To understand the organization of the biological networks that might potentially govern the pathogenesis of hormone refractory prostate cancer （HRPC）, we investigated the transcriptional circuitry and signaling in a...To understand the organization of the biological networks that might potentially govern the pathogenesis of hormone refractory prostate cancer （HRPC）, we investigated the transcriptional circuitry and signaling in androgen-dependent 22Rvl and MDA PCa 2b cells, androgen- and estrogen-dependent LNCaP cells, and androgen-independent DU 145 and PC-3 prostate cancer （PCa） cell lines. We used microarray analyses, quantitative real-time PCR, pathway prediction analyses, and determination of Transcription Factor Binding Site （TFBS） signatures to dissect HRPC regulatory networks. We generated graphical representations of global topology and local network motifs that might be important in prostate carcinogenesis. Many important putative biomarker ＇target hubs＇ were identified in the current study including AP-1, NF-KB, EGFR, ERK1/2, JNK, p38 MAPK, TGF beta, VEGF, PDGF, CD44, Akt, PI3K, NOTCH1, CASP1, MMP2 and AR. Our results suggest that complex cellular events including autoregulation, feedback loops and cross-talk might govern progression from early lesion to clinically diagnosed PCa, as well as metastatic potential of pre-existent high-grade prostate intraepithelial neoplasia （HG-PIN） and/or advancement to HRPC. The identification of TFBS signatures for TCF/LEF, SOX9 and ELK1 in the regulatory elements suggests additional biomarkers for the potential development of chemopreventive/therapeutic strategies against PCa. Taken together, in this study, we have identified putative biomarker ＇target hubs＇ in the architecture of PCa signaling networks, and investigated TFBS signatures that might enhance our understanding of key regulatory nodes in the progression and pathogenesis of HRPC.展开更多
本研究旨在探索血管活性肠肽I型受体(Vasoacitve intestinal peptide type I receptor,VIPR-1)基因5′调控区(-496～-1bp)多态性及其单倍型效应对鸡就巢性的影响,寻找影响肉鸡就巢性的分子标记,为降低或者剔除肉鸡就巢行为的育种研究提...本研究旨在探索血管活性肠肽I型受体(Vasoacitve intestinal peptide type I receptor,VIPR-1)基因5′调控区(-496～-1bp)多态性及其单倍型效应对鸡就巢性的影响,寻找影响肉鸡就巢性的分子标记,为降低或者剔除肉鸡就巢行为的育种研究提供相应依据。采用测序技术对498只清远麻鸡VIPR-1基因5′调控区进行多态性检测及基因型分析,利用最小二乘均数对VIPR-1基因5′调控区的多态位点与就巢性状进行相关分析,利用PHASE软件对多态位点进行单倍型分析。结果,VIPR-1基因5′调控区存在12个多态性位点,G-359T、G-266T、A-134G、A-94G、C-72G对18～43周龄的就巢持续天数影响达到显著水平(P<0.05),A-94G位点对18～54周龄的就巢率的影响达到显著水平(P<0.05);构建的单倍型对18～54周龄的就巢持续天数的影响达到极显著水平(P<0.01)。最小二乘分析结果表明,CCTGGGAAGCAG/TTGGGGAAGCAC型个体的就巢持续天数比其它单倍型个体极显著的延长(P<0.01)。结果表明,VIPR-1基因5′调控区(-496～-1bp)可能存在影响鸡就巢行为的分子标记,CCTGGGAAGCAG/TTGGGGAAGCAC型个体对鸡就巢性具有较大的遗传效应,可作为分子标记应用于家鸡就巢行为的筛选。展开更多
Aerobic Treatment Units (ATU) and Greywater Treatment Systems (GTS) are onsite wastewater treatment systems (OWTS) designed to treat wastewater to secondary effluent quality standards. Consequently, the electrical, me...Aerobic Treatment Units (ATU) and Greywater Treatment Systems (GTS) are onsite wastewater treatment systems (OWTS) designed to treat wastewater to secondary effluent quality standards. Consequently, the electrical, mechanical and chemical components of these OWTS need to be regularly maintained to ensure their consistent and reliable operation to the required standards. In Western Australia (WA), the Department of Health set out the regulatory requirements for the maintenance of OWTS as well as when and how it is to occur. This paper reviews the maintenance requirements for ATU and GTS in WA and provides recommendations for the proposed changes in guidelines and regulations. State and national guidelines were reviewed and information from industry and regulators was obtained through surveys. The review found that although the guidelines are generally satisfactory there are a number of areas which could be improved and specific recommendations are discussed.展开更多
