Nucleosomes play a vital role in chromatin organization and gene regulation,acting as key hubs that inter-act with various chromatin-associated factors through diverse binding mechanisms.Recent research has highlighte...Nucleosomes play a vital role in chromatin organization and gene regulation,acting as key hubs that inter-act with various chromatin-associated factors through diverse binding mechanisms.Recent research has highlighted the prevalence of mutations in linker histones across different types of cancer,emphasizing their critical involvement in cancer progression.These cancer-associated mutations in linker histones have been shown to disrupt nucleosome stacking and the formation of higher-order chromatin structures,which in turn significantly affect epigenetic regulatory processes.In this review,we provide a comprehensive analysis of how cancer-associated linker histone mutations alter their physicochemical properties,influencing their binding to nucleosomes,and overall chromatin architecture.Additionally,we explore the significant impact of mutations near post-translational modification sites,which further modulate chromatin dynamics and regulatory functions,offering insights into their role in oncogenesis and potential therapeutic targets.展开更多
Linkers were assembled on a glass surface based on the hydrolysis and condensation of 3-glycidoxy￣propyltrimethoxysilane (GPS). After the assembly of GPS, four approaches were tried to open the ending epoxide group o...Linkers were assembled on a glass surface based on the hydrolysis and condensation of 3-glycidoxy￣propyltrimethoxysilane (GPS). After the assembly of GPS, four approaches were tried to open the ending epoxide group of GPS or to further elongate the linkers. The effect of these approaches on DNA in situ synthesis and hybridization was investigated. For the spacing of the synthesis initiation sites, the wettability of the support and the length of the linking group that attaches the initiation site to the surface have direct influences on the yield of coupling reactions and the subsequent hybridization events. X-ray photoelectron spectroscopy (XPS) and mean contact angles of deionized water of the above slides were measured to assess the linker's characteristics in each procedure. It was proved that the glass slides were successfully modified and became excellent supports for the oligonucleotides synthesis. In addition, it proved best for the in situ oligonucleotides synthesis that a glass slide was in turn treated with ethylenediamine, glutaradehyde, ethanolamine and sodium borohydride solution at ambient temperature after silanized with GPS.展开更多
Objective To design and develop a novel, sensitive and versatile method for in vivo foot printing and studies of DNA damage, such as DNA adducts and strand breaks. Methods Starting with mammalian genomic DNA, singl...Objective To design and develop a novel, sensitive and versatile method for in vivo foot printing and studies of DNA damage, such as DNA adducts and strand breaks. Methods Starting with mammalian genomic DNA, single-stranded products were made by repeated primer extension, these products were ligated to a double-stranded linker having a randomized 3 overhang, and used for PCR. DNA breaks in p53 gene produced by restriction endonuclease AfaI were detected by using this new method followed by Southern hybridization with DIG-labeled probe. Results This randomized terminal linker-dependent PCR (RDPCR) method could generate band signals many-fold stronger than conventional ligation-mediated PCR (LMPCR), and it was more rapid, convenient and accurate than the terminal transferase-dependent PCR (TDPCR). Conclusion DNA strand breakage can be detected sensitively in the gene level by RDPCR. Any lesion that blocks primer extension should be detectable.展开更多
Carbon super-heterostructures with high nitrogen contents from the covalent hybrid precursors of covalent triazine frameworks(CTFs)and zeolitic imidazolic frameworks(ZIFs)are scarcely explored because of CTF's ord...Carbon super-heterostructures with high nitrogen contents from the covalent hybrid precursors of covalent triazine frameworks(CTFs)and zeolitic imidazolic frameworks(ZIFs)are scarcely explored because of CTF's ordered structure and toxic superacid that dissolves or destabilizes the metal nodes.To solve this problem,herein,we report a straightforward two-step pathway for the covalent hybridization of disordered CTF(d–CTF)–ZIF composites via preincorporation of an imidazole(IM)linker into ordered CTFs,followed by the imidazole-site-specific covalent growth of ZIFs.Direct carbonization of these synthesized d–CTF−IM−ZIF hybrids results in unique hollow carbon super-heterostructures with ultrahigh nitrogen content(>18.6%),high specific surface area(1663m^(2)g^(−1)),and beneficial trace metal(Co/Zn NPs)contents for promoting the redox pseudocapacitance.As proof of concept,the obtained carbon super-heterostructure(Co–Zn–NC_(SNH)–800)is used as a positive electrode in an asymmetric supercapacitor,demonstrating a remarkable energy density of 61Wh kg^(−1)and extraordinary cyclic stability of 97%retention after 30,000 cycles at the cell level.Our presynthetic modifications of CTF and their covalent hybridization with ZIF crystals pave the way toward new design strategies for synthesizing functional porous carbon materials for promising energy applications.展开更多
