| 1. |
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| 2. |
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| 3. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 4. |
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| 8. |
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| 9. |
- Wiviott, Stephen D, et al.
(författare)
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Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes.
- 2019
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Ingår i: The New England journal of medicine. - 1533-4406. ; 380:4, s. 347-357
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Tidskriftsartikel (refereegranskat)abstract
- The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined.We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to <60 ml per minute per 1.73 m2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause.We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, who were followed for a median of 4.2 years. In the primary safety outcome analysis, dapagliflozin met the prespecified criterion for noninferiority to placebo with respect to MACE (upper boundary of the 95% confidence interval [CI], <1.3; P<0.001 for noninferiority). In the two primary efficacy analyses, dapagliflozin did not result in a lower rate of MACE (8.8% in the dapagliflozin group and 9.4% in the placebo group; hazard ratio, 0.93; 95% CI, 0.84 to 1.03; P=0.17) but did result in a lower rate of cardiovascular death or hospitalization for heart failure (4.9% vs. 5.8%; hazard ratio, 0.83; 95% CI, 0.73 to 0.95; P=0.005), which reflected a lower rate of hospitalization for heart failure (hazard ratio, 0.73; 95% CI, 0.61 to 0.88); there was no between-group difference in cardiovascular death (hazard ratio, 0.98; 95% CI, 0.82 to 1.17). A renal event occurred in 4.3% in the dapagliflozin group and in 5.6% in the placebo group (hazard ratio, 0.76; 95% CI, 0.67 to 0.87), and death from any cause occurred in 6.2% and 6.6%, respectively (hazard ratio, 0.93; 95% CI, 0.82 to 1.04). Diabetic ketoacidosis was more common with dapagliflozin than with placebo (0.3% vs. 0.1%, P=0.02), as was the rate of genital infections that led to discontinuation of the regimen or that were considered to be serious adverse events (0.9% vs. 0.1%, P<0.001).In patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease, treatment with dapagliflozin did not result in a higher or lower rate of MACE than placebo but did result in a lower rate of cardiovascular death or hospitalization for heart failure, a finding that reflects a lower rate of hospitalization for heart failure. (Funded by AstraZeneca; DECLARE-TIMI 58 ClinicalTrials.gov number, NCT01730534 .).
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| 10. |
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| 11. |
- Brown, P., et al.
(författare)
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Meeting the Magnetic Emc Challenges for the In-Situ Field Measurements on the Juice Mission
- 2019
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Ingår i: Proceedings of 2019 ESA Workshop on Aerospace EMC (Aerospace EMC). - : IEEE. - 9789082684780
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Konferensbidrag (refereegranskat)abstract
- The JUICE (JUpiter ICy moon Explorer) mission features instrument designs tailored to meet the specific challenges of the respective measuring environment, including EMC constraints. We describe the magnetic field science requirements for this mission and show how they drive the EMC requirements on the spacecraft and selected in-situ instrument configurations. We describe the results of two mutual interference campaigns and discuss the design mitigations employed in order to realise in-situ magnetic and electric field data in-flight with the accuracy required to meet very challenging mission science goals.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Hamann, Joerg, et al.
(författare)
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International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein-Coupled Receptors
- 2015
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Ingår i: Pharmacological Reviews. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0031-6997 .- 1521-0081. ; 67:2, s. 338-367
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Forskningsöversikt (refereegranskat)abstract
- The Adhesion family forms a large branch of the pharmacologically important superfamily of G protein-coupled receptors (GPCRs). As Adhesion GPCRs increasingly receive attention from a wide spectrum of biomedical fields, the Adhesion GPCR Consortium, together with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification, proposes a unified nomenclature for Adhesion GPCRs. The new names have ADGR as common dominator followed by a letter and a number to denote each subfamily and subtype, respectively. The new names, with old and alternative names within parentheses, are: ADGRA1 (GPR123), ADGRA2 (GPR124), ADGRA3 (GPR125), ADGRB1 (BAI1), ADGRB2 (BAI2), ADGRB3 (BAI3), ADGRC1 (CELSR1), ADGRC2 (CELSR2), ADGRC3 (CELSR3), ADGRD1 (GPR133), ADGRD2 (GPR144), ADGRE1 (EMR1, F4/80), ADGRE2 (EMR2), ADGRE3 (EMR3), ADGRE4 (EMR4), ADGRE5 (CD97), ADGRF1 (GPR110), ADGRF2 (GPR111), ADGRF3 (GPR113), ADGRF4 (GPR115), ADGRF5 (GPR116, Ig-Hepta), ADGRG1 (GPR56), ADGRG2 (GPR64, HE6), ADGRG3 (GPR97), ADGRG4 (GPR112), ADGRG5 (GPR114), ADGRG6 (GPR126), ADGRG7 (GPR128), ADGRL1 (latrophilin-1, CIRL-1, CL1), ADGRL2 (latrophilin-2, CIRL-2, CL2), ADGRL3 (latrophilin-3, CIRL-3, CL3), ADGRL4 (ELTD1, ETL), and ADGRV1 (VLGR1, GPR98). This review covers all major biologic aspects of Adhesion GPCRs, including evolutionary origins, interaction partners, signaling, expression, physiologic functions, and therapeutic potential.
