目的分析1例Dandy-Walker综合征(DWM)的遗传学病因。方法收集胎儿B超、MRI、出生后症状、染色体核型分析、CNV-seq检查以及WES测序结果,并利用Sanger测序对致病变异位点进行确认。检索The Human Protein Atlas数据库、STRING数据库,分...目的分析1例Dandy-Walker综合征(DWM)的遗传学病因。方法收集胎儿B超、MRI、出生后症状、染色体核型分析、CNV-seq检查以及WES测序结果,并利用Sanger测序对致病变异位点进行确认。检索The Human Protein Atlas数据库、STRING数据库,分析候选致病基因的组织表达特点和生物学功能。构建致病基因野生型以及变异型蛋白三维结构,利用Gromacs软件对野生型和变异型蛋白进行分子动力学模拟。检索ClinVar数据库分析已报道致病和可能致病性变异在蛋白结构域分布。结果孕妇有DWM妊娠史。胎儿在孕22周开始出现DWM相关症状。胎儿羊水染色体核型分析以及CNV-seq检测未见异常。全外显子测序结果显示,胎儿携带纤维蛋白溶酶原(plasminogen,PLG)复合杂合变异:c.2251G>A(p.G751R)和c.1781G>A(p.W594*)。这两个可能致病性变异分别遗传自父亲、母亲,且均位于PLG的Peptidase S1结构域,c.1781G>A(p.W594*)未见报道。c.2251G>A(p.G751R)可以影响PLG蛋白的RMSD、RMSF以及回旋半径,进而影响蛋白生物功能。结论PLG基因2251G>A(p.G751R)和c.1781G>A(p.W594*)复合杂合变异是导致DWM的病因。展开更多
Nowadays,due to excellent biological and polymeric characteristics,DNA has been widely noted as an emerging building block to construct diverse materials for biosensing,in vivo imaging,drug delivery,and disease therap...Nowadays,due to excellent biological and polymeric characteristics,DNA has been widely noted as an emerging building block to construct diverse materials for biosensing,in vivo imaging,drug delivery,and disease therapy.Particularly,relying on programmability,predictability,and stability of DNA,DNA walkers have opened new and exciting opportunities in modern life sciences for target detection and biological analysis,which are constructed by self-assembly of DNA or combining DNA with other nanomaterials(e.g.,quantum dots,gold nanoparticles,magnetic nanoparticles,polymers).Compared with conventional nanomaterials(lanthanide-doped upconversion nanoparticles,magnetic nanomaterials,carbon dots,silicon dots,and so on),DNA walkers showed convenient modification,lower biotoxicity,excellent biocompatibility and high biostability,improving the biological application.Meanwhile,with high-speed operating efficiency and sustainable operation,DNA walkers powered by strand displacement reaction or protein enzyme/DNAzyme reaction,have highly sensitive detection and signal amplification abilities,which are applied in biosensing,material assembly and synthesis,and early cancer diagnosis.Worthily,DNA walkers could be regarded as signal amplifiers,which enhanced the signal transduction and amplified biosensor sensing signals.Herein,we systematically and comprehensively summarized the operating principles of various DNA walkers,categorized rational design of the DNA walker,and outlined the application of DNA walker in biosensors.Furthermore,the challenges and future trends of DNA walkers were discussed.展开更多
This work uses cloud-resolving simulations to study mock-Walker cells driven by a specified sea surface temperature(SST).The associated precipitation in the mock-Walker cells exhibits three different modes,including a...This work uses cloud-resolving simulations to study mock-Walker cells driven by a specified sea surface temperature(SST).The associated precipitation in the mock-Walker cells exhibits three different modes,including a single peak of precipitation over the SST maximum(mode 1),symmetric double peaks of precipitation straddling the SST maximum(mode 2),and a single peak of precipitation on one side of the SST maximum(mode 3).The three modes are caused by three distinct convective activity center migration traits.Analyses indicate that the virtual effect of water vapor plays an important role in differentiating the three modes.When the SST gradient is large,the virtual effect may be strong enough to overcome the temperature effect,generating a low-level low-pressure anomaly below the ascending branch of the Walker cell off the center.The results here highlight the importance of the virtual effect of water vapor and its interaction with convection and large-scale circulation in the Walker circulation.展开更多
