Hematopoiesis is crucial for organismal health,and Drosophila serves as an effective genetic model due to conserved regulatory mechanisms with vertebrates.In larvae,hematopoiesis primarily occurs in the lymph gland,wh...Hematopoiesis is crucial for organismal health,and Drosophila serves as an effective genetic model due to conserved regulatory mechanisms with vertebrates.In larvae,hematopoiesis primarily occurs in the lymph gland,which contains distinct zones,including the cortical zone,intermediate zone,medullary zone,and posterior signaling center(PSC).Rab1 is vital for membrane trafficking and maintaining the localization of cell adhesion molecules,yet its role in hematopoietic homeostasis is not fully understood.This study investigates the effects of Rab1 dysfunction on β-integrin trafficking within circulating hemocytes and lymph gland cells.Rab1 impairment disrupts the endosomal trafficking of β-integrin,leading to its abnormal localization on cell membranes,which promotes lamellocyte differentiation and alters progenitor dynamics in circulating hemocytes and lymph glands,respectively.We also show that the mislocalization of β-integrin is dependent on the adhesion protein DE-cadherin.The reduction of β-integrin at cell boundaries in PSC cells leads to fewer PSC cells and lamellocyte differentiation.Furthermore,Rab1 regulates the trafficking of β-integrin via the Q-SNARE protein Syntaxin 17(Syx17).Our findings indicate that Rab1 and Syx17 regulate distinct trafficking pathways for β-integrin in different hematopoietic compartments and maintain hematopoietic homeostasis of Drosophila.展开更多
[Objective] The aim was to clone Syntaxin genes in Limonium sinense Kuntze. [Method] Limonium sinense Kuntze leaves were used as materials and total RNA was extracted and transcribed reversely. Nested primers were des...[Objective] The aim was to clone Syntaxin genes in Limonium sinense Kuntze. [Method] Limonium sinense Kuntze leaves were used as materials and total RNA was extracted and transcribed reversely. Nested primers were designed based on EST sequences at 5’ region of Syntaxin, and cDNA obtained through reverse reaction was taken as the template. Sequences of Syntaxin gene at 3’ region were obtained through two rounds of PCR amplifications. [Result] DNA fragments （1 096 bp） were obtained. For LsSyntaxin, open reading frame （ORF） was 816 bp and the encoded amino acids were 271. The relative molecular weight of Syntaxin was 30 254.3 Da and isoelectric point in theory was 5.55. [Conclusion] Syntaxin genes from Limonium sinense Kuntze were cloned. The research laid foundation for the study on Syntaxin gene function in Limonium sinense Kuntze and salt-secreted process.展开更多
Syntaxin 1A(Syx1A)has diverse and indispensable functions in animals.Pre-vious studies have mainly focused on the roles of Syx1A in Drosophila,and so how Syx1A operates during the development of other insects remains ...Syntaxin 1A(Syx1A)has diverse and indispensable functions in animals.Pre-vious studies have mainly focused on the roles of Syx1A in Drosophila,and so how Syx1A operates during the development of other insects remains poorly understood.This study in-vestigated whether disrupting LmSyx1A using RNA interference(RNAi)affects the growth and development of Locusta migratoria.LmSyx1A was expressed in all tissues tested,with the highest expression observed in the fat body.After 5th-instar nymphs were injected with double-stranded LmSyx1A(dsLmSyx1A),none of the nymphs were able to molt normally and all eventually died.The silencing of LmSyx1A resulted in the cessation of feeding,body weight loss,and atrophy of the midgut and gastric cecum in locusts.Hematoxylin and eosin(H&E)staining showed that the columnar cells in the midgut were severely dam-aged,with microvilli defects visible in dsLmSyx1A-injected nymphs.Secretory vesicles were observed with transmission electron microscopy(TEM).In addition,reverse tran-scription quantitative polymerase chain reaction(RT-qPCR)further indicates that silenc-ing LmSyx1A repressed the expression of genes involved in the insulin/mammalian target of rapamycin(mTOR)-associated nutritional pathway.Taken together,these results sug-gest that LmSyx1A significantly affects the midgut cell layer of locust nymphs,which was partially associated with the downregulation of the insulin/mTOR-associated nutritional pathway.Thus,we argue that LmSyx1A is a suitable target for developing dsRNA-based biological pesticides for managing L.migratoria.展开更多
Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)hav...Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms underlying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Utilizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expression QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4110,NControls=13569),we implemented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Association Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.展开更多
基金supported by the National Natural Science Foundation of China(32170484 and 32300384)the Fundamental Research Funds for the Central Universities(2572022DQ07 and 2572020AW04).
