Nostalgia isn’t what it used to be: the collected works of Haruki Murakami

Graduate Winner: 1st Place, 2012. 25th Annual Carl Neureuther Student Book Collection Competitio

Post-Translational Regulation of FAS-Mediated PPARα Activation

The liver is a central organ to whole-body metabolism and mediates many of the adaptive responses to changes in nutrient availability, such that the appropriate energy sources are used and blood glucose levels maintained, whether directly after a meal or after a twelve-hour fast. The adaptive responses to fasting in liver are largely mediated by the nuclear receptor peroxisome proliferator-activated receptor α, or PPARα. PPARα can be activated by a de novo synthesized lipid ligand—16:0/18:1- glycerophosphocholine (16:0/18:1-GPC)—the synthesis of which is dependent on fatty acid synthase (FAS), but little is known about the regulation of this pathway. My thesis focused on post-translational mechanisms controlling endogenous activation of PPARα in the liver and used mouse liver and a hepatocyte cell line as model systems. In addition to its role in PPARα activation during fasting, FAS helps store excess calories as fat during feeding. We demonstrated that this paradoxical relationship involves the differential regulation of FAS in at least two distinct subcellular pools: cytoplasmic and membrane-associated FAS, the latter being attached to membranes by a strong peripheral membrane association. To find candidate proteins mediating FAS membrane localization we used a proteomics approach to identify compartment-specific FAS-associated proteins. We identified three proteins—Septin-2, Septin-7, and 40S ribosomal protein S18—that in two different liver model systems associate with FAS exclusively in the membrane fraction. Because the septins are involved in membrane structuring and scaffolding, these proteins may be involved in FAS membrane localization. The ratio of cytoplasmic to membrane FAS specific activity was increased with fasting or in the absence of insulin, indicating higher cytoplasmic FAS activity under conditions associated with PPARα activation. This effect was due to a nutrient-dependent and compartment-selective covalent modification of FAS: cytoplasmic FAS was preferentially phosphorylated during feeding or insulin treatment at Thr-1029 and Thr-1033, which flank a dehydratase domain catalytic residue. Mutating these sites to alanines promoted PPAR� target gene expression. mTORC1, a mediator of the feeding/insulin signal to induce lipogenesis, emerged as a mediator of FAS phosphorylation, inhibiting cytoplasmic FAS activity and reducing PPARα target gene expression in a FAS-dependent manner. Next, we investigated the role of ligand transport in FAS-mediated PPARα activation. 16:0/18:1-GPC is synthesized in the cytoplasm and it is not known how it reaches the nuclear PPARα. We identified phosphatidylcholine transfer protein (PCTP) as a possible transport protein for this ligand. PCTP knockdown in Hepa1-6 hepatocytes caused dramatic reductions in expression of PPARα target genes, and PCTP co-immunoprecipitated with PPARα. Immunofluorescent imaging showed that starvation of cells caused an accumulation of PCTP in the nucleus, consistent with a shuttling function controlled by nutrition. Using mass spectrometry, we demonstrated that PCTP binds 16:0/18:1-GPC. We further showed that the binding of this ligand to PCTP is FAS-dependent: in mice with liver-specific knockout of FAS, the amount of 16:0/18:1-GPC bound to PCTP in the nucleus was significantly reduced. Together, these findings suggest that multiple modes of post-translational regulation of FAS combined with regulation of lipid delivery by PCTP control fasting-induced PPARα activation in liver

Why not teach "diversity" to public sector managers?

Purpose - Equality and diversity are generally positioned as special interests, marginal to the mainstream of social policy teaching and learning. The purpose of this paper is to make the case for shifting equality and diversity out of the margins and into the centre of education for mid career public managers, and offers practical methods for doing so. Design/methodology/approach - The current EU policy framework requires public services to go beyond eliminating discrimination, and to promote equality. The paper suggests that while this offers great opportunities for advancing the cause of social justice, the cultures that predominate in public policy may lead to loss and failure. Academic research and experience demonstrate that these changes are highly complex, touching on issues that are integral to our sense of who we are, and how we relate to each other as educators and students, and as enforcers, beneficiaries and implementers of these policies. The paper touches on deeply held emotions, showing that more exploration of appropriate pedagogical methods is needed. Findings - The paper finds that only by raising issues of equality and diversity to mainstream social policy teaching and learning is there likely to be a shift in thinking and commitment that will encourage integration of equality measures within management and leadership of public. Originality/value - The paper offers three dimensions of pedagogy for enabling public service managers to engage with diversity and the equality agenda within educational contexts, and offers three illustrations of pedagogic processes that support this learning

Lungerehabilitering. En effektiv behandling for å redusere reinnleggelser hos KOLS-pasienter?