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| 17. |
- Vilardell, A. M., et al.
(författare)
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Influence of surface topography on fatigue behavior of Ti6Al4V alloy by laser powder bed fusion
- 2018
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Ingår i: Procedia CIRP. - : Elsevier. ; , s. 49-52
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Konferensbidrag (refereegranskat)abstract
- This article deals with the understanding of the influence of surface topography on fatigue behavior of Ti6Al4V alloy specimens produced by laser powder bed fusion (LPBF). The same laser parameters and scan strategy were used for all specimens, giving a sample density higher than 99.5 %. Two different surface topographies were obtained by using the top and side surfaces of the specimens. The surface topography and morphology were investigated by optical surface profilometry and focus variation microscopy. Four-point bending fatigue test was performed on specimens with top and side surfaces as the highest stressed surface respectively. Machined specimens were used as reference. The features of the fracture surface, such as crack initiation and propagation, were analyzed by focus variation and scanning electron microscopy (SEM). Both, fatigue results and fracture surface investigations, were correlated and discussed in relation to surface topography and microstructure, as well as manufacturing parameters.
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| 18. |
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| 19. |
- Bertilsson, J., et al.
(författare)
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Use of pepper spray in policing : retrospective study of situational characteristics and implications for violent situations
- 2017
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Ingår i: Police Practice & Research. - : Routledge. - 1561-4263 .- 1477-271X. ; 18:4, s. 391-406
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Tidskriftsartikel (refereegranskat)abstract
- Pepper spray (OC) is a policing tool aimed to prevent or stop aggressive behavior by quickly and temporarily incapacitate without injuring. To date, few studies have investigated OC's operational usefulness and limitations. OC reduced violent behavior in 93% of the 936 incidents investigated. However, the operative range was often <2m and it took between 3 and 5 s of spraying before obtaining effect, partly owing to the difficulties of hitting a small, sometimes erratically moving target. Collateral hits were noted in 24% of the incidents, whereof 90% were other officers. Noteworthy, in 21% of incidents officers put themselves at large personal risk by using OC at close range against people armed with lethal weapons. Hence, OC emerges as a suitable tool for handling low threat situations but lacks key traits to ensure safe and efficient policing of high threat situations, e.g., handling armed assailants.
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| 20. |
- Boström, A., et al.
(författare)
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Risk factors for acute and overuse sport injuries in Swedish children 11 to 15 years old : What about resistance training with weights?
- 2016
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 26:3, s. 317-323
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Tidskriftsartikel (refereegranskat)abstract
- To determine the 1-year self-reported incidence of overuse and traumatic sport injuries and risk factors for injuries in children participating in a summer sports camp representing seven different sports. 4363 children, 11 to 15 years old participating in a summer camp in seven different sports answered a questionnaire. Injury in this cross-sectional study was defined as a sport-related trauma or overload leading to pain and dysfunction preventing the person from participation in training or competition for at least 1 week. A number of risk factors for injury were investigated such as sex, age, number of hours spent on training in general, and on resistance training with weights. Nearly half [49%, 95% confidence interval (CI) 48–51%] of the participants had been injured as a result of participation in a sport during the preceding year, significantly more boys than girls (53%, 95% CI 50–55% vs 46%, 95% CI 43–48%; P < 0.001). Three factors contributed to increased incidence of sport injuries: age, sex, and resistance training with weights. Time spent on resistance training with weights was significantly associated with sport injuries in a logistic regression analysis. In children age 11 to 15 years, the risk of having a sport-related injury increased with age and occurred more often in boys than in girls. Weight training was the only modifiable risk factor that contributed to a significant increase in the incidence of sport injuries.
