| 1. |
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| 2. |
- Scott, Robert A., et al.
(författare)
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A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
- 2016
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
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| 3. |
- Jansson, Anna, et al.
(författare)
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Straw as an Alternative to Grass Forage in Horses-Effects on Post-Prandial Metabolic Profile, Energy Intake, Behaviour and Gastric Ulceration
- 2021
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Ingår i: Animals. - : MDPI AG. - 2076-2615. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Many leisure horses have low energy requirements and obesity is common. Straw has a low energy content and could be a forage option for these horses. However, a previous study suggested that providing straw as the only forage was associated with an increased risk for gastric ulcers. This study evaluated replacing 50% of the daily forage allowance with a good hygienic quality wheat straw. Six horses were fed both the control diet (grass forage only, CON) and the straw diet (50:50 grass forage and straw, S). Each diet was fed for three weeks and all horses were evaluated on both diets. Diet did not affect the prevalence of gastric ulcers. Feed intake time was longer and daily energy intake lower on diet S, compared to CON. Plasma insulin levels were lower on diet S compared to CON, which could be beneficial for horses with overweight or insulin dysregulation. The results suggest that good hygienic wheat straw provided at 50% of the forage ration does not cause gastric ulcers, but may prolong feeding time and promote a metabolic profile more suitable for overweight horses. Including straw as part of the ration therefore may improve welfare for horses with low energy requirements. Straw's low energy content means it is a roughage option for horses with low energy requirements. Previously, in a field study, straw was associated with an increased risk for gastric ulcers. This study evaluated the effect on gastric ulcers, metabolic profile and behaviour of replacing, in a forage-only ration, 50% of the daily allowance with wheat straw. Six equines were studied in a 2 x 21-day cross-over design. The control diet (CON: 100% grass forage) and the straw diet (S: 50% grass forage and 50% straw [DM basis]) were iso-energetic. Gastroscopy was performed prior to the study and on day 21 and blood samples were collected and behavioural observations were performed. Diet did not affect squamous or glandular gastric ulcer scores (p > 0.05). Feed intake time was longer (p < 0.05) plus energy intake and plasma insulin concentrations were lower on diet S compared to CON (p < 0.0001). Plasma serotonin concentrations tended to be higher on diet S compared to CON (p = 0.05). The results suggest that good hygienic quality wheat straw can be included for up to 50% of the diet without causing gastric ulcers and that it can extend feeding time and promote a metabolic profile more suitable for overweight horses.
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| 4. |
- Jansson, Nina, 1976, et al.
(författare)
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Activation of Placental mTOR Signaling and Amino Acid Transporters in Obese Women Giving Birth to Large Babies.
- 2013
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 98:1, s. 105-13
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Tidskriftsartikel (refereegranskat)abstract
- Context: Babies of obese women are often large at birth, which is associated with perinatal complications and metabolic syndrome later in life. The mechanisms linking maternal obesity to fetal overgrowth are largely unknown. Objective: We tested the hypothesis that placental insulin/IGF-I and mammalian target of rapamycin (mTOR) signaling is activated and amino acid transporter activity is increased in large babies of obese women. Design and Setting: Pregnant women were recruited prospectively for collection of placental tissue at a university hospital and academic biomedical center. Patients or Other Participants: Twenty-three Swedish pregnant women with first trimester body mass index ranging from 18.5 to 44.9 kg/m(2) and with uncomplicated pregnancies participated in the study. Interventions: There were no interventions. Main Outcome Measures: We determined the phosphorylation of key signaling molecules (including Akt, IRS-1, S6K1, 4EBP-1, RPS6, and AMPK) in the placental insulin/IGF-I, AMPK, and mTOR signaling pathways. The activity and protein expression of the amino acid transporter systems A and L were measured in syncytiotrophoblast microvillous plasma membranes. Results: Birth weights (range, 3025-4235 g) were positively correlated to maternal body mass index (P < 0.05). The activity of placental insulin/IGF-I and mTOR signaling was positively correlated (P < 0.001), whereas AMPK phosphorylation was inversely (P < 0.05) correlated to birth weight. Microvillous plasma membrane system A, but not system L, activity and protein expression of the system A isoform SNAT2 were positively correlated to birth weight (P < 0.001). Conclusions: Up-regulation of specific placental amino acid transporter isoforms may contribute to fetal overgrowth in maternal obesity. This effect may be mediated by activation of insulin/IGF-I and mTOR signaling pathways, which are positive regulators of placental amino acid transporters.
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| 5. |
- Roos, Sara, 1979, et al.
(författare)
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Mammalian target of rapamycin in the human placenta regulates leucine transport and is down-regulated in restricted fetal growth.
- 2007
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Ingår i: The Journal of physiology. - : Wiley. - 0022-3751. ; 582:Pt 1, s. 449-59
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Tidskriftsartikel (refereegranskat)abstract
- Pathological fetal growth is associated with perinatal morbidity and the development of diabetes and cardiovascular disease later in life. Placental nutrient transport is a primary determinant of fetal growth. In human intrauterine growth restriction (IUGR) the activity of key placental amino acid transporters, such as systems A and L, is decreased. However the mechanisms regulating placental nutrient transporters are poorly understood. We tested the hypothesis that the mammalian target of rapamycin (mTOR) signalling pathway regulates amino acid transport in the human placenta and that the activity of the placental mTOR pathway is reduced in IUGR. Using immunohistochemistry and culture of trophoblast cells, we show for the first time that the mTOR protein is expressed in the transporting epithelium of the human placenta. We further demonstrate that placental mTOR regulates activity of the l-amino acid transporter, but not system A or taurine transporters, by determining the mediated uptake of isotope-labelled leucine, methylaminoisobutyric acid and taurine in primary villous fragments after inhibition of mTOR using rapamycin. The protein expression of placental phospho-S6K1 (Thr-389), a measure of the activity of the mTOR signalling pathway, was markedly reduced in placentas obtained from pregnancies complicated by IUGR. These data identify mTOR as an important regulator of placental amino acid transport, and provide a mechanism for the changes in placental leucine transport in IUGR previously demonstrated in humans. We propose that mTOR functions as a placental nutrient sensor, matching fetal growth with maternal nutrient availability by regulating placental nutrient transport.
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| 6. |
- Wessel, Jennifer, et al.
(författare)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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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.
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| 7. |
- Aasa, Ulrika, et al.
