The multiple-layer structure of the cerebral cortex is important for its functions. Such a structure is generated based on the proliferation and differentiation of neural stem/progenitor cells. Notch functions as a mo...The multiple-layer structure of the cerebral cortex is important for its functions. Such a structure is generated based on the proliferation and differentiation of neural stem/progenitor cells. Notch functions as a molecular switch for neural stem/progenitor cell fate during cortex development but the mechanism remains unclear. Biochemical and cellular studies showed that Notch receptor activation induces several proteases to release the Notch intracellular domain （NICD）. A Disintegrin and Metalloprotease 10 （ADAM10） might be a physiological rate-limiting $2 enzyme for Notch activation. Nestin-driven conditional ADAM10 knockout in mouse cortex showed that ADAM10 is cdtical for maintenance of the neural stem cell population during early embryonic cortex development. However, the expression pattern and function of ADAM10 during later cerebral cortex development remains poorly understood. We performed in situ hybridization for ADAMIO mRNA and immunofluorescent analysis to determine the expression of ADAM10 and NICD in mouse cortex from embryonic day 9 （E14.5） to postnatal day 1 （P1）. ADAM10 and NICD were highly co-localized in the cortex of E16.5 to P1 mice. Comparisons of expression patterns of ADAM10 with Nestin （neural stem cell marker）, Tujl （mature neuron marker）, and S100β （gila marker） showed that ADAM10 expression highly matched that of S10013 and partially matched that of Tujl at later embryonic to early postnatal cortex developmental stages. Such expression patterns indicated that ADAM10-Notch signaling might have a critical function in neuronal maturation and gliogenesis during cortex development.展开更多
A single mammalian transcript normally encodes one protein, but the transcript of GNAS （G-protein u-subunit） contains two reading frames and produces two structurally unrelated proteins, XLas and ALEX. No other conf...A single mammalian transcript normally encodes one protein, but the transcript of GNAS （G-protein u-subunit） contains two reading frames and produces two structurally unrelated proteins, XLas and ALEX. No other confirmed GNAS-Iike dual-coding transcripts have been reported to date, even though many such candidate genes have been predicted by bioinformatics analysis. In this study, we constructed a series of vectors to test how two protein products were translated from a single transcript in vitro. The length of the ORF （open reading frame）, position of the first AUG and the Kozak motif were found to be important factors. These factors, as well as 55-bp NMD （nonsense-mediated mRNA decay） rule, were used in a bioinformatics search for candidate dual-coding transcripts. A total of 1307, 750 and 474 two-ORF-containing transcripts were found in human, mouse and rat, respectively, of which 170, 89 and 70, respectively, were found to be potential dual-coding transcripts. Most transcripts showed low conservation among species. Interestingly, dual-coding transcripts were significantly enriched for transcripts from the zinc-finger protein family, which are usually DNA-binding proteins involved in regulation of the transcription process.展开更多
The study of nanocrystalline SnO2 (n-SnO2) and SiO2-doped SnO2 (n-Si-SnO2) samples pre-pared by the sol-gel process showed that SiO2 doping can effectively restrained the growth of nanocrystalline SnO2 grains, thus im...The study of nanocrystalline SnO2 (n-SnO2) and SiO2-doped SnO2 (n-Si-SnO2) samples pre-pared by the sol-gel process showed that SiO2 doping can effectively restrained the growth of nanocrystalline SnO2 grains, thus improving thermal stability of the materials.展开更多
Heparan sulfate proteoglycan 2(HSPG2)gene encodes the matrix protein Perlecan,and genetic inactivation of this gene creates mice that are embryonic lethal with severe neural tube defects(NTDs).We discovered rare genet...Heparan sulfate proteoglycan 2(HSPG2)gene encodes the matrix protein Perlecan,and genetic inactivation of this gene creates mice that are embryonic lethal with severe neural tube defects(NTDs).We discovered rare genetic variants of HSPG2 in 10%cases compared to only 4%in controls among a cohort of 369 NTDs.Endorepellin,a peptide cleaved from the domain V of Perlecan,is known to promote angiogenesis and autophagy in endothelial cells.The roles of enderepellin in neurodevelopment remain unclear so far.Our study revealed that endorepellin can migrate to the neuroepithelial cells and then be recognized and bind with the neuroepithelia receptor neurexin in vivo.Through the endocytic pathway,the interaction