The Archaeologist In-Between

Olov Janse was an archaeologist with a remarkable life. From his birth in Sweden 1892 to his death in the United States 1985, he travelled several times across the world and was present in some of the most important episodes of 20th century world history. His works and networks connected museums and political institutions in Sweden, France, Vietnam and the United States: from the Swedish History Museum, the Museum of Far Easter Antiquities, the French Musée d’antiquites nationales, the Cernuchi museum, and the French research institute EFEO in Hanoi, to UNESCO, the Harvard Peabody Museum, the Smithsonian Institution, and the U.S. Department of State. He left behind artefacts and documents in museum collections and archives across the world. But his name is largely unknown, and his most important contributions – the connection of people and ideas between continents and contexts – have remained invisible in historical accounts of all these institutions. He was, in every sense, an archaeologist in-between. This book follows in the footsteps of Olov Janse and his wife Renée, as they move between continents and contexts, connecting key actors and institutions in social and professional networks across the world. It tells the formidable story of an archaeologist navigating through world politics, from a late 19th century industrial town in Sweden, to early 20th century Parisian museums, to French Indochina and the Philippines in the 1930s, to the formation of UNESCO in 1946, and ending with public diplomacy for the U.S. Department of State at the verge of the Vietnam War

Att förbjuda en åsikt: Hur västerländska demokratier hanterar extrema partier.

Vår uppsats grundar sig i någonting som kallas Toleransparadoxen ­ ett statsvetenskapligt problem som handlar om hur demokratiska stater hanterar odemokratiska åsikter. Vi valde att testa frågan i praktiken genom att titta på hur fyra olika västerländska demokratier har valt att bemöta extrema partier ­ vilket vi definierar som partier som inte efterlever de grundläggande demokratiska värderingarna. Framförallt ville vi veta hur partierna påverkas av statens linje ­ tynade de bort eller ökade de? Till vår hjälp hade vi ett antal författare ­ såväl historiska som samtida ­ med varsin tolkning av frågan. Länderna vi valde var Tyskland, USA, Storbritannien och Ungern som alla representerar olika grader i hanteringen av extrema partier. I vår text betonar vi ofta det historiska perspektivet och arvet efter andra världskriget, som vi menar har spelat en stor roll i att forma debatten. Vi gjorde därefter en analys över specifika partier i de länderna och jämförde dem med varandra. Vår slutsats var att en offensiv stat medför vissa risker. Vi poängterar frågans komplexitet, men lutar åt att en stat som försöker förbjuda vissa åsikter kan vara kontraproduktivt. Bland annat riskerar ett aktivt motarbetande av extrema partier att ge dem ökad uppmärksamhet och stimulera dess radikala grenar. Vi argumenterar också för att en inkluderande stil kan ha en demokratiserande effekt på sagda partier. Avslutningsvis lyfter vi även ett etiskt perspektiv, genom yttrandefrihetens betydelsefulla roll i samhället

The hepatocyte nuclear factor 4 (HNF-4) represses the mitochondrial HMG-CoA synthase gene

We have recently shown that the gene for the mitochondrial HMG-CoA synthase is a target for PPAR and that this receptor mediates the induction of this gene by fatty acids. With the aim of gaining further insight into the function and regulation of this gene we examined the effect of other members of the nuclear hormone receptor superfamily on its expression. We previously identified a regulatory element in the mitochondrial HMG-CoA synthase gene promoter that confers transcriptional regulation by PPAR, RXR and the orphan nuclear receptor COUP-TF, In this study we demonstrate a trans-repressing regulatory function for HNF-4 at this same nuclear receptor response element (NRRE). HNF-4 binds to the mitochondrial HMG-CoA synthase NRRE, and, in cotransfection assays in HepG2 cells, it represses PPAR-dependent activation of a reporter gene linked to the mitochondrial HMG-CoA synthase gene promoter. These results suggest that the mitochondrial HMG-CoA synthase gene is subject to differential regulation by the interplay of multiple members of the nuclear hormone receptor superfamily

Malonyl-CoA Mediates Leptin Hypothalamic Control of Feeding Independent of Inhibition of CPT-1a

Hypothalamic fatty acid metabolism is involved in central nervous system controls of feeding and energy balance. Malonyl-CoA, an intermediate of fatty acid biosynthesis, is emerging as a significant player in these processes. Notably, hypothalamic malonyl-CoA has been implicated in leptin's feeding effect. Leptin treatment increases malonyl-CoA level in the hypothalamic arcuate nucleus (Arc), and this increase is required for leptin-induced decrease in food intake. However, the intracellular downstream mediators of malonyl-CoA's feeding effect have not been identified. A primary biochemical action of malonyl-CoA is the inhibition of the acyltransferase activity of carnitine palmitoyltransferase-1 (CPT-1). In the hypothalamus, the predominant isoform of CPT-1 that possesses the acyltransferase activity is CPT-1 liver type (CPT-1a). To address the role of CPT-1a in malonyl-CoA's anorectic action, we used a recombinant adenovirus expressing a mutant CPT-1a that is insensitive to malonyl-CoA inhibition. We show that Arc overexpression of the mutant CPT-1a blocked the malonyl-CoA-mediated inhibition of CPT-1 activity. However, the overexpression of this mutant did not affect the anorectic actions of leptin or central cerulenin for which an increase in Arc malonyl-CoA level is also required. Thus, CPT-1a does not appear to be involved in the malonyl-CoA's anorectic actions induced by leptin. Furthermore, long-chain fatty acyl-CoAs, substrates of CPT-1a, dissociate from malonyl-CoA's actions in the Arc under different feeding states. Together, our results suggest that Arc intracellular mechanisms of malonyl-CoA's anorectic actions induced by leptin are independent of CPT-1a. The data suggest that target(s), rather than CPT-1a, mediates malonyl-CoA action on feeding

