Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells

Obesity confers an increased risk of developing specific cancer forms. Although the mechanisms are unclear, increased fat cell secretion of specific proteins (adipokines) may promote/facilitate development of malignant tumors in obesity via cross-talk between adipose tissue(s) and the tissues prone to develop cancer among obese. We searched for novel adipokines that were overexpressed in adipose tissue of obese subjects as well as in tumor cells derived from cancers commonly associated with obesity. For this purpose expression data from human adipose tissue of obese and non-obese as well as from a large panel of human cancer cell lines and corresponding primary cells and tissues were explored. We found expression of ceruloplasmin to be the most enriched in obesity-associated cancer cells. This gene was also significantly up-regulated in adipose tissue of obese subjects. Ceruloplasmin is the body's main copper carrier and is involved in angiogenesis. We demonstrate that ceruloplasmin is a novel adipokine, which is produced and secreted at increased rates in obesity. In the obese state, adipose tissue contributed markedly (up to 22%) to the total circulating protein level. In summary, we have through bioinformatic screening identified ceruloplasmin as a novel adipokine with increased expression in adipose tissue of obese subjects as well as in cells from obesity-associated cancers. Whether there is a causal relationship between adipose overexpression of ceruloplasmin and cancer development in obesity cannot be answered by these cross-sectional comparisons

Knockdown of SF-1 and RNF31 Affects Components of Steroidogenesis, TGFβ, and Wnt/β-catenin Signaling in Adrenocortical Carcinoma Cells

The orphan nuclear receptor Steroidogenic Factor-1 (SF-1, NR5A1) is a critical regulator of development and homeostasis of the adrenal cortex and gonads. We recently showed that a complex containing E3 ubiquitin ligase RNF31 and the known SF-1 corepressor DAX-1 (NR0B1) interacts with SF-1 on target promoters and represses transcription of steroidogenic acute regulatory protein (StAR) and aromatase (CYP19) genes. To further evaluate the role of SF-1 in the adrenal cortex and the involvement of RNF31 in SF-1-dependent pathways, we performed genome-wide gene-expression analysis of adrenocortical NCI-H295R cells where SF-1 or RNF31 had been knocked down using RNA interference. We find RNF31 to be deeply connected to cholesterol metabolism and steroid hormone synthesis, strengthening its role as an SF-1 coregulator. We also find intriguing evidence of negative crosstalk between SF-1 and both transforming growth factor (TGF) β and Wnt/β-catenin signaling. This crosstalk could be of importance for adrenogonadal development, maintenance of adrenocortical progenitor cells and the development of adrenocortical carcinoma. Finally, the SF-1 gene profile can be used to distinguish malignant from benign adrenocortical tumors, a finding that implicates SF-1 in the development of malignant adrenocortical carcinoma

User interface design in exercise-related computer gaming environments

Detta är ett 20 poäng stort examensarbete i Medieteknik utfört hösten 2005 samt våren 2006. Examensarbetets syfte är att skapa ett användargränssnitt till menysystemet för en produkt som skall komma med motionscyklar för hemmabruk. Examensarbetet har inneburit att genom hela designprocessen ha en hög grad av kontakt med potentiella slutanvändare till produkten. Detta har skett genom längre intervjuer, enkäter och tester. Gränssnittet skulle innehålla vissa funktioner som specificerades av uppdragsgivaren. Detta var till exempel vilka inställningar som bör kunna göras och vilka olika alternativ på cykling man har. Efter inledande dialog med potentiella slutanvändare och kvantitativ informationsinsamling togs ett antal designförslag fram som utvärderades av slutanvändare. Förslag på navigering och menyträd testades i experimentform, detta innebar att användarna ombads utföra ett antal uppgifter och fick förklara hur de tänkte lösa dessa. Slutligen sammanfogades resultaten till en prototyp till ett användargränssnitt. Det ingick även i examensarbetet att ta fram en ikon som skall visas då den personliga tränaren säger något till användaren under ett träningspass

User interface design in exercise-related computer gaming environments

Detta är ett 20 poäng stort examensarbete i Medieteknik utfört hösten 2005 samt våren 2006. Examensarbetets syfte är att skapa ett användargränssnitt till menysystemet för en produkt som skall komma med motionscyklar för hemmabruk. Examensarbetet har inneburit att genom hela designprocessen ha en hög grad av kontakt med potentiella slutanvändare till produkten. Detta har skett genom längre intervjuer, enkäter och tester. Gränssnittet skulle innehålla vissa funktioner som specificerades av uppdragsgivaren. Detta var till exempel vilka inställningar som bör kunna göras och vilka olika alternativ på cykling man har. Efter inledande dialog med potentiella slutanvändare och kvantitativ informationsinsamling togs ett antal designförslag fram som utvärderades av slutanvändare. Förslag på navigering och menyträd testades i experimentform, detta innebar att användarna ombads utföra ett antal uppgifter och fick förklara hur de tänkte lösa dessa. Slutligen sammanfogades resultaten till en prototyp till ett användargränssnitt. Det ingick även i examensarbetet att ta fram en ikon som skall visas då den personliga tränaren säger något till användaren under ett träningspass

Pairwise comparisons between cell fractions from adipose tissue

Annotated pairwise comparisons between all FACS-sorted fractions from adipose tissue. <div>Usage note:</div><div>Columns are separed with ; (not tab or comma)</div

Pairwise comparisons between cell fractions from adipose tissue

Annotated pairwise comparisons between all FACS-sorted fractions from adipose tissue. <div>Usage note:</div><div>Columns are separed with ; (not tab or comma)</div

R markdown file for enrichment analysis

R code with comments in markdown format. Code used to generate gene enrichment for the different FACS-sorted cell fractions from adipose tissu

Differential expression in obese vs non-obese adipocyte progenitors - nominal significance.

Comparison of gene expression in adipocyte progenitors from non-obese (n=10) and obese (n=9). Microarray data was RMA normalized, filtered so only probes with an associated gene symbols were kept, and then analyzed in limma to identify differentially expresssed genes. No significant genes were found after correction for multiple hypothesis testing. Genes were then filtered on nominal significance (uncorrected p-value < 0.05) and log fold change > |0.585|

Differential expression in obese vs non-obese adipocyte - nominal significance

DIfferential expression of lean_obese adipocytes from adipose tissue. PLEASE NOTE: nominal significance, as all adjusted p-values > 0.05. Reported genes have log fold change > 0.585<br

Tables of human adipose tissue cell type-specific genes

The data set includes:<div>1) "Celltype_enriched.txt" files separated by ";" that contain genes significantly enriched in one cell type compared to other three analyzed hWAT cell types according to the analysis described in R markdown file:</div><div>http://figshare.com/s/509ea9441af442a735ac</div><div>Adjusted p-value <0.05 for all pairwise comparisons, moderated F-statistics p-value <0.05 (from R package/bioconductor package Limma).</div><div><br></div><div>2) "Celltype_enriched_collected.txt" files separated by ";". These files contain tables that include mean expression of the gene in a fraction where it is enriched, log fold change (logFC) and adjusted P values (adj.P.val) compared to each of other fractions. Minimal logFC and maximal adj.P.Val against other fractions are included as separate columns to enable easy sorting of the data in search for best expressed, best enriched or most specific genes. </div><div><br></div><div>3) R-code used to generate "Celltype_enriched_collected.txt" tables is provided.</div><div><br></div><div>4) In addition, a table with 100 highest-ranked genes from each fraction (based on highest logFC_min and lowest adj.P.val_max) is also included ("Selected_enriched_genes_all_fractions" - separated by tab).</div><p></p