of endorepellin and neurexin physiologically triggers autophagy and appropriately modulates the differentiation of neural stem cells into neurons as a blocker,which is necessary for normal neural tube closure.We created knock-in(KI)mouse models with human-derived HSPG2 variants,using sperm-like stem cells that had been genetically edited by CRISPR/Cas9.We realized that any HSPG2 variants that affected the function of endorepellin were considered pathogenic causal variants for human NTDs given that the severe NTD phenotypes exhibited by these KI embryos occurred in a significantly higher response frequency compared to wildtype embryos.Our study provides a paradigm for effectively confirming pathogenic mutations in other genetic diseases.Furthermore,we demonstrated that using autophagy inhibitors at a cellular level can repress neuronal differentiation.Therefore,autophagy agonists may prevent NTDs resulting from failed autophagy maintenance and neuronal over-differentiation caused by deleterious endorepellin variants.展开更多
The sigma-1 receptor is a molecular chaperone protein highly enriched in the brain.Recent studies linked it to many diseases,such as drug addition,Alzheimer’s disease,stroke,depression,and even cancer.Sigma-1 recepto...The sigma-1 receptor is a molecular chaperone protein highly enriched in the brain.Recent studies linked it to many diseases,such as drug addition,Alzheimer’s disease,stroke,depression,and even cancer.Sigma-1 receptor is enriched in lipid rafts,which are membrane microdomains essential in signaling processes.One of those signaling processes is ADAM17-and ADAM10-dependent ectodomain shedding.By using an alkaline phosphatase tagged substrate reporter system,we have shown that ADAM10-dependent BTC shedding was very sensitive to both membrane lipid component change and sigma-1 receptor agonist DHEAS treatment while ADAM17-dependent HB-EGF shedding was not;and overexpression of sigma-1 receptor diminished ADAM17-and ADAM10-dependent shedding.Our results indicate that sigma-1 receptor plays an important role in modifying the function of transmembrane proteases.展开更多
Erratum to:Protein Cell 2012,3(2):153-159 DOI 10.1007/s13238-012-2006-9 Two mistakes in Fig.3A and 4A,respectively,were made due to typesetting errors.Figure 3A,on the left column of page 156,should be cor-rected as f...Erratum to:Protein Cell 2012,3(2):153-159 DOI 10.1007/s13238-012-2006-9 Two mistakes in Fig.3A and 4A,respectively,were made due to typesetting errors.Figure 3A,on the left column of page 156,should be cor-rected as follows.Figure 4A,on the left column of page 157,should be cor-rected as follows.展开更多
基金supported by the National Natural Science Foundation of China,No.30800322Shanghai Pujiang Program,No.08PJ1401300+4 种基金Shanghai Leading Academic Discipline Project,No.B111Ministry of Education Research Fund for New Teachers in Doctoral Program of Higher Educational Institutes,No.200802461050National Basic Research Program of China(973 Program),No.2011CB503703Ministry of Education Start Fund to Returned Overseas ScholarsZhuo Xue Program of Fudan University
文摘The multiple-layer structure of the cerebral cortex is important for its functions. Such a structure is generated based on the proliferation and differentiation of neural stem/progenitor cells. Notch functions as a molecular switch for neural stem/progenitor cell fate during cortex development but the mechanism remains unclear. Biochemical and cellular studies showed that Notch receptor activation induces several proteases to release the Notch intracellular domain （NICD）. A Disintegrin and Metalloprotease 10 （ADAM10） might be a physiological rate-limiting $2 enzyme for Notch activation. Nestin-driven conditional ADAM10 knockout in mouse cortex showed that ADAM10 is cdtical for maintenance of the neural stem cell population during early embryonic cortex development. However, the expression pattern and function of ADAM10 during later cerebral cortex development remains poorly understood. We performed in situ hybridization for ADAMIO mRNA and immunofluorescent analysis to determine the expression of ADAM10 and NICD in mouse cortex from embryonic day 9 （E14.5） to postnatal day 1 （P1）. ADAM10 and NICD were highly co-localized in the cortex of E16.5 to P1 mice. Comparisons of expression patterns of ADAM10 with Nestin （neural stem cell marker）, Tujl （mature neuron marker）, and S100β （gila marker） showed that ADAM10 expression highly matched that of S10013 and partially matched that of Tujl at later embryonic to early postnatal cortex developmental stages. Such expression patterns indicated that ADAM10-Notch signaling might have a critical function in neuronal maturation and gliogenesis during cortex development.
