| 1. |
|
|
| 2. |
- Turcot, Valerie, et al.
(författare)
-
Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
|
|
| 3. |
- Berg, Elisabeth Gräslund, et al.
(författare)
-
Praktiker som gör skillnad : Om den verb-inriktade metoden
- 2013
-
Ingår i: Historisk Tidskrift. - 0345-469X .- 2002-4827. ; 133:3, s. 335-354
-
Tidskriftsartikel (refereegranskat)abstract
- This article discusses the so-called verb-oriented method and its role in the research project Gender and Work in early modern Sweden (GaW), which is based at Uppsala University. It provides a presentation of the GaW-database, which has been designed to allow analysis according to the verb-method. Finally, the article points out that this method can be combined with a number of different theoretical approaches as long as the focus is on practices. It is therefore compatible with the approaches of e.g., Judith Butler, Michel de Certeau, and Amartya Sen. Work is defined as "time-use with the purpose of making a living" and the article discusses why data on time-use, or actual work activities, are better suited for research into early modern Swedish working life than other types of data. It shows that activities are usually described in the sources by verb-phrases, and explains how and from what sources verb-phrases are collected and analyzed within the project. In order to allow for generalizations the verb-method presupposes large amounts of data. This is the rationale for the GaW-database, which at present includes around 5000 verb-phrases and 75000 data posts.
|
|
| 4. |
- Delshammar, Tim, et al.
(författare)
-
Stadsodling – reflektioner och perspektiv från SLU Alnarp
- 2012
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Det är uppenbart att det mediala intresset för stadsodling har vuxit påtagligt de senaste åren. En sökning i databasen Retriever visar en ökande användning av begreppet ”urban odling” och en starkt ökande användning av ordet “stadsodling”. Olika medier påverkar så klart varandra. Radioprogrammet Odla med stadsgrönt började sändas våren 2009. Medier påverkar politiken som i sin tur påverkar medier. Den förste oktober 2009 lämnades motionen ”Stadsodling viktig i hållbara städer” in till riksdagen. Såväl media som politik påverkar och påverkas av praktiken. Våren 2009 började projektet Barn i stan odla i stadsdelen Seved i Malmö, ett projekt som uppmärksammats flitigt i media. Samma år började organisationen Stadsjord odla i stadsdelen Högsbo i Göteborg, även det flitigt uppmärksammat i media. Den statliga Delegationen för hållbara städer har beviljat bidrag till åtminstone fyra planeringsprojekt med inriktning mot stadsodling: SLU (sökt 2009), Plantagon (två projekt sökta 2010) samt Falun kommun (sökt 2012). Även investeringsprojekt har haft inslag av stadsodling, till exempel Malmö stads ansökan “Hållbar stadsomvandling Malmö, Fokus Rosengård” ( sökt 2010). Stadsodling finns med som ett inslag i flera aktuella stadsförnyelse- och stadsbyggnadsprojekt. Det har fått fungera som en symbol för kombinationen av ekologisk och social hållbarhet. En viktig fråga att reflektera över är därför hur hållbar stadsodling är. Vad kan vi ha för nytta av stadsodling? Hur kan odling ta plats i städerna? Hur kan vi stadsodla på ett hållbart sätt?
|
|
| 5. |
- Gennemark, Peter, et al.
(författare)
-
An oral antisense oligonucleotide for PCSK9 inhibition
- 2021
-
Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 13:593
-
Tidskriftsartikel (refereegranskat)abstract
- Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein (LDL) cholesterol and are used for treatment of dyslipidemia. Current PCSK9 inhibitors are administered via subcutaneous injection. We present a highly potent, chemically modified PCSK9 antisense oligonucleotide (ASO) with potential for oral delivery. Past attempts at oral delivery using earlier-generation ASO chemistries and transient permeation enhancers provided encouraging data, suggesting that improving potency of the ASO could make oral delivery a reality. The constrained ethyl chemistry and liver targeting enabled by N-acetylgalactosamine conjugation make this ASO highly potent. A single subcutaneous dose of 90 mg reduced PCSK9 by >90% in humans with elevated LDL cholesterol and a monthly subcutaneous dose of around 25 mg is predicted to reduce PCSK9 by 80% at steady state. To investigate the feasibility of oral administration, the ASO was coformulated in a tablet with sodium caprate as permeation enhancer. Repeated oral daily dosing in dogs resulted in a bioavailability of 7% in the liver (target organ), about fivefold greater than the plasma bioavailability. Target engagement after oral administration was confirmed by intrajejunal administration of a rat-specific surrogate ASO in solution with the enhancer to rats and by plasma PCSK9 and LDL cholesterol lowering in cynomolgus monkey after tablet administration. On the basis of an assumption of 5% liver bioavailability after oral administration in humans, a daily dose of 15 mg is predicted to reduce circulating PCSK9 by 80% at steady state, supporting the development of the compound for oral administration to treat dyslipidemia.
|
|
| 6. |
- Jansson, Linda, et al.
