Project description:Augmenter of liver regeneration (ALR) is a critical multi-isoform protein with its longer isoform, located in the mitochondrial intermembrane space, being part of the mitochondrial disulfide relay system (DRS). Upregulation of ALR was observed in multiple forms of cancer, among them hepatocellular carcinoma (HCC). To shed light into the ALR role in the DRS in HCC, we thus pharmacologically inhibited ALR, resulting in profound mitochondrial impairment and cancer cell proliferation deficits. These effects were mostly reversed by supplementation with bioavailable hemin b, linking the DRS, and specifically ALR function, to mitochondrial iron homeostasis. Since tumor cells are known for their increased iron demand and since increased iron levels in cancer are associated with poor clinical outcome, these results help to further advance the intricate relation between iron and mitochondria in liver cancer.
Project description:The commercially available zebrafish (Danio rerio) gene expression microarray (4x44K format, Agilent G2519F-026437) was used to characterise the changes in gene expression levels in the ovary and brain of adult female zebrafish after exposure to 55, 553 and 5442 ng/L DRS for 14 days. Also, the transcriptional response in the brain of adult female zebrafish was characterised after exposure to mixtures of DRS and P4 at concentrations of 27+0.8, 277+8, 3119+123 (ng/L), respectively. This study was designed to achieve an understanding of the mode of action of DRS and steroid mixtures in zebrafish.
Project description:DNA replication stress (DRS)-linked genomic instability has emerged as an important factor driving cancer development. To understand the mechanisms of DRS-associated genomic instability and phenotypic evolution, we mapped chromosomal alterations in a yeast strain with lowered expression of the replicative DNA polymerase δ. At a whole-genome level, we identified both hotspots of mitotic recombination and chromosome-specific aneuploidy dependent on decreased levels of DNA polymerase δ. The high rate of chromosome loss is likely a reflection of reduced DNA repair capacity in strains with low levels of DNA polymerase. Most recombinogenic DNA lesions were introduced during S or G2 phase, presumably as a consequence of broken replication forks.
Project description:Ethiopia indigenous chicken breeds are typically divided into low and high altitude chicken breeds. Firstly, representative city of low altitude such as Awash is an altitude of around 950 meters above sea level and have a climate which is humidity and high temperature with 37℃ between May and June. Secondly, representative city of high altitude such as Addis Ababa is the capital of Ethiopia in eastern Africa and this city is an altitude of over 2,400 meters above sea level and has a climate which is generally comparable with the average annual temperature of around 16℃. These chicken breeds are adapted to the environmental (climate, temperature and altitude) on the city. Moreover, in Awash, chicken breed is more adapted to heat resistance. So we generated RNA sequencing (RNA-seq) data of Ethiopia indigenous chicken breeds such as low altitude chicken breed (adapted heat) and high altitude chicken breed (Non-adapted heat) to compare the gene expression profiling induced by heat stress (HS). Therefore, we identified 13 hub differentially expressed genes (DEGs) using cuffdiff within cufflinks, which validated by real-time quantitative-PCR (qRT-PCR) in Kenya chicken breed for biological and technical validation. These hub DEGs were subjected to pathway enrichment, protein/protein interaction, and the partial correlation coefficient with information theory (PCIT) to determine their involvement in heat stress and immune response. Our findings suggest that not only hub DEGs but also many others DEGs may play a role in heat stress and immune response.
Project description:To determine differential gene expression in peripheral blood of asthmatic individuals undergoing allergen inhalation challenge between early responders (ERs) and dual responders (DRs) following allergen inhalation challenge Blood was collected immediately prior to, and two hours after challenge The change in gene expression (post expression minus pre expression) in ERs was compared with the change in gene expression in DRs using age and sex as covariates Preprocessing and probeset filtering were applied to the entire dataset (28 CEL files) using the Factor Analysis for Robust MicroArray Summarization (farms) package in R The Linear Models for MicroArrays (limma) package was used to determine differential gene expression using a Benjamini Hochberg FDR of 10%.
Project description:To determine differential gene expression in peripheral blood of asthmatic individuals undergoing allergen inhalation challenge between early responders (ERs) and dual responders (DRs) following allergen inhalation challenge