(författare)
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The Swedish physical activity and fitness cohort born in 1958 - dropout analysis and overview at 36-year follow-up
- 2017
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 27:4, s. 418-429
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Tidskriftsartikel (refereegranskat)abstract
- The main aim of the Swedish physical activity and fitness cohort study (SPAF-1958) was to describe physical fitness, physical activity, health, and lifestyle across part of the lifespan, and to assess the influences on these factors from the environment, personal factors, and genetics. There is inevitable dropout from longitudinal studies, and it may be systematic. The aim of this first paper of the second follow-up of SPAF-1958 was to provide a dropout analysis to consider to what extent the participants, at 52 years of age, remain a representative sample of the original adolescent study population. Additional aims were to provide an overview of the study protocol and the ongoing study population. Ongoing study participants in SPAF born in 1958 were, at the second follow-up at the age of 52, still representative of the study cohort in terms of sex, adolescent geographical area, upper secondary school program, adolescent body composition, muscular strength, and muscular endurance. However, a higher physical activity and, among women, a higher aerobic capacity in adolescence decreased the risk for dropout. It is important when interpreting results from longitudinal studies to adjust for the systematic dropout that could bias the conclusions drawn from the results.
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| 8. |
- Ahlberg, Erik, et al.
(författare)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
-
Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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| 9. |
- Al-Adili, Ali, et al.
(författare)
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Ion counting efficiencies at the IGISOL facility
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- At the IGISOL-JYFLTRAP facility, fission mass yields can be studied at high precision. Fission fragments from a U target are passing through a Ni foil and entering a gas filled chamber. The collected fragments are guided through a mass separator to a Penning trap where their masses are identified. This simulation work focuses on how different fission fragment properties (mass, charge and energy) affect the stopping efficiency in the gas cell. In addition, different experimental parameters are varied (e. g. U and Ni thickness and He gas pressure) to study their impact on the stopping efficiency. The simulations were performed using the Geant4 package and the SRIM code. The main results suggest a small variation in the stopping efficiency as a function of mass, charge and kinetic energy. It is predicted that heavy fragments are stopped about 9% less efficiently than the light fragments. However it was found that the properties of the U, Ni and the He gas influences this behavior. Hence it could be possible to optimize the efficiency.
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| 10. |
- Al-Adili, Ali, et al.
(författare)
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Simulations of the fission-product stopping efficiency in IGISOL
- 2015
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 51:59, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- At the Jyväskylä Ion Guide Isotope Separator On-Line (IGISOL) facility, independent fission yields are measured employing the Penning-trap technique. Fission products are produced, e.g. by impinging protons on a uranium target, and are stopped in a gas-filled chamber. The products are collected by a flow of He gas and guided through a mass separator to a Penning trap, where their masses are identified. This work investigates how fission-product properties, such as mass and energy, affect the ion stopping efficiency in the gas cell. The study was performed using the Geant4 toolkit and the SRIM code. The main results show a nearly mass-independent ion stopping with regard to the wide spread of ion masses and energies, with a proper choice of uranium target thickness. Although small variations were observed, in the order of 5%, the results are within the systematic uncertainties of the simulations. To optimize the stopping efficiency while reducing the systematic errors, different experimental parameters were varied; for instance material thicknesses and He gas pressure. Different parameters influence the mass dependence and could alter the mass dependencies in the ion stopping efficiency.
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| 11. |
- Alanärä, Anders, et al.
(författare)
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Utsättning av djur för jakt och fiske
- 2021
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Bok (populärvet., debatt m.m.)abstract
- SLUs vetenskapliga råd för djurskydd har fått i uppdrag av Jordbruksverket att sammanställa aktuell forskning kring utsättning av djur för jakt och fiske samt att belysa eventuella kunskapsluckor på området. Uppdraget omfattar gräsand, rapphöna, fasan och laxfiskar. Bruket att föda upp fåglar och fiskar för utsättning i syfte att gynna jakt och fiske ifrågasätts inte sällan av etiska skäl, men den diskussionen ligger utanför fokus för denna rapport. Utsättning av fågel och fisk är en antropogen verksamhet som, till skillnad från många andra typer av mänsklig påverkan, syftar till att gynna arterna i fråga. Det kan handla om naturvårdsinsatser, att återinföra försvunna arter eller att på andra sätt berika ekosystemet, inte sällan med ökade möjligheter till jakt eller fiske som slutändamål. Ofta förbereds och åtföljs utsättningar av habitatförbättrande åtgärder som inte endast gynnar de utsatta individerna och deras artfränder, utan även har positiva konsekvenser för biologisk mångfald och ekosystemet i stort. I utarbetandet av regelverket knutet till utsättning av fågel och fisk är det viktigt att även beakta de positiva föresatserna och de konsekvenser som verksamheten kan medföra. Annars riskerar man att engagemang och incitament förloras, till men för biologisk mångfald och en rik och levande landsbygd.
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| 12. |
- Alvarez, José M, et al.
(författare)
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The WUSCHEL-RELATED HOMEOBOX 3 gene PaWOX3 regulates lateral organ formation in Norway spruce
- 2015
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 208:4, s. 1078-1088
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Tidskriftsartikel (refereegranskat)abstract
- In angiosperms, WUSCHEL-RELATED HOMEOBOX 3 (WOX3) genes are required for the recruitment of founder cells from the lateral domains of shoot meristems that form lateral regions of leaves. However, the regulation of the formation of lateral organs in gymnosperms remains unknown. By using somatic embryos of Norway spruce ( Picea abies) we have studied the expression and function of PaWOX3 during embryo development. The mRNA abundance of PaWOX3 was determined by quantitative real-time PCR, and the spatial expression of PaWOX3 was analysed by histochemical beta-glucuronidase (GUS) assays and in situ mRNA hybridization. To investigate the function of PaWOX3, we analysed how downregulation of PaWOX3 in RNA interference lines affected embryo development and morphology. PaWOX3 was highly expressed in mature embryos at the base of each cotyledon close to the junction between the cotyledons, and in the lateral margins of cotyledons and needles, separating them into an adaxial and an abaxial side. Downregulation of the expression of PaWOX3 caused defects in lateral margin outgrowth in cotyledons and needles, and reduced root elongation. Our data suggest that the WOX3 function in margin outgrowth in lateral organs is conserved among the seed plants, whereas its function in root elongation may be unique to gymnosperms.
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| 13. |
- Andelid, Kristina, 1953, et al.
(författare)
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Systemic cytokine signaling via IL-17 in smokers with obstructive pulmonary disease: a link to bacterial colonization?
