Sektorinndeling innen næringsområdene P, Q og R. P. Undervisning Q. Helse- og sosialtjenester R. Kulturell virksomhet, underholdning og fritidsaktiviteter

I nasjonalregnskapet er fordelingen av økonomien på sektorer basert på definisjoner og prinsipper i et internasjonalt regelverk, der Norge er pålagt å følge den europeiske versjonen, European System of Accounts 2010 (ESA 2010) som en del av EØS-avtalen. Hovedsektorene i økonomien er finansielle og ikke-finansielle foretak, offentlig forvaltning, ideelle organisasjoner, husholdninger og utlandet. Nasjonalregnskapstall utarbeides på bakgrunn av annen økonomisk statistikk fra Statistisk sentralbyrå og andre kilder. Et helhetlig statistikksystem som skal sikre konsistens i nasjonalregnskapet må ivareta de samme inndelingene i registeret og i statistikken som utgjør nasjonalregnskapets kildegrunnlag. Nye krav fra Eurostat gjennom forordningen for European Business Statistics (EBS-forordningen) innebærer at Norge fremover må utarbeide og rapportere strukturstatistikk også på enkelte næringsområder som ikke er dekket med slik statistikk i dag: P. Undervisning (SN2007 85), Q. Helse- og sosialtjenester (SN2007 86-88) og R. Kulturell virksomhet, underholdning og fritidsaktiviteter (SN2007 90-93). Strukturstatistikk (NØKU1 ) skal dekke alle statistiske enheter (foretak/virksomheter) med markedsrettet aktivitet. Definisjonen av markedsrettet aktivitet henger sammen med sektor. En gjennomgang av avgrensningen mellom sektorer ble gjennomført i forkant av innføring av oppdaterte internasjonale retningslinjer i nasjonalregnskapet i 2014. Prinsippene er de samme nå som i 2014, men organiseringen av økonomien kan ha endret seg siden da. Som et ledd i kvalitetssikring av populasjonen ny statistikk skal bygge på har Statistisk sentralbyrå gått gjennom sektorinndelingen innen disse næringshovedområdene på nytt. Praktisk forvaltning av registeret og statistikken kan ikke baseres på prinsipielle manuelle vurderinger for hver eneste statistiske enhet i registeret. For det første er det ikke tilstrekkelige ressurser til det, dessuten må ulik skjønnsmessig vurdering av prinsipper unngås. Det er derfor et mål å komme frem til generelle pragmatiske regler basert på prinsippene som kan håndteres basert på tilgjengelige ressurser og informasjonsgrunnlag og som sikrer ensartet og dokumenterbar klassifisering av sammenlignbare enheter. Gjennomgangen innebar kun mindre endringer i de eksisterende sektoravgrensningene. Sektoren finansielle foretak er ikke berørt, siden den kun omfatter finansielle næringer. Avgrensningen av hovedsektorene offentlig forvaltning og husholdningssektoren er som tidligere, selv om det tilkjennegis at det kan stilles spørsmål om avgrensningen i enkelte tilfeller. For næringshovedområdene P, Q og R har det vært mest krevende å bestemme korrekt sektor i tilfeller der tjenestene produseres av privat eide foretak, men der kostnadene ved produksjon av tjenestene helt eller i stor grad fullfinansieres av offentlig forvaltning. For å kunne inngå i sektoren ideelle organisasjoner, er det en betingelse at den statistiske enheten ikke kan være en kilde til profitt for eiere eller stiftere gjennom for eksempel utbytte, men dette er ikke en tilstrekkelig betingelse. Det har også vært nødvendig å se nærmere på hvordan aktivitetene er organisert; kan betalingene de private selskapene mottar fra det offentlige anses som offentlig kjøp av tjenester, der det forekommer muligheter for markedstilpasning der kjøper kan velge mellom tilbydere