Linker histones, e.g., H1, are best known for their ability to bind to nucleosomes and stabilize both nucleosome structure and condensed higher-order chromatin structures. However, over the years many investigators ha...Linker histones, e.g., H1, are best known for their ability to bind to nucleosomes and stabilize both nucleosome structure and condensed higher-order chromatin structures. However, over the years many investigators have reported specific interactions between linker histones and proteins involved in important cellular processes. The purpose of this review is to highlight evidence indicating an important alternative mode of action for H1, namely protein-protein interactions. We first review key aspects of the traditional view of linker histone action, including the importance of the H1 C-terminal domain. We then discuss the current state of knowledge of linker histone interactions with other proteins, and, where possible, highlight the mechanism of linker histone-mediated protein-protein interactions. Taken together, the data suggest a combinatorial role for the linker histones, functioning both as primary chromatin architectural proteins and simultaneously as recruitment hubs for proteins involved in accessing and modifying the chromatin fiber.展开更多
Dimerization is an effective strategy for designing antimicrobial peptides that combine the advantages of different native peptides. In this study, we explored the effects of different linker amino acids, including le...Dimerization is an effective strategy for designing antimicrobial peptides that combine the advantages of different native peptides. In this study, we explored the effects of different linker amino acids, including leucine, proline and aminocaproic acid, on the anticancer, antimicrobial and hemolytic activities of the heteromeric antimicrobial peptides AM-1, AM-2, and AM-3. Proline and aminocaproic acid are ideal linkers for increasing the potency and selectivity of heteromeric antimicrobial peptides. The results of MD simulations provided a rationalization for this observation. Both AM-2, which had a proline linker,and AM-3, which had an aminocaproic acid linker, adopted a compact conformation in water and a bent conformation in membranes. This change in the flexible structures of AM-2 and AM-3 could have resulted in decreased binding of these peptides to zwitterionic lipid bilayers and increased damage to mixed lipid bilayers containing acidic phospholipids. In short, these findings obtained via assessing the effects of linker amino acids will contribute to the design of ideal heteromeric antimicrobial peptides with high selectivity and potency.展开更多
Herein,we report a microwave-assisted acid-induced post-treatment method for the formation of linker vacancies within Zr-based metal organic frameworks(Zr-MOFs).The number of linker vacancies can be easily regulated w...Herein,we report a microwave-assisted acid-induced post-treatment method for the formation of linker vacancies within Zr-based metal organic frameworks(Zr-MOFs).The number of linker vacancies can be easily regulated with this method by changing the concentration of the HCl solution and the duration of microwave irradiation.The optimized defective UiO-66 showed higher linker defects with a higher specific surface area and thermal stability.The results of the catalytic cyclization of citronella showed that the Zr-MOFs with more defects exhibited enhanced catalytic performance.This work may provide a new method for the creation of defective MOFs with high activity and stability.展开更多
Two new different metal-organic frameworks(MOFs)[Ba(L1)(H_(2)O)_(2)]_(n)·nH_(2)O(MOF 1)and[Ba(L2)(-n2 O)_(2)]_(n)·0.5 nDMF·0.5 nH_(2)O(MOF 2)were yielded by the assembly of oxygen-friendly Ba(Ⅱ)ions an...Two new different metal-organic frameworks(MOFs)[Ba(L1)(H_(2)O)_(2)]_(n)·nH_(2)O(MOF 1)and[Ba(L2)(-n2 O)_(2)]_(n)·0.5 nDMF·0.5 nH_(2)O(MOF 2)were yielded by the assembly of oxygen-friendly Ba(Ⅱ)ions and two similar linkers,namely 2-(imidazol-1-yl)terephthalic acid(H_(2)L1)and 2-(1 H-1,2,4-triazol-1-yl)terephthalic acid(H_(2)L2).Single-crystal X-ray diffractions(XRD)indicate that MOF1 is a new three-dimensional(3 D)stacking dense network formed by the one-dimensional(1 D)rod-shaped chains and L1 linkers,whereas MOF 2 presents a 3 D nanotube porous framework with cylindrical tunnels based on the 1 D loop chains as the secondary building units(SBUs)by replacing the imidazole group in H_(2)L1 with the triazole group in H_(2)L2.As a result,MOF 2 has a higher density of active sites and Lewis acid sites in the porous surface of nanotube than MOF 1.Thereby,the CO_(2)capture and separation capacity of MOF 2 is great higher than that of CH_(4)at298 K.展开更多
When rhodamine-based fluorescent probe dyes are used to track target molecules they always perturb the behavior of target molecules because of steric hindrance effect. In order to minimize potential steric problems, a...When rhodamine-based fluorescent probe dyes are used to track target molecules they always perturb the behavior of target molecules because of steric hindrance effect. In order to minimize potential steric problems, a kind of rhodamine-based fluorescent probe dye with spacer linker arm was designed and synthesized and its application in immunofluorescence histochemistry was investigated.展开更多
基金supported by the National Natural Science Foundation of China(No.12205112)financially supported by self-determined research funds of CCNU from the colleges’basic research and operation of MOE(CCNU24JC012)supported by Natural Science Foundation of Wuhan(No.2024040801020302).