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| 21. |
- Brusini, Irene, et al.
(författare)
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Changes in brain architecture are consistent with altered fear processing in domestic rabbits
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:28, s. 7380-7385
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Tidskriftsartikel (refereegranskat)abstract
- The most characteristic feature of domestic animals is their change in behavior associated with selection for tameness. Here we show, using high-resolution brain magnetic resonance imaging in wild and domestic rabbits, that domestication reduced amygdala volume and enlarged medial prefrontal cortex volume, supporting that areas driving fear have lost volume while areas modulating negative affect have gained volume during domestication. In contrast to the localized gray matter alterations, white matter anisotropy was reduced in the corona radiata, corpus callosum, and the subcortical white matter. This suggests a compromised white matter structural integrity in projection and association fibers affecting both afferent and efferent neural flow, consistent with reduced neural processing. We propose that compared with their wild ancestors, domestic rabbits are less fearful and have an attenuated flight response because of these changes in brain architecture.
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| 22. |
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| 23. |
- Caruso, Vanni, et al.
(författare)
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mRNA GPR162 changes are associated with decreased food intake in rat, and its human genetic variants with impairments in glucose homeostasis in two Swedish cohorts
- 2016
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Ingår i: Gene. - : Elsevier BV. - 0378-1119 .- 1879-0038. ; 581:2, s. 139-145
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Tidskriftsartikel (refereegranskat)abstract
- G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating intercellular interactions of fundamental physiological importance for survival including regulation of food intake, blood pressure, and hormonal sensing signaling, among other roles. Homeostatic alterations in the physiological status of GPCRs are often associated with underlying causes of disease, and to date, several orphan GPCRs are still uncharacterized. Findings from our previous study demonstrate that the Rhodopsin family protein GPR162 is widely expressed in GABAergic as well as other neurons within the mouse hippocampus, whereas extensive expression is observed in hypothalamus, amygdala, and ventral tegmental area, regions strictly interconnected and involved in the regulation of energy homeostasis and hedonic feeding. In this study, we provide a further anatomical characterization of GPR162 in mouse brain via in situ hybridization as well as detailed mRNA expression in a panel of rat tissues complementing a specie-specific mapping of the receptor. We also provide an attempt to demonstrate a functional implication of GPR162 in food intake-related behavior via antisense knockdown studies. Furthermore, we performed human genetic studies in which for the first time, variants of the GPR162 gene were associated with impairments in glucose homeostasis.
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| 24. |
- Evertsson, Maria, et al.
(författare)
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Combined Magnetomotive ultrasound, PET/CT, and MR imaging of (68)Ga-labelled superparamagnetic iron oxide nanoparticles in rat sentinel lymph nodes in vivo
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Current methods for intra-surgical guidance to localize metastases at cancer surgery are based on radioactive tracers that cause logistical challenges. We propose the use of a novel ultrasound-based method, magnetomotive ultrasound (MMUS) imaging that employ a nanoparticle-based contrast agent that also may be used for pre-operative PET/MRI imaging. Since MMUS is radiation free, this eliminates the dependence between pre- and intra-operative imaging and the radiation exposure for the surgical staff. This study investigates a hypothetical clinical scenario of pre-operative PET imaging, combined with intra-operative MMUS imaging, implemented in a sentinel lymph node (SLN) rat model. At one-hour post injection of (68)Ga-labelled magnetic nanoparticles, six animals were imaged with combined PET/CT. After two or four days, the same animals were imaged with MMUS. In addition, ex-vivo MRI was used to evaluate the amount of nanoparticles in each single SLN. All SLNs were detectable by PET. Four out of six SLNs could be detected with MMUS, and for these MMUS and MRI measurements were in close agreement. The MRI measurements revealed that the two SLNs undetectable with MMUS contained the lowest nanoparticle concentrations. This study shows that MMUS can complement standard pre-operative imaging by providing bedside real-time images with high spatial resolution.
