Characterization of glycine-N-acyltransferase like 1 (GLYATL1) in prostate cancer

BackgroundRecent microarray and sequencing studies of prostate cancer showed multiple molecular alterations during cancer progression. It is critical to evaluate these molecular changes to identify new biomarkers and targets. We performed analysis of glycine-N-acyltransferase like 1 (GLYATL1) expression in various stages of prostate cancer in this study and evaluated the regulation of GLYATL1 by androgen.MethodWe performed in silico analysis of cancer gene expression profiling and transcriptome sequencing to evaluate GLYATL1 expression in prostate cancer. Furthermore, we performed immunohistochemistry using specific GLYATL1 antibody using high-density prostate cancer tissue microarray containing primary and metastatic prostate cancer. We also tested the regulation of GLYATL1 expression by androgen and ETS transcription factor ETV1. In addition, we performed RNA-sequencing of GLYATL1 modulated prostate cancer cells to evaluate the gene expression and changes in molecular pathways.ResultsOur in silico analysis of cancer gene expression profiling and transcriptome sequencing we revealed an overexpression of GLYATL1 in primary prostate cancer. Confirming these findings by immunohistochemistry, we show that GLYATL1 is overexpressed in primary prostate cancer compared with metastatic prostate cancer and benign prostatic tissue. Low-grade cancers had higher GLYATL1 expression compared to high-grade prostate tumors. Our studies showed that GLYATL1 is upregulated upon androgen treatment in LNCaP prostate cancer cells which harbors ETV1 gene rearrangement. Furthermore, ETV1 knockdown in LNCaP cells showed downregulation of GLYATL1 suggesting potential regulation of GLYATL1 by ETS transcription factor ETV1. Transcriptome sequencing using the GLYATL1 knockdown prostate cancer cell lines LNCaP showed regulation of multiple metabolic pathways.ConclusionsIn summary, our study characterizes the expression of GLYATL1 in prostate cancer and explores the regulation of its regulation in prostate cancer showing role for androgen and ETS transcription factor ETV1. Future studies are needed to decipher the biological significance of these findings.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151252/1/pros23887.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151252/2/pros23887_am.pd

Expression and role of PAICS, a de novo purine biosynthetic gene in prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143605/1/pros23533_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143605/2/pros23533.pd

Tidig produktutveckling av en kompakt diskmaskin

Detta examensarbete har utförts på primärutvecklingsavdelningen för diskmaskiner på Electrolux AB i Stockholm, Sverige. Huvuduppgiften har varit att ta fram det fysiska utseendet och lösningar för två delar till en ny kompakt diskmaskin, dörren och en komponent som på grund av sekretess inte kan nämnas. Examensarbetet har varit en del av ett större projekt där uppgiften har varit att ta fram det fysiska utförandet av koncept som varit på idéstadiet. Arbetet har utförts enligt Electrolux arbetssätt: Product Management Flow (PMF) där huvudtanken är att ta fram produkter som motsvarar kundens önskningar och problem. Under arbetet har kunskap om konsumenterna och tekniska aspekter såsom diskmaskinskomponenter och material samlats. De två komponenterna har sedan delats upp i mindre delproblem. Utifrån denna kunskap har sedan otaliga idéer arbetats fram för vardera komponentens delproblem. För dörren har detta resulterat i två koncept gjorda i Catia där ritningarna är klara för att göra prototyper i SLS (3D-modeller i sintrad nylon) med fungerande rörlig mekanism, dämpning, lås och självöppning.This Master’s thesis was performed at the Primary Development Dish Care Department at Electrolux Major Appliances Europe, Stockholm, Sweden. The main objective of the thesis has been to study the feasibility of possible solutions for the door of a new dishwasher. This thesis has been a part of a bigger project and the task has been to develop different product concepts and design a physical solution addressing the feasibility of the concept. The work has been performed according to Electrolux’s working process: Product Management Flow (PMF) with an intention to develop products according to the customers’ wishes and problems. During the work knowledge about the consumer, technical aspects of dishwasher components and materials have been collected. For the door and its components, sub problems have been identified. On the basis of this, several solutions have been proposed for component’s sub problems. For the door this has resulted in two concepts made in Catia with drawings ready for prototype making in SLS (Selective Laser Sintering, 3D models from CAD files) with a working moving mechanism, dampening, lock and self-opener

Impact of metal binding on the antitumor activity and cellular imaging of a metal chelator cationic imidazopyridine derivative

A new water soluble cationic imidazopyridine species, viz. (1E)-1-((pyridin-2-yl)methyleneamino)-3-(3-(pyridin-2-yl)imidazo[1,5-a]pyridin-2(3H)-yl)propan-2-ol (1), as a metal chelator is prepared as its PF6 salt and characterized. Compound 1 shows fluorescence at 438 nm on excitation at 342 nm in Tris-HCl buffer giving a fluorescence quantum yield (φ) of 0.105 and a life-time of 5.4 ns. Compound 1, as an avid DNA minor groove binder, shows pUC19 DNA cleavage activity in UV-A light of 365 nm forming singlet oxygen species in a type-II pathway. The photonuclease potential of 1 gets enhanced in the presence of Fe2+, Cu2+ or Zn2+. Compound 1 itself displays anticancer activity in HeLa, HepG2 and Jurkat cells with an enhancement on addition of the metal ions. Photodynamic effect of 1 at 365 nm also gets enhanced in the presence of Fe2+ and Zn2+. Fluorescence-based cell cycle analysis shows a significant dead cell population in the sub-G1 phase of the cell cycle suggesting apoptosis via ROS generation. A significant change in the nuclear morphology is observed from Hoechst 33258 and an acridine orange/ethidium bromide (AO/EB) dual nuclear staining suggesting apoptosis in cells when treated with 1 alone or in the presence of the metal ions. Apoptosis is found to be caspase-dependent. Fluorescence imaging to monitor the distribution of 1 in cells shows that 1 in the presence of metal ions accumulates predominantly in the cytoplasm. Enhanced uptake of 1 into the cells within 12 h is observed in the presence of Fe2+ and Zn2+

Impact of metal binding on the antitumor activity and cellular imaging of a metal chelator cationic imidazopyridine derivative (vol 40, pg 4855, 2011)

During the course of revising the manuscript, the authors inadvertently selected an incorrect image for Fig. 9c (1 + Fe2+). This image was mistakenly duplicated from Fig. 9e during preparation of the figures. The correction to the image in Fig. 9c does not affect the conclusions of the paper. The corrected Fig. 9 is shown here. The text, the figure legends, and the conclusions of this article are not affected by this correction. The authors apologize for any inconvenience that these errors in final figure revision/preparation may have caused. (Figure Presented). The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers