The transcriptional factor GATA-6 gene produces two translational isoforms from a single mRNA through ribosomal leaky scanning. L-type GATA-6 has an extension of 146 amino acid residues at its amino terminus. In the e...The transcriptional factor GATA-6 gene produces two translational isoforms from a single mRNA through ribosomal leaky scanning. L-type GATA-6 has an extension of 146 amino acid residues at its amino terminus. In the extension, there is a unique PEST sequence (Glu31-Cys46), which is composed of an amino terminal Pro-rich segment and a carboxyl terminal Ser-cluster. Substitution of either half of the PEST sequence with Ala residues by cassette mutagenesis reduced the apparent molecular size of L-type GATA-6 on SDS-polyacrylamide gel-electrophoresis. However, the effect of substitution of the Pro-rich segment was much more significant;the mobility increase of the Pro-rich segment on the gel was 13% while that of the Ser-cluster was 8%. Substitution of each amino acid residue demonstrated that the effect of Pro substitution is greater than that of the Ser and Thr residues. Such increased mobility of L-type GATA-6 in the presence of a detergent may apparently correlate with the decrease in transcription activity in vivo as determined by means of luciferase reporter gene assay. The activity of ΔAla (with Ala residues instead of the PEST sequence) was reduced to one fifth of that of ΔA (with the PEST sequence). These results suggest that the PEST sequence of L-type GATA-6 does not function as a constitutive protein degradation signal, but rather plays structural and functional roles in the activation of gene expression on the GATA responsive promoter.展开更多
目的了解大气甲醛长期暴露与2型糖尿病发病风险之间的关联,为预防糖尿病发生和制定甲醛治理政策提供流行病学证据。方法基于2010—2016年在中国25个省份开展的中国家庭追踪调查(China Family Panel Studies,CFPS)收集参与者信息,甲醛数...目的了解大气甲醛长期暴露与2型糖尿病发病风险之间的关联,为预防糖尿病发生和制定甲醛治理政策提供流行病学证据。方法基于2010—2016年在中国25个省份开展的中国家庭追踪调查(China Family Panel Studies,CFPS)收集参与者信息,甲醛数据来源于比利时航天物理研究所(BIRA)提供的臭氧监测仪(OMI)数据,提取研究对象所在区县的对流层甲醛垂直柱平均浓度,代表参与者甲醛的长期暴露水平。采用R 4.1.3构建时间依存Cox比例风险回归模型,分析年均甲醛浓度与2型糖尿病发病风险的关联。结果共有29952名成年人纳入数据分析,平均随访年限为5.53年,总随访人年数为165679人年。甲醛浓度每提高一个四分位数间距(3.51×10^(15)molec/cm^(2)),2型糖尿病发病风险增加28%(HR=1.28,95%CI:1.09~1.51)。在年龄超过65岁的参与者(HR=1.44,95%CI:1.05~1.97)、女性(HR=1.40,95%CI:1.13~1.74)、北方居民(HR=1.34,95%CI:1.02~1.77)和使用非清洁燃料者(HR=1.46,95%CI:1.07~1.97)中,大气甲醛长期暴露与2型糖尿病发病风险关联性更强。结论大气甲醛长期暴露可能提高2型糖尿病发病风险。展开更多
文摘The transcriptional factor GATA-6 gene produces two translational isoforms from a single mRNA through ribosomal leaky scanning. L-type GATA-6 has an extension of 146 amino acid residues at its amino terminus. In the extension, there is a unique PEST sequence (Glu31-Cys46), which is composed of an amino terminal Pro-rich segment and a carboxyl terminal Ser-cluster. Substitution of either half of the PEST sequence with Ala residues by cassette mutagenesis reduced the apparent molecular size of L-type GATA-6 on SDS-polyacrylamide gel-electrophoresis. However, the effect of substitution of the Pro-rich segment was much more significant;the mobility increase of the Pro-rich segment on the gel was 13% while that of the Ser-cluster was 8%. Substitution of each amino acid residue demonstrated that the effect of Pro substitution is greater than that of the Ser and Thr residues. Such increased mobility of L-type GATA-6 in the presence of a detergent may apparently correlate with the decrease in transcription activity in vivo as determined by means of luciferase reporter gene assay. The activity of ΔAla (with Ala residues instead of the PEST sequence) was reduced to one fifth of that of ΔA (with the PEST sequence). These results suggest that the PEST sequence of L-type GATA-6 does not function as a constitutive protein degradation signal, but rather plays structural and functional roles in the activation of gene expression on the GATA responsive promoter.
文摘目的了解大气甲醛长期暴露与2型糖尿病发病风险之间的关联,为预防糖尿病发生和制定甲醛治理政策提供流行病学证据。方法基于2010—2016年在中国25个省份开展的中国家庭追踪调查(China Family Panel Studies,CFPS)收集参与者信息,甲醛数据来源于比利时航天物理研究所(BIRA)提供的臭氧监测仪(OMI)数据,提取研究对象所在区县的对流层甲醛垂直柱平均浓度,代表参与者甲醛的长期暴露水平。采用R 4.1.3构建时间依存Cox比例风险回归模型,分析年均甲醛浓度与2型糖尿病发病风险的关联。结果共有29952名成年人纳入数据分析,平均随访年限为5.53年,总随访人年数为165679人年。甲醛浓度每提高一个四分位数间距(3.51×10^(15)molec/cm^(2)),2型糖尿病发病风险增加28%(HR=1.28,95%CI:1.09~1.51)。在年龄超过65岁的参与者(HR=1.44,95%CI:1.05~1.97)、女性(HR=1.40,95%CI:1.13~1.74)、北方居民(HR=1.34,95%CI:1.02~1.77)和使用非清洁燃料者(HR=1.46,95%CI:1.07~1.97)中,大气甲醛长期暴露与2型糖尿病发病风险关联性更强。结论大气甲醛长期暴露可能提高2型糖尿病发病风险。