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| 25. |
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| 26. |
- Fredriksson, Magnus, 1970, et al.
(författare)
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Den kommunikativa blicken. En analys av principerna för svenska kommuners kommunikationsverksamheter
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Antagandet om att ”allt kommunicerar” har fört med sig att organisationer i allt större utsträckning beaktar sin kommunikation när de organiserar och planerar sina verksamheter, när de fördelar resurser och ansvar och när de avgör vilka verksamhetsområden som ska prioriteras. Hur svenska kommunförvaltningar förhåller sig till detta vet vi inte så mycket om. Det finns ingen studie som erbjuder en heltäckande analys av svenska kommuners kommunikationsverksamheter och hur olika former av kommunikation ska förstås i förhållande till varandra. Syftet med rapporten är att erbjuda en sådan analys och den besvarar två frågor. Dels frågan om vilka principer det är som styr kommunikationsarbetet i svenska kommuner dels frågan om det finns några systematiska skillnader mellan kommuner i vilka principer de prioriterar. Utgångspunkten för analysen är att organisationers kommunikation, på samma sätt som andra verksamheter, styrs av en uppsättning generella principer. Med det menas att det finns förväntningar och föreställningar om hur, när, vem, vad och varför organisationer ska kommunicera och vilka resultat det går att förvänta sig om kommunikation hanteras på ett särskilt vis. Varje sådan princip tillskriver vissa former av kommunikation och därmed vissa aktiviteter, roller, tekniker och symboler större värde än andra vilket i sin tur innebär att en viss form av kommunikation ofta anses vara bäst i ett särskilt sammanhang. Undersökningen omfattar alla svenska kommuner och med hjälp av en automatiserad textanalys och en närläsning av kommunernas styrdokument för kommunikation går det att skilja ut sju principer; 1) att organisera och skapa strukturer för kommunikationsarbetet, 2) att positionera verksamheten i förhållande till andra kommuner, 3) att skapa och upprätthålla rutiner för att kunna larma informera och kommunicera i samband med kriser och extraordinära händelser, 4) att uniformera verksamheten för att försäkra sig om att kommunen framträder konsekvent och samstämmigt, 5) att interagera med intressenter för att på ett tidigt stadium fånga upp åsikter om verksamheten, 6) att med hjälp av webbplatser och andra digitala tjänster betjäna medborgare och andra intressenter och slutligen 7) interagera med journalister och andra medierepresentanter för att på så vis förmedla information till aktörer i omvärlden. De sju principerna återkommer i stort sett i alla kommuners dokument men det går att skilja ut två orienteringar; dels en verksamhetsorientering dels en omvärldsorientering. De verksamhetsorienterade kommunerna är fler (68%) och de prioriterar principerna om att förmedla, organisera och larma. Till skillnad från de omvärldsorienterade kommunerna (32%) som snarare vänder blicken utåt och prioriterar att interagera, uniformera och positionera. Resultaten ska förstås i ljuset av (åtminstone) två saker; dels tendensen till isomorfi – att organisationer som bedriver liknande verksamheter ofta tenderar att göra det på liknande sätt utifrån att det uppfattas som ett önskvärt, idealiskt eller moraliskt korrekt. Dels en ökande konkurrens mellan kommunerna och en allmänt utbredd företagisering av offentliga organisationer. I rapportens sista del diskuteras (de begränsade) möjligheterna för kommunerna att leva upp till idealen som principerna vilar på. Det finns påtagliga spänningar mellan generella normer och organisationsspecifika förutsättningar och mellan olika principer vilket gör att kommunerna kommer behöva hantera situationer där det finns motstridiga krav och varierande förväntningar på hur de ska kommunicera. På så vis kan vi förvänta oss att vissa principer får större utrymme än andra i det dagliga arbetet. Det betyder i sin tur att vi kan förvänta oss att kommuner utvecklar rutiner och tillvägagångssätt som innebär att vissa delar av kommunikationsarbetet anses vara viktigare och att det är prioriteringar som sannolikt präglas av kommunens huvudsakliga inriktning/orientering för kommunikationsarbetet.
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| 27. |
- Fredriksson, Robert, et al.
