According to a genome-wide association study,intronic SNPs within the human sterile 20/SPS1-related proline/alanine-rich kinase(SPAK) gene was linked to 20% of the general population and may be associated with elevate...According to a genome-wide association study,intronic SNPs within the human sterile 20/SPS1-related proline/alanine-rich kinase(SPAK) gene was linked to 20% of the general population and may be associated with elevated blood pressure. As cell volume changes,mammalian SPAK kinases respond to phosphorylate and regulate cation-coupled chloride co-transporter activity. To our knowledge,phosphorylation of upstream with-no-lysine(K)(WNK) kinases would activate SPAK kinases. The activation of WNK-OSR1/SPAK cascade on the kidneys and aortic tissue is related to the development of hypertension. Several regulators of the WNK pathway such as the Kelch kinase protein 3-Cullin 3 E3 ligase,hyperinsulinemia,and low potassium intake to mediate hypertension have been identified. In addition,the SPAK kinases may affect the action of renin-angiotensin-aldosterone system on blood pressure as well. In 2010,two SPAK knock-in and knock-out mouse models have clarified the pathogenesis of lowering blood pressure by influencing the receptors on the kidneys and aortic smooth muscle. More recently,two novel SPAK inhibitors for mice,Stock 1S-14279 and Closantel were discovered in 2014. Targeting of SPAK seems to be promising for future antihypertensive therapy. Therefore we raised some viewpoints for the issue for the antihypertensive therapy on the SPAK(gene or kinase).展开更多
随着对海水、地热水资源越来越多的开发利用,测定其中的K+、Na+、Ca2+、Cl-含量的需求也随之增加。研究建立了一种双管线流动注射串联离子选择电极自动方法(FI-ISE-S),能用于海水、地热水中K+、Na+、Ca2+、Cl-同时、快速、自动测定。在...随着对海水、地热水资源越来越多的开发利用,测定其中的K+、Na+、Ca2+、Cl-含量的需求也随之增加。研究建立了一种双管线流动注射串联离子选择电极自动方法(FI-ISE-S),能用于海水、地热水中K+、Na+、Ca2+、Cl-同时、快速、自动测定。在研究过程中,对FI-ISE-S系统的各种影响因素,如系统流量、进样体积、混合盘管长度、干扰物质、总离子强度调节缓冲液的酸度及离子浓度等进行了考察和优化。在最优条件下,得到的分析速度为100样h 1,每次测定的样品用量仅为160μL,相对标准偏差小于1.96%(n=11),标准添加回收率为91.9%~109.6%,测定范围分别为1.0~8.0 mmol L 1K+、50~290 mmol L 1Na+、3.2~16.0 mmol L-1Ca2+、70~430 mmol L -1Cl-。该方法已成功应用于实际海水及地热水样品的测定。展开更多
文摘According to a genome-wide association study,intronic SNPs within the human sterile 20/SPS1-related proline/alanine-rich kinase(SPAK) gene was linked to 20% of the general population and may be associated with elevated blood pressure. As cell volume changes,mammalian SPAK kinases respond to phosphorylate and regulate cation-coupled chloride co-transporter activity. To our knowledge,phosphorylation of upstream with-no-lysine(K)(WNK) kinases would activate SPAK kinases. The activation of WNK-OSR1/SPAK cascade on the kidneys and aortic tissue is related to the development of hypertension. Several regulators of the WNK pathway such as the Kelch kinase protein 3-Cullin 3 E3 ligase,hyperinsulinemia,and low potassium intake to mediate hypertension have been identified. In addition,the SPAK kinases may affect the action of renin-angiotensin-aldosterone system on blood pressure as well. In 2010,two SPAK knock-in and knock-out mouse models have clarified the pathogenesis of lowering blood pressure by influencing the receptors on the kidneys and aortic smooth muscle. More recently,two novel SPAK inhibitors for mice,Stock 1S-14279 and Closantel were discovered in 2014. Targeting of SPAK seems to be promising for future antihypertensive therapy. Therefore we raised some viewpoints for the issue for the antihypertensive therapy on the SPAK(gene or kinase).
文摘随着对海水、地热水资源越来越多的开发利用,测定其中的K+、Na+、Ca2+、Cl-含量的需求也随之增加。研究建立了一种双管线流动注射串联离子选择电极自动方法(FI-ISE-S),能用于海水、地热水中K+、Na+、Ca2+、Cl-同时、快速、自动测定。在研究过程中,对FI-ISE-S系统的各种影响因素,如系统流量、进样体积、混合盘管长度、干扰物质、总离子强度调节缓冲液的酸度及离子浓度等进行了考察和优化。在最优条件下,得到的分析速度为100样h 1,每次测定的样品用量仅为160μL,相对标准偏差小于1.96%(n=11),标准添加回收率为91.9%~109.6%,测定范围分别为1.0~8.0 mmol L 1K+、50~290 mmol L 1Na+、3.2~16.0 mmol L-1Ca2+、70~430 mmol L -1Cl-。该方法已成功应用于实际海水及地热水样品的测定。
基金grants from the National Natural Science Foundation of China (No.31330037,91439205,and 81630013)National Institutes of Health of the United States (No.DK104072,HL135851, HL139689)VA Merit Review from the Department of Veterans Affairs (No.SIO1BX002817)。
