Cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) are involved in neuroprotection and mitigating endoplasmic reticulum (ER) stress in the brain and peripheral ...Cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) are involved in neuroprotection and mitigating endoplasmic reticulum (ER) stress in the brain and peripheral organs. In earlier work, an increase in histone acetylation, following treatment with an epigenetic modulator, valproic acid, was associated with induction of CDNF and MANF in cultured cells and rat brain. These findings prompted an investigation of the effects of DNA methyltransferase (DNMT) inhibitors, which can alter epigenetic function, on the expression of CDNF and MANF. Rat C6 glioma cells were treated with a micromolar range of DNMT inhibitors: 5-aza-2’-deoxycytidine (DAC or decitabine), 5-azacytidine (AZA) or zebularine (ZEB) for 24 h. Subsequently, qPCR analysis was used to examine the mRNA expression of DNMT1, ten-eleven translocation methylcytosine dioxygenase 2 (TET-2), CDNF and MANF. A significant dose-dependent decrease in DNMT1 mRNA levels, together with a significant increase in TET-2 expression, was observed following treatment with AZA or DAC. Importantly, DAC, AZA and ZEB caused a significant dose-dependent increase in CDNF mRNA levels. In contrast, MANF mRNA expression decreased following treatment with AZA, with no significant effects observed with DAC or ZEB. Western analysis revealed no significant changes in CDNF protein levels following treatment with DAC for 24 h. The significant increase in CDNF expression, following treatment with DNMT1 inhibitors, suggests that DNA methylation is involved in the regulation of this neurotrophic factor. Clarification of the epigenetic or other mechanisms underlying the regulation of CDNF may provide novel therapeutic approaches in neurodegenerative and ER stress-related disorders.展开更多
Radio Frequency Interferences (RFI), such as strong Continuous Wave Interferences (CWI), can influence the Quality of Service (QoS) of communications, increasing the Bit Error Rate (BER) and decreasing the Signal-to-N...Radio Frequency Interferences (RFI), such as strong Continuous Wave Interferences (CWI), can influence the Quality of Service (QoS) of communications, increasing the Bit Error Rate (BER) and decreasing the Signal-to-Noise Ratio (SNR) in any wireless transmission, including in a Digital Video Broadcasting (DVB-S2) receiver. Therefore, this paper presents an algorithm for detecting and mitigating a Multi-tone Continuous Wave Interference (MCWI) using a Multiple Adaptive Notch Filter (MANF), based on the lattice form structure. The Adaptive Notch Filter (ANF) is constructed using the second-order IIR NF. The approach consists in developing a robust low-complexity algorithm for removing unknown MCWI. The MANF model is a multistage model, with each stage consisting of two ANFs: the adaptive IIR notch filter <i>H</i><i><sub>l</sub></i>(<i>z</i>) and the adaptive IIR notch filter <i>H</i><i><sub>N</sub></i>(<i>z</i>), which can detect and mitigate CWI. In this model, the ANF is used for estimating the Jamming-to-Signal Ratio (JSR) and the frequency of the interference (<i>w(0)</i>) by using an LMS-based algorithm. The depth of the notch is then adjusted based on the estimation of the JSR. In contrast, the ANF <i>H</i><i><sub>N</sub></i>(<i>z</i>) is used to mitigate the CW interference. Simulation results show that the proposed ANF is an effective method for eliminating/reducing the effects of MCWI, and yields better system performance than full suppression (<i>k<sub>N</sub></i>=1) for low JSR values, and mostly the same performance for high JSR values. Moreover, the proposed can detect low and high JSR and track hopping frequency interference and provides better Bit error ratio (BER) performance compared to the case without an IIR notch filter.展开更多
