits a relatively stable selfadaptive system, especially to over-stimulation of agonist, and the amplitude and duration of signaling intermediates in it could be controlled by multiple self-adaptive effects, such as 'signal scattering', 'positive feedback', 'negative feedback' and 'B-Raf shunt'. Our results provide an approach to understanding the dynamic behaviors of complex biological systems.展开更多
The complexity of signal controlled traffic largely stems from the various driving behaviors developed in response to the traffic signal. However, the existing models take a few driving behaviors into account and cons...The complexity of signal controlled traffic largely stems from the various driving behaviors developed in response to the traffic signal. However, the existing models take a few driving behaviors into account and consequently the traffic dynamics has not been completely explored. Therefore, a new cellular automaton model, which incorporates the driving behaviors typically manifesting during the different stages when the vehicles are moving toward a traffic light, is proposed in this paper. Numerical simulations have demonstrated that the proposed model can produce the spontaneous traffic breakdown and the dissolution of the over-saturated traffic phenomena. Furthermore, the simulation results indicate that the slow-to-start behavior and the inch-forward behavior can foster the traffic breakdown. Particularly, it has been discovered that the over-saturated traffic can be revised to be an under-saturated state when the slow-down behavior is activated after the spontaneous breakdown. Finally, the contributions of the driving behaviors on the traffic breakdown have been examined.展开更多
The rapid developing of the fourth generation(4G)wireless communications has aroused tremendous demands for high speed data transmission due to the dissemination of various types of the intelligent user terminals as w...The rapid developing of the fourth generation(4G)wireless communications has aroused tremendous demands for high speed data transmission due to the dissemination of various types of the intelligent user terminals as well as the wireless multi-media services.It is predicted that the network throughput will increase展开更多
The interaction between dansyl-labeled pollen calmodulin (D-pCaM) and synthesized peptides was studied in the presence of Ca2+ by fluorescence spectra. It is Found that Gly/L-Ala --> D-Ala substitution in peptide c...The interaction between dansyl-labeled pollen calmodulin (D-pCaM) and synthesized peptides was studied in the presence of Ca2+ by fluorescence spectra. It is Found that Gly/L-Ala --> D-Ala substitution in peptide chains caused great changes in their affinity for pCaM. Besides. our data provided evidence on the dissimilarity of different CaMs although they have highly-conserved structures. A preliminary study was carried out on the effects of CaM-binding peptides on cellular signal transduction, cell proliferation, showing the participation of CaM in cell functions mentioned above.展开更多
Sorafenib, the unique drug as first-line treatment for advanced hepatocellular carcinoma (HCC), has opened a window of hope after searching for effective agents to combat HCC for decades. However, the overall outcomes...Sorafenib, the unique drug as first-line treatment for advanced hepatocellular carcinoma (HCC), has opened a window of hope after searching for effective agents to combat HCC for decades. However, the overall outcomes are far from satisfactory. One of the explanations is the genetic heterogeneity of HCC, which has led to identifying predictive biomarkers for primary resistance to sorafenib, and then applying the concept of personalized medicine, or seeking therapeutic strategies such as combining sorafenib with other anticancer agents. Some of the combinations have demonstrated a better effectiveness than sorafenib alone, with good tolerance. The acquired resistance to sorafenib has also drawn attention. As a multikinase inhibitor, sorafenib targets several cellular signaling pathways but simultaneously or sequentially the addiction switches and compensatory pathways are activated. Several mechanisms are involved in the acquired resistance to sorafenib, such as crosstalks involving PI3K/Akt and JAK-STAT pathways, hypoxia-inducible pathways, epithelial-mesenchymal transition, etc . Based on the investigated mechanisms,some other molecular targeted drugs have been applied as second-line treatment for treat HCC after the failure of sorafenib therapy and more are under evaluation in clinical trials. However, the exact mechanisms accounting for sorafenib resistance remains unclear. Further investigation on the crosstalk and relationship of associated pathways will better our understanding of the mechanisms and help to find effective strategies for overcoming sorafenib resistance in HCC.展开更多