(författare)
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The polyamine transporter Slc18b1(VPAT) is important for both short and long time memory and for regulation of polyamine content in the brain.
- 2019
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 15:12
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Tidskriftsartikel (refereegranskat)abstract
- SLC18B1 is a sister gene to the vesicular monoamine and acetylcholine transporters, and the only known polyamine transporter, with unknown physiological role. We reveal that Slc18b1 knock out mice has significantly reduced polyamine content in the brain providing the first evidence that Slc18b1 is functionally required for regulating polyamine levels. We found that this mouse has impaired short and long term memory in novel object recognition, radial arm maze and self-administration paradigms. We also show that Slc18b1 KO mice have altered expression of genes involved in Long Term Potentiation, plasticity, calcium signalling and synaptic functions and that expression of components of GABA and glutamate signalling are changed. We further observe a partial resistance to diazepam, manifested as significantly lowered reduction in locomotion after diazepam treatment. We suggest that removal of Slc18b1 leads to reduction of polyamine contents in neurons, resulting in reduced GABA signalling due to long-term reduction in glutamatergic signalling.
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| 28. |
- Fredriksson, Sam, 1966, et al.
(författare)
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Surface shear stress dependence of gas transfer velocity parameterizations using DNS
- 2016
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Ingår i: Journal of Geophysical Research: Oceans. - 2169-9275 .- 2169-9291 .- 0148-0227 .- 2156-2202. ; 121:10, s. 7369-7389
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Tidskriftsartikel (refereegranskat)abstract
- Air-water gas-exchange is studied in direct numerical simulations (DNS) of free-surface flows driven by natural convection and weak winds. The wind is modeled as a constant surface-shear-stress and the gas-transfer is modeled via a passive scalar. The simulations are characterized via a Richardson number Ri=Bν/u*4 where B, ν, and u* are the buoyancy flux, kinematic viscosity, and friction velocity respectively. The simulations comprise 0Ric or kg=Ashearu*Sc-n, Ri
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| 29. |
- Fredriksson, Sam T, et al.
(författare)
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Estimating air-water gas transfer velocity during low wind condition with and without buoyancy
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This work aims at refining the gas transfer velocity parameterization during low wind conditions with and withoutbuoyancy, to be used in regional and global climate models. This parameterization and the enhanced understanding of the smallscale processes present in the vicinity of the air-water interfaces can of course be used for other purposes as well such as chemical and environmental engineering.
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| 30. |
- Herisson, F. M., et al.
(författare)
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Oxytocin Acting in the Nucleus Accumbens Core Decreases Food Intake
- 2016
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Ingår i: Journal of neuroendocrinology. - : Wiley. - 0953-8194 .- 1365-2826. ; 28:4
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Tidskriftsartikel (refereegranskat)abstract
- Central oxytocin (OT) promotes feeding termination in response to homeostatic challenges, such as excessive stomach distension, salt loading and toxicity. OT has also been proposed to affect feeding reward by decreasing the consumption of palatable carbohydrates and sweet tastants. Because the OT receptor (OTR) is expressed in the nucleus accumbens core (AcbC) and shell (AcbSh), a site regulating diverse aspects of eating behaviour, we investigated whether OT acts there to affect appetite in rats. First, we examined whether direct AcbC and AcbSh OT injections affect hunger- and palatability-driven consumption. We found that only AcbC OT infusions decrease deprivation-induced chow intake and reduce the consumption of palatable sucrose and saccharin solutions in nondeprived animals. These effects were abolished by pretreatment with an OTR antagonist, L-368,899, injected in the same site. AcbC OT at an anorexigenic dose did not induce a conditioned taste aversion, which indicates that AcbC OT-driven anorexia is not caused by sickness/malaise. The appetite-specific effect of AcbC OT is supported by the real-time polymerase chain reaction analysis of OTR mRNA in the AcbC, which revealed that food deprivation elevates OTR mRNA expression, whereas saccharin solution intake decreases OTR transcript levels. We also used c-Fos immunohistochemistry as a marker of neuronal activation and found that AcbC OT injection increases activation of the AcbC itself, as well as of two feeding-related sites: the hypothalamic paraventricular and supraoptic nuclei. Finally, considering the fact that OT plays a significant role in social behaviour, we examined whether offering animals a meal in a social setting would modify their hypophagic response to AcbC OT injections. We found that a social context abolishes the anorexigenic effects of AcbC OT. We conclude that OT acting via the AcbC decreases food intake driven by hunger and reward in rats offered a meal in a nonsocial setting.