目的:探索中脑星形胶质细胞源性神经营养因子(mesencephalic astrocyte-derived neurotrophic factor,MANF)在乙型肝炎病毒(hepatitis B virus,HBV)慢性感染后不同疾病进展患者外周血中蛋白表达水平的差异及其与临床特征的相关性.方法:...目的:探索中脑星形胶质细胞源性神经营养因子(mesencephalic astrocyte-derived neurotrophic factor,MANF)在乙型肝炎病毒(hepatitis B virus,HBV)慢性感染后不同疾病进展患者外周血中蛋白表达水平的差异及其与临床特征的相关性.方法:采用酶联免疫吸附方法检测正常健康对照(healthy controls,HC)、乙型肝炎病毒携带者(asymptomatic hepatitis B virus surface antigen carriers,ASC)、慢性乙型肝炎(chronic hepatitis B,CHB)患者、乙型肝炎后肝硬化代偿期(compensatory liver cirrhosis,CLC)患者及乙型肝炎后肝硬化失代偿期(decompensated liver cirrhosis,DLC)患者外周血中MANF蛋白的表达水平,分析其在不同阶段慢性HBV感染者中的差异.结果:ASC组、CHB组、CLC组、DLC组和H C组5组之间M A N F的表达差异有统计学意义,F=7.391,P=0.00;进一步进行两两组间分析显示,与HC组、ASC组和CHB组相比较,CLC及DLC组MANF蛋白的表达水平差异均有统计学意义(P<0.01),但HC组与ASC组、CHB组之间两两比较差异均无统计学意义.MANF蛋白的表达水平在不同水平乙型肝炎表面抗原分组(<1500 IU/m L,1500-20000 IU/m L和>20000 IU/m L)之间的差异具有统计学意义(F=9.420,P=0.000);M A N F蛋白的表达水平在不同水平的谷草转氨酶和总胆红素组的差异具有统计学意义(F=3.188,P=0.045;t=2.867,P=0.005);M A N F蛋白的表达水平在不同水平的谷丙转氨酶分组、HBV DNA分组和E抗原状态等分组中未见明显统计学差异.结论:MANF蛋白表达水平下降可能与HBV慢性感染后的疾病进展相关.展开更多
Background:Mesencephalic astrocyte-derived neurotrophic factor(MANF)is a new candidate growth factor for dopaminergic neurons against endoplasmic reticulum stress(ER stress).HSP70 family,a chaperon like heat shock pro...Background:Mesencephalic astrocyte-derived neurotrophic factor(MANF)is a new candidate growth factor for dopaminergic neurons against endoplasmic reticulum stress(ER stress).HSP70 family,a chaperon like heat shock protein family,was proved to be involved in the MANF induced survival pathway in 6-OHDA treated SHSY-5Y cells.However,the ER stress relative transcriptome,in MANF signaling cascades is still investigated.The involvement of HSP70,a 70kd member of HSP70 family,need further to be verified.Methods:The cell apoptosis was assayed by MTT,TUNEL staining and western blot of cleaved Caspase-3.The differentially expressed genes in SHSY-5Y cells under different conditions(control,6-OHDA,6-OHDA+MANF)were investigated by RNA-seq.Expression of HSP70 was further confirmed by real-time PCR.RNAi knockdown for HSP70 was performed to investigate the role of HSP70 in the MANF signaling pathway.Results:MANF inhibits 6-OHDA-induced apoptosis in SHSY-5Y cells.Six ER stress relative genes(HSP70,GRP78,xbp-1,ATF-4,ATF-6,MAPK)were found enriched in 6-OHDA+MANF treatment group.HSP70 was the most significantly up-regulated gene under 6-OHDA+MANF treatment in SHSY-5Y cells.RNAi knockdown for HSP70 inhibits the protective effects of MANF against 6-OHDA toxicity in SHSY-5Y cells.Conclusion:MANF exerts a protective role against 6-OHDA induced apoptosis in SHSY-5Y cells via up-regulating some ER stress genes,including HSP70 family members.The HSP70 expression level plays a key role in MANFmediated survival pathway.展开更多
文摘Cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) are involved in neuroprotection and mitigating endoplasmic reticulum (ER) stress in the brain and peripheral organs. In earlier work, an increase in histone acetylation, following treatment with an epigenetic modulator, valproic acid, was associated with induction of CDNF and MANF in cultured cells and rat brain. These findings prompted an investigation of the effects of DNA methyltransferase (DNMT) inhibitors, which can alter epigenetic function, on the expression of CDNF and MANF. Rat C6 glioma cells were treated with a micromolar range of DNMT inhibitors: 5-aza-2’-deoxycytidine (DAC or decitabine), 5-azacytidine (AZA) or zebularine (ZEB) for 24 h. Subsequently, qPCR analysis was used to examine the mRNA expression of DNMT1, ten-eleven translocation methylcytosine dioxygenase 2 (TET-2), CDNF and MANF. A significant dose-dependent decrease in DNMT1 mRNA levels, together with a significant increase in TET-2 expression, was observed following treatment with AZA or DAC. Importantly, DAC, AZA and ZEB caused a significant dose-dependent increase in CDNF mRNA levels. In contrast, MANF mRNA expression decreased following treatment with AZA, with no significant effects observed with DAC or ZEB. Western analysis revealed no significant changes in CDNF protein levels following treatment with DAC for 24 h. The significant increase in CDNF expression, following treatment with DNMT1 inhibitors, suggests that DNA methylation is involved in the regulation of this neurotrophic factor. Clarification of the epigenetic or other mechanisms underlying the regulation of CDNF may provide novel therapeutic approaches in neurodegenerative and ER stress-related disorders.