- 2015
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Ingår i: International Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1178-2005. ; 10, s. 689-702
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Tidskriftsartikel (refereegranskat)abstract
- We examined whether systemic cytokine signaling via interleukin (IL)-17 and growth-related oncogene-alpha (GRO-alpha) is impaired in smokers with obstructive pulmonary disease including chronic bronchitis (OPD-CB). We also examined how this systemic cytokine signaling relates to bacterial colonization in the airways of the smokers with OPD-CB. Currently smoking OPD-CB patients (n=60, corresponding to Global initiative for chronic Obstructive Lung Disease [ GOLD] stage I-IV) underwent recurrent blood and sputum sampling over 60 weeks, during stable conditions and at exacerbations. We characterized cytokine protein concentrations in blood and bacterial growth in sputum. Asymptomatic smokers (n=10) and never-smokers (n=10) were included as control groups. During stable clinical conditions, the protein concentrations of IL-17 and GRO-alpha were markedly lower among OPD-CB patients compared with never-smoker controls, whereas the asymptomatic smoker controls displayed intermediate concentrations. Notably, among OPD-CB patients, colonization by opportunistic pathogens was associated with markedly lower IL-17 and GRO-alpha, compared with colonization by common respiratory pathogens or oropharyngeal flora. During exacerbations in the OPD-CB patients, GRO-alpha and neutrophil concentrations were increased, whereas protein concentrations and messenger RNA for IL-17 were not detectable in a reproducible manner. In smokers with OPD-CB, systemic cytokine signaling via IL-17 and GRO-alpha is impaired and this alteration may be linked to colonization by opportunistic pathogens in the airways. Given the potential pathogenic and therapeutic implications, these findings deserve to be validated in new and larger patient cohorts.
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| 14. |
- Andersson, Karin, 1990-, et al.
(författare)
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Continued sport and physical exercise during COVID-19: Strategies of staying active in Sweden
- 2021
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The COVID-19 pandemic has had devastating effects both for the global sport community as well as for individual exercisers around the world. Due to a wide range of imposed measurements to prevent the disease, day-to-day physical activities for entire populations are restricted by physical distancing, cancelled tournaments, and closed gyms. Sweden has chosen to apply recommendations instead of restrictions, however, little is known about how individuals in Sweden reason around, and act out their personal sport participation. Accordingly, the aim of this study is to increase knowledge of how sport participation was motivated from a micro perspective during the first wave of COVID-19. The paper is based on a mixed-methods-study with data from a questionnaire (N = 1,141) and material from semi-structured interviews (N =90). The results indicate that respondents who were already active before the pandemic remained active or even increased their activity levels. To investigate this further, the interviews were analyzed with critical discourse analysis to uncover how respondents justified their continued/increased personal sport participation. These could be summarized as (discursive) strategies of perpetuation based on (i) specific contexts, (ii) scientific and (personal) experienced knowledge of covid-19, and (iii) trust in others’ ability to follow recommendations to prevent the spread. Accordingly, this study contributes with new knowledge of how sport participation in Sweden was motivated, and, from a larger perspective, how a pandemic may influence attitudes toward health and exercise in an advanced Western capitalist society.
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| 15. |
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| 16. |
- Andersson, Karin, 1990-, et al.
(författare)
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Spatial transitions, levels of activity, and motivations to exercise during COVID-19 : a literature review
- 2022
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Ingår i: Sport in Society. - : Routledge. - 1743-0437 .- 1743-0445. ; 25:7, s. 1231-1251
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Forskningsöversikt (refereegranskat)abstract
- The COVID-19 pandemic and its related measurements have challenged physical activity in various ways, ranging from closed fitness facilities to virtual curfews. Correspondingly, there is currently a rising scholarly interest in investigating how people have navigated their physical activity during the pandemic, and, especially, if physical activity has decreased or not. Accordingly, surveys and studies are rapidly accumulating. Therefore, the purpose of this literature review is to summarize, categorize, and map literature published before May 2021 on physical activity amid COVID-19.This study consists of a mixed methods explanatory sequential design, based on an outcome-oriented pragmatism of the middle. Firstly, a systematic literature review on Scopus was conducted, followed by a VOS-viewer bibliometric analysis. Subsequently, a focused literature review was written. The point of integration of methods was embedded. The systematic review resulted in 1,335 articles, which were used for two separate VOS-viewer visualizations. The illustrations reveal where research comes from, which journals have published most on physical activity during COVID-19, and how the research is globally cited. Furthermore, based on the review, three clear topical trends of research emerge; spatial transitions, frequencies of physical activity, and motivations to exercise during COVID-19. The bibliometric data demonstrates that research from only a few countries seem to be impactful, whereas the review portrays that conclusions in regard to whether physical activity has decreased or not lack agreement, possibly as a result of disclosing different definitions of physical activity.
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| 17. |
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| 18. |
- Ashar, Foram N., et al.
(författare)
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A comprehensive evaluation of the genetic architecture of sudden cardiac arrest
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 39:44, s. 3961-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA.Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk.Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.
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| 19. |
- Asimus, Sara, 1976, et al.
(författare)
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Artemisinin antimalarials moderately affect cytochrome P450 enzyme activity in healthy subjects.
- 2007
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Ingår i: Fundamental & Clinical Pharmacology. - : Wiley. - 0767-3981 .- 1472-8206. ; 21:3, s. 307-316
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate which principal human cytochrome P450 (CYP450) enzymes are affected by artemisinin and to what degree the artemisinin derivatives differ with respect to their respective induction and inhibition capacity. Seventy-five healthy adults were randomized to receive therapeutic oral doses of artemisinin, dihydroartemisinin, arteether, artemether or artesunate for 5 days (days 1–5). A six-drug cocktail consisting of caffeine, coumarin, mephenytoin, metoprolol, chlorzoxazone and midazolam was administered orally on days −6, 1, 5 and 10 to assess the activities of CYP1A2, CYP2A6, CYP2C19, CYP2D6, CYP2E1 and CYP3A, respectively. Four-hour plasma concentrations of parent drugs and corresponding metabolites and 7-hydroxycoumarin urine concentrations were quantified by liquid chromatography-tandem mass spectrometry. The 1-hydroxymidazolam/midazolam 4-h plasma concentration ratio (CYP3A) was increased on day 5 by artemisinin [2.66-fold (98.75% CI: 2.10–3.36)], artemether [1.54 (1.14–2.09)] and dihydroartemisinin [1.25 (1.06–1.47)] compared with day −6. The S-4'-hydroxymephenytoin/S-mephenytoin ratio (CYP2C19) was increased on day 5 by artemisinin [1.69 (1.47–1.94)] and arteether [1.33 (1.15–1.55)] compared with day −6. The paraxanthine/caffeine ratio (CYP1A2) was decreased on day 1 after administration of artemisinin [0.27 (0.18–0.39)], arteether [0.70 (0.55–0.89)] and dihydroartemisinin [0.73 (0.59–0.90)] compared with day −6. The α-hydroxymetoprolol/metoprolol ratio (CYP2D6) was lower on day 1 compared with day −6 in the artemisinin [0.82 (0.70–0.96)] and dihydroartemisinin [0.83 (0.71–0.96)] groups, respectively. In the artemisinin-treated subjects this decrease was followed by a 1.34-fold (1.14–1.58) increase from day 1 to day 5. These results show that intake of artemisinin antimalarials affect the activities of several principal human drug metabolizing CYP450 enzymes. Even though not significant in all treatment groups, changes in the individual metrics were of the same direction for all the artemisinin drugs, suggesting a class effect that needs to be considered in the development of new artemisinin derivatives and combination treatments of malaria.