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| 31. |
- Hägglund, Maria G A, et al.
(författare)
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Transport of L-glutamine, L-alanine, L-arginine and L-histidine by the neuron-specific Slc38a8 (SNAT8) in CNS
- 2015
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 427:6, s. 1495-1512
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Tidskriftsartikel (refereegranskat)abstract
- Glutamine transporters are important for regulating levels of glutamate and GABA in the brain. To date, six members of the SLC38 family (SNATs) have been characterized and functionally subdivided into System A (SNAT1, SNAT2 and SNAT4) and System N (SNAT3, SNAT5 and SNAT7). Here we present a first functional characterization of SLC38A8, one of the previous orphan transporters from the family and we suggest that the encoded protein should be named SNAT8 to adhere with the SNAT nomenclature. We show that SLC38A8 have preference for transporting L-glutamine, L-alanine, L-arginine, L-histidine, and L-aspartate using a Na(+)-dependent transport mechanism and that the functional characteristics of SNAT8 has highest similarity to the known System A transporters. We also provide a comprehensive CNS expression profile in mouse brain for the Slc38a8 gene and the SNAT8 protein. We show that Slc38a8 (SNAT8) is expressed in all neurons, both excitatory and inhibitory, in mouse brain using in situ hybridization and immunohistochemistry. Furthermore, proximity ligation assay show highly similar subcellular expression of SNAT7 and SNAT8. In conclusion, the neuronal SLC38A8 have a broad amino acid transport profile and is the first identified neuronal System A transporter. This suggests a key role of SNAT8 in the glutamine/glutamate(GABA) cycle in the brain.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Lekholm, Emilia, et al.
(författare)
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Putative Membrane-Bound Transporters MFSD14A and MFSD14B Are Neuronal and Affected by Nutrient Availability
- 2017
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Ingår i: Frontiers in Molecular Neuroscience. - : Frontiers Media SA. - 1662-5099. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of orphan transporters is of importance due to their involvement in cellular homeostasis but also in pharmacokinetics and pharmacodynamics. The tissue and cellular localization, as well as function, is still unknown for many of the solute carriers belonging to the major facilitator superfamily (MFS) Pfam clan. Here, we have characterized two putative novel transporters MFSD14A (HIAT1) and MFSD14B (HIATL1) in the mouse central nervous system and found protein staining throughout the adult mouse brain. Both transporters localized to neurons and MFSD14A co-localized with the Golgi marker Giantin in primary embryonic cortex cultures, while MFSD14B staining co-localized with an endoplasmic retention marker, KDEL. Based on phylogenetic clustering analyses, we predict both to have organic substrate profiles, and possible involvement in energy homeostasis. Therefore, we monitored gene regulation changes in mouse embryonic primary cultures after amino acid starvations and found both transporters to be upregulated after 3 h of starvation. Interestingly, in mice subjected to 24 h of food starvation, both transporters were downregulated in the hypothalamus, while Mfsdl4a was also downregulated in the brainstem. In addition, in mice fed a high fat diet (HFD), upregulation of both transporters was seen in the striatum. Both MFSD14A and MFSD14B were intracellular neuronal membrane bound proteins, expressed in the Golgi and Endoplasmic reticulum, affected by both starvation and HFD to varying degree in the mouse brain.
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| 36. |
- McGinn, Steven, et al.
(författare)
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New Technologies for DNA analysis-A review of the READNA Project.
- 2016
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Ingår i: New Biotechnology. - : Elsevier BV. - 1876-4347 .- 1871-6784.
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Forskningsöversikt (refereegranskat)abstract
- The REvolutionary Approaches and Devices for Nucleic Acid analysis (READNA) project received funding from the European Commission for 4 1/2 years. The objectives of the project revolved around technological developments in nucleic acid analysis. The project partners have discovered, created and developed a huge body of insights into nucleic acid analysis, ranging from improvements and implementation of current technologies to the most promising sequencing technologies that constitute a 3(rd) and 4(th) generation of sequencing methods with nanopores and in situ sequencing, respectively.
