IMP3 RNP safe houses prevent miRNA-directed <i>HMGA2</i> mRNA decay in cancer and development

Summary: The IMP3 RNA-binding protein is associated with metastasis and poor outcome in human cancer. Using solid cancer transcriptome data, we found that IMP3 correlates with HMGA2 mRNA expression. Cytoplasmic IMP3 granules contain HMGA2, and IMP3 dose-dependently increases HMGA2 mRNA. HMGA2 is regulated by let-7, and let-7 antagomiRs make HMGA2 refractory to IMP3. Removal of let-7 target sites eliminates IMP3-dependent stabilization, and IMP3-containing bodies are depleted of Ago1-4 and miRNAs. The relationship between Hmga2 mRNA and IMPs also exists in the developing limb bud, where IMP1-deficient embryos show dose-dependent Hmga2 mRNA downregulation. Finally, IMP3 ribonucleoproteins (RNPs) contain other let-7 target mRNAs, including LIN28B, and a global gene set enrichment analysis demonstrates that miRNA-regulated transcripts in general are upregulated following IMP3 induction. We conclude that IMP3 RNPs may function as cytoplasmic safe houses and prevent miRNA-directed mRNA decay of oncogenes during tumor progression. : The RNA-binding protein IMP3 is associated with metastasis and poor outcome in human cancer. Jønson et al. now show that IMP3 RNPs function as cytoplasmic safe houses in preventing miRNA-directed mRNA decay of oncogenes such as HMGA2 and LIN28B during cancer and development. This explains why poor outcome is a hallmark of IMP3-positive tumors and demonstrates how posttranscriptional events can be involved in tumor progression

Produktplasseringens effekt

I denne bacheloroppgaven er tar vi for oss effekten av produktplassering i norske TV-programmer. Produktplassering i Norge er et relativt nytt fenomen, som tilsier at det foreligger lite forskning på dette området. I Januar 2013 ble produktplassering tillat på de kommersielle TV-kanalene i Norge. På bakgrunn av lite forskning, det endrede mediebildet og ny teknologi, tror vi at produktplassering vil få et større fokus i tiden fremover. Vi ønsker å belyse effekten av dette fenomen, og se på hvordan dette påvirker respondentenes kjennskap, holdninger og atferd til ett merke. For å kunne kartlegge effekten har vi tatt utgangspunkt i Berghaus som hadde produktplassering i Dropped - Heltens kamp, på TV 2 våren 2015. I forhold til tidligere studier som er gjennomført på området baseres oppgaven hovedsaklig på forskning fra Cristel Antionia Russel (2002), hvor effekten av produktplassering i USA er blitt undersøkt. Vi har gjennom deler av oppgaven sammenlignet effekten av produktplassering i USA med vår undersøkelse i Norge. Dette ble gjort for å undersøke om resultatene våre kunne underbygges med tidligere forskning. For å svare på problemstillingen har vi valgt å ta i bruk en kvantitativ metode. Vi har brukt et kvasieksperiment hvor det ble gjennomført en undersøkelse før og etter programmet ble sendt på TV. Respondentene i den siste undersøkelsen ble utsatt for et stimuli, som var produktplasseringen av Berghaus i Dropped - Heltenes kamp. Dette ble gjennomført ved hjelp av et spørreskjema, med et utvalg på 100 respondenter i hver gruppe. Resultatene fra undersøkelsen er drøftet opp mot teorien oppgaven tar utgangspunkt i. Funnene viser at produktplasseringen har hatt en relativt stor effekt på hjulpen kjennskap. Av resultatene kan vi også se at det er en positiv, signifikant forskjell mellom gruppene, i forhold til holdninger og atferd til merket. Da studien til Russel (2002) viser til en positiv effekt av produktplassering, kan vi trekke paralleller opp til vårt studie. Vi håper denne oppgaven vil bidra til interessant lesning og videre forskning på dette området i Norg

Metabolic and molecular signatures of improved growth in Atlantic salmon (Salmo salar) fed surplus levels of methionine, folic acid, vitamin B6 and B12 throughout smoltification.

A moderate surplus of the 1C nutrients methionine, folic acid, vitamin B6 and B12 above dietary recommendations for Atlantic salmon has shown to improve growth and reduce hepatosomatic index in the on-growing salt water period when fed throughout smoltification. Metabolic properties and molecular mechanisms determining the improved growth are unexplored. Here, we investigate metabolic and transcriptional signatures in skeletal muscle taken before and after smoltification to acquire deeper insight into pathways and possible nutrient-gene-interactions. A control feed (Ctrl) or 1C nutrient surplus feed (1C+) were fed to Atlantic salmon six weeks prior to smoltification until three months after salt water transfer. Both metabolic and gene expression signatures revealed significant 1C nutrient-dependent changes already at pre-smolt, but differences intensified when analysing post-smolt muscle. Transcriptional differences revealed a lower expression of genes related to translation, growth, and amino acid metabolization in post-smolt muscle when fed additional 1C nutrients. The 1C+ group showed less free amino acid and putrescine levels, and higher methionine and glutathione (GSH) amounts in muscle. For Ctrl muscle, the overall metabolic profile suggests a lower amino acid utilization for protein synthesis, and increased methionine metabolization in polyamine and redox homeostasis, whereas transcription changes are indicative of compensatory growth regulation at local tissue level. These findings point to fine-tuned nutrient-gene-interactions fundamental for improved growth capacity through better amino acid utilization for protein accretion when salmon was fed additional 1C nutrients throughout smoltification. It also highlights potential nutritional programming strategies on improved post-smolt growth through 1C+ supplementation before and throughout smoltification.acceptedVersio

Somatostatin analogue treatment primarily induce miRNA expression changes and up-regulates growth inhibitory miR-7 and miR-148a in neuroendocrine cells

Somatostatin (SST) analogues are used to control the proliferation and symptoms of neuroendocrine tumors (NETs). MicroRNAs (miRNA) are small non-coding RNAs that modulate posttranscriptional gene expression. We wanted to characterize the miRNAs operating under the control of SST to elucidate to what extent they mediate STT actions. NCI-H727 carcinoid cell line was treated with either a chimeric SST/dopamine analogue; a SST or dopamine analogue for proliferation assays and for identifying differentially expressed miRNAs using miRNA microarray. The miRNAs induced by SST analogue treatment are investigated in carcinoid cell lines NCI-H727 and CNDT2 using in situ hybridization, qPCR and proliferation assays. SST analogues inhibited the growth of carcinoid cells more potently compared to the dopamine analogue. Principal Component Analysis (PCA) of the samples based on miRNA expression clearly separated the samples based on treatment. Two miRNAs which were highly induced by SST analogues, miR-7 and miR-148a, were shown to inhibit the proliferation of NCI-H727 and CNDT2 cells. SST analogues also produced a general up-regulation of the let-7 family members. SST analogues control and induce distinct miRNA expression patterns among which miR-7 and miR-148a both have growth inhibitory properties

Cancers of unknown primary origin (CUP) are characterized by chromosomal instability (CIN) compared to metastasis of know origin

BACKGROUND: Cancers of unknown primary (CUPs) constitute ~5% of all cancers. The tumors have an aggressive biological and clinical behavior. The aim of the present study has been to uncover whether CUPs exhibit distinct molecular features compared to metastases of known origin. METHODS: Employing genome wide transcriptome analysis, Linear Discriminant Analysis (LDA) and Quadratic Discriminant Analysis (QDA), we defined the putative origins of a large series of CUP and how closely related a particular CUP was to corresponding metastases of known origin. LDA predictions were subsequently used to define a universal CUP core set of differentially expressed genes, that by means of gene set enrichment analysis was exploited to depict molecular pathways characterizing CUP. RESULTS: The analyses show that CUPs are distinct from metastases of known origin. CUPs exhibit inconsistent expression of conventional cancer biomarkers and QDA derived outlier scores show that CUPs are more distantly related to their primary tumor class than corresponding metastases of known origin. Gene set enrichment analysis showed that CUPs display increased expression of genes involved in DNA damage repair and mRNA signatures of chromosome instability (CIN), indicating that CUPs are chromosome unstable compared to metastases of known origin. CONCLUSIONS: CIN may account for the uncommon clinical presentation, chemoresistance and poor outcome in patients with CUP and warrant selective diagnostic strategies and treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1128-x) contains supplementary material, which is available to authorized users

Tissue-Specific Orchestration of Gilthead Sea Bream Resilience to Hypoxia and High Stocking Density

