The WD40 domain exhibits aβ-propeller architecture,often comprising seven blades.The WD40 domain is one of the most abundant domains and also among the top interacting domains in eukaryotic genomes.In this review,we ...The WD40 domain exhibits aβ-propeller architecture,often comprising seven blades.The WD40 domain is one of the most abundant domains and also among the top interacting domains in eukaryotic genomes.In this review,we will discuss the identification,definition and architecture of the WD40 domains.WD40 domain proteins are involved in a large variety of cellular processes,in which WD40 domains function as a protein-protein or protein-DNA interaction platform.WD40 domain mediates molecular recognition events mainly through the smaller top surface,but also through the bottom surface and sides.So far,no WD40 domain has been found to display enzymatic activity.We will also discuss the different binding modes exhibited by the large versatile family of WD40 domain proteins.In the last part of this review,we will discuss how post-translational modifications are recognized by WD40 domain proteins.展开更多
MAP kinases are evolutionarily conserved signaling regulators from budding yeast to mammals and play essential roles in both innate and adaptive immune responses.There are three main families of MAPKs in mammals.Each ...MAP kinases are evolutionarily conserved signaling regulators from budding yeast to mammals and play essential roles in both innate and adaptive immune responses.There are three main families of MAPKs in mammals.Each of them has its own activators,inactivators,substrates and scaffolds,which altogether form a fine signaling network in response to different extracellular or intracellular stimulation.In this review,we summarize recent advances in understanding of the regulation of MAP kinases and the roles of MAP kinases in innate and adaptive immune responses.Cellular & Molecular Immunology.2005;2(1):20-27.展开更多
As a newly discovered type of RNA, circular RNAs(circRNAs) are widespread throughout the eukaryotic genome. The expression of circRNAs is regulated by both cis-elements and trans-factors, and the expression pattern of...As a newly discovered type of RNA, circular RNAs(circRNAs) are widespread throughout the eukaryotic genome. The expression of circRNAs is regulated by both cis-elements and trans-factors, and the expression pattern of circRNAs is cell type-and diseasespecific. Similar to other types of non-coding RNAs, functions of circRNAs are also versatile. CircRNAs have been reported previously to function as microRNA(miRNA) sponges, protein sponges, coding RNAs or scaffolds for protein complexes.Recently, several circRNAs have been reported to play important roles in human malignancies, including glioma. Here, we reviewed several reports related to circRNAs and glioma, as well as the potential diagnostic and therapeutic applications of circRNAs in brain cancer. In general, some circRNAs, such as circSMARCA5 and circCFH, are found to be expressed in a gliomaspecific pattern, these circRNAs may be used as tumor biomarkers. In addition, some circRNAs have been found to play oncogenic roles in glioma(e.g., circNFIX and circNT5E), whereas others have been reported to function as tumor suppressors(e.g.,circFBXW7 and circSHPRH). Furthermore, circRNA is a good tool for protein expression because of its higher stability compared to linear RNAs. Thus, circRNAs may also be an ideal choice for gene/protein delivery in future brain cancer therapies. There are some challenges in circRNA research in glioma and other diseases. Research related to circRNAs in glioma is comparatively new and many mysteries remain to be solved.展开更多
Spinal cord injury results in the loss of motor and sensory pathways and spontaneous regeneration of adult mammalian spinal cord neurons is limited. Chitosan and sodium alginate have good biocompatibility, biodegradab...Spinal cord injury results in the loss of motor and sensory pathways and spontaneous regeneration of adult mammalian spinal cord neurons is limited. Chitosan and sodium alginate have good biocompatibility, biodegradability, and are suitable to assist the recovery of damaged tissues, such as skin, bone and nerve. Chitosan scaffolds, sodium alginate scaffolds and chitosan-sodium alginate scaffolds were separately transplanted into rats with spinal cord hemisection. Basso-Beattie-Bresnahan locomotor rating scale scores and electrophysiological results showed that chitosan scaffolds promoted recovery of locomotor capacity and nerve transduction of the experimental rats.Sixty days after surgery, chitosan scaffolds retained the original shape of the spinal cord. Compared with sodium alginate scaffolds- and chitosan-sodium alginate scaffolds-transplanted rats, more neurofilament-H-immunoreactive cells （regenerating nerve fibers） and less glial fibrillary acidic protein-immunoreactive cells （astrocytic scar tissue） were observed at the injury site of experimental rats in chitosan scaffold-transplanted rats. Due to the fast degradation rate of sodium alginate, sodium alginate scaffolds and composite material scaffolds did not have a supporting and bridging effect on the damaged tissue. Above all, compared with sodium alginate and composite material scaffolds, chitosan had better biocompatibility, could promote the regeneration of nerve fibers and prevent the formation of scar tissue,and as such, is more suitable to help the repair of spinal cord injury.展开更多
Proteins are a class of biomaterials having a vast array of functions, including the catalysis of metabolic reactions, DNA replication, stimuli response and transportation of molecules. Recent progress in laser-based...Proteins are a class of biomaterials having a vast array of functions, including the catalysis of metabolic reactions, DNA replication, stimuli response and transportation of molecules. Recent progress in laser-based fabrication technologies has enabled the formation of three-dimensional （3D） proteinaceous micro- and nano-structures by femtosecond laser cross-linking, which has expanded the possible applications of proteins. This article reviews the current knowledge andrecent advancements in the femtosecond laser cross-linking of proteins. An overview of previous studies related to fabri-cation using a variety of proteins and detailed discussions of the associated mechanisms are provided. In addition, ad-vances and applications utilizing specific protein functions are introduced. This review thus provides a valuable summaryof the 3D micro- and nano-fabrication of proteins for biological and medical applications.展开更多
Recently,a number of studies reported that casein was composed of various multifunctional bioactive peptides such as casein phosphopeptide andβ-casochemotide-1 that bind calcium ions and induce macrophage chemotaxis,...Recently,a number of studies reported that casein was composed of various multifunctional bioactive peptides such as casein phosphopeptide andβ-casochemotide-1 that bind calcium ions and induce macrophage chemotaxis,which is crucial for bone homeostasis and bone fracture repair by cytokines secreted in the process.We hypothesized that the effects of the multifunctional biopeptides in casein would contribute to improving bone regeneration.Thus,we designed a tissue engineering platform that consisted of casein and polyvinyl alcohol,which was a physical-crosslinked scaffold(milk-derived protein;MDP),via simple freeze-thaw cycles and performed surface modification using 3,4-dihydroxy-L-phenylalanine(DOPA),a mussel adhesive protein,for immobilizing adhesive proteins and cytokines for recruiting cells in vivo(MDP-DOPA).Both the MDP and MDP-DOPA groups proved indirectly contribution of macrophages migration as RAW 264.7 cells were highly migrated toward materials by contained bioactive peptides.We implanted MDP and MDP-DOPA in a mouse calvarial defect orthotopic model and evaluated whether MDP-DOPA showed much faster mineral deposition and higher bone density than that of the no-treatment and MDP groups.The MDP-DOPA group showed the accumulation of host M2 macrophages and mesenchymal stem cells(MSCs)around the scaffold,whereas MDP presented mostly M1 macrophages in the early stage.展开更多
Spinal cord injury results in the loss of motor and sensory pathways and spontaneous regeneration of adult mammalian spinal cord neurons is limited. Chitosan and sodium alginate have good biocompatibility, biodegradab...Spinal cord injury results in the loss of motor and sensory pathways and spontaneous regeneration of adult mammalian spinal cord neurons is limited. Chitosan and sodium alginate have good biocompatibility, biodegradability, and are suitable to assist the recovery of damaged tissues, such as skin, bone and nerve. Chitosan scaffolds, sodium alginate scaffolds and chitosan-sodium alginate scaffolds were separately transplanted into rats with spinal cord hemisection. Basso-Beattie-Bresnahan locomotor rating scale scores and electrophysiological results showed that chitosan scaffolds promoted recovery of locomotor capacity and nerve transduction of the experimental rats.Sixty days after surgery, chitosan scaffolds retained the original