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| 20. |
- Baguma, Yona, et al.
(författare)
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Expression patterns of the gene encoding starch branching enzyme II in the storage roots of cassava (Manihot esculenta Crantz)
- 2003
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Ingår i: Plant Science. - 0168-9452 .- 1873-2259. ; 164:5, s. 833-839
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Tidskriftsartikel (refereegranskat)abstract
- Spatial and temporal expression patterns of the sbeII and sbeI genes, encoding starch branching enzyme II and I, respectively, in cassava (Manihot esculenta Crantz) were studied at different phenological stages of the crop. A partial cDNA for sbeII in cassava was cloned and used along with a cDNA-specific fragment of sbeI. As the cassava plant aged, the transcriptional activity of the sbeII and sbeI genes in the underground storage roots increased, whereas the activity in other organs remained the same or declined. At 180 days after planting (d.a.p.), levels of sbeII and sbeI transcripts in storage roots were very low, whereas at 360 d.a.p., the levels had increased dramatically. The 360 d.a.p. old storage roots also accumulated gbssII and gbssI transcripts, as well as a longer gbssI transcript, gbssI′. The difference between the gbssI and gbssI′ transcripts was shown to be due to differential splicing, whereby the gbssI′ transcript retained the first three introns. Unexpectedly, expression of sbeII and sbeI in the 360 d.a.p. storage roots exhibited fluctuations during the 24 h cycle, both under the normal light/dark regime and under continuous light or continuous dark conditions.
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| 21. |
- Bergenfelz, Caroline, et al.
(författare)
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Systemic Monocytic-MDSCs Are Generated from Monocytes and Correlate with Disease Progression in Breast Cancer Patients.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid cells, which increase in cancer patients. The molecular mechanism behind their generation and function is unclear. Whereas granulocytic-MDSCs correlate with poor overall survival in breast cancer, the presence and relevance of monocytic-MDSCs (Mo-MDSCs) is unknown. Here we report for the first time an enrichment of functional blood Mo-MDSCs in breast cancer patients before they acquire a typical Mo-MDSC surface phenotype. A clear population of Mo-MDSCs with the typical cell surface phenotype (CD14+HLA-DRlow/-CD86low/-CD80low/-CD163low/-) increased significantly first during disease progression and correlated to metastasis to lymph nodes and visceral organs. Furthermore, monocytes, comprising the Mo-MDSC population, from patients with metastatic breast cancer resemble the reprogrammed immunosuppressive monocytes in patients with severe infections, both by their surface and functional phenotype but also at their molecular gene expression profile. Our data suggest that monitoring the Mo-MDSC levels in breast cancer patients may represent a novel and simple biomarker for assessing disease progression.
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| 22. |
- Betta, Gian-Franco Dalla, et al.
(författare)
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Comments by the Senior Editor
- 2022
-
Ingår i: IEEE Transactions on Nuclear Science. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9499 .- 1558-1578. ; 69:4, s. 647-647
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The 7th edition of the International Conference on “Advancements in Nuclear Instrumentation Measurement Methods and their Applications” (ANIMMA) was held in Prague, Czech Republic, on June 21–25, 2021, in hybrid mode. The ANIMMA-2021 welcomed 320 attendees from 29 nationalities including 65 graduated students coming from academy, research institutes, and industry to discuss new scientific and technical prospects in all fields where nuclear instrumentation and measurements techniques play a major role. 30% of the attendees participated physically and 70% attended remotely.
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| 23. |
- Bäck, Marcus, et al.
(författare)
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Design, synthesis and SAR of potent statine-based BACE-1 inhibitors : Exploration of P1 phenoxy and benzyloxy residues
- 2008
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 16:21, s. 9471-9486
-
Tidskriftsartikel (refereegranskat)abstract
- Several BACE-1 inhibitors with low nanomolar level activities, encompassing a statine-based core structure with phenyloxymethyl- and benzyloxymethyl residues in the P1 position, are presented. The novel P1 modi. cation introduced to allow the facile exploration of the S1 binding pocket of BACE-1, delivered highly promising inhibitors.
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| 24. |
- Börjeson, Lowe, et al.
(författare)
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Open Access to Rural Landscapes!
- 2014
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Ingår i: Rural Landscapes. - : Stockholm University Press. - 2002-0104. ; 1:1, s. 1-2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The academic study of rural landscapes covers a broad range of academic disciplines and thematic, methodological and theoretical concerns and interests; including questions concerned with resource use (e.g. agriculture, forestry, water and mining), settlement, livelihoods, conflicts, conservation, culture and identity. This diversity is clearly a strength (the rich empirical and intellectual base), but also presents a challenge, as the dissemination of research findings is distributed through a plethora of publishing channels, which do not necessarily encourage exchange of results and ideas that are not already perceived as germane to already established academic networks.
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| 25. |
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| 26. |
- Cheng, Xiaoxiao, et al.