Two different O-2 levels (normoxia: 75-85% O-2 saturation; moderate hypoxia: 42-43% O-2 saturation) and stocking densities (LD: 9.5, and HD: 19 kg/m(3)) were assessed on gilthead sea bream (Sparus aurata) in a 3-week feeding trial. Reduced O-2 availability had a negative impact on feed intake and growth rates, which was exacerbated by HD despite of the improvement in feed efficiency. Blood physiological hallmarks disclosed the enhancement in O-2-carrying capacity in fish maintained under moderate hypoxia. This feature was related to a hypo-metabolic state to cope with a chronic and widespread environmental O-2 reduction, which was accompanied by a differential regulation of circulating cortisol and growth hormone levels. Customized PCR-arrays were used for the simultaneous gene expression profiling of 34-44 selected stress and metabolic markers in liver, white skeletal muscle, heart, and blood cells. The number of differentially expressed genes ranged between 22 and 19 in liver, heart, and white skeletal muscle to 5 in total blood cells. Partial Least-Squares Discriminant Analysis (PLS-DA) explained [R2Y(cum)] and predicted [Q2Y(cum)] up to 95 and 65% of total variance, respectively. The first component (R2Y = 0.2889) gathered fish on the basis of O-2 availability, and liver and cardiac genes on the category of energy sensing and oxidative metabolism (cs, hif-1 alpha, pgc1 alpha, pgc1 beta, sirts 1-2-4-5-6-7), antioxidant defense and tissue repair (prdx5, sod2, mortalin, gpx4, gr, grp-170, and prdx3) and oxidative phosphorylation (nd2, nd5, and coxi) highly contributed to this separation. The second component (R2Y = 0.2927) differentiated normoxic fish at different stocking densities, and the white muscle clearly promoted this separation by a high over-representation of genes related to GH/IGF system (ghr-i, igfbp6b, igfbp5b, insr, igfbp3, and igf-i). The third component (R2Y = 0.2542) discriminated the effect of stocking density in fish exposed to moderate hypoxia by means of hepatic fatty acid desaturases (fads2, scd1a, and scd1b) and muscle markers of fatty acid oxidation (cpt1a). All these findings disclose the different contribution of analyzed tissues (liver >= heart > muscle > blood) and specific genes to the hypoxic- and crowding stress-mediated responses. This study will contribute to better explain and understand the different stress resilience of farmed fish across individuals and species

Promoter polymorphism -119C/G in MYG1 (C12orf10) gene is related to vitiligo susceptibility and Arg4Gln affects mitochondrial entrance of Myg1

<p>Abstract</p> <p>Background</p> <p><it>MYG1 </it>(<it>Melanocyte proliferating gene 1</it>, also C12orf10 in human) is a ubiquitous nucleo-mitochondrial protein, involved in early developmental processes and in adult stress/illness conditions. We recently showed that <it>MYG1 </it>mRNA expression is elevated in the skin of vitiligo patients. Our aim was to examine nine known polymorphisms in the <it>MYG1 </it>gene, to investigate their functionality, and to study their association with vitiligo susceptibility.</p> <p>Methods</p> <p>Nine single nucleotide polymorphisms (SNPs) in the <it>MYG1 </it>locus were investigated by SNPlex assay and/or sequencing in vitiligo patients (n = 124) and controls (n = 325). <it>MYG1 </it>expression in skin biopsies was detected by quantitative-real time PCR (Q-RT-PCR) and polymorphisms were further analysed using luciferase and YFP reporters in the cell culture.</p> <p>Results</p> <p>Control subjects with -119G promoter allele (rs1465073) exhibited significantly higher <it>MYG1 </it>mRNA levels than controls with -119C allele (<it>P </it>= 0.01). Higher activity of -119G promoter was confirmed by luciferase assay. Single marker association analysis showed that the -119G allele was more frequent in vitiligo patients (47.1%) compared to controls (39.3%, <it>P </it>< 0.05, OR 1.37, 95%CI 1.02-1.85). Analysis based on the stage of progression of the vitiligo revealed that the increased frequency of -119G allele occurred prevalently in the group of patients with active vitiligo (n = 86) compared to the control group (48.2% <it>versus </it>39.3%, <it>P </it>< 0.05; OR 1.44, 95%CI 1.02-2.03). Additionally, we showed that glutamine in the fourth position (in Arg4Gln polymorphism) completely eliminated mitochondrial entrance of YFP-tagged Myg1 protein in cell culture. The analysis of available EST, cDNA and genomic DNA sequences revealed that Myg1 4Gln allele is remarkably present in human populations but is never detected in homozygous state according to the HapMap database.</p> <p>Conclusions</p> <p>Our study demonstrated that both <it>MYG1 </it>promoter polymorphism -119C/G and Arg4Gln polymorphism in the mitochondrial signal of Myg1 have a functional impact on the regulation of the <it>MYG1 </it>gene and promoter polymorphism (-119C/G) is related with suspectibility for actively progressing vitiligo.</p

Borehole stability on Yme

Master's thesis in Petroleum engineeringThe main object of this thesis it to perform an in-situ stress and borehole stability evaluation of the wells in the Yme field. The Inversion technique was used find the maximum and minimum horizontal stresses. The stresses were found for the whole well and for the location around each casing shoe. The field was found to be anisotropic. The outcome of the analysis was used together with data form each well to calculate fracture and collapse gradients for the wells. The fracturing gradient became unrealistic large for several of the wells, and too low for well 9/2 A-8. The cause for this may be data inconsistency from collection of the data from many different sources. Also a geological uncertainty related to the faults and tectonic forces present represents a factor. The effect of azimuth and inclination on the stability is commented by comparing the fracture and collapse gradients for the different wells. Azimuth is observed to have a large effect on the fracturing gradient and a smaller effect on the collapse gradient

Er det bedre å bruke elementer enn plasstøpt betong?