shape of the spinal cord. Compared with sodium alginate scaffolds- and chitosan-sodium alginate scaffolds-transplanted rats, more neurofilament-H-immunoreactive cells （regenerating nerve fibers） and less glial fibrillary acidic protein-immunoreactive cells （astrocytic scar tissue） were observed at the injury site of experimental rats in chitosan scaffold-transplanted rats. Due to the fast degradation rate of sodium alginate, sodium alginate scaffolds and composite material scaffolds did not have a supporting and bridging effect on the damaged tissue. Above all, compared with sodium alginate and composite material scaffolds, chitosan had better biocompatibility, could promote the regeneration of nerve fibers and prevent the formation of scar tissue,and as such, is more suitable to help the repair of spinal cord injury.展开更多
Asymmetric cell division is an important mechanism for creating diversity in a cellular population. Stem cells commonly perform asymmetric division to generate both a daughter stem cell for self-renewal and a more dif...Asymmetric cell division is an important mechanism for creating diversity in a cellular population. Stem cells commonly perform asymmetric division to generate both a daughter stem cell for self-renewal and a more differentiated daughter cell to populate the tissue. During asymmetric cell division, protein cell fate determinants asymmetrically localize to the opposite poles of a dividing cell to cause distinct cell fate. However, it remains unclear whether cell fate determination is robust to fluctuations and noise during this spatial allocation process. To answer this question, we engineered Caulobacter, a bacterial model for asymmetric division, to express synthetic scaffolds with modular protein interaction domains. These scaffolds perturbed the spatial distribution of the PleC-DivJ- DivK phospho-signaling network without changing their endogenous expression levels. Surprisingly, enforcing symmetrical distribution of these cell fate de terminants did not result in symmetric daughter fate or any morphological defects. Further computational analysis suggested that PleC and DivJ form a robust phospho-switch that can tolerate high amount of spatial variation. This insight may shed light on the presence of similar phospho-switches in stem cell asymmetric division regulation. Overall, our study demonstrates that synthetic protein scaffolds can provide a useful tool to probe biological systems for better understanding of their operating principles.展开更多
基金This research was supported by the Structural Genomics Consortium,a registered charity(No.1097737)that receives funds fromthe Canadian Institutes for Health Research,the Canadian Foundation for Innovation,Genome Canada through the Ontario GenomicsInstitute,Glaxo Smith Kline,Karolinska Institutet,the Knut and Alice Wallenberg Foundation,the Ontario lnnovation Trust,the Ontario Ministry for Research and Innovation,Merck&Co.,Inc.,the Novartis Research Foundation,the Swedish Agency for Innovation Systems,the Swedish Foundation for Strategic Research and the Wellcome Trust.
文摘The WD40 domain exhibits aβ-propeller architecture,often comprising seven blades.The WD40 domain is one of the most abundant domains and also among the top interacting domains in eukaryotic genomes.In this review,we will discuss the identification,definition and architecture of the WD40 domains.WD40 domain proteins are involved in a large variety of cellular processes,in which WD40 domains function as a protein-protein or protein-DNA interaction platform.WD40 domain mediates molecular recognition events mainly through the smaller top surface,but also through the bottom surface and sides.So far,no WD40 domain has been found to display enzymatic activity.We will also discuss the different binding modes exhibited by the large versatile family of WD40 domain proteins.In the last part of this review,we will discuss how post-translational modifications are recognized by WD40 domain proteins.
文摘MAP kinases are evolutionarily conserved signaling regulators from budding yeast to mammals and play essential roles in both innate and adaptive immune responses.There are three main families of MAPKs in mammals.Each of them has its own activators,inactivators,substrates and scaffolds,which altogether form a fine signaling network in response to different extracellular or intracellular stimulation.In this review,we summarize recent advances in understanding of the regulation of MAP kinases and the roles of MAP kinases in innate and adaptive immune responses.Cellular & Molecular Immunology.2005;2(1):20-27.