Liver regeneration is a complex and well-orchestrated process,during which hepatic cells are activated to produce large signal molecules in response to liver injury or mass reduction.These signal molecules,in turn,set...Liver regeneration is a complex and well-orchestrated process,during which hepatic cells are activated to produce large signal molecules in response to liver injury or mass reduction.These signal molecules,in turn,set up the connections and cross-talk among liver cells to promote hepatic recovery.In this review,we endeavor to summarize the network of signal molecules that mediates hepatic cell communication in the regulation of liver regeneration.展开更多
Since damaged neural circuits are not generally self-recovered, developing methods to stimulate neurogenesis is critically required. Most studies have examined the effects of soluble pharma- cological factors on the c...Since damaged neural circuits are not generally self-recovered, developing methods to stimulate neurogenesis is critically required. Most studies have examined the effects of soluble pharma- cological factors on the cellular neurogenesis. On the other hand, it is now recognized that the other extracellular factors, including material and mechanical cues, also have a strong potential to induce cellular neurogenesis. This article will review recent data on the material （chemical patterning, micro/nano-topography, carbon nanotube, graphene） and mechanical （static cue from substrate stiffness, dynamic cue from stretch and flow shear） stimulations of cellular neuro- genesis. These approaches may provide new neural regenerative medicine protocols. Scaffolding material templates capable of triggering cellular neurogenesis can be explored in the presence of neurogenesis-stimulatory mechanical environments, and also with conventional soluble factors, to enhance axonal growth and neural network formation in neural tissue engineering.展开更多
OAM (Operations, Administration and Maintenance) system is a very impo rtant component of 3G cellular network. In order to acquire overall managemen t, fast response and steady operation, an SCTP (Stream Control Trans...OAM (Operations, Administration and Maintenance) system is a very impo rtant component of 3G cellular network. In order to acquire overall managemen t, fast response and steady operation, an SCTP (Stream Control Transmission Prot ocol) based OAM, i.e., SOAM system was proposed. SOAM implements new characters of SCTP such as multi-stream, enforced SACK and heartbeat mechanism on its tran sport layer. These characters help SOAM decrease the message transmission delay and accelerate the link failure detection. Besides, a new component named SOAM agent was introduced to improve the operation efficiency of SOAM. The experim ental results prove the proposed SOAM system achieves better performance on sign aling transmission compared with conventional TCP based OAM system.展开更多
基金supported by National Natural Science Foundation of China(Number:8187061400)。
文摘Giant cell arteritis(GCA)is a commonly occurring large vacuities characterized by angiopathy of medium and large-sized vessels.GCA granulomatous formation plays an important role in the pathogenesis of GCA.Analysis of T cell lineages and signaling pathways in GCA have revealed the essential role of T cells in the pathology of GCA.T cells are the dominant population present in GCA lesions.CD4+T cell subtypes that are present include Th1,Th2,Th9,Th17,follicular helper T(Tfh)cells,and regulatory T(Treg)cells.CD8 T cells can primarily differentiate into cytotoxic CD8+T lymphocytes and Treg cells.The instrumental part of GCA is the interplay between dendritic cells,macrophages and endothelial cells,which can result in the vascular injury and the characteristics granulomatous infiltrates formation.During the inflammatory loop of GCA,several signaling pathways have been reported to play an essential role in recruiting,activating and differentiating T cells,including T-cell receptor(TCR)signaling,vascular endothelial growth factor(VEGF)-Jagged-Notch signaling and the Janus kinase and signal transducer and activator of transcription(STAT)pathway(JAK-STAT)pathway.In this review,we have focused on the role of T cells and their potential signaling mechanism(s)that are involved in the pathogenesis of GCA.A better understanding of the role of T cells mediated complicated orchestration during the homeostasis and the changes could possibly favor developments of novel treatment strategies against immunological disorders associated with GCA.