RNA sequencing-based single sample predictors of molecular subtype and risk of recurrence for clinical assessment of early-stage breast cancer

BackgroundMultigene expression assays for molecular subtypes and biomarkers can aid clinical management of early invasive breast cancer. Based on RNA-sequencing we aimed to develop single-sample predictor (SSP) models for conventional clinical markers, molecular intrinsic subtype and risk of recurrence (ROR).MethodsA uniformly accrued breast cancer cohort of 7743 patients with RNA-sequencing data from fresh tissue was divided into a training set and a reserved test set. We trained SSPs for PAM50 molecular subtypes and ROR assigned by nearest-centroid (NC) and SSPs for conventional clinical markers from histopathology data. Additionally, SSP classifications were compared with Prosigna® in two external cohorts. Prognostic value was assessed using distant recurrence-free interval.ResultsIn the test set, agreement between SSP and NC classifications for PAM50 (five subtypes) and Subtype (four subtypes) was high (85%, Kappa=0.78) and very high (90%, Kappa=0.84) respectively. Accuracy for ROR risk category was high (84%, Kappa=0.75, weighted Kappa=0.90). The prognostic value for SSP and NC was assessed as equivalent. Agreement for SSP and histopathology was very high or high for receptor status, while moderate and poor for Ki67 status and Nottingham histological grade, respectively. SSP concordance with Prosigna® was high for subtype and moderate and high for ROR risk category. In pooled analysis, concordance between SSP and Prosigna® for emulated treatment recommendation for chemotherapy (yes vs. no) was high (85%, Kappa=0.66). In postmenopausal ER+/HER2-/N0 patients SSP application suggested changed treatment recommendations for up to 17% of patients, with nearly balanced escalation and de-escalation of chemotherapy.ConclusionsSSP models for histopathological variables, PAM50, and ROR classifications can be derived from RNA-sequencing that closely matches clinical tests. Agreement and outcome analyses suggest that NC and SSP models are interchangeable on a group-level and nearly so on a patient level. Retrospective evaluation in postmenopausal ER+/HER2-/N0 patients suggested that molecular testing could lead to a changed therapy recommendation for almost one-fifth of patients

Viittomakielisten muistiasiantuntijoiden näkemyksiä CERAD-tehtäväsarjan viittomakielisestä käännöksestä