文摘As a newly discovered type of RNA, circular RNAs(circRNAs) are widespread throughout the eukaryotic genome. The expression of circRNAs is regulated by both cis-elements and trans-factors, and the expression pattern of circRNAs is cell type-and diseasespecific. Similar to other types of non-coding RNAs, functions of circRNAs are also versatile. CircRNAs have been reported previously to function as microRNA(miRNA) sponges, protein sponges, coding RNAs or scaffolds for protein complexes.Recently, several circRNAs have been reported to play important roles in human malignancies, including glioma. Here, we reviewed several reports related to circRNAs and glioma, as well as the potential diagnostic and therapeutic applications of circRNAs in brain cancer. In general, some circRNAs, such as circSMARCA5 and circCFH, are found to be expressed in a gliomaspecific pattern, these circRNAs may be used as tumor biomarkers. In addition, some circRNAs have been found to play oncogenic roles in glioma(e.g., circNFIX and circNT5E), whereas others have been reported to function as tumor suppressors(e.g.,circFBXW7 and circSHPRH). Furthermore, circRNA is a good tool for protein expression because of its higher stability compared to linear RNAs. Thus, circRNAs may also be an ideal choice for gene/protein delivery in future brain cancer therapies. There are some challenges in circRNA research in glioma and other diseases. Research related to circRNAs in glioma is comparatively new and many mysteries remain to be solved.
基金supported by the National Natural Science Foundation of China,No.81671243 and 81373429
文摘Spinal cord injury results in the loss of motor and sensory pathways and spontaneous regeneration of adult mammalian spinal cord neurons is limited. Chitosan and sodium alginate have good biocompatibility, biodegradability, and are suitable to assist the recovery of damaged tissues, such as skin, bone and nerve. Chitosan scaffolds, sodium alginate scaffolds and chitosan-sodium alginate scaffolds were separately transplanted into rats with spinal cord hemisection. Basso-Beattie-Bresnahan locomotor rating scale scores and electrophysiological results showed that chitosan scaffolds promoted recovery of locomotor capacity and nerve transduction of the experimental rats.Sixty days after surgery, chitosan scaffolds retained the original shape of the spinal cord. Compared with sodium alginate scaffolds- and chitosan-sodium alginate scaffolds-transplanted rats, more neurofilament-H-immunoreactive cells （regenerating nerve fibers） and less glial fibrillary acidic protein-immunoreactive cells （astrocytic scar tissue） were observed at the injury site of experimental rats in chitosan scaffold-transplanted rats. Due to the fast degradation rate of sodium alginate, sodium alginate scaffolds and composite material scaffolds did not have a supporting and bridging effect on the damaged tissue. Above all, compared with sodium alginate and composite material scaffolds, chitosan had better biocompatibility, could promote the regeneration of nerve fibers and prevent the formation of scar tissue,and as such, is more suitable to help the repair of spinal cord injury.
文摘Proteins are a class of biomaterials having a vast array of functions, including the catalysis of metabolic reactions, DNA replication, stimuli response and transportation of molecules. Recent progress in laser-based fabrication technologies has enabled the formation of three-dimensional （3D） proteinaceous micro- and nano-structures by femtosecond laser cross-linking, which has expanded the possible applications of proteins. This article reviews the current knowledge andrecent advancements in the femtosecond laser cross-linking of proteins. An overview of previous studies related to fabri-cation using a variety of proteins and detailed discussions of the associated mechanisms are provided. In addition, ad-vances and applications utilizing specific protein functions are introduced. This review thus provides a valuable summaryof the 3D micro- and nano-fabrication of proteins for biological and medical applications.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2020R1A6A3A01098495,2020R1A6A1A03043283)by the Bio&Medical Technology Development Program of the National Research Foundation(NRF)funded by the Korean government(MSIT)(2018M3A9E2023259)supported by Basic Science Research Capacity Enhancement Project through Korea Basic Science Institute(National research Facilities and Equipment Center)grant funded by the Ministry of Education(2019R1A6C1010033).
