The Biological Role of Androgen Receptor in Prostate Cancer Progression

Prostate cancer is the most commonly diagnosed cancer in men all over the world. Localized cancers in the early stages can be well managed by surgical or radiation therapy. Metastatic prostate cancer is treated with androgen deprivation therapy because androgen signaling is essential to the prostate tumor growth and anti-apoptotic ability. However, resistance develops quickly in the clinical course and leads to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) functions as a nuclear receptor to facilitate ligand-dependent transcriptional activation in the nucleus. AR interacts with several tissue-specific transcription factors such as forkhead box protein A1 (FOXA1) and regulates epigenetic status by recruiting epigenetic factors. In addition, AR transcriptional activity is modulated by interacting directly or indirectly with non-coding RNAs such as long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs). Notably, enhanced AR signaling in CRPC has been documented in several studies; however, which of these factors are important for the biological function it remains poorly understood. Here, I review our current knowledge of the mechanistic roles of AR involved in prostate cancer progression and discuss the importance of the prostate cancer-associated signals

A Quantum Beam Driver for the Future Inertial Fusion

Several heavy ion drivers for the inertial fusion have been proposed in Europe and US based on the existing the RF technology and the linear induction linac technology, though their concepts don’t still achieve the reality in a gigantic large scale. Developing accelerator technology may allow a compact and relatively cheap quantum beam driver for the future inertial fusion as an alternative scheme..

A Quantum Beam Driver for the Future Inertial Fusion

Several heavy ion drivers for the inertial fusion have been proposed in Europe and US based on the existing the RF technology and the linear induction linac technology, though their concepts don’t still achieve the reality in a gigantic large scale. Developing accelerator technology may allow a compact and relatively cheap quantum beam driver for the future inertial fusion as an alternative scheme..

Role of piRNA biogenesis and its neuronal function in the development of neurodegenerative diseases

Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), are caused by neuronal loss and dysfunction. Despite remarkable improvements in our understanding of these pathogeneses, serious worldwide problems with significant public health burdens are remained. Therefore, new efficient diagnostic and therapeutic strategies are urgently required. PIWI-interacting RNAs (piRNAs) are a major class of small non-coding RNAs that silence gene expression through transcriptional and post-transcriptional processes. Recent studies have demonstrated that piRNAs, originally found in the germ line, are also produced in non-gonadal somatic cells, including neurons, and further revealed the emerging roles of piRNAs, including their roles in neurodevelopment, aging, and neurodegenerative diseases. In this review, we aimed to summarize the current knowledge regarding the piRNA roles in the pathophysiology of neurodegenerative diseases. In this context, we first reviewed on recent updates on neuronal piRNA functions, including biogenesis, axon regeneration, behavior, and memory formation, in humans and mice. We also discuss the aberrant expression and dysregulation of neuronal piRNAs in neurodegenerative diseases, such as AD, PD, and ALS. Moreover, we review pioneering preclinical studies on piRNAs as biomarkers and therapeutic targets. Elucidation of the mechanisms underlying piRNA biogenesis and their functions in the brain would provide new perspectives for the clinical diagnosis and treatment of AD and various neurodegenerative diseases

Lung of Fgf10-CRISPR mosaic mouse

CRISPR/Cas9-mediated gene editing often generates founder generation (F0) mice that exhibit somatic mosaicism in the targeted gene(s). It has been known that Fibroblast growth factor 10 (Fgf10)-null mice exhibit limbless and lungless phenotypes, while intermediate limb phenotypes (variable defective limbs) are observed in the Fgf10-CRISPR F0 mice. However, how the lung phenotype in the Fgf10-mosaic mutants is related to the limb phenotype and genotype has not been investigated. In this study, we examined variable lung phenotypes in the Fgf10-targeted F0 mice to determine if the lung phenotype was correlated with percentage of functional Fgf10 genotypes. Firstly, according to a previous report, Fgf10-CRISPR F0 embryos on embryonic day 16.5 (E16.5) were classified into three types: type I, no limb; type II, limb defect; and type III, normal limbs. Cartilage and bone staining showed that limb truncations were observed in the girdle, (type I), stylopodial, or zeugopodial region (type II). Deep sequencing of the Fgf10-mutant genomes revealed that the mean proportion of codons that encode putative functional FGF10 was 8.3 ± 6.2% in type I, 25.3 ± 2.7% in type II, and 54.3 ± 9.5% in type III (mean ± standard error of the mean) mutants at E16.5. Histological studies showed that almost all lung lobes were absent in type I embryos. The accessory lung lobe was often absent in type II embryos with other lobes dysplastic. All lung lobes formed in type III embryos. The number of terminal tubules was significantly lower in type I and II embryos, but unchanged in type III embryos. To identify alveolar type 2 epithelial (AECII) cells, known to be reduced in the Fgf10-heterozygous mutant, immunostaining using anti-surfactant protein C (SPC) antibody was performed: In the E18.5 lungs, the number of AECII was correlated to the percentage of functional Fgf10 genotypes. These data suggest the Fgf10 gene dose-related loss of the accessory lobe and decrease in the number of alveolar type 2 epithelial cells in mouse lung. Since dysfunction of AECII cells has been implicated in the pathogenesis of parenchymal lung diseases, the Fgf10-CRISPR F0 mouse would present an ideal experimental system to explore it

Fgf10-CRISPR mosaic mutants demonstrate the gene dose-related loss of the accessory lobe and decrease in the number of alveolar type 2 epithelial cells in mouse lung

CRISPR/Cas9-mediated gene editing often generates founder generation (F0) mice that exhibit somatic mosaicism in the targeted gene(s). It has been known thatFibroblast growth factor 10(Fgf10)-null mice exhibit limbless and lungless phenotypes, while intermediate limb phenotypes (variable defective limbs) are observed in theFgf10-CRISPR F0 mice. However, how the lung phenotype in theFgf10-mosaic mutants is related to the limb phenotype and genotype has not been investigated. In this study, we examined variable lung phenotypes in theFgf10-targeted F0 mice to determine if the lung phenotype was correlated with percentage of functionalFgf10genotypes. Firstly, according to a previous report,Fgf10-CRISPR F0 embryos on embryonic day 16.5 (E16.5) were classified into three types: type I, no limb; type II, limb defect; and type III, normal limbs. Cartilage and bone staining showed that limb truncations were observed in the girdle, (type I), stylopodial, or zeugopodial region (type II). Deep sequencing of theFgf10-mutant genomes revealed that the mean proportion of codons that encode putative functional FGF10 was 8.3 +/- 6.2% in type I, 25.3 +/- 2.7% in type II, and 54.3 +/- 9.5% in type III (mean +/- standard error of the mean) mutants at E16.5. Histological studies showed that almost all lung lobes were absent in type I embryos. The accessory lung lobe was often absent in type II embryos with other lobes dysplastic. All lung lobes formed in type III embryos. The number of terminal tubules was significantly lower in type I and II embryos, but unchanged in type III embryos. To identify alveolar type 2 epithelial (AECII) cells, known to be reduced in theFgf10-heterozygous mutant, immunostaining using anti-surfactant protein C (SPC) antibody was performed: In the E18.5 lungs, the number of AECII was correlated to the percentage of functionalFgf10genotypes. These data suggest theFgf10gene dose-related loss of the accessory lobe and decrease in the number of alveolar type 2 epithelial cells in mouse lung. Since dysfunction of AECII cells has been implicated in the pathogenesis of parenchymal lung diseases, theFgf10-CRISPR F0 mouse would present an ideal experimental system to explore it