Circular RNAs （circRNAs）, a kind of covalently closed RNA molecule, were used to be considered a type of byproducts of mis-splicing events and were discovered sporadically due to the technological limits in the earl...Circular RNAs （circRNAs）, a kind of covalently closed RNA molecule, were used to be considered a type of byproducts of mis-splicing events and were discovered sporadically due to the technological limits in the early years. With the great technological progress such as high-throughput next-generation sequencing, numerous circRNAs have recently been detected in many species. CircRNAs were expressed in a spatio-temporally specific manner, suggesting their regulatory functional potentials were overlooked previously. Intriguingly, some circRNAs were indeed found with critical physiological functions in certain circumstances. CircRNAs have a more stable molecular st;＇ucture that can resist to exoribonuclease comparing to those linear ones, and their molecular functions include microRNA sponge, regulatory roles in transcription, mRNA traps that compete with linear splicing, templates for translation and possibly other presently unknown roles. Here, we review the discovery and characterization of circRNAs, the origination and formation mechanism, the physiological functions and the molecular roles, along with the methods for detection of circRNAs. We further look into the future and propose key questions to be answered for these magical RNA molecules.展开更多
Chronic hepatitis B is a global health problem. The clinical outcomes of chronic hepatitis B infection include asymptomatic carrier state, chronic hepatitis(CH), liver cirrhosis(LC), and hepatocellular carcinoma(HCC)....Chronic hepatitis B is a global health problem. The clinical outcomes of chronic hepatitis B infection include asymptomatic carrier state, chronic hepatitis(CH), liver cirrhosis(LC), and hepatocellular carcinoma(HCC). Because of the spontaneous error rate inherent to viral reverse transcriptase, the hepatitis B virus(HBV) genome evolves during the course of infection under the antiviral pressure of host immunity. The clinical significance of pre-S/S variants has become increasingly recognized in patients with chronic HBV infection. Pre-S/S variants are often identified in hepatitis B carriers with CH, LC, and HCC, which suggests that these naturally occurring pre-S/S variants may contribute to the development of progressive liver damage and hepatocarcinogenesis. This paper reviews the function of the pre-S/S region along with recent findings related to the role of pre-S/S variants in liver diseases. According to the mutation type, five pre-S/S variants have been identified: pre-S deletion, pre-S point mutation, pre-S1 splice variant, C-terminus S point mutation, and pre-S/S nonsense mutation. Their associations with HBV genotype and the possible pathogenesis of pre-S/S variants are discussed. Different pre-S/S variants cause liver diseases through different mechanisms. Most cause the intracellular retention of HBV envelope proteins and induction of endoplasmic reticulum stress, which results in liver diseases. Pre-S/S variants should be routinely determined in HBV carriers to help identify individuals who may be at a high risk of less favorable liver disease progression. Additional investigations are required to explore the molecular mechanisms of the pre-S/S variants involved in the pathogenesis of each stage of liver disease.展开更多
Prostate cancer cells demonstrate a remarkable ＂addiction＂ to androgen receptor （AR） signaling in all stages of disease progression. As such, suppression of AR signaling remains the therapeutic goal in systemic tr...Prostate cancer cells demonstrate a remarkable ＂addiction＂ to androgen receptor （AR） signaling in all stages of disease progression. As such, suppression of AR signaling remains the therapeutic goal in systemic treatment of prostate cancer. A number of molecular alterations arise in patients treated with AR-directed therapies. These molecular alterations may indicate the emergence of treatment resistance and may be targeted for the development of novel agents for prostate cancer. The presence of functional androgen receptor splice variants may represent a potential explanation for resistance to abiraterone and enzalutamide, newer AR-directed agents developed to treat metastatic castration-resistant prostate cancer （mCRPC）. In the last 8 years, many androgen receptor splice variants have been identified and characterized. Among these, androgen receptor splice variant-7 （AR-V7） has been investigated extensively. In AR-V7, the entire COOH-terminal ligand-binding domain of the canonical AR is truncated and replaced with a variant-specific peptide of 16 amino acids. Functionally, AR-V7 is capable of mediating constitutive nuclear localization and androgen receptor signaling in the absence of androgens, or in the presence of enzalutamide. In this review, we will focus on clinical translational studies involving detection/measurement of AR-V7. Methods have been developed to detect AR-V7 in clinical mCRPC specimens. AR-V7 can be reliably measured in both tissue and circulating tumor cells derived from mCRPC patients, making it possible to conduct both cross-sectional and longitudinal clinical correlative studies. Current evidence derived from studies focusing on detection of AR-V7 in mCRPC support its potential clinical utility as a treatment selection marker.展开更多
As shown in our previous study, two alternatively spliced androgen receptor(AR) variants, which are exclusively expressed in the granulosa cells of patients with polycystic ovary syndrome, exhibit retarded nuclear tra...As shown in our previous study, two alternatively spliced androgen receptor(AR) variants, which are exclusively expressed in the granulosa cells of patients with polycystic ovary syndrome, exhibit retarded nuclear translocation compared with wild-type AR. However, researchers have not yet determined whether these abnormalities correlate with heat shock protein 90(HSP90)and importin α(the former is a generally accepted co-chaperone of AR, and the latter is a component of classical nuclear import complexes). Here, these two variants were mainly retained in cytoplasm with HSP90 and importin α in the presence of dihydrotestosterone(DHT), and their levels in nucleus were significantly reduced, according to the immunofluorescence staining. The binding affinity of two AR variants for importin α was consistently decreased, while it was increased in WT-AR following DHT stimulation, leading to reduced nuclear import, particularly for the insertion-AR(Ins-AR). However, the binding affinities of two AR variants for HSP90 were increased in the absence of DHT compared with WT-AR, which functioned to maintain spatial structural stability, particularly for the deletion-AR(Del-AR). Therefore, the retarded nuclear translocation of two AR variants is associated with HSP90 and importin α, and the abnormal binding affinities for them play critical roles in this process.展开更多
This study proposes an innovative precast shear wall system, called an EVE precast hollow shear wall structure (EVE-PHSW). Precast panels in EVE-PHSW are simultaneously precast with vertical and horizontal holes. Nonc...This study proposes an innovative precast shear wall system, called an EVE precast hollow shear wall structure (EVE-PHSW). Precast panels in EVE-PHSW are simultaneously precast with vertical and horizontal holes. Noncontact lap splices of rebars are used in vertical joints connecting adjacent precast panels for automated prefabrication and easy in situ erection. The seismic behavior of EVE walls was examined through a series of tests on six wall specimens with aspect ratios of 1.0~1.3. Test results showed that EVE wall specimens with inside cast-in situ concrete achieved the desired “strong bending and weak shear” and failed in shear mode. Common main diagonal cracks and brittle shear failure in squat cast-in situ walls were prevented. Inside cast-in situ concrete could signifi cantly improve the shear strength and stiff ness of EVE walls. The details of boundary elements (cast-in situ or prefabricated) and vertical joints (contiguous or spaced) had little eff ect on the global behavior of EVE walls. Noncontact lap splices in vertical joints could enable EVE walls to exhibit stable load-carrying capacity through extensive deformations. Evaluation on design codes revealed that both JGJ 3-2010 and ACI 318-14 provide conservative estimation of shear strength of EVE walls, and EVE walls achieved shear strength reserves comparative to cast-in situ walls. The recommended eff ective stiff ness for cast-in situ walls in ASCE 41-17 appeared to be appropriate for EVE walls.展开更多
To develop a new DNA maker, which could be used in genetic diversity analysis and genetic map construction in plants, IT-ISJ （intron targeted intron-exon splice junction） primer combinations, which were designed acc...To develop a new DNA maker, which could be used in genetic diversity analysis and genetic map construction in plants, IT-ISJ （intron targeted intron-exon splice junction） primer combinations, which were designed according to the intronexon splice junction conserved sequences, were used to construct cotton genetic linkage map in the present study. 49 out of 704 IT-ISJ primer combinations showed polymorphism between upland cotton high quality cultivar Yumian 1 and multiple dominant gene line T586, and the polymorphic primer combinations accounted for 7.0% of total primer combinations. 49 IT-ISJ primer combinations were used to genotype 270 F2：7 recombinant inbred lines developed from （Yumian 1 × T586） F2, and 58 IT-ISJ loci were obtained. 58 IT-ISJ, together with 150 SSR and 8 morphological loci, were used to conduct linkage analysis, and a linkage map including 22 linkage groups and 113 loci （49 IT-ISJ, 62 SSR, and 2 morphological loci） was constructed. The linkage map covered 714.5 cM with an average interval of 6.3 cM between two markers, accounting for 16.1% of cotton genome. The present study demonstrated that the polymorphism of IT-ISJ marker is high, and it could be effectively applied in plant genetic map construction.展开更多
文摘Circular RNAs （circRNAs）, a kind of covalently closed RNA molecule, were used to be considered a type of byproducts of mis-splicing events and were discovered sporadically due to the technological limits in the early years. With the great technological progress such as high-throughput next-generation sequencing, numerous circRNAs have recently been detected in many species. CircRNAs were expressed in a spatio-temporally specific manner, suggesting their regulatory functional potentials were overlooked previously. Intriguingly, some circRNAs were indeed found with critical physiological functions in certain circumstances. CircRNAs have a more stable molecular st;＇ucture that can resist to exoribonuclease comparing to those linear ones, and their molecular functions include microRNA sponge, regulatory roles in transcription, mRNA traps that compete with linear splicing, templates for translation and possibly other presently unknown roles. Here, we review the discovery and characterization of circRNAs, the origination and formation mechanism, the physiological functions and the molecular roles, along with the methods for detection of circRNAs. We further look into the future and propose key questions to be answered for these magical RNA molecules.
