Large-scale genetic population used for genetic breeding researches covers a large area in the field experiment,and the effect of local control would be gradually weakened.The block in replication(BIR)design is suitab...Large-scale genetic population used for genetic breeding researches covers a large area in the field experiment,and the effect of local control would be gradually weakened.The block in replication(BIR)design is suitable for large population,which is applied to the field experiment of genetic population.The statistical methods of analysis of variance(ANOVA)and heritability estimation in single and multiple environments were derived and implemented using the statistical analysis system(SAS)program for the analysis of BIR.As a work example,a comparison of statistical analysis between BIR design and the completely random block(CRB)design were conducted for the protein content from a panel containing 455 soybean germplasms.The results indicated the different estimates of average heritability in multiple environments.The research results provided technical support for the application of BIR design in genetics and breeding studies.展开更多
IAP(inhibitor of apoptosis)是内源性凋亡抑制蛋白家族,其中效力最强的是X连锁凋亡抑制蛋白(X chromosome linked inhibitor of apoptosis protein,XIAP)。它主要通过BIR结构域和RING锌指结构域抑制caspase活性、调节核因子NF2κB并参...IAP(inhibitor of apoptosis)是内源性凋亡抑制蛋白家族,其中效力最强的是X连锁凋亡抑制蛋白(X chromosome linked inhibitor of apoptosis protein,XIAP)。它主要通过BIR结构域和RING锌指结构域抑制caspase活性、调节核因子NF2κB并参与信号的转导过程。XIAP受到不均一核糖核酸蛋白C1和C2等的正向调节和XAF1和Smac/DIABLO等的负向调节。近年来XIAP在临床方面的研究也取得了很大进展。展开更多
AIM:To evaluate the safety and efficacy of tenofovir monotherapy in pregnant females resistant to lamivudine or telbivudine.The effect of tenofovir on the fetus was also assessed.METHODS:The clinical data of 17 female...AIM:To evaluate the safety and efficacy of tenofovir monotherapy in pregnant females resistant to lamivudine or telbivudine.The effect of tenofovir on the fetus was also assessed.METHODS:The clinical data of 17 females were reviewed in this study.Adverse events and pregnancy outcomes from January 1,2011 to June 30,2013 were evaluated in the Department of Gynecology and Obstetrics of BeijingDitan Hospital,Capital Medical University,Beijing,China.These pregnant females developed lamivudine(LAM)-or telbivudine(Ld T)-resistant chronic hepatitis B and received tenofovir(TDF)therapy(300 mg/d),and its curative effect,maternal and perinatal adverse events,fetal growth and development,and neonatal prognosis were evaluated.RESULTS:The median hepatitis B virus(HBV)DNA level in the pregnant females with LAM or Ld T resistance was 5.9(range,4.2-7.2)log10 copies/m L before the initiation of TDF.Ten of these females had abnormal alanine aminotransferase(ALT)levels.The patients were treated with TDF for a median of 24 wk(range,12-40 wk).Fourteen females(82.4%)had an HBV DNA level of<500 copies/m L at the time of delivery.This decrease was statistically significant(P<0.0001).Serum ALT levels were normalized in all subjects with an elevated serum ALT level at baseline(P=0.0003).There were no significant changes in serum creatinine and phosphorus levels during TDF treatment.In addition,no adverse events related to TDF treatment were observed.Seventeen females delivered 17 live infants,and all infants had good Apgar scores.The mean birth weight was 3226.5±331.7 g,and the mean length at birth was 50.4±1.1 cm.The growth and development of the infants was normal at birth,and no infants had birth defects related to TDF treatment.Eleven infants completed HBV vaccination and had no evidence of vertical transmission.CONCLUSION:The use of TDF in pregnant females with chronic HBV and LAM or Ld T resistance was safe and effective.展开更多
Survivin基因是凋亡抑制蛋白(Inhibitor of apoptosis protein, IAP)家族成员之一,具有一个典型的杆状病毒重复序列(Baculovirus inhibitior of apoptosis protein repeat, BIR)。Survivin在控制细胞周期和抑制细胞凋亡方面具有十分重...Survivin基因是凋亡抑制蛋白(Inhibitor of apoptosis protein, IAP)家族成员之一,具有一个典型的杆状病毒重复序列(Baculovirus inhibitior of apoptosis protein repeat, BIR)。Survivin在控制细胞周期和抑制细胞凋亡方面具有十分重要的作用。本文对Survivin基因结构、生物学功能以及在不同物种中的研究进展进行了综述,并对其在海洋无脊椎动物中的应用进行了展望。展开更多
BACKGROUND BIR repeat-containing ubiquitin conjugating enzyme(BRUCE)is a liver tumor suppressor,which is downregulated in a large number of patients with liver diseases.BRUCE facilitates DNA damage repair to protect t...BACKGROUND BIR repeat-containing ubiquitin conjugating enzyme(BRUCE)is a liver tumor suppressor,which is downregulated in a large number of patients with liver diseases.BRUCE facilitates DNA damage repair to protect the mouse liver against the hepatocarcinogen diethylnitrosamine(DEN)-dependent acute liver injury and carcinogenesis.While there exists an established pathologic connection between fibrosis and hepatocellular carcinoma(HCC),DEN exposure alone does not induce robust hepatic fibrosis.Further studies are warranted to identify new suppressive mechanisms contributing to DEN-induced fibrosis and HCC.AIM To investigate the suppressive mechanisms of BRUCE in hepatic fibrosis and HCC development.METHODS Male C57/BL6/J control mice[loxp/Loxp;albumin-cre(Alb-cre)-]and BRUCE Alb-Cre KO