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| 37. |
- Rask-Andersen, Mathias, et al.
(författare)
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Determination of obesity associated gene variants related to TMEM18 through ultra-deep targeted re-sequencing in a case-control cohort for pediatric obesity.
- 2015
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Ingår i: Genetical Research. - 0016-6723 .- 1469-5073. ; 97
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have revealed association of a locus approximately 25b downstream of the TMEM18 gene with body mass and obesity. We utilized targeted re-sequencing of the body mass associated locus in proximity of TMEM18 in a case-control population of severely obese children and adolescents from the Stockholm area. We expanded our study to include the TMEM18 gene itself, with the aim of identifying body mass associated genetic variants. Sequencing was performed on the SOLiD platform, on long-range PCR fragments generated through targeted amplification of the regions of interest. Candidate single nucleotide polymorphisms (SNPs) were validated by TaqMan genotyping. We were able to observe 131 SNPs across the re-sequenced regions. Chi squared tests comparing the allele frequencies between cases and controls revealed 57 SNPs as candidates for association with obesity. Validation and replication genotyping revealed robust associations for SNPs within the haplotype block region located downstream from the TMEM18 gene. This study provides a high resolution map of the genetic variation pattern in the TMEM18 gene, as well as the associated haplotype block, and further strengthens the association of variants within the proximal haplotype block with obesity and body mass.
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| 38. |
- Rosenberg, E, et al.
(författare)
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No increased risk of relapse of breast cancer for women who give birth after assisted conception.
- 2019
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Ingår i: Human reproduction open. - : Oxford University Press (OUP). - 2399-3529. ; 2019:4
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Tidskriftsartikel (refereegranskat)abstract
- Is childbirth after IVF associated with a risk of relapse in breast cancer?Women who had been diagnosed with breast cancer and completed treatment had no increased risk of relapse if they gave birth after conceiving with IVF.Pregnancy and childbirth have not been shown to increase the risk of relapse in breast cancer. Ovarian stimulation during IVF increases the oestrogen levels and could theoretically increase the risk of relapse in breast cancer.This is a retrospective register study, using national Swedish register data from the National Patient Register, the Medical Birth Register, the Swedish National Cancer Register, the National Breast Cancer Register, the National Quality Registry of Assisted Reproduction (Q-IVF), the National IVF Dataset, the Swedish Prescribed Drug Register and the Cause of Death Register. All women diagnosed with breast cancer who were between 20 and 44years of age during the years 1982 to 2014 and identified in the cancer registries were assessed.Women, previously diagnosed with breast cancer, who had given birth after IVF (29 after completed breast cancer treatment and 8 after fertility preservation) were compared with a matched control group who had given birth after spontaneous conception. Matching was done in a ratio 1:4, based on T-stage (size of the tumour) and year of diagnosis +/-5years.We found 26114 women that had been diagnosed with breast cancer when 20-44years old and of those 860 had subsequently given birth, 823 after spontaneous and 37 after IVF conception. Follow-up time was similar between the groups, ranging from 2.6 to 24.0years, with a mean follow-up time of 10.3 (SD 4.2) years in the IVF group and 10.7 (SD 4.4) years in the control group. There were no relapses (0/37) in the IVF group. The relapse rate for the matched controls was 36/148 (24.8%). Ten women who suffered relapse died due to breast cancer.This is reassuring data; however, the result is based on a few cases. The poor coverage of important prognostic variables in the register resulted in uncertain comparability of the groups. The main limitation in this study is the extent of missing data on tumour-related variables, due to poor coverage from the early years of the National Breast Cancer Register. It is possible that the women accepted for IVF had a less aggressive breast cancer and were generally healthier than women delivering after conceiving spontaneously and therefore had a lower risk of relapse. Other limitations are the lack of information on the anticancer therapies used and type of disease relapse, plus the older of the two IVF registers did not hold information on unsuccessful IVF cycles, leaving only cycles leading to birth, to be analysed.We found no indication that women who had been diagnosed with breast cancer had an increased risk of relapse if they gave birth after conceiving with IVF. Based on our findings, there is no evidence to advise against IVF treatment in this group of women. More detailed registry data would be valuable for future studies, enabling proper matching of tumour characteristics between groups.The study was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-720291), The Assar Gabrielsson Fund (FB 15-20), The Breast Cancer Fund and the Swedish Association of Local Authorities and Regions, SKL. There are no conflicts of interest to declare.