基金National Institutes of Health(Grant No.RO1 CA118947 and RO1 CA152826 to Ah-Ng Tony Kong and R21 CA133675 to Li Cai)
文摘To understand the organization of the biological networks that might potentially govern the pathogenesis of hormone refractory prostate cancer （HRPC）, we investigated the transcriptional circuitry and signaling in androgen-dependent 22Rvl and MDA PCa 2b cells, androgen- and estrogen-dependent LNCaP cells, and androgen-independent DU 145 and PC-3 prostate cancer （PCa） cell lines. We used microarray analyses, quantitative real-time PCR, pathway prediction analyses, and determination of Transcription Factor Binding Site （TFBS） signatures to dissect HRPC regulatory networks. We generated graphical representations of global topology and local network motifs that might be important in prostate carcinogenesis. Many important putative biomarker ＇target hubs＇ were identified in the current study including AP-1, NF-KB, EGFR, ERK1/2, JNK, p38 MAPK, TGF beta, VEGF, PDGF, CD44, Akt, PI3K, NOTCH1, CASP1, MMP2 and AR. Our results suggest that complex cellular events including autoregulation, feedback loops and cross-talk might govern progression from early lesion to clinically diagnosed PCa, as well as metastatic potential of pre-existent high-grade prostate intraepithelial neoplasia （HG-PIN） and/or advancement to HRPC. The identification of TFBS signatures for TCF/LEF, SOX9 and ELK1 in the regulatory elements suggests additional biomarkers for the potential development of chemopreventive/therapeutic strategies against PCa. Taken together, in this study, we have identified putative biomarker ＇target hubs＇ in the architecture of PCa signaling networks, and investigated TFBS signatures that might enhance our understanding of key regulatory nodes in the progression and pathogenesis of HRPC.
文摘本研究旨在探索血管活性肠肽I型受体(Vasoacitve intestinal peptide type I receptor,VIPR-1)基因5′调控区(-496～-1bp)多态性及其单倍型效应对鸡就巢性的影响,寻找影响肉鸡就巢性的分子标记,为降低或者剔除肉鸡就巢行为的育种研究提供相应依据。采用测序技术对498只清远麻鸡VIPR-1基因5′调控区进行多态性检测及基因型分析,利用最小二乘均数对VIPR-1基因5′调控区的多态位点与就巢性状进行相关分析,利用PHASE软件对多态位点进行单倍型分析。结果,VIPR-1基因5′调控区存在12个多态性位点,G-359T、G-266T、A-134G、A-94G、C-72G对18～43周龄的就巢持续天数影响达到显著水平(P<0.05),A-94G位点对18～54周龄的就巢率的影响达到显著水平(P<0.05);构建的单倍型对18～54周龄的就巢持续天数的影响达到极显著水平(P<0.01)。最小二乘分析结果表明,CCTGGGAAGCAG/TTGGGGAAGCAC型个体的就巢持续天数比其它单倍型个体极显著的延长(P<0.01)。结果表明,VIPR-1基因5′调控区(-496～-1bp)可能存在影响鸡就巢行为的分子标记,CCTGGGAAGCAG/TTGGGGAAGCAC型个体对鸡就巢性具有较大的遗传效应,可作为分子标记应用于家鸡就巢行为的筛选。
文摘Aerobic Treatment Units (ATU) and Greywater Treatment Systems (GTS) are onsite wastewater treatment systems (OWTS) designed to treat wastewater to secondary effluent quality standards. Consequently, the electrical, mechanical and chemical components of these OWTS need to be regularly maintained to ensure their consistent and reliable operation to the required standards. In Western Australia (WA), the Department of Health set out the regulatory requirements for the maintenance of OWTS as well as when and how it is to occur. This paper reviews the maintenance requirements for ATU and GTS in WA and provides recommendations for the proposed changes in guidelines and regulations. State and national guidelines were reviewed and information from industry and regulators was obtained through surveys. The review found that although the guidelines are generally satisfactory there are a number of areas which could be improved and specific recommendations are discussed.