基金Deutsche Forschungsgemeinschaft (Lu 669/2-1, GRK1045/1, and Lu 669/5-1)Joint program of Deutscher Akademischer Austauschdienst and Chinese Academy of Science
文摘The presence of hepatitis B virus (HBV) proteins leads to changes in the cellular gene expression. As a consequence, the cellular signaling processes are influenced by the actions of HBV proteins. It has been shown that HBV nucleocapsid protein and the amino-terminal part of polymerase termed as terminal protein (TP) could inhibit interferon signaling. Further, the global gene expression profiles differ in hepatoma cells with and without HBV gene expression and replication. The expression of interferon (IFN) stimulated genes (ISGs) was differently regulated in cells with HBV replication and could be modulated by antiviral treatments. The HBV TP has been found to modulate the ISG expression and enhance the HBV replication. The modulation of the cellular signaling processes by HBV may have significant implications for pathogenesis.
文摘The regulatory mechanisms in cellular signaling systems have been studied intensively from the viewpoint that the malfunction of the regulation is thought to be one of the substantial causes of cancer formation. On the other hand, it is rather difficult to develop the theoretical framework for investigation of the regulatory mechanisms due to their complexity and nonlinearity. In this study, more general approach is proposed for elucidation of characteristics of the stability in cellular signaling systems by construction of mathematical models for a class of cellular signaling systems and stability analysis of the models over variation of the network architectures and the parameter values. The model system is formulated as regulatory network in which every node represents a phosphorylation-dephosphorylation cyclic reaction for respective constituent enzyme. The analysis is performed for all variations of the regulatory networks comprised of two nodes with multiple feedback regulation loops. It is revealed from the analysis that the regulatory networks become mono-stable, bi-stable, tri-stable, or oscillatory and that the negative mutual feedback or positive mutual feedback is favorable for multi-stability, which is augmented by a negatively regulated node with a positive auto-regulation. Furthermore, the multi-stability or the oscillation is more likely to emerge in the case of low value of the Michaelis constant than in the case of high value, implying that the condition of higher saturation levels induces stronger nonlinearity in the networks. The analysis for the parameter regions yielding the multi-stability and the oscillation clarified that the stronger regulation shifts the systems toward multi-stability.
基金This research is supported by the National Natural Science Foundation of China (No. 70071040).
文摘In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to the changes (emergency) of kinetic behaviors of signaling system compared with single molecule or pathway. Depending on the known experimental data, we have constructed a model for complex cellular signaling transduction system, which is derived from signaling transduction of epidermal growth factor receptor in neuron. By the computational simulating methods, the self-adaptive controls of this system have been investigated. We find that this model exhibits a relatively stable selfadaptive system, especially to over-stimulation of agonist, and the amplitude and duration of signaling intermediates in it could be controlled by multiple self-adaptive effects, such as 'signal scattering', 'positive feedback', 'negative feedback' and 'B-Raf shunt'. Our results provide an approach to understanding the dynamic behaviors of complex biological systems.
基金supported by the National Basic Research Program of China(Grand No.2012CB723303)the Beijing Committee of Science and Technology,China(Grand No.Z1211000003120100)
文摘The complexity of signal controlled traffic largely stems from the various driving behaviors developed in response to the traffic signal. However, the existing models take a few driving behaviors into account and consequently the traffic dynamics has not been completely explored. Therefore, a new cellular automaton model, which incorporates the driving behaviors typically manifesting during the different stages when the vehicles are moving toward a traffic light, is proposed in this paper. Numerical simulations have demonstrated that the proposed model can produce the spontaneous traffic breakdown and the dissolution of the over-saturated traffic phenomena. Furthermore, the simulation results indicate that the slow-to-start behavior and the inch-forward behavior can foster the traffic breakdown. Particularly, it has been discovered that the over-saturated traffic can be revised to be an under-saturated state when the slow-down behavior is activated after the spontaneous breakdown. Finally, the contributions of the driving behaviors on the traffic breakdown have been examined.
