AIM:To identify mutations in the genes of a fourgeneration Chinese family with congenital membranous cataracts and investigate the morphologic changes and possible functional damage underlying the role of the mutant g...AIM:To identify mutations in the genes of a fourgeneration Chinese family with congenital membranous cataracts and investigate the morphologic changes and possible functional damage underlying the role of the mutant gene.METHODS:Whole exome analysis of thirteen members of a four-generation pedigree affected with congenital membranous cataracts was performed;co-segregation analysis of identified variants was validated by Sanger sequencing.All members underwent detailed physical and complete eye examinations.The physical changes caused by the mutation were analyzed in silico through homology modeling.The lens fiber block from a patient was observed under a scanning electron microscope(SEM).Cell membrane proteins and cytoplasmic proteins from the human lenses donated by one patient with cataract in this family and from the dislocated lens resulted from the penetrating ocular trauma of a patient unrelated with this family were extracted,and the expression and localization of MP20 and Cx46 were detected by Western blot(WB)assay in these proteins.RESULTS:A novel LIM2 heterozygous mutation(c.388 C>T,p.R130 C)was identified with congenital membranous cataracts inherited by an autosomal dominant(AD)pattern.Nystagmus and amblyopia were observed in all patients of this family,and exotropia and long axial length were observed in most patients.A/B ultrasound scan and ultrasound biomicroscopy revealed obvious thin crystalline lenses from 1.7 to 2.7 mm in central thickness in all cataract eyes.The bioinformatic analysis showed that the mutation was deleterious to the physiological function of LIM2-encoded MP20.Furthermore,by SEM,ultrastructure of the cataract nucleus showed that lens fiber cells(LFCs)remained morphologic characteristics of immature fiber cells,including flap cell surface with straight edges and lacking normal ball-and-socket joint boundaries,which implied that the differentiation of LFCs might be inhibited.Accumulation of MP20 and Cx46 in the cytoplasm was observed in the cytoplasm of the LFCs in human cataract lens.CONCLUSION:We identify a novel heterozygous LIM2(c.388 C>T,p.R130 C)mutation inherited by an AD pattern.This LIM2 mutation causes the abnormal sub-localization of MP20 and Cx46 in LFCs resulting in membranous cataracts.展开更多
Based on a coupled ocean-sea ice model,this study investigates how changes in the mean state of the atmosphere in different CO2 emission scenarios (RCP 8.5,6.0,4.5 and 2.6) may affect the sea ice in the Bohai Sea,Chin...Based on a coupled ocean-sea ice model,this study investigates how changes in the mean state of the atmosphere in different CO2 emission scenarios (RCP 8.5,6.0,4.5 and 2.6) may affect the sea ice in the Bohai Sea,China,especially in the Liaodong Bay,the largest bay in the Bohai Sea. In the RCP 8.5 scenario,an abrupt change of the atmospheric state happens around 2070. Due to the abrupt change,wintertime sea ice of the Liaodong Bay can be divided into 3 periods: a mild decreasing period (2021–2060),in which the sea ice severity weakens at a near-constant rate;a rapid decreasing period (2061–2080),in which the sea ice severity drops dramatically;and a stabilized period (2081–2100). During 2021–2060,the dates of first ice are approximately unchanged,suggesting that the onset of sea ice is probably determined by a cold-air event and is not sensitive to the mean state of the atmosphere. The mean and maximum sea ice thickness in the Liaodong Bay is relatively stable before 2060,and then drops rapidly in the following decade. Different from the RCP 8.5 scenario,atmospheric state changes smoothly in the RCP 6.0,4.5 and 2.6 scenarios. In the RCP 6.0 scenario,the sea ice severity in the Bohai