Master's thesis in Structural engineeringDenne oppgaven ble skrevet på bakgrunn av den voksende bruken av prefabrikerte betongelementer, og dermed å sammenligne bruken av elementer og plasstøpt betong. Hensikten og problemstillingen for denne oppgaven er å finne ut ‘’hva er mest fordelaktig av å bruke betongelementer eller plasstøpt betong til referansebygget på Moi?’’ Eller som navnet er på om oppgaven : Er det bedre å bruke elementer enn plasstøpt betong? [...

Regulation of appetite and growth of Atlantic salmon (Salmo salar L.) and effect of water oxygen, temperature and dietary energy

High water temperature combined with low dissolved oxygen (LO or hypoxia) is one of the most challenging environmental conditions farmed fish experience. The oxygen requirement of fish increases in parallel to this, which limits the aerobic energy metabolism and consequently reduces feed intake and growth of fish. The global ocean warming followed by reduced oxygen availability, is expected to exacerbate associated physiological stress on fish in several areas where Atlantic salmon are currently farmed. Understanding the impact of temperature and limited oxygen on growth regulatory mechanisms and the energy metabolism, will be of significant relevance to both cultured and wild fish populations. Conditions of high temperature and hypoxia are related with reduced feed intake and growth in fish. It is unclear whether the low oxygen availability directly affects growth regulatory mechanisms, and if low feed intake is the primary cause of depressed growth under LO conditions. Studies of appetite and growth regulation in salmon under such conditions are few, and considerations of the fluctuating character of endocrine signals and nutrient absorption are scarce. Limitation of the aerobic energy metabolism under reduced oxygen availability is further restricted by a thermal increase. It is therefore interesting to find out how high energy diets can potentially impact appetite and growth regulation under LO conditions. This thesis therefore investigated mechanisms by which LO and high temperature conditions impact appetite and growth regulation in seawater adapted Atlantic salmon. Free amino acid (FAA) and endocrine dynamics in relation to meal time were also studied. Four fish trials were conducted, including the following variables; dissolved oxygen (DO; LO and high, HO), temperature and digestible energy (low and high, LE and HE). Endocrine appetite and growth signalling was investigated through analyses of plasma ghrelin and IGF-1 concentration, and mRNA levels of the growth hormone receptor (ghr1) and insulin like growth factor-1 (igf1) in liver and muscle tissue. LO conditions demonstrated direct depressed effects on appetite and growth in salmon across temperatures. Reduced growth in salmon under LO was not caused only by a reduced feed intake, but appeared to be a combined effect of impairment of growth regulation and increased metabolic costs, as demonstrated by a pair-feeding technique. Increased metabolic costs by LO were indicated by responses in oxyregulating mechanisms, such as increased haemoglobin, reduced blood pH and imbalanced osmoregulation. Reduced specific growth rate (SGR) and feed intake were also found for salmon under LO compared to HO groups, at both optimal and high temperatures. High temperature demonstrated a diminished growth potential in salmon compared to an optimal temperature. This was reflected in a faster 24 hour postprandial catabolism of absorbed FAA, and generally lower and faster declines of IGF-1 (plasma and mRNA) at 19&deg;C compared to 13&deg;C. Ghrelin was found to signal feed anticipation in salmon, consistent with mammalian findings, and reflected by clear preprandial plasma ghrelin peaks at 12&deg;C. Ghrelin and GHIGF factors responded to LO at a high temperature, but further studies should focus on a postprandial perspective to confirm the preprandial peaks at 12&deg;C. Results from feeding HE diets to salmon, indicate that it is possible to stimulate growth, feed utilisation and the energy metabolism under LO conditions through DE level, regardless of temperature. To summarise, the thesis shows that growth regulation in seawater adapted salmon is negatively affected by LO at optimal and high temperatures. Positive effects from feeding HE diets under LO, demonstrate possibilities to support energy metabolism through dietary means under challenging environmental conditions. Diet effects and environmental impact on growth regulation are of great relevance to salmon farming, as further knowledge can improve growth, welfare, health and future farming possibilities