文摘Hematopoiesis is crucial for organismal health,and Drosophila serves as an effective genetic model due to conserved regulatory mechanisms with vertebrates.In larvae,hematopoiesis primarily occurs in the lymph gland,which contains distinct zones,including the cortical zone,intermediate zone,medullary zone,and posterior signaling center(PSC).Rab1 is vital for membrane trafficking and maintaining the localization of cell adhesion molecules,yet its role in hematopoietic homeostasis is not fully understood.This study investigates the effects of Rab1 dysfunction on β-integrin trafficking within circulating hemocytes and lymph gland cells.Rab1 impairment disrupts the endosomal trafficking of β-integrin,leading to its abnormal localization on cell membranes,which promotes lamellocyte differentiation and alters progenitor dynamics in circulating hemocytes and lymph glands,respectively.We also show that the mislocalization of β-integrin is dependent on the adhesion protein DE-cadherin.The reduction of β-integrin at cell boundaries in PSC cells leads to fewer PSC cells and lamellocyte differentiation.Furthermore,Rab1 regulates the trafficking of β-integrin via the Q-SNARE protein Syntaxin 17(Syx17).Our findings indicate that Rab1 and Syx17 regulate distinct trafficking pathways for β-integrin in different hematopoietic compartments and maintain hematopoietic homeostasis of Drosophila.
基金Supported by National Natural Science Foundation of China(30870199)Shandong Natural Science Foundation(Y2007D34+1 种基金ZR2011CM006)Key Projects of Shandong Natural Science Foundation(2010GNC10937)~~
文摘[Objective] The aim was to clone Syntaxin genes in Limonium sinense Kuntze. [Method] Limonium sinense Kuntze leaves were used as materials and total RNA was extracted and transcribed reversely. Nested primers were designed based on EST sequences at 5’ region of Syntaxin, and cDNA obtained through reverse reaction was taken as the template. Sequences of Syntaxin gene at 3’ region were obtained through two rounds of PCR amplifications. [Result] DNA fragments （1 096 bp） were obtained. For LsSyntaxin, open reading frame （ORF） was 816 bp and the encoded amino acids were 271. The relative molecular weight of Syntaxin was 30 254.3 Da and isoelectric point in theory was 5.55. [Conclusion] Syntaxin genes from Limonium sinense Kuntze were cloned. The research laid foundation for the study on Syntaxin gene function in Limonium sinense Kuntze and salt-secreted process.
基金supported by the National Key R&D Program of China(2022YFD1700200)the Natural Science Foundation of Shanxi Province,China(20210302123440)the Fund for Shanxi“1331 Project”and the Graduate Education Innovation Project of Shanxi Province,China(2023SJ033).
文摘Syntaxin 1A(Syx1A)has diverse and indispensable functions in animals.Pre-vious studies have mainly focused on the roles of Syx1A in Drosophila,and so how Syx1A operates during the development of other insects remains poorly understood.This study in-vestigated whether disrupting LmSyx1A using RNA interference(RNAi)affects the growth and development of Locusta migratoria.LmSyx1A was expressed in all tissues tested,with the highest expression observed in the fat body.After 5th-instar nymphs were injected with double-stranded LmSyx1A(dsLmSyx1A),none of the nymphs were able to molt normally and all eventually died.The silencing of LmSyx1A resulted in the cessation of feeding,body weight loss,and atrophy of the midgut and gastric cecum in locusts.Hematoxylin and eosin(H&E)staining showed that the columnar cells in the midgut were severely dam-aged,with microvilli defects visible in dsLmSyx1A-injected nymphs.Secretory vesicles were observed with transmission electron microscopy(TEM).In addition,reverse tran-scription quantitative polymerase chain reaction(RT-qPCR)further indicates that silenc-ing LmSyx1A repressed the expression of genes involved in the insulin/mammalian target of rapamycin(mTOR)-associated nutritional pathway.Taken together,these results sug-gest that LmSyx1A significantly affects the midgut cell layer of locust nymphs,which was partially associated with the downregulation of the insulin/mTOR-associated nutritional pathway.Thus,we argue that LmSyx1A is a suitable target for developing dsRNA-based biological pesticides for managing L.migratoria.
文摘Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms underlying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Utilizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expression QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4110,NControls=13569),we implemented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Association Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.