Sea weakens with time to the end of the twenty-first century. In the RCP 4.5 scenario,the sea ice severity weakens with time until reaching a stable state around the 2070s. In the RCP 2.6 scenario,the sea ice severity weakens until the 2040s,stabilizes from then,and starts intensifying after the 2080s. The sea ice condition in the other bays of the Bohai Sea is also discussed under the four CO_(2) emissions scenarios. Among atmospheric factors,air temperature is the leading one for the decline of the sea ice extent. Specific humidity also plays an important role in the four scenarios. The surface downward shortwave/longwave radiation and meridional wind only matter in certain scenarios,while effects from the zonal wind and precipitation are negligible.展开更多
目的通过SGC-823胃癌细胞上皮细胞间质转化(EMT)模型,研究四个半结构域蛋白2(FHL2)的改变和相关分子生物学特性的改变。方法 (1)体外培养人胃癌细胞株SCCT-823细胞(对照组),采用奥沙利铂持续刺激法诱导SGC-823细胞成为耐奥沙利铂胃癌细...目的通过SGC-823胃癌细胞上皮细胞间质转化(EMT)模型,研究四个半结构域蛋白2(FHL2)的改变和相关分子生物学特性的改变。方法 (1)体外培养人胃癌细胞株SCCT-823细胞(对照组),采用奥沙利铂持续刺激法诱导SGC-823细胞成为耐奥沙利铂胃癌细胞,制作EMT模型(实验组);(2)采用倒置相差显微镜观察实验组和对照组形态学差异;(3)采用Transwell侵袭实验检测两组细胞侵袭能力;(4)采用Western blot实验检测两组细胞波形蛋白、E-钙黏蛋白和FHL2蛋白表达。结果 (1)与对照组相比,实验组表型由上皮样细胞向间质样细胞表型转变;(2)对照组穿过膜的细胞数为65.7±11.65,实验组穿过膜的细胞数为123.4±28.13,实验组细胞的侵袭能力增强,差异具有统计学意义(t=12.434,P<0.01);(3)与对照组相比,实验组胃癌细胞E-钙黏蛋白表达水平下调(1.47±0.13 vs 0.76±0.1),波形蛋白(0.65±0.21 vs 1.01±0.25)和FHL2蛋白(0.34±0.09 vs 0.71±0.11)表达水平上调(P均<0.05)。结论经奥沙利铂刺激后,SGC-823胃癌细胞发生EMT,细胞表型由上皮样细胞向间质细胞表型变化,且将具有更强的侵袭能力,E-钙黏蛋白表达水平下调,波形蛋白和FHL2蛋白表达水平上调。展开更多
基金Supported by the National Natural Science Foundation of China(No.81370998)Department of Science and Technology of Shaanxi Province(No.2019JM-065)。
文摘AIM:To identify mutations in the genes of a fourgeneration Chinese family with congenital membranous cataracts and investigate the morphologic changes and possible functional damage underlying the role of the mutant gene.METHODS:Whole exome analysis of thirteen members of a four-generation pedigree affected with congenital membranous cataracts was performed;co-segregation analysis of identified variants was validated by Sanger sequencing.All members underwent detailed physical and complete eye examinations.The physical changes caused by the mutation were analyzed in silico through homology modeling.The lens fiber block from a patient was observed under a scanning electron microscope(SEM).Cell membrane proteins and cytoplasmic proteins from the human lenses donated by one patient with cataract in this family and from the dislocated lens resulted from the penetrating ocular trauma of a patient unrelated with this family were extracted,and the expression and localization of MP20 and Cx46 were detected by Western blot(WB)assay in these proteins.RESULTS:A novel LIM2 heterozygous mutation(c.388 C>T,p.R130 C)was identified with congenital membranous cataracts inherited by an autosomal dominant(AD)pattern.Nystagmus and amblyopia were observed in all patients of this family,and exotropia and long axial length were observed in most patients.A/B ultrasound scan and ultrasound biomicroscopy revealed obvious thin crystalline lenses from 1.7 to 2.7 mm in central thickness in all cataract eyes.The bioinformatic analysis showed that the mutation was deleterious to the physiological function of LIM2-encoded MP20.Furthermore,by SEM,ultrastructure of the cataract nucleus showed that lens fiber cells(LFCs)remained morphologic characteristics of immature fiber cells,including flap cell surface with straight edges and lacking normal ball-and-socket joint boundaries,which implied that the differentiation of LFCs might be inhibited.Accumulation of MP20 and Cx46 in the cytoplasm was observed in the cytoplasm of the LFCs in human cataract lens.CONCLUSION:We identify a novel heterozygous LIM2(c.388 C>T,p.R130 C)mutation inherited by an AD pattern.This LIM2 mutation causes the abnormal sub-localization of MP20 and Cx46 in LFCs resulting in membranous cataracts.