基金Supported by the grant from the National Science Council(NSC 96-2320-B-030-004-MY3),Executive Yuan,Taiwan
文摘Chronic hepatitis B is a global health problem. The clinical outcomes of chronic hepatitis B infection include asymptomatic carrier state, chronic hepatitis(CH), liver cirrhosis(LC), and hepatocellular carcinoma(HCC). Because of the spontaneous error rate inherent to viral reverse transcriptase, the hepatitis B virus(HBV) genome evolves during the course of infection under the antiviral pressure of host immunity. The clinical significance of pre-S/S variants has become increasingly recognized in patients with chronic HBV infection. Pre-S/S variants are often identified in hepatitis B carriers with CH, LC, and HCC, which suggests that these naturally occurring pre-S/S variants may contribute to the development of progressive liver damage and hepatocarcinogenesis. This paper reviews the function of the pre-S/S region along with recent findings related to the role of pre-S/S variants in liver diseases. According to the mutation type, five pre-S/S variants have been identified: pre-S deletion, pre-S point mutation, pre-S1 splice variant, C-terminus S point mutation, and pre-S/S nonsense mutation. Their associations with HBV genotype and the possible pathogenesis of pre-S/S variants are discussed. Different pre-S/S variants cause liver diseases through different mechanisms. Most cause the intracellular retention of HBV envelope proteins and induction of endoplasmic reticulum stress, which results in liver diseases. Pre-S/S variants should be routinely determined in HBV carriers to help identify individuals who may be at a high risk of less favorable liver disease progression. Additional investigations are required to explore the molecular mechanisms of the pre-S/S variants involved in the pathogenesis of each stage of liver disease.
文摘Prostate cancer cells demonstrate a remarkable ＂addiction＂ to androgen receptor （AR） signaling in all stages of disease progression. As such, suppression of AR signaling remains the therapeutic goal in systemic treatment of prostate cancer. A number of molecular alterations arise in patients treated with AR-directed therapies. These molecular alterations may indicate the emergence of treatment resistance and may be targeted for the development of novel agents for prostate cancer. The presence of functional androgen receptor splice variants may represent a potential explanation for resistance to abiraterone and enzalutamide, newer AR-directed agents developed to treat metastatic castration-resistant prostate cancer （mCRPC）. In the last 8 years, many androgen receptor splice variants have been identified and characterized. Among these, androgen receptor splice variant-7 （AR-V7） has been investigated extensively. In AR-V7, the entire COOH-terminal ligand-binding domain of the canonical AR is truncated and replaced with a variant-specific peptide of 16 amino acids. Functionally, AR-V7 is capable of mediating constitutive nuclear localization and androgen receptor signaling in the absence of androgens, or in the presence of enzalutamide. In this review, we will focus on clinical translational studies involving detection/measurement of AR-V7. Methods have been developed to detect AR-V7 in clinical mCRPC specimens. AR-V7 can be reliably measured in both tissue and circulating tumor cells derived from mCRPC patients, making it possible to conduct both cross-sectional and longitudinal clinical correlative studies. Current evidence derived from studies focusing on detection of AR-V7 in mCRPC support its potential clinical utility as a treatment selection marker.