文摘Recently,a number of studies reported that casein was composed of various multifunctional bioactive peptides such as casein phosphopeptide andβ-casochemotide-1 that bind calcium ions and induce macrophage chemotaxis,which is crucial for bone homeostasis and bone fracture repair by cytokines secreted in the process.We hypothesized that the effects of the multifunctional biopeptides in casein would contribute to improving bone regeneration.Thus,we designed a tissue engineering platform that consisted of casein and polyvinyl alcohol,which was a physical-crosslinked scaffold(milk-derived protein;MDP),via simple freeze-thaw cycles and performed surface modification using 3,4-dihydroxy-L-phenylalanine(DOPA),a mussel adhesive protein,for immobilizing adhesive proteins and cytokines for recruiting cells in vivo(MDP-DOPA).Both the MDP and MDP-DOPA groups proved indirectly contribution of macrophages migration as RAW 264.7 cells were highly migrated toward materials by contained bioactive peptides.We implanted MDP and MDP-DOPA in a mouse calvarial defect orthotopic model and evaluated whether MDP-DOPA showed much faster mineral deposition and higher bone density than that of the no-treatment and MDP groups.The MDP-DOPA group showed the accumulation of host M2 macrophages and mesenchymal stem cells(MSCs)around the scaffold,whereas MDP presented mostly M1 macrophages in the early stage.
文摘Spinal cord injury results in the loss of motor and sensory pathways and spontaneous regeneration of adult mammalian spinal cord neurons is limited. Chitosan and sodium alginate have good biocompatibility, biodegradability, and are suitable to assist the recovery of damaged tissues, such as skin, bone and nerve. Chitosan scaffolds, sodium alginate scaffolds and chitosan-sodium alginate scaffolds were separately transplanted into rats with spinal cord hemisection. Basso-Beattie-Bresnahan locomotor rating scale scores and electrophysiological results showed that chitosan scaffolds promoted recovery of locomotor capacity and nerve transduction of the experimental rats.Sixty days after surgery, chitosan scaffolds retained the original shape of the spinal cord. Compared with sodium alginate scaffolds- and chitosan-sodium alginate scaffolds-transplanted rats, more neurofilament-H-immunoreactive cells （regenerating nerve fibers） and less glial fibrillary acidic protein-immunoreactive cells （astrocytic scar tissue） were observed at the injury site of experimental rats in chitosan scaffold-transplanted rats. Due to the fast degradation rate of sodium alginate, sodium alginate scaffolds and composite material scaffolds did not have a supporting and bridging effect on the damaged tissue. Above all, compared with sodium alginate and composite material scaffolds, chitosan had better biocompatibility, could promote the regeneration of nerve fibers and prevent the formation of scar tissue,and as such, is more suitable to help the repair of spinal cord injury.
文摘Asymmetric cell division is an important mechanism for creating diversity in a cellular population. Stem cells commonly perform asymmetric division to generate both a daughter stem cell for self-renewal and a more differentiated daughter cell to populate the tissue. During asymmetric cell division, protein cell fate determinants asymmetrically localize to the opposite poles of a dividing cell to cause distinct cell fate. However, it remains unclear whether cell fate determination is robust to fluctuations and noise during this spatial allocation process. To answer this question, we engineered Caulobacter, a bacterial model for asymmetric division, to express synthetic scaffolds with modular protein interaction domains. These scaffolds perturbed the spatial distribution of the PleC-DivJ- DivK phospho-signaling network without changing their endogenous expression levels. Surprisingly, enforcing symmetrical distribution of these cell fate de terminants did not result in symmetric daughter fate or any morphological defects. Further computational analysis suggested that PleC and DivJ form a robust phospho-switch that can tolerate high amount of spatial variation. This insight may shed light on the presence of similar phospho-switches in stem cell asymmetric division regulation. Overall, our study demonstrates that synthetic protein scaffolds can provide a useful tool to probe biological systems for better understanding of their operating principles.