mice(loxp/Loxp;Alb-Cre+)were injected with a single dose of DEN at postnatal day 15 and sacrificed at different time points to examine liver disease progression.RESULTS By using a liver-specific BRUCE knockout(LKO)mouse model,we found that BRUCE deficiency,in conjunction with DEN exposure,induced hepatic fibrosis in both premalignant as well as malignant stages,thus recapitulating the chronic fibrosis background often observed in HCC patients.Activated in fibrosis and HCC,β-catenin activity depends on its stabilization and subsequent translocation to the nucleus.Interestingly,we observed that livers from BRUCE KO mice demonstrated an increased nuclear accumulation and elevated activity ofβ-catenin in the three stages of carcinogenesis:Pre-malignancy,tumor initiation,and HCC.This suggests that BRUCE negatively regulatesβ-catenin activity during liver disease progression.β-catenin can be activated by phosphorylation by protein kinases,such as protein kinase A(PKA),which phosphorylates it at Ser-675(pSer-675-β-catenin).Mechanistically,BRUCE and PKA were colocalized in the cytoplasm of hepatocytes where PKA activity is maintained at the basal level.However,in BRUCE deficient mouse livers or a human liver cancer cell line,both PKA activity and pSer-675-β-catenin levels were observed to be elevated.CONCLUSION Our data support a“BRUCE-PKA-β-catenin”signaling axis in the mouse liver.The BRUCE interaction with PKA in hepatocytes suppresses PKA-dependent phosphorylation and activation ofβ-catenin.This study implicates BRUCE as a novel negative regulator of both PKA andβ-catenin in chronic liver disease progression.Furthermore,BRUCE-liver specific KO mice serve as a promising model for understanding hepatic fibrosis and HCC in patients with aberrant activation of PKA andβ-catenin.展开更多
基金Supported by Key Research and Development Project of Heilongjiang Province(GA21B009-6)Heilongjiang Province Natural Science Foundation(C2015009)。
文摘Large-scale genetic population used for genetic breeding researches covers a large area in the field experiment,and the effect of local control would be gradually weakened.The block in replication(BIR)design is suitable for large population,which is applied to the field experiment of genetic population.The statistical methods of analysis of variance(ANOVA)and heritability estimation in single and multiple environments were derived and implemented using the statistical analysis system(SAS)program for the analysis of BIR.As a work example,a comparison of statistical analysis between BIR design and the completely random block(CRB)design were conducted for the protein content from a panel containing 455 soybean germplasms.The results indicated the different estimates of average heritability in multiple environments.The research results provided technical support for the application of BIR design in genetics and breeding studies.
文摘IAP(inhibitor of apoptosis)是内源性凋亡抑制蛋白家族,其中效力最强的是X连锁凋亡抑制蛋白(X chromosome linked inhibitor of apoptosis protein,XIAP)。它主要通过BIR结构域和RING锌指结构域抑制caspase活性、调节核因子NF2κB并参与信号的转导过程。XIAP受到不均一核糖核酸蛋白C1和C2等的正向调节和XAF1和Smac/DIABLO等的负向调节。近年来XIAP在临床方面的研究也取得了很大进展。
基金Supported by Grants from Beijing Municipal Natural Science Foundation,No.D12110700390000
文摘AIM:To evaluate the safety and efficacy of tenofovir monotherapy in pregnant females resistant to lamivudine or telbivudine.The effect of tenofovir on the fetus was also assessed.METHODS:The clinical data of 17 females were reviewed in this study.Adverse events and pregnancy outcomes from January 1,2011 to June 30,2013 were evaluated in the Department of Gynecology and Obstetrics of BeijingDitan Hospital,Capital Medical University,Beijing,China.These pregnant females developed lamivudine(LAM)-or telbivudine(Ld T)-resistant chronic hepatitis B and received tenofovir(TDF)therapy(300 mg/d),and its curative effect,maternal and perinatal adverse events,fetal growth and development,and neonatal prognosis were evaluated.RESULTS:The median hepatitis B virus(HBV)DNA level in the pregnant females with LAM or Ld T resistance was 5.9(range,4.2-7.2)log10 copies/m L before the initiation of TDF.Ten of these females had abnormal alanine aminotransferase(ALT)levels.The patients were treated with TDF for a median of 24 wk(range,12-40 wk).Fourteen females(82.4%)had an HBV DNA level of<500 copies/m L at the time of delivery.This decrease was statistically significant(P<0.0001).Serum ALT levels were normalized in all subjects with an elevated serum ALT level at baseline(P=0.0003).There were no significant changes in serum creatinine and phosphorus levels during TDF treatment.In addition,no adverse events related to TDF treatment were observed.Seventeen females delivered 17 live infants,and all infants had good Apgar scores.The mean birth weight was 3226.5±331.7 g,and the mean length at birth was 50.4±1.1 cm.The growth and development of the infants was normal at birth,and no infants had birth defects related to TDF treatment.Eleven infants completed HBV vaccination and had no evidence of vertical transmission.CONCLUSION:The use of TDF in pregnant females with chronic HBV and LAM or Ld T resistance was safe and effective.