FOXA Genes in Lung Cancer In Vitro and In Vivo

Lung cancer is the leading cause of cancer-related deaths worldwide. Lung cancer survival rates have remained poor, mainly due to late diagnosis at advanced stages in addition to scanty treatment options. The main cause of lung cancer is tobacco smoke, accounting for up to 90% of all cases. Exposure to other environmental carcinogens also contributes to the disease. It is important to understand the underlying mechanisms of carcinogen-induced lung cancer to establish better treatment targets and novel biomarkers for cancer detection. This thesis aimed at identifying the role of the two proteins FOXA1 and FOXA2 in lung cancer and lung cell transformation. FOXA1 and FOXA2 are pioneer transcription factors that regulate gene expression by binding forkhead DNA-motifs in condensed chromatin resulting in an open chromatin structure. The pioneer factors further guide other transcription factors to their respective binding sites where they exert their regulatory function. FOXA1 and FOXA2 have been implicated in maintaining an epithelial phenotype, and their altered expression has been indicated in different cancer types. An in vitro transformation model using immortalized, non-transformed human bronchial epithelial cells (HBECs), was utilized for studying FOXA1 and FOXA2 during carcinogen-induced cell transformation. Exposure of two HBECs (HBEC2 and HBEC12) to cigarette smoke condensate, benzo[a]pyrene (B[a]P), and methylnitrosouera resulted in transformed cells with the acquired ability to grow anchorage-independent in soft-agar. All cell colonies isolated from soft-agar showed diminished transcription of both FOXA1 and FOXA2. Also, the transformed cells displayed features of epithelial to mesenchymal transition, evident by gene expression patterns, altered morphology, and increased invasiveness. The expression levels of FOXA1 and FOXA2 was next studied in matched tumor and non-tumor tissue in vivo from three geographically independent cohorts from Norway, Italy, and the USA. Lung tumors expressed significantly higher levels of FOXA1 than matched non-tumor lung tissue. A small subset of the tumors harbored FOXA1 gene amplifications, accounting for the higher FOXA1 mRNA levels in this subgroup. The lung tumors expressed significantly lower levels of FOXA2 compared to non-tumor. CpG-islands located in or near the FOXA2 gene were more methylated in tumors than in non-tumor tissues. Two publicly available databases (TCGA and CURELUNG) confirmed increased DNA-methylation in FOXA2. The changes in DNA methylation suggest that lung tumors suppress FOXA2 activity through epigenetic regulation. The transformed cell lines showed altered expression of CYP1A1 and CYP1B1. A study using RNA interference to knock down FOXA1 was performed to investigate the role of FOXA1 in the regulation of CYP450 enzymes and the implications for B[a]P and estradiol metabolism. Knock-down of FOXA1 led to increased expression of CYP1B1 but had no apparent effect on CYP1A1 expression. Chromatin immunoprecipitation identified FOXA1 binding in a CYP1B1 enhancer. No binding of FOXA1 was observed in CYP1A1 regulatory regions. B[a]P and 17ß-estradiol metabolites were measured by LC/MS/MS in cell culture media and B[a]P-DNA and 32P-postlabeling was used to measure adduct levels. These analyses did not identify any changes in metabolism or DNA-adduct formation in cells with knocked down FOXA1, in spite of increased expression of CYP1B1. These findings suggest that FOXA1 can regulate CYP1B1 expression, but this regulation may not be sufficient for affecting metabolic capacity. Taken together, the three studies conducted for this thesis support a role of the transcription factors FOXA1 and FOXA2 in lung cancer in vitro and in vivo

MicroRNA, environmental carcinogens and risk of lung cancer

Lung cancer is the leading cause of cancer related deaths world wide. The major cause of lung cancer is tobacco smoking. Tobacco smoke contains many different carcinogens including polycyclic aromatic hydrocarbons (PAH), which are known to cause DNA damage and initiate tumourigenesis.The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix protein of the PER-ARNT-SIM (PAS) family of transcription factors, which is involved in many biological processes including development, cell cycle regulation, cell differentiation, cell-cell signalling, cellular growth, and circadian rhythms. Most of the known function of AHR, however, is regarding its role in transcriptional induction of xenobiotic metabolis- ing enzymes (XMEs). In the lung, PAHs bind and activate the AHR, leading to transcriptional induction of members of the cytochrome P450 (CYP) enzyme family that are involved in activation of pro-carcinogenic PAHs to carcinogenic metabolites.MicroRNAs (miRNAs), a group of short non-coding RNA molecules, mediate sequence specific silencing of messenger RNAs (mRNAs) and are important in regulation of gene expression. The deregula- tion of certain miRNAs has been observed in several types of cancer, including lung cancer. Like mRNAs, miRNAs belong to the class II type of genes, and transcription of these types of RNA can therefore be regulated by the same transcription factors.Little is known regarding the role of miRNAs in environmental toxicology. The aim of this thesis was to identify miRNAs regulated by the AHR, and consequently may be important in mediating toxicity of tobacco smoke carcinogens.Expression levels of 750 miRNAs in mouse lung of Ahr wild-type and knockout animals were pro- filed by RT-qPCR arrays. Fifteen miRNAs were found to be differentially expressed between the groups, of which only one was up-regulated. The biological pathways in which these miRNAs may be involved were studied by an bioinformatic approach. Four miRNAs from the mouse experiment, whose expression were most significantly divergent, together with three miRNAs previously reported to be regulated by the Ahr in murine cell lines, were studied in an RNA interference (RNAi) experiment in immortalised human lung epithelial cell lines. Two of these miRNAs, both selected from the literature, were found to have altered expression in AHR knockdown cells compared to control cells. Discrepancies between AHR regulated miRNAs identified in the in vivo and in vitro experiments were observed. Taken together this suggest a difference between effect of the AHR in vivo and in vitro, rather than differences between species.In conclusion, it was found that expression of several miRNAs possibly is regulated in an AHR- dependent manner in lung. Discrepancies between in vivo and in vitro experiments suggest that care must be taken when extrapolating miRNA expression data from cell culture studies to whole organs or organisms