文摘Nucleosomes play a vital role in chromatin organization and gene regulation,acting as key hubs that inter-act with various chromatin-associated factors through diverse binding mechanisms.Recent research has highlighted the prevalence of mutations in linker histones across different types of cancer,emphasizing their critical involvement in cancer progression.These cancer-associated mutations in linker histones have been shown to disrupt nucleosome stacking and the formation of higher-order chromatin structures,which in turn significantly affect epigenetic regulatory processes.In this review,we provide a comprehensive analysis of how cancer-associated linker histone mutations alter their physicochemical properties,influencing their binding to nucleosomes,and overall chromatin architecture.Additionally,we explore the significant impact of mutations near post-translational modification sites,which further modulate chromatin dynamics and regulatory functions,offering insights into their role in oncogenesis and potential therapeutic targets.
文摘Linkers were assembled on a glass surface based on the hydrolysis and condensation of 3-glycidoxy￣propyltrimethoxysilane (GPS). After the assembly of GPS, four approaches were tried to open the ending epoxide group of GPS or to further elongate the linkers. The effect of these approaches on DNA in situ synthesis and hybridization was investigated. For the spacing of the synthesis initiation sites, the wettability of the support and the length of the linking group that attaches the initiation site to the surface have direct influences on the yield of coupling reactions and the subsequent hybridization events. X-ray photoelectron spectroscopy (XPS) and mean contact angles of deionized water of the above slides were measured to assess the linker's characteristics in each procedure. It was proved that the glass slides were successfully modified and became excellent supports for the oligonucleotides synthesis. In addition, it proved best for the in situ oligonucleotides synthesis that a glass slide was in turn treated with ethylenediamine, glutaradehyde, ethanolamine and sodium borohydride solution at ambient temperature after silanized with GPS.
基金天津市高等学校科技发展计划基金(20030309)天津医科大学科学基金(2003Ky33)+1 种基金Supported by Foundation for Science Technology Program of Tianjin Higher Education(20030309)the Science Foundation of Tianjin Medical University(2003ky33)
基金This work was supported by the National Natural Science Foundation of China (Grant No.30070648).
文摘Objective To design and develop a novel, sensitive and versatile method for in vivo foot printing and studies of DNA damage, such as DNA adducts and strand breaks. Methods Starting with mammalian genomic DNA, single-stranded products were made by repeated primer extension, these products were ligated to a double-stranded linker having a randomized 3 overhang, and used for PCR. DNA breaks in p53 gene produced by restriction endonuclease AfaI were detected by using this new method followed by Southern hybridization with DIG-labeled probe. Results This randomized terminal linker-dependent PCR (RDPCR) method could generate band signals many-fold stronger than conventional ligation-mediated PCR (LMPCR), and it was more rapid, convenient and accurate than the terminal transferase-dependent PCR (TDPCR). Conclusion DNA strand breakage can be detected sensitively in the gene level by RDPCR. Any lesion that blocks primer extension should be detectable.
基金Ministry of Trade,Industry&Energy of Korea,Grant/Award Number:RS‐2022‐00155717National Research Foundation of Korea,Grant/Award Numbers:2020H1D3A1A04081472,2022M3J1A1054323。
文摘Carbon super-heterostructures with high nitrogen contents from the covalent hybrid precursors of covalent triazine frameworks(CTFs)and zeolitic imidazolic frameworks(ZIFs)are scarcely explored because of CTF's ordered structure and toxic superacid that dissolves or destabilizes the metal nodes.To solve this problem,herein,we report a straightforward two-step pathway for the covalent hybridization of disordered CTF(d–CTF)–ZIF composites via preincorporation of an imidazole(IM)linker into ordered CTFs,followed by the imidazole-site-specific covalent growth of ZIFs.Direct carbonization of these synthesized d–CTF−IM−ZIF hybrids results in unique hollow carbon super-heterostructures with ultrahigh nitrogen content(>18.6%),high specific surface area(1663m^(2)g^(−1)),and beneficial trace metal(Co/Zn NPs)contents for promoting the redox pseudocapacitance.As proof of concept,the obtained carbon super-heterostructure(Co–Zn–NC_(SNH)–800)is used as a positive electrode in an asymmetric supercapacitor,demonstrating a remarkable energy density of 61Wh kg^(−1)and extraordinary cyclic stability of 97%retention after 30,000 cycles at the cell level.Our presynthetic modifications of CTF and their covalent hybridization with ZIF crystals pave the way toward new design strategies for synthesizing functional porous carbon materials for promising energy applications.