文摘Radio Frequency Interferences (RFI), such as strong Continuous Wave Interferences (CWI), can influence the Quality of Service (QoS) of communications, increasing the Bit Error Rate (BER) and decreasing the Signal-to-Noise Ratio (SNR) in any wireless transmission, including in a Digital Video Broadcasting (DVB-S2) receiver. Therefore, this paper presents an algorithm for detecting and mitigating a Multi-tone Continuous Wave Interference (MCWI) using a Multiple Adaptive Notch Filter (MANF), based on the lattice form structure. The Adaptive Notch Filter (ANF) is constructed using the second-order IIR NF. The approach consists in developing a robust low-complexity algorithm for removing unknown MCWI. The MANF model is a multistage model, with each stage consisting of two ANFs: the adaptive IIR notch filter <i>H</i><i><sub>l</sub></i>(<i>z</i>) and the adaptive IIR notch filter <i>H</i><i><sub>N</sub></i>(<i>z</i>), which can detect and mitigate CWI. In this model, the ANF is used for estimating the Jamming-to-Signal Ratio (JSR) and the frequency of the interference (<i>w(0)</i>) by using an LMS-based algorithm. The depth of the notch is then adjusted based on the estimation of the JSR. In contrast, the ANF <i>H</i><i><sub>N</sub></i>(<i>z</i>) is used to mitigate the CW interference. Simulation results show that the proposed ANF is an effective method for eliminating/reducing the effects of MCWI, and yields better system performance than full suppression (<i>k<sub>N</sub></i>=1) for low JSR values, and mostly the same performance for high JSR values. Moreover, the proposed can detect low and high JSR and track hopping frequency interference and provides better Bit error ratio (BER) performance compared to the case without an IIR notch filter.
文摘目的:探索中脑星形胶质细胞源性神经营养因子(mesencephalic astrocyte-derived neurotrophic factor,MANF)在乙型肝炎病毒(hepatitis B virus,HBV)慢性感染后不同疾病进展患者外周血中蛋白表达水平的差异及其与临床特征的相关性.方法:采用酶联免疫吸附方法检测正常健康对照(healthy controls,HC)、乙型肝炎病毒携带者(asymptomatic hepatitis B virus surface antigen carriers,ASC)、慢性乙型肝炎(chronic hepatitis B,CHB)患者、乙型肝炎后肝硬化代偿期(compensatory liver cirrhosis,CLC)患者及乙型肝炎后肝硬化失代偿期(decompensated liver cirrhosis,DLC)患者外周血中MANF蛋白的表达水平,分析其在不同阶段慢性HBV感染者中的差异.结果:ASC组、CHB组、CLC组、DLC组和H C组5组之间M A N F的表达差异有统计学意义,F=7.391,P=0.00;进一步进行两两组间分析显示,与HC组、ASC组和CHB组相比较,CLC及DLC组MANF蛋白的表达水平差异均有统计学意义(P<0.01),但HC组与ASC组、CHB组之间两两比较差异均无统计学意义.MANF蛋白的表达水平在不同水平乙型肝炎表面抗原分组(<1500 IU/m L,1500-20000 IU/m L和>20000 IU/m L)之间的差异具有统计学意义(F=9.420,P=0.000);M A N F蛋白的表达水平在不同水平的谷草转氨酶和总胆红素组的差异具有统计学意义(F=3.188,P=0.045;t=2.867,P=0.005);M A N F蛋白的表达水平在不同水平的谷丙转氨酶分组、HBV DNA分组和E抗原状态等分组中未见明显统计学差异.结论:MANF蛋白表达水平下降可能与HBV慢性感染后的疾病进展相关.
基金This study is supported by the National Major Scientific and Technological Special Project for Significant New Drugs Development(2014ZX09102043-003)National Natural Science Foundation of China(81371403)+1 种基金Shanghai Science and Technology Commission(13JC1401102)Natural Science Foundation of Jiangsu Province of China(BK20140275).
文摘Background:Mesencephalic astrocyte-derived neurotrophic factor(MANF)is a new candidate growth factor for dopaminergic neurons against endoplasmic reticulum stress(ER stress).HSP70 family,a chaperon like heat shock protein family,was proved to be involved in the MANF induced survival pathway in 6-OHDA treated SHSY-5Y cells.However,the ER stress relative transcriptome,in MANF signaling cascades is still investigated.The involvement of HSP70,a 70kd member of HSP70 family,need further to be verified.Methods:The cell apoptosis was assayed by MTT,TUNEL staining and western blot of cleaved Caspase-3.The differentially expressed genes in SHSY-5Y cells under different conditions(control,6-OHDA,6-OHDA+MANF)were investigated by RNA-seq.Expression of HSP70 was further confirmed by real-time PCR.RNAi knockdown for HSP70 was performed to investigate the role of HSP70 in the MANF signaling pathway.Results:MANF inhibits 6-OHDA-induced apoptosis in SHSY-5Y cells.Six ER stress relative genes(HSP70,GRP78,xbp-1,ATF-4,ATF-6,MAPK)were found enriched in 6-OHDA+MANF treatment group.HSP70 was the most significantly up-regulated gene under 6-OHDA+MANF treatment in SHSY-5Y cells.RNAi knockdown for HSP70 inhibits the protective effects of MANF against 6-OHDA toxicity in SHSY-5Y cells.Conclusion:MANF exerts a protective role against 6-OHDA induced apoptosis in SHSY-5Y cells via up-regulating some ER stress genes,including HSP70 family members.The HSP70 expression level plays a key role in MANFmediated survival pathway.