(författare)
-
Individual shedder status and the origin of touch DNA
- 2022
-
Ingår i: Forensic Science International: Genetics. - : Elsevier BV. - 1872-4973 .- 1878-0326. ; 56
-
Tidskriftsartikel (refereegranskat)abstract
- Due to improved laboratory techniques, touched surfaces and items are increasingly employed as sources of forensic DNA evidence. This has urged a need to better understand the mechanisms of DNA transfer between individuals. Shedder status (i.e. the propensity to leave DNA behind) has been identified as one major factor regulating DNA transfer. It is known that some individuals tend to shed more DNA than others, but the mechanisms behind shedder status are largely unknown. By comparing the amounts of DNA deposited from active hands (i.e. used “as usual”) and inactive hands (i.e. not allowed to touch anything), we show that some of the self-DNA deposited from hands is likely to have accumulated on hands from other parts of the body or previously handled items (active hands: 2.1 ± 2.7 ng, inactive hands: 0.83 ± 1.1 ng, paired t-test: p = 0.014, n = 27 pairs of hands). Further investigation showed that individual levels of deposited DNA are highly associated with the level of DNA accumulation on the skin of the face (Pearson's correlation: r = 0.90, p < 0.00001 and Spearman's ranked correlation: rs = 0.56, p = 0.0016, n = 29). We hypothesized that individual differences in sebum secretion levels could influence the amount of DNA accumulation in facial areas, but no such correlation was seen (Pearson's correlation: r = − 0.13, p = 0.66, n = 14). Neither was there any correlation between DNA levels on hands or forehead and the time since hand or face wash. We propose that the amount of self-DNA deposited from hands is highly influenced by the individual levels of accumulated facial DNA, and that cells/DNA is often transferred to hands by touching or rubbing one's face.
|
|
| 7. |
- Sverrisdóttir, Yrsa Bergmann, 1960, et al.
(författare)
-
Muscle sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy individuals.
- 2010
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:2
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Evidence from animal studies indicates the importance of an interaction between the sympathetic nervous system and the endothelium for cardiovascular regulation. However the interaction between these two systems remains largely unexplored in humans. The aim of this study was to investigate whether directly recorded sympathetic vasoconstrictor outflow is related to a surrogate marker of endothelial function in healthy individuals. METHODS AND RESULTS: In 10 healthy normotensive subjects (3 f/7 m), (age 37+/-11 yrs), (BMI 24+/-3 kg/m(2)) direct recordings of sympathetic action potentials to the muscle vascular bed (MSNA) were performed and endothelial function estimated with the Reactive Hyperaemia- Peripheral Arterial Tonometry (RH-PAT) technique. Blood samples were taken and time spent on leisure-time physical activities was estimated. In all subjects the rate between resting flow and the maximum flow, the Reactive Hyperemic index (RH-PAT index), was within the normal range (1.9-3.3) and MSNA was as expected for age and gender (13-44 burst/minute). RH-PAT index was inversely related to MSNA (r = -0.8, p = 0.005). RH-PAT index and MSNA were reciprocally related to time (h/week) spent on physical activity (p = 0.005 and p = 0.006 respectively) and platelet concentration (PLT) (p = 0.02 and p = 0.004 respectively). CONCLUSIONS: Our results show that sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy normotensive individuals, indicating that sympathetic outflow may be modulated by changes in endothelial function. In this study time spent on physical activity is identified as a predictor of sympathetic nerve activity and endothelial function in a group of healthy individuals. The results are of importance in understanding mechanisms underlying sympathetic activation in conditions associated with endothelial dysfunction and emphasise the importance of a daily exercise routine for maintenance of cardiovascular health.
|
|
| 8. |
- Wessel, Jennifer, et al.
(författare)
-
Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
|
|
| 9. |
|
|