文摘Linker histones, e.g., H1, are best known for their ability to bind to nucleosomes and stabilize both nucleosome structure and condensed higher-order chromatin structures. However, over the years many investigators have reported specific interactions between linker histones and proteins involved in important cellular processes. The purpose of this review is to highlight evidence indicating an important alternative mode of action for H1, namely protein-protein interactions. We first review key aspects of the traditional view of linker histone action, including the importance of the H1 C-terminal domain. We then discuss the current state of knowledge of linker histone interactions with other proteins, and, where possible, highlight the mechanism of linker histone-mediated protein-protein interactions. Taken together, the data suggest a combinatorial role for the linker histones, functioning both as primary chromatin architectural proteins and simultaneously as recruitment hubs for proteins involved in accessing and modifying the chromatin fiber.
基金the National Natural Science Foundation of China(Nos. 81773566, 21602092, 81473095)the Fundamental Research Funds for the Central Universities(Nos. lzujbky-2017-134, lzujbky-2017-120, lzujbky-2016-21)
文摘Dimerization is an effective strategy for designing antimicrobial peptides that combine the advantages of different native peptides. In this study, we explored the effects of different linker amino acids, including leucine, proline and aminocaproic acid, on the anticancer, antimicrobial and hemolytic activities of the heteromeric antimicrobial peptides AM-1, AM-2, and AM-3. Proline and aminocaproic acid are ideal linkers for increasing the potency and selectivity of heteromeric antimicrobial peptides. The results of MD simulations provided a rationalization for this observation. Both AM-2, which had a proline linker,and AM-3, which had an aminocaproic acid linker, adopted a compact conformation in water and a bent conformation in membranes. This change in the flexible structures of AM-2 and AM-3 could have resulted in decreased binding of these peptides to zwitterionic lipid bilayers and increased damage to mixed lipid bilayers containing acidic phospholipids. In short, these findings obtained via assessing the effects of linker amino acids will contribute to the design of ideal heteromeric antimicrobial peptides with high selectivity and potency.
基金supported by the National Natural Science Foundation of China (No.21573063)the Hunan Provincial Natural Science Foundation of Youth Fund (No.2020JJ3002)+1 种基金Open Fund from Hunan Provincial Key Laboratory of Advanced Materials for New Energy Storage and Conversion (No.2018TP1037201902)the Training Program of Hunan University of Youth Fund。
文摘Herein,we report a microwave-assisted acid-induced post-treatment method for the formation of linker vacancies within Zr-based metal organic frameworks(Zr-MOFs).The number of linker vacancies can be easily regulated with this method by changing the concentration of the HCl solution and the duration of microwave irradiation.The optimized defective UiO-66 showed higher linker defects with a higher specific surface area and thermal stability.The results of the catalytic cyclization of citronella showed that the Zr-MOFs with more defects exhibited enhanced catalytic performance.This work may provide a new method for the creation of defective MOFs with high activity and stability.
基金the National Natural Science Foundation of China(Nos.21971207 and21801111)the Project of Central Plains Science and Technology Innovation Leading Talents of Henan Province(No.204200510001)the Natural Science Foundation of Shaanxi Province(No.2019JM-013)。
文摘Two new different metal-organic frameworks(MOFs)[Ba(L1)(H_(2)O)_(2)]_(n)·nH_(2)O(MOF 1)and[Ba(L2)(-n2 O)_(2)]_(n)·0.5 nDMF·0.5 nH_(2)O(MOF 2)were yielded by the assembly of oxygen-friendly Ba(Ⅱ)ions and two similar linkers,namely 2-(imidazol-1-yl)terephthalic acid(H_(2)L1)and 2-(1 H-1,2,4-triazol-1-yl)terephthalic acid(H_(2)L2).Single-crystal X-ray diffractions(XRD)indicate that MOF1 is a new three-dimensional(3 D)stacking dense network formed by the one-dimensional(1 D)rod-shaped chains and L1 linkers,whereas MOF 2 presents a 3 D nanotube porous framework with cylindrical tunnels based on the 1 D loop chains as the secondary building units(SBUs)by replacing the imidazole group in H_(2)L1 with the triazole group in H_(2)L2.As a result,MOF 2 has a higher density of active sites and Lewis acid sites in the porous surface of nanotube than MOF 1.Thereby,the CO_(2)capture and separation capacity of MOF 2 is great higher than that of CH_(4)at298 K.
文摘When rhodamine-based fluorescent probe dyes are used to track target molecules they always perturb the behavior of target molecules because of steric hindrance effect. In order to minimize potential steric problems, a kind of rhodamine-based fluorescent probe dye with spacer linker arm was designed and synthesized and its application in immunofluorescence histochemistry was investigated.