文摘目的分析1例Dandy-Walker综合征(DWM)的遗传学病因。方法收集胎儿B超、MRI、出生后症状、染色体核型分析、CNV-seq检查以及WES测序结果,并利用Sanger测序对致病变异位点进行确认。检索The Human Protein Atlas数据库、STRING数据库,分析候选致病基因的组织表达特点和生物学功能。构建致病基因野生型以及变异型蛋白三维结构,利用Gromacs软件对野生型和变异型蛋白进行分子动力学模拟。检索ClinVar数据库分析已报道致病和可能致病性变异在蛋白结构域分布。结果孕妇有DWM妊娠史。胎儿在孕22周开始出现DWM相关症状。胎儿羊水染色体核型分析以及CNV-seq检测未见异常。全外显子测序结果显示,胎儿携带纤维蛋白溶酶原(plasminogen,PLG)复合杂合变异:c.2251G>A(p.G751R)和c.1781G>A(p.W594*)。这两个可能致病性变异分别遗传自父亲、母亲,且均位于PLG的Peptidase S1结构域,c.1781G>A(p.W594*)未见报道。c.2251G>A(p.G751R)可以影响PLG蛋白的RMSD、RMSF以及回旋半径,进而影响蛋白生物功能。结论PLG基因2251G>A(p.G751R)和c.1781G>A(p.W594*)复合杂合变异是导致DWM的病因。
基金Financial support was from Hunan Provincial Natural Science Foundation(Nos.2023JJ40210,2023JJ40211)Hunan Provincial Innovation Training Program for College Students(No.202211342042)+2 种基金Hunan Provincial Natural Science Foundation(No.2021JJ10001)Key Areas Research and Development Plan of Hunan Province(No.2021SK2038)Huxiang High Level Talent Gathering Project(No.2021RC5011)。
文摘Nowadays,due to excellent biological and polymeric characteristics,DNA has been widely noted as an emerging building block to construct diverse materials for biosensing,in vivo imaging,drug delivery,and disease therapy.Particularly,relying on programmability,predictability,and stability of DNA,DNA walkers have opened new and exciting opportunities in modern life sciences for target detection and biological analysis,which are constructed by self-assembly of DNA or combining DNA with other nanomaterials(e.g.,quantum dots,gold nanoparticles,magnetic nanoparticles,polymers).Compared with conventional nanomaterials(lanthanide-doped upconversion nanoparticles,magnetic nanomaterials,carbon dots,silicon dots,and so on),DNA walkers showed convenient modification,lower biotoxicity,excellent biocompatibility and high biostability,improving the biological application.Meanwhile,with high-speed operating efficiency and sustainable operation,DNA walkers powered by strand displacement reaction or protein enzyme/DNAzyme reaction,have highly sensitive detection and signal amplification abilities,which are applied in biosensing,material assembly and synthesis,and early cancer diagnosis.Worthily,DNA walkers could be regarded as signal amplifiers,which enhanced the signal transduction and amplified biosensor sensing signals.Herein,we systematically and comprehensively summarized the operating principles of various DNA walkers,categorized rational design of the DNA walker,and outlined the application of DNA walker in biosensors.Furthermore,the challenges and future trends of DNA walkers were discussed.
基金the National Key R&D Program of China(Grant No.2022YFC3003902)the National Natural Science Foundation of China(Grant No.42075146).
文摘This work uses cloud-resolving simulations to study mock-Walker cells driven by a specified sea surface temperature(SST).The associated precipitation in the mock-Walker cells exhibits three different modes,including a single peak of precipitation over the SST maximum(mode 1),symmetric double peaks of precipitation straddling the SST maximum(mode 2),and a single peak of precipitation on one side of the SST maximum(mode 3).The three modes are caused by three distinct convective activity center migration traits.Analyses indicate that the virtual effect of water vapor plays an important role in differentiating the three modes.When the SST gradient is large,the virtual effect may be strong enough to overcome the temperature effect,generating a low-level low-pressure anomaly below the ascending branch of the Walker cell off the center.The results here highlight the importance of the virtual effect of water vapor and its interaction with convection and large-scale circulation in the Walker circulation.