Fordypningsoppgave i videreutdanning i akuttmedisinsk sykepleie, 2020Bakgrunn: Cirka 6 % av den norske befolkningen over 40 år lever med kronisk obstruktiv lungesykdom (KOLS). Sykdommen kan gi betydelig funksjonsnedsettelse og føre til gjentatte sykehusinnleggelser. Av KOLS-pasientene i Norge som innlegges hvert år, reinnlegges 29 % i løpet av en måned. Lungerehabilitering er et behandlingstilbud som omfatter undervisning og trening. Målet med rehabilitering er å unngå eksaserbasjoner, redusere dyspne, øke livskvalitet og bedre lungefunksjon og fysisk kapasitet. Mål: Målet med denne oppgaven er å finne ut om lungerehabilitering kan redusere reinnleggelser hos KOLS-pasienter. For å vurdere mulige årsaker til en eventuell nedgang i reinnleggelser, vil en også se på hvordan lungerehabilitering påvirker livskvalitet, lungefunksjon og fysisk kapasitet. Metode: Oppgaven er en litteraturstudie. Etter systematisk litteratursøk i ulike databaser ble fem artikler valgt. Artiklene ble gjennomgått og analysert. Resultat: Fem artikler som totalt involverte 397 pasienter ble valgt ut. Tre studier viste signifikant færre reinnleggelser etter lungerehabilitering. To av studiene viste en trend mot færre reinnleggelser de første tre månedene. Pasientene fikk signifikant bedre livskvalitet etter lungerehabilitering. Den fysiske kapasiteten ble også bedre etter rehabilitering, men bare en studie kunne påvise signifikant bedre lungekapasitet. Konklusjon: Lungerehabilitering ser ut til å være et effektivt tiltak for behandling av KOLS-pasienter etter forverring, både i forhold til å redusere risikoen for reinnleggelse, men også knyttet til forbedret livskvalitet og treningskapasitet

Lived religion and nonreligion among humanitarians in South Sudan

acceptedVersio

Å være tilfreds med sin egen kropp. En kvalitativ studie om hva som fremmer et positivt kroppsbilde blant kvinner

Denne oppgaven handler om hva som fremmer et positivt kroppsbilde blant kvinner. Studien undersøker kvinners vandring fra et negativt til et positivt kroppsbilde. Målet med oppgaven er øke kunnskapen, slik at det kan drives forebyggende arbeid mot et negativt kroppsbilde og fremme et positivt kroppsbilde i samfunnet. Studien baserer seg på et kvalitativt forskningsdesign hvor fem kvinner har blitt intervjuet. Sentrale funn i studiens analyse viser at det som fremmer et positivt kroppsbilde blant kvinner er å ha et kroppsfenomenologisk syn på sin egen kropp, hvor kroppen er både noe man er og har, hvor en bekymringsløs glemsel i forhold til sin egen kropp er tilstede. Samt det å lytte til ens egen kropps behov og ønsker, og ikke sammenligne seg med andres kropper. Videre funn viser at å ha en bred definisjon på skjønnhet, være kritisk til dagens kroppsidealer og være bevisst på hva en fyller seg med av sosiale medier også fremmer et positivt kroppsbilde. Det samme gjelder å gi slipp på overdreven kontroll over egen kropp, utseende, mat og trening. Fokus og takknemlighet på kroppens funksjon, samt at fysisk aktivitet gjøres fordi det er godt for kroppen, gir glede, energi og overskudd, fremmer også et positivt kroppsbilde. Samt det å være i gode miljøer som ikke er kroppsfikserte, og det å ha åpne og ærlige relasjoner rundt seg hvor en kan dele både gleder og sorger med ut i fra livets gang

Changes in Health Literacy during the first year following a kidney transplantation: Using the Health Literacy Questionnaire

Objectives The study aimed to identify changes in health literacy (HL) and associated variables during the first year following a kidney transplantation. Methods A total of 196 transplant recipients were included in a prospective follow-up study. The patients answered the Health Literacy Questionnaire (HLQ) at 5 days, 8 weeks, 6 and 12 months following the kidney transplantation. Mixed linear models were used to analyze changes in HL and backward elimination was used to identify variables associated with HL. Results Two main patterns of change were identified: a) HL increased during the first 8 weeks of close follow-up and b) in several domains, the positive increase from 5 days to 8 weeks flattened out from 5 days to 6 and 12 months. Self-efficacy, transplant-related knowledge, and general health were core variables associated with HL. Conclusions Overall, HL increased during the 8 weeks of close follow-up following the kidney transplantation, while 6 months seem to be a more vulnerable phase. Furthermore, low self-efficacy, less knowledge, and low self-perceived health may represent vulnerable characteristics in patients. Practical implications Future kidney transplant care should take into account patients’ access to and appraisal of health information and social support, and draw attention to potentially vulnerable groups.publishedVersio

The Health Literacy Questionnaire (HLQ): Initial validity testing in a Norwegian sample.

This study tested the Norwegian version of the Health Literacy Questionnaire. The questionnaire (44 items across nine scales) was completed by 368 nursing students. Despite some overlap between scale 7 (“navigating in the health care system”) and scale 8 (“ability to find good health information”), the questionnaire appears to serve as a good measurement for health literacy in the Norwegian population.publishedVersio