p63, more specifically its ΔNp63α isoform, plays essential roles in squamous cell carcinomas (SCCs), yet the mechanisms controlling its nuclear transport remain unknown. Nucleoporins (NUPs) are a family of proteins building nuclear pore complexes (NPC) and mediating nuclear transport across the nuclear envelope. Recent evidence suggests a cell type-specific function for certain NUPs; however, the significance of NUPs in SCC biology remains unknown. In this study, we show that nucleoporin 62 (NUP62) is highly expressed in stratified squamous epithelia and is further elevated in SCCs. Depletion of NUP62 inhibits proliferation and augments differentiation of SCC cells. The impaired ability to maintain the undifferentiated status is associated with defects in ΔNp63α nuclear transport. We further find that differentiation-inducible Rho kinase reduces the interaction between NUP62 and ΔNp63α by phosphorylation of phenylalanine-glycine regions of NUP62, attenuating ΔNp63α nuclear import. Our results characterize NUP62 as a gatekeeper for ΔNp63α and uncover its role in the control of cell fate through regulation of ΔNp63α nuclear transport in SCC.
Children with ependymoma have high mortality rates because ependymoma is resistant to conventional therapy. Genomic and transcriptomic studies have identified potential targets as significantly altered genes in ependymoma patients. Although several candidate oncogenes in ependymoma were recently reported, the detailed mechanisms for the roles of these candidate oncogenes in ependymoma progression remain unclear. Here, we report an oncogenic role of the nucleoporin TPR (translocated promoter region, nuclear basket protein) in regulating HSF1 (heat shock transcription factor 1) mRNA trafficking, maintaining MTORC1 activity to phosphorylate ULK1, and preventing macroautophagy/ autophagy induction in ependymoma. High expression of TPR were associated with increased HSF1 and HSPA/HSP70 expression in ependymoma patients. In an ependymoma mouse xenograft model, MTOR inhibition by rapamycin therapeutically suppressed TPR expression and reduced tumor size in vivo. Together, these results suggest that TPR may act as a biomarker for ependymoma, and pharmacological interventions targeting TPR-HSF1-MTOR may have therapeutic potential for ependymoma treatment.
The rhizomes of Curcuma aeruginosa (Zingiberaceae), locally known as Temu Hitam, is usually used as a traditional medicine. The bioactive compounds in this plant were known to have antibacterial activities. However, information regarding bioactive compounds on antibacterial activity contained in C. aeruginosa rhizomes is still limited. In continuing our study on Indonesian medicinal plants, the isolation of bioactive compounds from C. aeruginosa growing in Indonesia had been conducted. Curcumenol had been isolated from the methanol extract of C. aeruginosa rhizomes by using extraction methods and several chromatography techniques, i.e. vacuum liquid, radial, and preparative thin layer chromatography. Furthermore, this compound had been elucidated based on one-dimensional NMR ( 1 H and 13 C) and MS. The preliminary antibacterial assay of methanol extract of C. aeruginosa rhizomes on Salmonella typhi and Escherichia coli showed moderate activity with an inhibition zone of 7 mm (inhibition index of 1.17) and 6 mm (inhibition index of 1.00), in 50 ppm, respectively. Moreover, curcumenol also exhibited moderate activity in 50 ppm with 8 mm of inhibition zone (1.33 of inhibition index) on S. typhi while on E. coli showed weak activity in 50 ppm with 4 mm of inhibition zone (0.67 of inhibition index). However, both the methanol extract of C. aeruginosa rhizomes and curcumenol were inactive on Bacillus cereus and Staphylococcus aureus. It can be suggested that curcumenol played an important contribution to an antibacterial activity toward Gram-negative bacteria (S. typhi and E. coli) in C. aeruginosa rhizomes.
Abstract. Oil palms ((Elaeis guineensis Jacq.), have been widely cultivated in Sumatera for over two planting generations and occupied lands with various soil characteristics. In order to investigate microbial diversity in various soil characteristics of oil palm plantation, a molecular analysis called Terminal Restriction Length Polymorphism (T-RFLP) was adopted. The aim of this research was to analyze the bacterial diversity within several oil palm plantations in Sumatera. DNA extraction was performed using soil DNA extraction kit and analysis was performed using fragment analysis following T-RFLP techniques. Data analysis was performed using MICA III public database. The result showed that soil samples were grouped into two clusters based on their chemical properties. Both HhaI and HinfI digestions affected the number of culturable bacteria dominancy. HhaI was more suitable for revealing a possible culturable genera and species abundance. Dominant genera were detected in each cluster. Cluster-2, which consisted of peat soils, was dominated by Clostridium, Burkholderia, Catenibacterium and Pasteuria. As the diversity of microbes reveals soil fertility, the result showed that metagenomic approach could be used to predict soil fertility indicator, in order to improve agricultural practices for oil palm cultivation.
Sustainability infrastructure has become a crucial issue among decision-makers, developers, contractors, and consultants around the world. Value Engineering (VE) program is a method for improving project sustainability. This method present whether a decision increased or worsens the project’s performance. The purpose of this study to create and evaluate alternative ideas for expanding the project value. This study proposes VE analysis at the design level to achieve optimal project costs and duration. The case study is carried out on the Automated People Mover System (APMS) project. APMS project, at Soekarno Hatta International Airport, is the first Sky train in Indonesia. The length of the APMS track is 3.05 kilometres. APMS tracks are using for a simple pan bridge structure. On the APMS project, the initial design of the girder used the PC-U type with rarely-used dimensions. By using the VE program, stakeholders decided to replace PC-U type with the PC-V type, which has standard dimensions in PT. WIKA BETON as a supplier. The use of a PC-V type girder gains the benefit of efficiency in terms of time and cost. The percentage of production and erection time of the PC-V girder is 97% faster. Besides, the percentage of cost-saving is 9% of the total project cost.
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