基金supported by the National Key Research and Development Program of China (2017YFC1001303)International Cooperation Project of China and Canada NSFC (81661128010)+2 种基金National Natural Science Foundation of China (31471405, 81671456, 81671412)the National Key Basic Research Program (2013CB967404) the Doctoral Innovation Fund of School of Medicine, Shanghai Jiao Tong University (BXJ201640)
文摘As shown in our previous study, two alternatively spliced androgen receptor(AR) variants, which are exclusively expressed in the granulosa cells of patients with polycystic ovary syndrome, exhibit retarded nuclear translocation compared with wild-type AR. However, researchers have not yet determined whether these abnormalities correlate with heat shock protein 90(HSP90)and importin α(the former is a generally accepted co-chaperone of AR, and the latter is a component of classical nuclear import complexes). Here, these two variants were mainly retained in cytoplasm with HSP90 and importin α in the presence of dihydrotestosterone(DHT), and their levels in nucleus were significantly reduced, according to the immunofluorescence staining. The binding affinity of two AR variants for importin α was consistently decreased, while it was increased in WT-AR following DHT stimulation, leading to reduced nuclear import, particularly for the insertion-AR(Ins-AR). However, the binding affinities of two AR variants for HSP90 were increased in the absence of DHT compared with WT-AR, which functioned to maintain spatial structural stability, particularly for the deletion-AR(Del-AR). Therefore, the retarded nuclear translocation of two AR variants is associated with HSP90 and importin α, and the abnormal binding affinities for them play critical roles in this process.
基金Beijing Everest Green Building Technology Ltd. for the funding
文摘This study proposes an innovative precast shear wall system, called an EVE precast hollow shear wall structure (EVE-PHSW). Precast panels in EVE-PHSW are simultaneously precast with vertical and horizontal holes. Noncontact lap splices of rebars are used in vertical joints connecting adjacent precast panels for automated prefabrication and easy in situ erection. The seismic behavior of EVE walls was examined through a series of tests on six wall specimens with aspect ratios of 1.0~1.3. Test results showed that EVE wall specimens with inside cast-in situ concrete achieved the desired “strong bending and weak shear” and failed in shear mode. Common main diagonal cracks and brittle shear failure in squat cast-in situ walls were prevented. Inside cast-in situ concrete could signifi cantly improve the shear strength and stiff ness of EVE walls. The details of boundary elements (cast-in situ or prefabricated) and vertical joints (contiguous or spaced) had little eff ect on the global behavior of EVE walls. Noncontact lap splices in vertical joints could enable EVE walls to exhibit stable load-carrying capacity through extensive deformations. Evaluation on design codes revealed that both JGJ 3-2010 and ACI 318-14 provide conservative estimation of shear strength of EVE walls, and EVE walls achieved shear strength reserves comparative to cast-in situ walls. The recommended eff ective stiff ness for cast-in situ walls in ASCE 41-17 appeared to be appropriate for EVE walls.
基金the National Natural Science Foundation of China (30370898,30571187, 30871556)National High Tech Research and Development Program of China (2006AA10Z1D3,2006AA100105)
文摘To develop a new DNA maker, which could be used in genetic diversity analysis and genetic map construction in plants, IT-ISJ （intron targeted intron-exon splice junction） primer combinations, which were designed according to the intronexon splice junction conserved sequences, were used to construct cotton genetic linkage map in the present study. 49 out of 704 IT-ISJ primer combinations showed polymorphism between upland cotton high quality cultivar Yumian 1 and multiple dominant gene line T586, and the polymorphic primer combinations accounted for 7.0% of total primer combinations. 49 IT-ISJ primer combinations were used to genotype 270 F2：7 recombinant inbred lines developed from （Yumian 1 × T586） F2, and 58 IT-ISJ loci were obtained. 58 IT-ISJ, together with 150 SSR and 8 morphological loci, were used to conduct linkage analysis, and a linkage map including 22 linkage groups and 113 loci （49 IT-ISJ, 62 SSR, and 2 morphological loci） was constructed. The linkage map covered 714.5 cM with an average interval of 6.3 cM between two markers, accounting for 16.1% of cotton genome. The present study demonstrated that the polymorphism of IT-ISJ marker is high, and it could be effectively applied in plant genetic map construction.