(författare)
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Structure and Interactions of the Human Programmed Cell Death 1 Receptor
- 2013
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Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 288:17, s. 11771-11785
-
Tidskriftsartikel (refereegranskat)abstract
- PD-1, a receptor expressed by T cells, B cells, and monocytes, is a potent regulator of immune responses and a promising therapeutic target. The structure and interactions of human PD-1 are, however, incompletely characterized. We present the solution nuclear magnetic resonance (NMR)-based structure of the human PD-1 extracellular region and detailed analyses of its interactions with its ligands, PD-L1 and PD-L2. PD-1 has typical immunoglobulin superfamily topology but differs at the edge of the GFCC' sheet, which is flexible and completely lacks a C '' strand. Changes in PD-1 backbone NMR signals induced by ligand binding suggest that, whereas binding is centered on the GFCC' sheet, PD-1 is engaged by its two ligands differently and in ways incompletely explained by crystal structures of mouse PD-1.ligand complexes. The affinities of these interactions and that of PD-L1 with the costimulatory protein B7-1, measured using surface plasmon resonance, are significantly weaker than expected. The 3-4-fold greater affinity of PD-L2 versus PD-L1 for human PD-1 is principally due to the 3-fold smaller dissociation rate for PD-L2 binding. Isothermal titration calorimetry revealed that the PD-1/PD-L1 interaction is entropically driven, whereas PD-1/PD-L2 binding has a large enthalpic component. Mathematical simulations based on the biophysical data and quantitative expression data suggest an unexpectedly limited contribution of PD-L2 to PD-1 ligation during interactions of activated T cells with antigen-presenting cells. These findings provide a rigorous structural and biophysical framework for interpreting the important functions of PD-1 and reveal that potent inhibitory signaling can be initiated by weakly interacting receptors.
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| 27. |
- Connysson, Malin, et al.
(författare)
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Road transport and diet affect metabolic response to exercise in horses
- 2017
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Ingår i: Journal of Animal Science. - : Oxford University Press (OUP). - 0021-8812 .- 1525-3163. ; 95, s. 4869-4879
-
Tidskriftsartikel (refereegranskat)abstract
- This study investigated the effects of transport and diet on metabolic response during a subsequent race-like test in Standardbred horses in training fed a forage-only diet and a 50: 50 forage: oats diet. Six trained and raced Standardbred trotter mares were used. Two diets, 1 forage-only diet (FONLY) and 1 diet with 50% of DM intake from forage and 50% from oats (FOATS), were fed for two 29-d periods in a crossover design. At Day 21, the horses were subjected to transport for 100 km before and after they performed an exercise test (transport test [TT]). At Day 26, the horses performed a control test (CT), in which they were kept in their stall before and after the exercise test. Blood samples were collected throughout the study, and heart rate and water intake were recorded. Heart rate and plasma cortisol, glucose, and NEFA concentrations were greater for the TT than for the CT (P = 0.008, P = 0.020, P = 0.010, and P = 0.0002, respectively) but were not affected by diet. Plasma acetate concentration was lower during the TT than during the CT (P = 0.034) and greater for the FONLY than for the FOATS (P = 0.003). There were no overall effects of the TT compared with the CT on total plasma protein concentration (TPP), but TPP was lower with the FONLY than with the FOATS (P = 0.016). There was no overall effect of the TT compared with the CT on water intake, but water intake was greater with the FONLY than the FOATS (P = 0.011). There were no overall effects of transport or diet on BW, plasma lactate, or plasma urea concentration. It was concluded that both transport and diet affect metabolic response during exercise in horses. Aerobic energy supply was most likely elevated by transportation and by the FONLY. The FONLY also decreased exercise-induced effects on extracellular fluid regulation. These results highlight the importance of experimental design in nutrition studies. If the aim is to examine how a diet affects exercise response in competition horses, transport should preferably be included in the experimental design, because horses are likely to be transported before a competition.
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| 28. |
- Creignou, Maria, et al.
(författare)
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Early transfusion patterns improve the Molecular International Prognostic Scoring System (IPSS-M) prediction in myelodysplastic syndromes
- 2024
-
Ingår i: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796.
-
Tidskriftsartikel (refereegranskat)abstract
- Background The Molecular International Prognostic Scoring System (IPSS-M) is the new gold standard for diagnostic outcome prediction in patients with myelodysplastic syndromes (MDS). This study was designed to assess the additive prognostic impact of dynamic transfusion parameters during early follow-up. Methods We retrieved complete transfusion data from 677 adult Swedish MDS patients included in the IPSS-M cohort. Time-dependent erythrocyte transfusion dependency (E-TD) was added to IPSS-M features and analyzed regarding overall survival and leukemic transformation (acute myeloid leukemia). A multistate Markov model was applied to assess the prognostic value of early changes in transfusion patterns. Results Specific clinical and genetic features were predicted for diagnostic and time-dependent transfusion patterns. Importantly, transfusion state both at diagnosis and within the first year strongly predicts outcomes in both lower (LR) and higher-risk (HR) MDSs. In multivariable analysis, 8-month landmark E-TD predicted shorter survival independently of IPSS-M (p < 0.001). A predictive model based on IPSS-M and 8-month landmark E-TD performed significantly better than a model including only IPSS-M. Similar trends were observed in an independent validation cohort (n = 218). Early transfusion patterns impacted both future transfusion requirements and outcomes in a multistate Markov model. Conclusion The transfusion requirement is a robust and available clinical parameter incorporating the effects of first-line management. In MDS, it provides dynamic risk information independently of diagnostic IPSS-M and, in particular, clinical guidance to LR MDS patients eligible for potentially curative therapeutic intervention.
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| 29. |
- Dahlberg, Marie, et al.
(författare)
-
Why publish? : An interview study exploring patient innovators’ reasons for and experiences of scientific publishing
- 2024
-
Ingår i: Research Involvement and Engagement. - : BioMed Central (BMC). - 2056-7529. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Scientific publications featuring patient-driven innovations (i.e., innovations that are developed and driven by patients or informal caregivers) are increasing. By understanding patient innovators' experiences of research publication, the scientific community may be better prepared to support or partner with patient innovators. Thus, the aim of this study was to explore patient innovators' reasons for and experiences of authoring scientific publications about their innovations.Methods: Qualitative semi-structured interviews were conducted with 15 international patient innovators from three continents who had published in scientific journals. Participants were identified through a scoping review on patient-driven innovations and snowball sampling. Interviews were conducted from June to October 2022 and the data was analyzed using the Framework Method.Findings: Participants' reasons for publishing in scientific journals were to strengthen the roles and voices of patients and informal caregivers, and to get recognition for their innovations. Some published as a response to serendipitous opportunities. Several positive experiences were reported: collaborations defined by transparency, mutual respect, and meaningful participation; learning and competence development; and gained confidence regarding the value of lived experiences in research. Participants also reported negative experiences, such as cultural barriers manifested as conservatism in academia and power imbalances between participants and researchers, and structural barriers regarding academic affiliations and research funding.Conclusions: Despite progress in increasing patient and public involvement in research and publication, our study found that patient innovators still experience barriers. This suggests that continued efforts are needed to facilitate contributions from patient innovators and other public actors to the production of relevant and meaningful research.
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| 30. |
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| 31. |
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| 32. |
- Edlund, Anna, et al.
(författare)
-
Active bacterial community structure along vertical redox gradients in Baltic Sea sediment
- 2008
-
Ingår i: Environmental Microbiology. - United Kingdom : Wiley-Blackwell Publishing Ltd.. - 1462-2912 .- 1462-2920. ; 10:8, s. 2051-2063
-
Tidskriftsartikel (refereegranskat)abstract
- Community structures of active bacterial populations were investigated along a vertical redox profile in coastal Baltic Sea sediments by terminal-restriction fragment length polymorphism (T-RFLP) and clone library analysis. According to correspondence analysis of T-RFLP results and sequencing of cloned 16S rRNA genes, the microbial community structures at three redox depths (179, -64 and -337 mV) differed significantly. The bacterial communities in the community DNA differed from those in bromodeoxyuridine (BrdU)-labelled DNA, indicating that the growing members of the community that incorporated BrdU were not necessarily the most dominant members. The structures of the actively growing bacterial communities were most strongly correlated to organic carbon followed by total nitrogen and redox potentials. Bacterial identification by sequencing of 16S rRNA genes from clones of BrdU-labelled DNA and DNA from reverse transcription polymerase chain reaction showed that bacterial taxa involved in nitrogen and sulfur cycling were metabolically active along the redox profiles. Several sequences had low similarities to previously detected sequences, indicating that novel lineages of bacteria are present in Baltic Sea sediments. Also, a high number of different 16S rRNA gene sequences representing different phyla were detected at all sampling depths.
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| 33. |
- Edlund, Anna, et al.
(författare)
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Microbial community structure in polluted Baltic Sea sediments
- 2006
-
Ingår i: Environmental Microbiology. - United Kingdom : Wiley-Blackwell Publishing Ltd.. - 1462-2912 .- 1462-2920. ; 8:2, s. 223-232
-
Tidskriftsartikel (refereegranskat)abstract
- Nearly half the seabed of the Baltic Proper is incapable of supporting life of higher organisms as a consequence of oxygen depletion resulting from eutrophication. However, these areas are actually teeming with microbial life. Here we used terminal-restriction fragment length polymorphism (T-RFLP) to investigate the dominant archaeal and bacterial groups, with respect to community structure, in surface layers of bottom sediments of the Baltic Sea along a coastal pollution gradient. Both archaeal and bacterial communities formed distinct clusters along the pollution gradient and the community compositions were different at the polluted sites compared with the relatively clean reference sites. The structures of the bacterial communities were most strongly correlated to water depth, followed by organic carbon, oxygen, salinity and silicate levels. In contrast, the structures of the archaeal communities were most strongly correlated to oxygen, salinity, organic carbon, silicate and nitrate levels. Some members of the microbial communities were identified using a combination of traditional and molecular approaches. Isolates obtained on different culture media were identified by partial sequencing of their 16S rRNA genes and some novel species were found. In addition, we developed a computer program, APLAUS, to elucidate the putative identities of the most dominant community members by T-RFLP.
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| 34. |
- Ekström, Sara, et al.
(författare)
-
Micro-teaching i Grundlärarprogrammet : Ett utvecklings- och forskningsprojekt för att stödja lärarstudenter att utveckla yrkesspecifik kunskap i matematik
- 2023
-
Ingår i: Abstracts för Decemberkonferensen. - Trollhättan : Högskolan Väst. ; , s. 1-1
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Vid matematikutbildningen i lärarprogrammen vid Högskolan Väst (HV) genomförs ett utvecklings- och forskningsprojekt (med flera delstudier) för att stödja lärarstudenter att utveckla specifik yrkeskunskap som förbereder dem för undervisningens komplexitet. Kontexten i den här studien är förskoleklassen, den skolform som ska knyta samman förskolans och skolans pedagogik. I en granskning av undervisningen i förskoleklassen (Skolinspektionen, 2015) framkom att endast en fjärdedel av eleverna får en undervisning som motsvarar läroplanens övergripande mål för kunskaper. Det finns därför ett stort behov av att utveckla undervisningen i förskoleklass. Detta gäller särskilt undervisningen i matematik.Teoretisk utgångspunkt i projektet är Banduras teori om självtillit i att undervisa (1997). Forskningen behandlar individens föreställningar om sin kompetens och inte den reella undervisningsförmågan. Det finns dock en tydlig koppling mellan lärares uppfattningar om sin kompetens och vad deras elever presterar. I studien undersöker vi lärarstudenters tilltro till deras egen förmåga att undervisa i matematik och hur den förändras när studenterna får genomföra micro-teaching inför sin VFU (Pekdağ et al., 2020).Studien inleddes med att studenterna fick undervisning i matematik och därefter med handledningsstöd planera en matematiklektion. Lärarutbildare och studentkollegor gav feedback via ett strukturerat observationsprotokoll i ett intilliggande hybridklassrum. Samma undervisningssession genomfördes sedan på VFU där läraren observerade och gav feedback. Datainsamling har skett genom fokusgrupper för att fånga studenternas upplevelse av micro-teaching och om/hur den förändrat deras tillit till att undervisa i matematik. Teoretiskt analysverktyg är fyra aspekter som stöd för utveckling av självtillit (Bandura, 1997).Generellt upplevde studenterna micro-teaching som lärorikt och vill gärna möta liknande upplägg igen. Kontinuerlig återkoppling på ett begränsat innehåll upplevdes positivt. Studenterna tyckte tekniken med micro-teaching var en bra lärsituation, som blandade teori och praktik samt gav dem nya perspektiv på deras egen undervisning, en “levande kunskap”.
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| 35. |
- Espínola, Fernando, et al.
(författare)
-
Metagenomic Analysis of Subtidal Sediments from Polar and Subpolar Coastal Environments Highlights the Relevance of Anaerobic Hydrocarbon Degradation Processes
- 2018
-
Ingår i: Microbial Ecology. - : Springer. - 0095-3628 .- 1432-184X. ; :1, s. 123-139
-
Tidskriftsartikel (refereegranskat)abstract
- In this work, we analyzed the community structure and metabolic potential of sediment microbial communities in high-latitude coastal environments subjected to low to moderate levels of chronic pollution. Subtidal sediments from four low-energy inlets located in polar and subpolar regions from both Hemispheres were analyzed using large-scale 16S rRNA gene and metagenomic sequencing. Communities showed high diversity (Shannon's index 6.8 to 10.2), with distinct phylogenetic structures (<40% shared taxa at the Phylum level among regions) but similar metabolic potential in terms of sequences assigned to KOs. Environmental factors (mainly salinity, temperature, and in less extent organic pollution) were drivers of both phylogenetic and functional traits. Bacterial taxa correlating with hydrocarbon pollution included families of anaerobic or facultative anaerobic lifestyle, such as Desulfuromonadaceae, Geobacteraceae, and Rhodocyclaceae. In accordance, biomarker genes for anaerobic hydrocarbon degradation (bamA, ebdA, bcrA, and bssA) were prevalent, only outnumbered by alkB, and their sequences were taxonomically binned to the same bacterial groups. BssA-assigned metagenomic sequences showed an extremely wide diversity distributed all along the phylogeny known for this gene, including bssA sensu stricto, nmsA, assA, and other clusters from poorly or not yet described variants. This work increases our understanding of microbial community patterns in cold coastal sediments, and highlights the relevance of anaerobic hydrocarbon degradation processes in subtidal environments.
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| 36. |
- Farman, Helen H., 1983, et al.
(författare)
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Female Mice Lacking Estrogen Receptor-alpha in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass
- 2016
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 157:8, s. 3242-3252
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor(ER)alpha. Central ER alpha exerts an inhibitory role on bone mass. ER alpha is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ER alpha in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ER alpha expression specifically in POMC neurons (POMC-ER alpha(-/-)). Female POMC-ER alpha(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 mu g/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ER alpha(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+ 126 +/- 34%, P < .01) and mechanical strength (+ 193 +/- 38%, P <.01). To test whether ER alpha in VMN is involved in the regulation of bone mass, ER alpha was silenced using an adeno-associated viral vector. Silencing of ER alpha in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ER alpha in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ER alpha activity in hypothalamic POMC neuronsin ARC and stimulatory peripheral ER alpha-mediated effects in bone determines cortical bone mass in female mice.
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| 37. |
- Forsare, Carina, et al.
(författare)
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Evolution of estrogen receptor status from primary tumors to metastasis and serially collected circulating tumor cells
- 2020
-
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:8
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The estrogen receptor (ER) can change expression between primary tumor (PT) and distant metastasis (DM) in breast cancer. A tissue biopsy reflects a momentary state at one location, whereas circulating tumor cells (CTCs) reflect real-time tumor progression. We evaluated ER-status during tumor progression from PT to DM and CTCs, and related the ER-status of CTCs to prognosis. Methods: In a study of metastatic breast cancer, blood was collected at different timepoints. After CellSearch® enrichment, CTCs were captured on DropMount slides and evaluated for ER expression at baseline (BL) and after 1 and 3 months of therapy. Comparison of the ER-status of PT, DM, and CTCs at different timepoints was performed using the McNemar test. The primary endpoint was progression-free survival (PFS). Results: Evidence of a shift from ER positivity to negativity between PT and DM was demonstrated (p = 0.019). We found strong evidence of similar shifts from PT to CTCs at different timepoints (p <0.0001). ER-positive CTCs at 1 and 3 months were related to better prognosis. Conclusions: A shift in ER-status from PT to DM/CTCs was demonstrated. ER-positive CTCs during systemic therapy might reflect the retention of a favorable phenotype that still responds to therapy.
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| 38. |
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| 39. |
- Gaccioli, F., et al.
(författare)
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Expression and functional characterisation of System L amino acid transporters in the human term placenta
- 2015
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Ingår i: Reproductive Biology and Endocrinology. - : Springer Science and Business Media LLC. - 1477-7827. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Background: System L transporters LAT1 (SLC7A5) and LAT2 (SLC7A8) mediate the uptake of large, neutral amino acids in the human placenta. Many System L substrates are essential amino acids, thus representing crucial nutrients for the growing fetus. Both LAT isoforms are expressed in the human placenta, but the relative contribution of LAT1 and LAT2 to placental System L transport and their subcellular localisation are not well established. Moreover, the influence of maternal body mass index (BMI) on placental System L amino acid transport is poorly understood. Therefore the aims of this study were to determine: i) the relative contribution of the LAT isoforms to System L transport activity in primary human trophoblast (PHT) cells isolated from term placenta; ii) the subcellular localisation of LAT transporters in human placenta; and iii) placental expression and activity of System L transporters in response to maternal overweight/obesity. Methods: System L mediated leucine uptake was measured in PHT cells after treatment with si-RNA targeting LAT1 and/or LAT2. The localisation of LAT isoforms was studied in isolated microvillous plasma membranes (MVM) and basal membranes (BM) by Western blot analysis. Results were confirmed by immunohistochemistry in sections of human term placenta. Expression and activity System L transporters was measured in isolated MVM from women with varying pre-pregnancy BMI. Results: Both LAT1 and LAT2 isoforms contribute to System L transport activity in primary trophoblast cells from human term placenta. LAT1 and LAT2 transporters are highly expressed in the MVM of the syncytiotrophoblast layer at term. LAT2 is also localised in the basal membrane and in endothelial cells lining the fetal capillaries. Measurements in isolated MVM vesicles indicate that System L transporter expression and activity is not influenced by maternal BMI. Conclusions: LAT1 and LAT2 are present and functional in the syncytiotrophoblast MVM, whereas LAT2 is also expressed in the BM and in the fetal capillary endothelium. In contrast to placental System A and beta amino acid transporters, MVM System L activity is unaffected by maternal overweight/obesity.
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| 40. |
- Gagnemo Persson, Rebecca, et al.
(författare)
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Läkemedel
- 2016. - 1
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Ingår i: Omvårdnad & medicin. - 9789144076645 ; , s. 125-138
-
Bokkapitel (populärvet., debatt m.m.)
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| 41. |
- Grim, Katarina, 1971-, et al.