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| 39. |
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| 40. |
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| 41. |
- Wadsten, Charlotta, et al.
(författare)
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Risk of ischemic heart disease after radiotherapy for ductal carcinoma in situ
- 2018
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Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 171:1, s. 95-101
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The use of adjuvant radiotherapy (RT) in the management of ductal carcinoma in situ (DCIS) is increasing. Left-sided breast irradiation may involve exposure of the heart to ionising radiation, increasing the risk of ischemic heart disease (IHD). We examined the incidence of IHD in a population-based cohort of women with DCIS.Methods: The Breast Cancer DataBase Sweden (BCBase) cohort includes women registered with invasive and in situ breast cancers 1992-2012 and age-matched women without a history of breast cancer. In this analysis, 6270 women with DCIS and a comparison cohort of 31,257 women were included. Through linkage with population-based registers, data on comorbidity, socioeconomic status and incidence of IHD was obtained. Hazard ratios (HR) for IHD with 95% confidence intervals (CI) were analysed.Results: Median follow-up time was 8.8 years. The risk of IHD was not increased for women with DCIS versus women in the comparison cohort (HR 0.93; 95% CI 0.82-1.06), after treatment with radiotherapy versus surgery alone (HR 0.77; 95% CI 0.60-0.98) or when analysing RT by laterality (HR 0.85; 95% CI 0.53-1.37 for left-sided versus right-sided RT).Conclusions: The risk of IHD was lower for women with DCIS allocated to RT compared to non-irradiated women and to the comparison cohort, probably due to patient selection. Comparison of RT by laterality did not show any over-risk for irradiation of the left breast.
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| 42. |
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| 43. |
- Wiemerslage, Lyle, et al.
(författare)
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The Drosophila ortholog of TMEM18 regulates insulin and glucagon-like signaling
- 2016
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Ingår i: Journal of Endocrinology. - 0022-0795 .- 1479-6805. ; 229:3, s. 233-243
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Tidskriftsartikel (refereegranskat)abstract
- Transmembrane protein 18 (TMEM18) is an ill-described, obesity-related gene, but few studies have explored its molecular function. We found single-nucleotide polymorphism data, suggesting that TMEM18 may be involved in the regulation/physiology of metabolic syndrome based on associations with insulin, homeostatic model assessment-beta (HOMA beta), triglycerides, and blood sugar. We then found an ortholog in the Drosophila genome, knocked down Drosophila Tmem18 specifically in insulin-producing cells, and tested for its effects on metabolic function. Our results suggest that TMEM18 affects substrate levels through insulin and glucagon signaling, and its downregulation induces a metabolic state resembling type 2 diabetes. This work is the first to experimentally describe the metabolic consequences of TMEM18 knockdown, and further supports its association with obesity.
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| 44. |
- Zheleznyakova, Galina Yu, et al.
(författare)
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Methylation Levels of SLC23A2 and NCOR2 Genes Correlate with Spinal Muscular Atrophy Severity
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Spinal muscular atrophy (SMA) is a monogenic neurodegenerative disorder subdivided into four different types. Whole genome methylation analysis revealed 40 CpG sites associated with genes that are significantly differentially methylated between SMA patients and healthy individuals of the same age. To investigate the contribution of methylation changes to SMA severity, we compared the methylation level of found CpG sites, designed as "targets", as well as the nearest CpG sites in regulatory regions of ARHGAP22, CDK2AP1, CHML, NCOR2, SLC23A2 and RPL9 in three groups of SMA patients. Of notable interest, compared to type I SMA male patients, the methylation level of a target CpG site and one nearby CpG site belonging to the 5'UTR of SLC23A2 were significantly hypomethylated 19-22% in type III-IV patients. In contrast to type I SMA male patients, type III-IV patients demonstrated a 16% decrease in the methylation levels of a target CpG site, belonging to the 5'UTR of NCOR2. To conclude, this study validates the data of our previous study and confirms significant methylation changes in the SLC23A2 and NCOR2 regulatory regions correlates with SMA severity.
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