文摘A single mammalian transcript normally encodes one protein, but the transcript of GNAS （G-protein u-subunit） contains two reading frames and produces two structurally unrelated proteins, XLas and ALEX. No other confirmed GNAS-Iike dual-coding transcripts have been reported to date, even though many such candidate genes have been predicted by bioinformatics analysis. In this study, we constructed a series of vectors to test how two protein products were translated from a single transcript in vitro. The length of the ORF （open reading frame）, position of the first AUG and the Kozak motif were found to be important factors. These factors, as well as 55-bp NMD （nonsense-mediated mRNA decay） rule, were used in a bioinformatics search for candidate dual-coding transcripts. A total of 1307, 750 and 474 two-ORF-containing transcripts were found in human, mouse and rat, respectively, of which 170, 89 and 70, respectively, were found to be potential dual-coding transcripts. Most transcripts showed low conservation among species. Interestingly, dual-coding transcripts were significantly enriched for transcripts from the zinc-finger protein family, which are usually DNA-binding proteins involved in regulation of the transcription process.
文摘The study of nanocrystalline SnO2 (n-SnO2) and SiO2-doped SnO2 (n-Si-SnO2) samples pre-pared by the sol-gel process showed that SiO2 doping can effectively restrained the growth of nanocrystalline SnO2 grains, thus improving thermal stability of the materials.
基金supported by the National Key Research and Development Program of China(2021YFC2701100)the National Natural Science Foundation of China(81930036,32293230 and 8215008)+1 种基金the Commission for Science and Technology of Shanghai Municipality(20JC1418500 and 20ZR1404800)Project supported by Shanghai Municipal Science and Technology Major Project。
文摘Heparan sulfate proteoglycan 2(HSPG2)gene encodes the matrix protein Perlecan,and genetic inactivation of this gene creates mice that are embryonic lethal with severe neural tube defects(NTDs).We discovered rare genetic variants of HSPG2 in 10%cases compared to only 4%in controls among a cohort of 369 NTDs.Endorepellin,a peptide cleaved from the domain V of Perlecan,is known to promote angiogenesis and autophagy in endothelial cells.The roles of enderepellin in neurodevelopment remain unclear so far.Our study revealed that endorepellin can migrate to the neuroepithelial cells and then be recognized and bind with the neuroepithelia receptor neurexin in vivo.Through the endocytic pathway,the interaction of endorepellin and neurexin physiologically triggers autophagy and appropriately modulates the differentiation of neural stem cells into neurons as a blocker,which is necessary for normal neural tube closure.We created knock-in(KI)mouse models with human-derived HSPG2 variants,using sperm-like stem cells that had been genetically edited by CRISPR/Cas9.We realized that any HSPG2 variants that affected the function of endorepellin were considered pathogenic causal variants for human NTDs given that the severe NTD phenotypes exhibited by these KI embryos occurred in a significantly higher response frequency compared to wildtype embryos.Our study provides a paradigm for effectively confirming pathogenic mutations in other genetic diseases.Furthermore,we demonstrated that using autophagy inhibitors at a cellular level can repress neuronal differentiation.Therefore,autophagy agonists may prevent NTDs resulting from failed autophagy maintenance and neuronal over-differentiation caused by deleterious endorepellin variants.
基金by the Shanghai Leading Academic Discipline Project(B111)NSFC(Grant No.30800322)+4 种基金Shanghai Pujiang Program(08PJ1401300)Ministry of Education Start Fund to Returned Overseas ScholarsMinistry of Education Research Fund for New Teachers in Doctoral Program of Higher Educational InstitutesNational Basic Research Program of China(973 Program)(Grant No.2011CB503703)and Institute of Brain Sciences at Fudan University.The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘The sigma-1 receptor is a molecular chaperone protein highly enriched in the brain.Recent studies linked it to many diseases,such as drug addition,Alzheimer’s disease,stroke,depression,and even cancer.Sigma-1 receptor is enriched in lipid rafts,which are membrane microdomains essential in signaling processes.One of those signaling processes is ADAM17-and ADAM10-dependent ectodomain shedding.By using an alkaline phosphatase tagged substrate reporter system,we have shown that ADAM10-dependent BTC shedding was very sensitive to both membrane lipid component change and sigma-1 receptor agonist DHEAS treatment while ADAM17-dependent HB-EGF shedding was not;and overexpression of sigma-1 receptor diminished ADAM17-and ADAM10-dependent shedding.Our results indicate that sigma-1 receptor plays an important role in modifying the function of transmembrane proteases.
文摘Erratum to:Protein Cell 2012,3(2):153-159 DOI 10.1007/s13238-012-2006-9 Two mistakes in Fig.3A and 4A,respectively,were made due to typesetting errors.Figure 3A,on the left column of page 156,should be cor-rected as follows.Figure 4A,on the left column of page 157,should be cor-rected as follows.
