| 1. |
- Magnusson, Björn, 1976, et al.
(författare)
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Cell death-inducing DFF45-like effector C is reduced by caloric restriction and regulates adipocyte lipid metabolism.
- 2008
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Ingår i: Metabolism: clinical and experimental. - : Elsevier BV. - 1532-8600. ; 57:9, s. 1307-13
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Tidskriftsartikel (refereegranskat)abstract
- Members of the cell death-inducing DFF45-like effector (CIDE) gene family have been shown to regulate lipid metabolism. In this article, we report that the third member of the human CIDE family, CIDEC, is down-regulated in response to a reduced caloric intake. The down-regulation was demonstrated by microarray and real-time polymerase chain reaction analysis of subcutaneous adipose tissue in 2 independent studies on obese patients undergoing treatment with a very low calorie diet. By analysis of CIDEC expression in 65 human tissues, we conclude that human CIDEC is predominantly expressed in subcutaneous adipocytes. Together, these observations led us to investigate the effect of decreased CIDEC expression in cultured 3T3-L1 adipocytes. Small interfering RNA-mediated knockdown of CIDEC resulted in an increased basal release of nonesterified fatty acids, decreased responsiveness to adrenergic stimulation of lipolysis, and increased oxidation of endogenous fatty acids. Thus, we suggest that CIDEC is a regulator of adipocyte lipid metabolism and may be important for the adipocyte to adapt to changes in energy availability.
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| 2. |
- Nystedt, Björn, et al.
(författare)
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The Norway spruce genome sequence and conifer genome evolution
- 2013
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 497:7451, s. 579-584
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Tidskriftsartikel (refereegranskat)abstract
- Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.
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| 3. |
- Svensson, Per Anders, 1959, et al.
(författare)
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Identification of genes predominantly expressed in human macrophages
- 2004
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Ingår i: Atherosclerosis. - : Elsevier BV. ; 177, s. 287-290
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Tidskriftsartikel (refereegranskat)abstract
- Identification of cell and tissue specific genes may provide novel insights to signaling systems and functions. Macrophages play a key role in many diseases including atherosclerosis. Using DNA microarrays we compared the expression of approximately 10,000 genes in 56 human tissues and identified 23 genes with predominant expression in macrophages. The identified genes include both genes known to be macrophage specific and genes previously not well described in this cell type. Tissue distribution of two genes, liver X receptor (LXR) alpha and interleukin-1 receptor antagonist (IL1RN), was verified by real-time RT-PCR. We conclude that comparison of expression profiles from a large number of tissues can be used to identify genes that are predominantly expressed in certain tissues. Identification of novel macrophage specific genes may increase our understanding of the role of this cell in different diseases.
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| 4. |
- Svensson, Per-Arne, 1969, et al.
(författare)
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Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques
- 2005
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Ingår i: BMC Cardiovasc Disord. - : Springer Science and Business Media LLC. - 1471-2261. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The protective role of high-density lipoprotein (HDL) in the cardiovascular system is related to its role in the reverse transport of cholesterol from the arterial wall to the liver for subsequent excretion via the bile. Scavenger receptor class B type I (SR-BI) binds HDL and mediates selective uptake of cholesterol ester and cellular efflux of cholesterol to HDL. The role of SR-BI in atherosclerosis has been well established in murine models but it remains unclear whether SR-BI plays an equally important role in atherosclerosis in humans. The aim of this study was to investigate the expression of SR-BI and its isoforms in human macrophages and atherosclerotic plaques. METHODS: The effect of hypoxia and minimally modified low-density lipoprotein (mmLDL), two proatherogenic stimuli, on SR-BI expression was studied in human monocyte-derived macrophages from healthy subjects using real-time PCR. In addition, SR-BI expression was determined in macrophages obtained from subjects with atherosclerosis (n = 15) and healthy controls (n = 15). Expression of SR-BI isoforms was characterized in human atherosclerotic plaques and macrophages using RT-PCR and DNA sequencing. RESULTS: SR-BI expression was decreased in macrophages after hypoxia (p < 0.005). In contrast, SR-BI expression was increased by exposure to mmLDL (p < 0.05). There was no difference in SR-BI expression in macrophages from patients with atherosclerosis compared to controls. In both groups, SR-BI expression was increased by exposure to mmLDL (p < 0.05). Transcripts corresponding to SR-BI and SR-BII were detected in macrophages. In addition, a third isoform, referred to as SR-BIII, was discovered. All three isoforms were also expressed in human atherosclerotic plaque. Compared to the other isoforms, the novel SR-BIII isoform was predicted to have a unique intracellular C-terminal domain containing 53 amino acids. CONCLUSION: We conclude that SR-BI is regulated by proatherogenic stimuli in humans. However, we found no differences between subjects with atherosclerosis and healthy controls. This indicates that altered SR-BI expression is not a common cause of atherosclerosis. In addition, we identified SR-BIII as a novel isoform expressed in human macrophages and in human atherosclerotic plaques.
