BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the ...BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the LAMA2 gene,c.715C>G(resulting in a change of nucleotide number 715 in the coding region from cytosine to gua-nine),induced an amino acid alteration p.R239G(No.239)in the patient,repre-senting a missense mutation.This observation may be elucidated by the neonatal creatine monitoring mechanism,a phenomenon not previously reported.CASE SUMMARY We analysed the case of a neonate presenting solely with elevated CK levels who was eventually discharged after supportive treatment.The chief complaint was identification of increased CK levels for 15 d and higher CK values for 1 d.Ad-mission occurred at 18 d of age,and despite prolonged treatment with creatine and vitamin C,the elevated CK levels showed limited improvement.Whole exo-me sequencing revealed the presence of a c.715C>G mutation in LAMA2 in the newborn,correlating with a clinical phenotype.However,the available informa-tion offers insufficient evidence for clinical pathogenicity.CONCLUSION Mutations in LAMA2 are associated with the clinical phenotype of increased neonatal CK levels,for which no specific treatment exists.Whole genome sequen-cing facilitates early diagnosis.展开更多
The objective of the study was to characterize the clays of the Lama depression in Benin. Macroscopic examination of hand soundings, dynamic penetration test and stratigraphic correlation of water borehole logs, as we...The objective of the study was to characterize the clays of the Lama depression in Benin. Macroscopic examination of hand soundings, dynamic penetration test and stratigraphic correlation of water borehole logs, as well as scanning electron microscopy (SEM) combined with energy-dispersive X-ray microanalysis (EDX) method were made on compact or stratified clays. The large grains are embedded in a sintered matrix. The texture is heterogeneous and open, including quartz, carbonates and organic matter. The fine fraction is dominated by mineral paragenesis characterizing Kaolinite-Quartz-Calcite-Gypsum dioctahedral smectites composed of: Oxygen, Silica, Carbon, Aluminum, Iron, Zinc, Titanium and Magnesium. This smectic and regular structure includes coarse grains of the order of 800 μm. The pore diameters vary from 130 μm to 1.14 μm. The inter-particle porosity is poorly developed unlike the inter-aggregate pores larger than 0.05 μm. The texture is laminar and shows elongated turbo static particles with more or less rounded edges and honeycomb particles. Quartz and carbonates induce an increase in heterogeneities which develop mechanical sensitivity and hydraulic conductivity. High contents of silica, iron or aluminum and low contents of calcium and magnesium, as well as the presence of other trace elements suggest an alumino-ferriferous clay resulting from the hydrothermal alteration of the acid granite massif. These heterogeneities promote less tortuous pores or paths, making these clays more permeable. Finally, other stabilization studies and improvements to hydraulic products and binders should favor the use of the studied clay as improved backfill or drilling muds.展开更多
目的探讨LAMA4调控TGF-β1/SMAD Western blot检测LAMA4在肝癌细胞Huh7和HepG2及正常肝细胞L02中的表达;MMT法和流式细胞技术检测LAMA4和TGF-β1/SMAD信号传导途径对Huh7细胞增殖和凋亡的影响;RT-qPCR和Western blot检测LAMA4对TGF-β1/...目的探讨LAMA4调控TGF-β1/SMAD Western blot检测LAMA4在肝癌细胞Huh7和HepG2及正常肝细胞L02中的表达;MMT法和流式细胞技术检测LAMA4和TGF-β1/SMAD信号传导途径对Huh7细胞增殖和凋亡的影响;RT-qPCR和Western blot检测LAMA4对TGF-β1/SMAD信号转导通路和细胞免疫因子TNF-α、IFN-γ、TGF-β1的影响。结果 RT-qPCR和Western blot检测结果显示:LAMA4在肝癌细胞Huh7和HepG2中mRNA表达显著上调;LAMA4在肝癌细胞Huh7和HepG2中蛋白表达显著上调;沉默LAMA4使TGF-β1和SMAD4表达显著上调,SMAD6、IFN-γ和TNF-α的含量显著降低,过表达LAMA4则结果相反;MMT法和流式细胞技术检测结果显示:敲低LAMA4可使Huh7细胞活力下降,细胞凋亡率增加,而过表达LAMA4则结果相反;Ly364947干扰TGF-β1/SMAD信号传导路径后,Huh7细胞的活力增加,细胞凋亡率显著下降,IFN-γ和TNF-α的含量显著升高,TGF-β1显著降低,且Ly364947可部分逆转沉默LAMA4对肝癌细胞Huh7的免疫逃逸因子和凋亡的调控作用。结论 LAMA4可通过调控TGF-β1/SMAD信号传导途径影响肝癌细胞免疫逃逸和凋亡。展开更多
基金Supported by The Suzhou Science and Technology Development Plan Guiding Project,No.SZSYYXH-2023-YB5The Suzhou Science and Technology Development Plan Project,No.SKY2023002The Suzhou Key Laboratory of Children's Structural Deformities,No.SZS2022018.
文摘BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the LAMA2 gene,c.715C>G(resulting in a change of nucleotide number 715 in the coding region from cytosine to gua-nine),induced an amino acid alteration p.R239G(No.239)in the patient,repre-senting a missense mutation.This observation may be elucidated by the neonatal creatine monitoring mechanism,a phenomenon not previously reported.CASE SUMMARY We analysed the case of a neonate presenting solely with elevated CK levels who was eventually discharged after supportive treatment.The chief complaint was identification of increased CK levels for 15 d and higher CK values for 1 d.Ad-mission occurred at 18 d of age,and despite prolonged treatment with creatine and vitamin C,the elevated CK levels showed limited improvement.Whole exo-me sequencing revealed the presence of a c.715C>G mutation in LAMA2 in the newborn,correlating with a clinical phenotype.However,the available informa-tion offers insufficient evidence for clinical pathogenicity.CONCLUSION Mutations in LAMA2 are associated with the clinical phenotype of increased neonatal CK levels,for which no specific treatment exists.Whole genome sequen-cing facilitates early diagnosis.
文摘The objective of the study was to characterize the clays of the Lama depression in Benin. Macroscopic examination of hand soundings, dynamic penetration test and stratigraphic correlation of water borehole logs, as well as scanning electron microscopy (SEM) combined with energy-dispersive X-ray microanalysis (EDX) method were made on compact or stratified clays. The large grains are embedded in a sintered matrix. The texture is heterogeneous and open, including quartz, carbonates and organic matter. The fine fraction is dominated by mineral paragenesis characterizing Kaolinite-Quartz-Calcite-Gypsum dioctahedral smectites composed of: Oxygen, Silica, Carbon, Aluminum, Iron, Zinc, Titanium and Magnesium. This smectic and regular structure includes coarse grains of the order of 800 μm. The pore diameters vary from 130 μm to 1.14 μm. The inter-particle porosity is poorly developed unlike the inter-aggregate pores larger than 0.05 μm. The texture is laminar and shows elongated turbo static particles with more or less rounded edges and honeycomb particles. Quartz and carbonates induce an increase in heterogeneities which develop mechanical sensitivity and hydraulic conductivity. High contents of silica, iron or aluminum and low contents of calcium and magnesium, as well as the presence of other trace elements suggest an alumino-ferriferous clay resulting from the hydrothermal alteration of the acid granite massif. These heterogeneities promote less tortuous pores or paths, making these clays more permeable. Finally, other stabilization studies and improvements to hydraulic products and binders should favor the use of the studied clay as improved backfill or drilling muds.