文摘The rapid developing of the fourth generation(4G)wireless communications has aroused tremendous demands for high speed data transmission due to the dissemination of various types of the intelligent user terminals as well as the wireless multi-media services.It is predicted that the network throughput will increase
文摘The interaction between dansyl-labeled pollen calmodulin (D-pCaM) and synthesized peptides was studied in the presence of Ca2+ by fluorescence spectra. It is Found that Gly/L-Ala --> D-Ala substitution in peptide chains caused great changes in their affinity for pCaM. Besides. our data provided evidence on the dissimilarity of different CaMs although they have highly-conserved structures. A preliminary study was carried out on the effects of CaM-binding peptides on cellular signal transduction, cell proliferation, showing the participation of CaM in cell functions mentioned above.
基金Supported by Grants from the National Natural Scientific Foundation of China,No.30973474 and 81272467
文摘Sorafenib, the unique drug as first-line treatment for advanced hepatocellular carcinoma (HCC), has opened a window of hope after searching for effective agents to combat HCC for decades. However, the overall outcomes are far from satisfactory. One of the explanations is the genetic heterogeneity of HCC, which has led to identifying predictive biomarkers for primary resistance to sorafenib, and then applying the concept of personalized medicine, or seeking therapeutic strategies such as combining sorafenib with other anticancer agents. Some of the combinations have demonstrated a better effectiveness than sorafenib alone, with good tolerance. The acquired resistance to sorafenib has also drawn attention. As a multikinase inhibitor, sorafenib targets several cellular signaling pathways but simultaneously or sequentially the addiction switches and compensatory pathways are activated. Several mechanisms are involved in the acquired resistance to sorafenib, such as crosstalks involving PI3K/Akt and JAK-STAT pathways, hypoxia-inducible pathways, epithelial-mesenchymal transition, etc . Based on the investigated mechanisms,some other molecular targeted drugs have been applied as second-line treatment for treat HCC after the failure of sorafenib therapy and more are under evaluation in clinical trials. However, the exact mechanisms accounting for sorafenib resistance remains unclear. Further investigation on the crosstalk and relationship of associated pathways will better our understanding of the mechanisms and help to find effective strategies for overcoming sorafenib resistance in HCC.
文摘Liver regeneration is a complex and well-orchestrated process,during which hepatic cells are activated to produce large signal molecules in response to liver injury or mass reduction.These signal molecules,in turn,set up the connections and cross-talk among liver cells to promote hepatic recovery.In this review,we endeavor to summarize the network of signal molecules that mediates hepatic cell communication in the regulation of liver regeneration.
基金supported by NE EPSCo R Trans-disciplinary Neuroscience Research Seed GrantNSF CAREER Award 1351570+2 种基金AHA Scientist Development Grant 12SDG12030109Osteology Foundation Grant 12-006Nebraska Research Initiative
文摘Since damaged neural circuits are not generally self-recovered, developing methods to stimulate neurogenesis is critically required. Most studies have examined the effects of soluble pharma- cological factors on the cellular neurogenesis. On the other hand, it is now recognized that the other extracellular factors, including material and mechanical cues, also have a strong potential to induce cellular neurogenesis. This article will review recent data on the material （chemical patterning, micro/nano-topography, carbon nanotube, graphene） and mechanical （static cue from substrate stiffness, dynamic cue from stretch and flow shear） stimulations of cellular neuro- genesis. These approaches may provide new neural regenerative medicine protocols. Scaffolding material templates capable of triggering cellular neurogenesis can be explored in the presence of neurogenesis-stimulatory mechanical environments, and also with conventional soluble factors, to enhance axonal growth and neural network formation in neural tissue engineering.
基金High-Tech Research and DevelopmentProgram of China (No. 2003AA123310)
文摘OAM (Operations, Administration and Maintenance) system is a very impo rtant component of 3G cellular network. In order to acquire overall managemen t, fast response and steady operation, an SCTP (Stream Control Transmission Prot ocol) based OAM, i.e., SOAM system was proposed. SOAM implements new characters of SCTP such as multi-stream, enforced SACK and heartbeat mechanism on its tran sport layer. These characters help SOAM decrease the message transmission delay and accelerate the link failure detection. Besides, a new component named SOAM agent was introduced to improve the operation efficiency of SOAM. The experim ental results prove the proposed SOAM system achieves better performance on sign aling transmission compared with conventional TCP based OAM system.