基金The National Key R&D Program of China under contract No.2019YFC1408403the Outstanding Young Talents Funding Project of the Cultivation Project for High-level-innovation Talents in Science and Technology,Ministry of Natural Resources,under contract No.12110600000018003923.
文摘Based on a coupled ocean-sea ice model,this study investigates how changes in the mean state of the atmosphere in different CO2 emission scenarios (RCP 8.5,6.0,4.5 and 2.6) may affect the sea ice in the Bohai Sea,China,especially in the Liaodong Bay,the largest bay in the Bohai Sea. In the RCP 8.5 scenario,an abrupt change of the atmospheric state happens around 2070. Due to the abrupt change,wintertime sea ice of the Liaodong Bay can be divided into 3 periods: a mild decreasing period (2021–2060),in which the sea ice severity weakens at a near-constant rate;a rapid decreasing period (2061–2080),in which the sea ice severity drops dramatically;and a stabilized period (2081–2100). During 2021–2060,the dates of first ice are approximately unchanged,suggesting that the onset of sea ice is probably determined by a cold-air event and is not sensitive to the mean state of the atmosphere. The mean and maximum sea ice thickness in the Liaodong Bay is relatively stable before 2060,and then drops rapidly in the following decade. Different from the RCP 8.5 scenario,atmospheric state changes smoothly in the RCP 6.0,4.5 and 2.6 scenarios. In the RCP 6.0 scenario,the sea ice severity in the Bohai Sea weakens with time to the end of the twenty-first century. In the RCP 4.5 scenario,the sea ice severity weakens with time until reaching a stable state around the 2070s. In the RCP 2.6 scenario,the sea ice severity weakens until the 2040s,stabilizes from then,and starts intensifying after the 2080s. The sea ice condition in the other bays of the Bohai Sea is also discussed under the four CO_(2) emissions scenarios. Among atmospheric factors,air temperature is the leading one for the decline of the sea ice extent. Specific humidity also plays an important role in the four scenarios. The surface downward shortwave/longwave radiation and meridional wind only matter in certain scenarios,while effects from the zonal wind and precipitation are negligible.
文摘目的通过SGC-823胃癌细胞上皮细胞间质转化(EMT)模型,研究四个半结构域蛋白2(FHL2)的改变和相关分子生物学特性的改变。方法 (1)体外培养人胃癌细胞株SCCT-823细胞(对照组),采用奥沙利铂持续刺激法诱导SGC-823细胞成为耐奥沙利铂胃癌细胞,制作EMT模型(实验组);(2)采用倒置相差显微镜观察实验组和对照组形态学差异;(3)采用Transwell侵袭实验检测两组细胞侵袭能力;(4)采用Western blot实验检测两组细胞波形蛋白、E-钙黏蛋白和FHL2蛋白表达。结果 (1)与对照组相比,实验组表型由上皮样细胞向间质样细胞表型转变;(2)对照组穿过膜的细胞数为65.7±11.65,实验组穿过膜的细胞数为123.4±28.13,实验组细胞的侵袭能力增强,差异具有统计学意义(t=12.434,P<0.01);(3)与对照组相比,实验组胃癌细胞E-钙黏蛋白表达水平下调(1.47±0.13 vs 0.76±0.1),波形蛋白(0.65±0.21 vs 1.01±0.25)和FHL2蛋白(0.34±0.09 vs 0.71±0.11)表达水平上调(P均<0.05)。结论经奥沙利铂刺激后,SGC-823胃癌细胞发生EMT,细胞表型由上皮样细胞向间质细胞表型变化,且将具有更强的侵袭能力,E-钙黏蛋白表达水平下调,波形蛋白和FHL2蛋白表达水平上调。