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| 5. |
- Aevarsson, Arnthór, et al.
(författare)
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Going to extremes - a metagenomic journey into the dark matter of life
- 2021
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Ingår i: FEMS Microbiology Letters. - : Oxford University Press (OUP). - 1574-6968. ; 368:12
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Forskningsöversikt (refereegranskat)abstract
- The Virus-X-Viral Metagenomics for Innovation Value-project was a scientific expedition to explore and exploit uncharted territory of genetic diversity in extreme natural environments such as geothermal hot springs and deep-sea ocean ecosystems. Specifically, the project was set to analyse and exploit viral metagenomes with the ultimate goal of developing new gene products with high innovation value for applications in biotechnology, pharmaceutical, medical, and the life science sectors. Viral gene pool analysis is also essential to obtain fundamental insight into ecosystem dynamics and to investigate how viruses influence the evolution of microbes and multicellular organisms. The Virus-X Consortium, established in 2016, included experts from eight European countries. The unique approach based on high throughput bioinformatics technologies combined with structural and functional studies resulted in the development of a biodiscovery pipeline of significant capacity and scale. The activities within the Virus-X consortium cover the entire range from bioprospecting and methods development in bioinformatics to protein production and characterisation, with the final goal of translating our results into new products for the bioeconomy. The significant impact the consortium made in all of these areas was possible due to the successful cooperation between expert teams that worked together to solve a complex scientific problem using state-of-the-art technologies as well as developing novel tools to explore the virosphere, widely considered as the last great frontier of life.
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| 6. |
- Afghahi, Henri, 1966, et al.
(författare)
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Ongoing treatment with renin-angiotensin-aldosterone-blocking agents does not predict normoalbuminuric renal impairment in a general type 2 diabetes population.
- 2013
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Ingår i: Journal of diabetes and its complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 27:3, s. 229-34
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To examine the prevalence and the clinical characteristics associated with normoalbuminuric renal impairment (RI) in a general type 2 diabetes (T2D) population. METHODS: We included 94 446 patients with T2D (56% men, age 68.3±11.6years, BMI 29.6±5.3kg/m(2), diabetes duration 8.5±7.1years; means±SD) with renal function (serum creatinine) reported to the Swedish National Diabetes Register (NDR) in 2009. RI was defined as estimated glomerular filtration (eGFR)<60ml/min/1.73m(2) and albuminuria as a urinary albumin excretion rate (AER)>20μg/min. We linked the NDR to the Swedish Prescribed Drug Register, and the Swedish Cause of Death and the Hospital Discharge Register to evaluate ongoing medication and clinical outcomes. RESULTS: 17% of the patients had RI, and 62% of these patients were normoalbuminuric. This group of patients had better metabolic control, lower BMI, lower systolic blood pressure and were more often women, non-smokers and more seldom had a history of cardiovascular disease as compared with patients with albuminuric RI. 28% of the patients with normoalbuminuric RI had no ongoing treatment with any RAAS-blocking agent. Retinopathy was most common in patients with RI and albuminuria (31%). CONCLUSIONS: The majority of patients with type 2 diabetes and RI were normoalbuminuric despite the fact that 25% of these patients had no ongoing treatment with RAAS-blocking agents. Thus, RI in many patients with type 2 diabetes is likely to be caused by other factors than diabetic microvascular disease and ongoing RAAS-blockade.
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| 7. |
- Afghahi, Henri, 1966, et al.
(författare)
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Risk factors for the development of albuminuria and renal impairment in type 2 diabetes—the Swedish National Diabetes Register (NDR)
- 2010
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 26:4, s. 1236-1243
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Tidskriftsartikel (refereegranskat)abstract
- Background. The aim of this study was to identify clinical risk factors associated with the development of albuminuria and renal impairment in patients with type 2 diabetes (T2D). In addition, we evaluated if different equations to estimate renal function had an impact on interpretation of data. This was done in a nationwide population-based study using data from the Swedish National Diabetes Register. Methods. Three thousand and six hundred sixty-seven patients with T2D aged 30-74 years with no signs of renal dysfunction at baseline (no albuminuria and eGFR >60 mL/min/1.73 m(2) according to MDRD) were followed up for 5 years (2002-2007). Renal outcomes, development of albuminuria and/or renal impairment [eGFR < 60 mL/min/1.73 m(2) by MDRD or eCrCl > 60 mL/min by Cockgroft-Gault (C-G)] were assessed at follow-up. Univariate regression analyses and stepwise regression models were used to identify significant clinical risk factors for renal outcomes. Results. Twenty percent of patients developed albuminuria, and 11% renal impairment; thus, ~6-7% of all patients developed non-albuminuric renal impairment. Development of albuminuria or renal impairment was independently associated with high age (all P < 0.001), high systolic BP (all P < 0.02) and elevated triglycerides (all P < 0.02). Additional independent risk factors for albuminuria were high BMI (P < 0.01), high HbA1c (P < 0.001), smoking (P < 0.001), HDL (P < 0.05) and male sex (P < 0.001), and for renal impairment elevated plasma creatinine at baseline and female sex (both P < 0.001). High BMI was an independent risk factor for renal impairment when defined by MDRD (P < 0.01), but low BMI was when defined by C-G (P < 0.001). Adverse effects of BMI on HbA1c, blood pressure and lipids accounted for ~50% of the increase risk for albuminuria, and for 41% of the increased risk for renal impairment (MDRD). Conclusions. Distinct sets of risk factors were associated with the development of albuminuria and renal impairment consistent with the concept that they are not entirely linked in patients with type 2 diabetes. Obesity and serum triglycerides are semi-novel risk factors for development of renal dysfunction and BMI accounted for a substantial proportion of the increased risk. The equations used to estimate renal function (MDRD vs. C-G) had an impact on interpretation of data, especially with regard to body composition and gender.
