Heterogeneous nuclear ribonucleoprotein (hnRNP) C plays a key role in RNA processing but also exerts a dominant negative effect on responses to 1,25-dihydroxyvitamin D (1,25(OH)2D) by functioning as a vitamin D ...Heterogeneous nuclear ribonucleoprotein (hnRNP) C plays a key role in RNA processing but also exerts a dominant negative effect on responses to 1,25-dihydroxyvitamin D (1,25(OH)2D) by functioning as a vitamin D response element-binding protein (VDRE-BP). hnRNPC acts a tetramer of hnRNPC1 (huC1) and hnRNPC2 (huC2), and organization of these subunits is critical to in vivo nucleic acid-binding. Overexpression of either huC1 or huC2 in human osteoblasts is sufficient to confer VDRE-BP suppression of 1,25(OH)2D-mediated transcription. However, huC1 or huC2 alone did not suppress 1,25(OH)2D-induced transcription in mouse osteoblastic cells. By contrast, overexpression of huC1 and huC2 in combination or transfection with a bone-specific polycistronic vector using a "self-cleaving" 2A peptide to co-express huC1/C2 suppressed 1,25D-mediated induction of osteoblast target gene expression. Structural diversity of hnRNPC between human/NWPs and mouse/rat/rabbit/dog was investigated by analysis of sequence variations within the hnRNP CLZ domain. The predicted loss of distal helical function in hnRNPC from lower species provides an explanation for the altered interaction between huC1/C2 and their mouse counterparts. These data provide new evidence of a role for hnRNPC1/C2 in 1,25(OH)2D-driven gene expression, and further suggest that species-specific tetramerization is a crucial determinant of its actions as a regulator of VDR-directed transactivation.展开更多
随着高压直流输电工程的不断投产,以及风电项目的增多,越来越多的风电场出现在电网换相换流器高压直流输电(line-commutated-converter based high voltage direct current,LCC-HVDC)受端换流站近区,两者构成的系统存在振荡风险。为此,...随着高压直流输电工程的不断投产,以及风电项目的增多,越来越多的风电场出现在电网换相换流器高压直流输电(line-commutated-converter based high voltage direct current,LCC-HVDC)受端换流站近区,两者构成的系统存在振荡风险。为此,该文针对直流受端馈入站与近区风电场系统的振荡特性展开研究。首先,建立并验证系统的状态空间模型,基于该模型计算出系统特征值,确定LCC-HVDC与风电场共同参与的振荡主导模式并进行参与因子分析。进一步地,通过对比是否接入LCC-HVDC的主导模式,得到LCC-HVDC的接入会削弱系统阻尼的结论。最后,从系统额定容量、交流系统短路比、风电场并网线路长度等方面探究系统稳定性的影响因素,并分析系统的不同短路比、潮流比对风机网侧换流器(grid-side converter,GSC)外环控制和换流站定电流控制器性能的影响。展开更多
基金supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number 5R01AR037399the UCLA Vector Core (Emmanuelle Faure and Kip Hermann) for vector and viral preparations supported by JCCC/P30 CA016042 and CURE/P30 DK41301
文摘Heterogeneous nuclear ribonucleoprotein (hnRNP) C plays a key role in RNA processing but also exerts a dominant negative effect on responses to 1,25-dihydroxyvitamin D (1,25(OH)2D) by functioning as a vitamin D response element-binding protein (VDRE-BP). hnRNPC acts a tetramer of hnRNPC1 (huC1) and hnRNPC2 (huC2), and organization of these subunits is critical to in vivo nucleic acid-binding. Overexpression of either huC1 or huC2 in human osteoblasts is sufficient to confer VDRE-BP suppression of 1,25(OH)2D-mediated transcription. However, huC1 or huC2 alone did not suppress 1,25(OH)2D-induced transcription in mouse osteoblastic cells. By contrast, overexpression of huC1 and huC2 in combination or transfection with a bone-specific polycistronic vector using a "self-cleaving" 2A peptide to co-express huC1/C2 suppressed 1,25D-mediated induction of osteoblast target gene expression. Structural diversity of hnRNPC between human/NWPs and mouse/rat/rabbit/dog was investigated by analysis of sequence variations within the hnRNP CLZ domain. The predicted loss of distal helical function in hnRNPC from lower species provides an explanation for the altered interaction between huC1/C2 and their mouse counterparts. These data provide new evidence of a role for hnRNPC1/C2 in 1,25(OH)2D-driven gene expression, and further suggest that species-specific tetramerization is a crucial determinant of its actions as a regulator of VDR-directed transactivation.
文摘随着高压直流输电工程的不断投产,以及风电项目的增多,越来越多的风电场出现在电网换相换流器高压直流输电(line-commutated-converter based high voltage direct current,LCC-HVDC)受端换流站近区,两者构成的系统存在振荡风险。为此,该文针对直流受端馈入站与近区风电场系统的振荡特性展开研究。首先,建立并验证系统的状态空间模型,基于该模型计算出系统特征值,确定LCC-HVDC与风电场共同参与的振荡主导模式并进行参与因子分析。进一步地,通过对比是否接入LCC-HVDC的主导模式,得到LCC-HVDC的接入会削弱系统阻尼的结论。最后,从系统额定容量、交流系统短路比、风电场并网线路长度等方面探究系统稳定性的影响因素,并分析系统的不同短路比、潮流比对风机网侧换流器(grid-side converter,GSC)外环控制和换流站定电流控制器性能的影响。
基金Space Medical Experiment Project of Chinese Manned Space Program (HYZHXM05003)Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences (CI2021A04905)。