(författare)
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Legitimizing user knowledge in mental health services : Epistemic (in)justice and barriers to knowledge integration
- 2022
-
Ingår i: Frontiers in Psychiatry. - Lausanne : Frontiers Media S.A.. - 1664-0640. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Including the voices and knowledge of service users is essential for developing recovery-oriented and evidence-based mental health services. Recent studies have however, suggested that challenges remain to the legitimization of user knowledge in practice. To further explore such challenges, a co-production study was conducted by a team of researchers and representatives from user organizations in Sweden. The aim of the study was to explore the barriers and facilitators to the legitimacy of user knowledge, as a central factor in sustainably implementing user influence in mental health practice. A series of workshops, with representatives of mental health services and user organizations were conducted by the research team to explore these issues. The analysis built on the theoretical framework of epistemic injustice, and the underlying aspects, testimonial, hermeneutic and participation-based injustice, were utilized as a framework for a deductive analysis. Results suggest that this is a useful model for exploring the complex dynamics related to the legitimacy of user knowledge in mental health systems. The analysis suggests that the legitimacy of user knowledge is related to the representativeness of the knowledge base, the systematic formulation of this knowledge inapplicable methods, access to resources and positions within the mental health system and participation in the process of integrating this knowledge-base in mental health contexts. Legitimizing user knowledge in practice additionally challenges mental health systems to support readiness for change in working environments and to address the power and role issues that these changes involve. Copyright © 2022 Grim, Näslund, Allaskog, Andersson, Argentzell, Broström, Jenneteg, Jansson, Schön, Svedberg, Svensson, Wåhlstedt and Rosenberg.
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Hedman, Harald, et al.
(författare)
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Analysis of the WUSCHEL-RELATED HOMEOBOX gene family in the conifer picea abies reveals extensive conservation as well as dynamic patterns
- 2013
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Ingår i: BMC Plant Biology. - : Springer Science and Business Media LLC. - 1471-2229. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Conclusions: Our study shows that all major radiations within the WOX gene family took place before the angiosperm-gymnosperm split and that there has been a recent expansion within the intermediate clade in the Pinaceae family. Furthermore, we show that the genes from the intermediate clade are preferentially expressed during embryo development in Picea abies. Our data also indicates that there are clear orthologs of both WUS and WOX5 present in the P. abies genome.
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| 46. |
- Hjort, Karin, et al.
(författare)
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Chitinase genes revealed and compared in bacterial isolates, DNA extracts and a metagenomic library from a phytopathogen-suppressive soil
- 2010
-
Ingår i: FEMS Microbiology Ecology. - United Kingdom : Wiley-Blackwell Publishing Ltd.. - 0168-6496 .- 1574-6941. ; 71:2, s. 197-207
-
Tidskriftsartikel (refereegranskat)abstract
- Soil that is suppressive to disease caused by fungal pathogens is an interesting source to target for novel chitinases that might be contributing towards disease suppression. In this study, we screened for chitinase genes, in a phytopathogen-suppressive soil in three ways: (1) from a metagenomic library constructed from microbial cells extracted from soil, (2) from directly extracted DNA and (3) from bacterial isolates with antifungal and chitinase activities. Terminal restriction fragment length polymorphism (T-RFLP) of chitinase genes revealed differences in amplified chitinase genes from the metagenomic library and the directly extracted DNA, but approximately 40% of the identified chitinase terminal restriction fragments (TRFs) were found in both sources. All of the chitinase TRFs from the isolates were matched to TRFs in the directly extracted DNA and the metagenomic library. The most abundant chitinase TRF in the soil DNA and the metagenomic library corresponded to the TRF103 of the isolate Streptomyces mutomycini and/or Streptomyces clavifer. There were good matches between T-RFLP profiles of chitinase gene fragments obtained from different sources of DNA. However, there were also differences in both the chitinase and the 16S rRNA gene T-RFLP patterns depending on the source of DNA, emphasizing the lack of complete coverage of the gene diversity by any of the approaches used.
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| 47. |
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| 48. |
- Holmlund, Sara, et al.
(författare)
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Lean i praktiken : en studie av produktionen på Englundshus AB
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Bakgrunden till projektet som resulterat i denna rapport, ligger i ett behov att förbättra effektiviteten i fabriken hos Englundshus AB. Syftet är att se över fabrikslayouten, hitta flöden, flaskhalsar och slöseri. Den teoribas som använts, finns inom ramen för Lean Production även kallat Lean Construction inom byggbranschen. Studien har genomförts i tre steg med lika många företagsbesök. Vid det första besöket studerades hela fabrikslayouten och samtliga delprocesser. Besöket resulterade i ett konstaterande att det som i teorierna beskrivs som 5S snabbt skulle skapa mervärde till hela fabriksprocessen. I samband med det andra besöket fokuserades på de två största processerna som är vägg- och golvtillverkning. Ur företagets tidsuppföljning konstaterades att väggtillverkningen var flaskhalsen för delprocesserna. Under besöket drogs även slutsatsen att materialflödet är kritiskt och bör ses över.För att hitta aktiviteten som orsakar flaskhalsen i väggtillverkningen gjordes under besök tre en värdeflödeskartläggning. Den visade att den sista stationen, där panel monteras, är flaskhalsen inom delprocessen.För att minska slöseriet och få ett bättre flöde genom fabriken och därmed minska effekten av flaskhalsen har ett förslag på ny fabrikslayout tagits fram. Förslaget innebär att borden omplaceras så att varje station ges möjlighet till ett bättre materialflöde.
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| 49. |
- James, John R., et al.
(författare)
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The T Cell Receptor Triggering Apparatus Is Composed of Monovalent or Monomeric Proteins
- 2011
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Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology, Inc.. - 0021-9258 .- 1083-351X. ; 286:37, s. 31993-32001
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the component stoichiometry of the T cell antigen receptor (TCR) triggering apparatus is essential for building realistic models of signal initiation. Recent studies suggesting that the TCR and other signaling-associated proteins are preclustered on resting T cells relied on measurements of the behavior of membrane proteins at interfaces with functionalized glass surfaces. Using fluorescence recovery after photo-bleaching, we show that, compared with the apical surface, the mobility of TCRs is significantly reduced at Jurkat T cell/glass interfaces, in a signaling-sensitive manner. Using two biophysical approaches that mitigate these effects, bioluminescence resonance energy transfer and two-color coincidence detection microscopy, we show that, within the uncertainty of the methods, the membrane components of the TCR triggering apparatus, i.e. the TCR complex, MHC molecules, CD4/Lck and CD45, are exclusively monovalent or monomeric in human T cell lines, implying that TCR triggering depends only on the kinetics of TCR/pMHC interactions. These analyses also showed that constraining proteins to two dimensions at the cell surface greatly enhances random interactions versus those between the membrane and the cytoplasm. Simulations of TCR-pMHC complex formation based on these findings suggest how unclustered TCR triggering-associated proteins might nevertheless be capable of generating complex signaling outputs via the differential recruitment of cytosolic effectors to the cell membrane.
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