Suomessa laajasti käytössä olevasta muistitestistä, CERAD-tehtäväsarjasta, tuotettiin vuonna 2010 käännös suomalaiselle viittomakielelle. Käännöksen tuotti Kuurojen Palvelusäätiön Memo-projekti Ra-ha-automaattiyhdistyksen tuella. Projektin jatkona toimiva niin ikään RAY:n tukema Memo-ohjelma tuottaa käännöksestä uutta versiota, jossa pyritään korjaamaan ensimmäisessä käännöksessä havaitut puutteet. Opinnäytetyöni tehtävänä on tukea käännöksen tekemistä kokoamalla tietoa siitä, millaisia näkemyksiä ja kokemuksia viittomakielisten muistiasiantuntijoilla on ensimmäisestä käännöksestä. Halusin työlläni selvittää mitkä viittomakielisen tehtäväsarjan osa-alueista ovat osoittautuneet ongel-mallisiksi ja millä tavalla. Selvitän siis, millaisia kielellisiä ja kulttuurisia muutoksia tehtäväsarjaan on tarpeellista tehdä. Opinnäytetyö on tilaustyö ja tilaajana toimii Kuurojen Palvelusäätiö, joka on valtakunnallinen viittoma-kielisiä palveluja tuottava sosiaalialan järjestö. Tutkimukseni tuloksia voidaan hyödyntää Kuurojen Pal-velusäätiön Memo-ohjelmassa, jonka tehtävänä on tukea monin tavoin viittomakielisiä muistisairaita ja heidän läheisiään. Opinnäytetyöni tutkimusmenetelmänä toimi puolistrukturoitu teemahaastattelu. Haastattelin kahta asiantuntijaa, joilla on laajaa kokemusta ja tietoa viittomakielisistä muistisairaista sekä käytännön kokemusta viittomakielisen CERAD-tehtäväsarjan käytöstä. Molempien haastateltavien kokemusten mukaan viittomakielisestä käännöksestä löytyy osa-alueita, jotka vaativat kehittämistä, jotta ne testaisivat luotettavasti muistia. Suurin osa ongelmista liittyy tehtä-vien ohjeistuksiin, joita tulisi kehittää ymmärrettävämmiksi. Suurin osa muutostarpeista liittyy juuri kult-tuurisiin seikkoihin. Sen sijaan kielellisiä muutostarpeita oli vähemmän. Erityisen toimivia osia viittoma-kielisessä tehtäväsarjassa ovat ne, jotka perustuvat visuaalisuuteen. Tällaisia ovat esimerkiksi kuvioi-den kopiointitehtävä, viivästetty mieleenpalautus ja kellotaulun piirtäminen.CERAD neuropsychological assessment battery is a widely used memory test in Finland. In the year 2010 the Service Foundation for the Deaf translated it into Finnish sign language. Finland’s Slot Ma-chine Association (RAY) funded the project and it was coordinated by Memo-project, which operated under the Service Foundation for the Deaf. However, it has been found that the translation does not correctly assess the deaf person’s memory. Now translation is being improved by the Memo-programme and my thesis supports that project. In my thesis I wanted to research which parts of the translation are problematic and how. I focused on finding out what kind of linguistic and cultural changes need to be done to the new translation. The subscriber of the thesis is the Service Foundation for the Deaf, which is a national organization in the social sector. Results of my research will support and document the Memo-programme’s transla-tion project. My research method was a semi-structured interview. I interviewed two memory disorder experts who have comprehensive knowledge of memory disorders among the deaf and experience of using the translated CERAD. My research shows that there are a few parts in the Finnish sign language translation of the CERAD assessment battery that needs improvement. Especially instructions of some of the assignments need to be more comprehensible. Most of the problems of the translation are cultural and only few are of linguistic matter. Particularly reliable were assignments based on visuality, for example assignment where the person being assessed copies shapes or draws a clock face

Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin.

Recent data suggest that ghrelin exerts its orexigenic action through regulation of hypothalamic AMP-activated protein kinase (AMPK) pathway, leading to a decline in malonyl-CoA levels and desinhibition of carnitine palmitoyltransferase 1A (CPT1A), which increases mitochondrial fatty acid oxidation and ultimately enhances the expression of the orexigenic neuropeptides agouti-related protein (AgRP) and neuropeptide Y (NPY). However, it is unclear whether the brain-specific isoform CPT1C, which is located in the endoplasmic reticulum (ER) of neurons, may play a role on this action. Here, we demonstrate that ghrelin's orexigenic action is totally blunted in CPT1C knock-out (KO) mice, despite having the canonical ghrelin signaling pathway activated. We also demonstrate that ghrelin elicits a marked upregulation of hypothalamic C18:0-ceramide levels mediated by CPT1C. Notably, central inhibition of ceramide synthesis with myriocin negated ghrelin's orexigenic action and normalized the levels of AgRP and NPY, as well as their key transcription factors pCREB and FoxO1. Finally, central treatment with ceramide induced food intake and orexigenic neuropeptides expression in CPT1C KO mice. Overall, these data indicate that, in addition to formerly reported mechanisms, ghrelin also induces food intake through regulation of hypothalamic CPT1C and ceramide metabolism, a finding of potential importance for the understanding and treatment of obesity

Cornelia de Lange syndrome with NIBPL mutation and mosaic Turner syndrome in the same individual

Background: Cornelia de Lange syndrome (CdLS) is a dominantly inherited disorder characterized by facial dysmorphism, growth and cognitive impairment, limb malformations and multiple organ involvement. Mutations in NIPBL gene account for about 60% of patients with CdLS. This gene encodes a key regulator of the Cohesin complex, which controls sister chromatid segregation during both mitosis and meiosis. Turner syndrome (TS) results from the partial or complete absence of one of the X chromosomes, usually associated with congenital lymphedema, short stature, and gonadal dysgenesis. Case presentation: Here we report a four-year-old female with CdLS due to a frameshift mutation in the NIPBL gene (c.1445_1448delGAGA), who also had a tissue-specific mosaic 45,X/46,XX karyotype. The patient showed a severe form of CdLS with craniofacial dysmorphism, pre- and post-natal growth delay, cardiovascular abnormalities, hirsutism and severe psychomotor retardation with behavioural problems. She also presented with minor clinical features consistent with TS, including peripheral lymphedema and webbed neck. The NIPBL mutation was present in the two tissues analysed from different embryonic origins (peripheral blood lymphocytes and oral mucosa epithelial cells). However, the percentage of cells with monosomy X was low and variable in tissues. These findings indicate that, ontogenically, the NIPBL mutation may have appeared before the mosaic monosomy X. Conclusions: The coexistence in several patients of these two rare disorders raises the issue of whether there is indeed a cause-effect association. The detailed clinical descriptions indicate predominant CdLS phenotype, although additional TS manifestations may appear in adolescence