文摘Survivin基因是凋亡抑制蛋白(Inhibitor of apoptosis protein, IAP)家族成员之一,具有一个典型的杆状病毒重复序列(Baculovirus inhibitior of apoptosis protein repeat, BIR)。Survivin在控制细胞周期和抑制细胞凋亡方面具有十分重要的作用。本文对Survivin基因结构、生物学功能以及在不同物种中的研究进展进行了综述,并对其在海洋无脊椎动物中的应用进行了展望。
基金Supported by NIH(Du CY),No.R21CA241025-01NIH(Du CY),No.RO1CA158323+3 种基金NCI RO1 Diversity Supplement(Du CY),No.R01CA158323-05SNational Center for Advancing Translational Sciences of the National Institutes of Health(Du CY),No.2UL1TR001425-05A1University of Cincinnati Center for Environmental Genetics-NIH/NIEHS Award(Du CY),No.P30 ES006096Pathways to Cancer Therapeutics T32(Du CY and Vilfranc CL),No.CA117846-12.
文摘BACKGROUND BIR repeat-containing ubiquitin conjugating enzyme(BRUCE)is a liver tumor suppressor,which is downregulated in a large number of patients with liver diseases.BRUCE facilitates DNA damage repair to protect the mouse liver against the hepatocarcinogen diethylnitrosamine(DEN)-dependent acute liver injury and carcinogenesis.While there exists an established pathologic connection between fibrosis and hepatocellular carcinoma(HCC),DEN exposure alone does not induce robust hepatic fibrosis.Further studies are warranted to identify new suppressive mechanisms contributing to DEN-induced fibrosis and HCC.AIM To investigate the suppressive mechanisms of BRUCE in hepatic fibrosis and HCC development.METHODS Male C57/BL6/J control mice[loxp/Loxp;albumin-cre(Alb-cre)-]and BRUCE Alb-Cre KO mice(loxp/Loxp;Alb-Cre+)were injected with a single dose of DEN at postnatal day 15 and sacrificed at different time points to examine liver disease progression.RESULTS By using a liver-specific BRUCE knockout(LKO)mouse model,we found that BRUCE deficiency,in conjunction with DEN exposure,induced hepatic fibrosis in both premalignant as well as malignant stages,thus recapitulating the chronic fibrosis background often observed in HCC patients.Activated in fibrosis and HCC,β-catenin activity depends on its stabilization and subsequent translocation to the nucleus.Interestingly,we observed that livers from BRUCE KO mice demonstrated an increased nuclear accumulation and elevated activity ofβ-catenin in the three stages of carcinogenesis:Pre-malignancy,tumor initiation,and HCC.This suggests that BRUCE negatively regulatesβ-catenin activity during liver disease progression.β-catenin can be activated by phosphorylation by protein kinases,such as protein kinase A(PKA),which phosphorylates it at Ser-675(pSer-675-β-catenin).Mechanistically,BRUCE and PKA were colocalized in the cytoplasm of hepatocytes where PKA activity is maintained at the basal level.However,in BRUCE deficient mouse livers or a human liver cancer cell line,both PKA activity and pSer-675-β-catenin levels were observed to be elevated.CONCLUSION Our data support a“BRUCE-PKA-β-catenin”signaling axis in the mouse liver.The BRUCE interaction with PKA in hepatocytes suppresses PKA-dependent phosphorylation and activation ofβ-catenin.This study implicates BRUCE as a novel negative regulator of both PKA andβ-catenin in chronic liver disease progression.Furthermore,BRUCE-liver specific KO mice serve as a promising model for understanding hepatic fibrosis and HCC in patients with aberrant activation of PKA andβ-catenin.