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| 10. |
- Ammenberg, Jonas, et al.
(författare)
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Biogas Research Center, BRC : Slutrapport för etapp 1
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Biogas Research Center (BRC) är ett kompetenscentrum för biogasforskning som finansieras av Energimyndigheten, LiU och ett flertal externa organisationer med en tredjedel vardera. BRC har en mycket bred tvärvetenskaplig inriktning och sammanför biogasrelaterad kompetens från flera olika områden för att skapa interaktion på flera olika plan:mellan näringsliv, akademi och samhälle,mellan olika perspektiv, samtmellan olika discipliner och kompetensområden.BRC:s vision är:Resurseffektiva biogaslösningar finns genomförda i många nya tillämpningar och bidrar till en mer hållbar energiförsörjning, förbättrat miljötillstånd och goda affärer.BRC:s särskilda roll för att uppnå denna vision är att bidra med kunskapsförsörjning och process-/teknikutveckling för att facilitera utveckling, innovation och implementering av biogaslösningar. Resurseffektivitet är ett nyckelord, vilket handlar om att förbättra befintliga processer och system samt utveckla biogaslösningar i nya sektorer och möjliggöra användning av nya substrat.For BRC:s etapp 1, den första tvåårsperioden mellan 2012-2014, var forskningsprojekten organiserade enligt tabellen nedan. Den visar viktiga utmaningar för biogasproducenter och andra intressenter, samt hur dessa ”angreps” med åtta forskningsprojekt. Fem av projekten var av explorativ karaktär i bemärkelsen att de var bredare och mer framtidsorienterade - exempelvis utvärderade flera möjliga tekniska utvecklingsmöjligheter (EP1-5). Tre projekt hade ett tydligare fokus på teknik- och processutveckling (DP6-8).I den här slutrapporten ges en kortfattad bakgrundsbeskrivning och det finns en introduktion till vad den här typen av kompetenscentrum innebär generellt. Därefter finns mer detaljerad information om BRC, exempelvis gäller det centrumets etablering, relevans, vision, hörnstenar och utveckling. De deltagande organisationerna presenteras, både forskargrupperna vid Linköpings universitet och partners och medlemmar. Vidare finns en mer utförlig introduktion till och beskrivning av utmaningarna i tabellen och kortfattat information om forskningsprojekten, följt av ett kapitel som berör måluppfyllelse och den externa utvärdering som gjorts av BRC:s verksamhet. Detaljerad, listad information finns till stor del i bilagorna.Kortfattat kan det konstateras att måluppfyllelsen överlag är god. Det är speciellt positivt att så många vetenskapliga artiklar publicerats (eller är på gång att publiceras) kopplat till forskningsprojekten och även i det vidare centrumperspektivet. Helt klart förekommer en omfattande verksamhet inom och kopplat till BRC. I etapp 2 är det viktigt att öka andelen mycket nöjda partner och medlemmar, där nu hälften är nöjda och hälften mycket nöjda. Det handlar framför allt om stärkt kommunikation, interaktion och projektledning. Under 2015 förväntas åtminstone två doktorsexamina, där avhandlingarna har stor koppling till forskningen inom etapp 1.I början på år 2014 skedde en extern utvärdering av verksamheten vid BRC med huvudsyftet att bedöma hur väl centrumet lyckats med etableringen samt att granska om det fanns förutsättningar för framtida framgångsrik verksamhet. Generellt var utfallet mycket positivt och utvärderarna konstaterade att BRC på kort tid lyckats etablera en verksamhet som fungerar väl och engagerar det stora flertalet deltagande aktörer, inom relevanta områden och där de flesta involverade ser BRC som en befogad och väl fungerande satsning, som de har för avsikt att även fortsättningsvis stödja. Utvärderingen bidrog också med flera relevant tips och till att belysa utmaningar.Utöver denna slutrapport finns separata publikationer från forskningsprojekten.Arbetet som presenteras i rapporten har finansierats av Energimyndigheten och de medverkande organisationerna.
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