| 1. |
- Petersen, Julian, et al.
(författare)
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A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- In this study we use comparative genomics to uncover a gene with uncharacterized function (1700011H14Rik/C14orf105/CCDC198), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decreased energy expenditure in Fame knockout animals, corresponding to genome-wide association studies linking FAME with higher body mass index in humans. Gene expression and subcellular localization analyses reveal that FAME is a membrane-bound protein enriched in the kidneys. Although the gene knockout results in structurally normal kidneys, we detect higher albumin in urine and lowered ferritin in the blood. Through experimental validation, we confirm interactions between FAME and ferritin and show co-localization in vesicular and plasma membranes.
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| 2. |
- Szucs, Edina, et al.
(författare)
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Synthesis, biochemical, pharmacological characterization and in silico profile modelling of highly potent opioid orvinol and thevinol derivatives
- 2020
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Ingår i: European Journal of Medicinal Chemistry. - : ELSEVIER. - 0223-5234 .- 1768-3254. ; 191
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Tidskriftsartikel (refereegranskat)abstract
- Morphine and its derivatives play inevitably important role in the m-opioid receptor (MOR) targeted antinociception. A structure-activity relationship study is presented for novel and known orvinol and thevinol derivatives with varying 3-O, 6-O, 17-N and 20-alkyl substitutions starting from agonists, antagonists and partial agonists. In vitro competition binding experiments with [H-3]DAMGO showed low subnanomolar affinity to MOR. Generally, 6-O-demethylation increased the affinity toward MOR and decreased the efficacy changing the pharmacological profile in some cases. In vivo tests in osteoarthritis inflammation model showed significant antiallodynic effects of thevinol derivatives while orvinol derivatives did not. The pharmacological character was modelled by computational docking to both active and inactive state models of MOR. Docking energy difference for the two states separates agonists and antagonists well while partial agonists overlapped with them. An interaction pattern of the ligands, involving the interacting receptor atoms, showed more efficient separation of the pharmacological profiles. In rats, thevinol derivatives showed antiallodynic effect in vivo. The orvinol derivatives, except for 6-O-desmethyl-dihydroetorfin (2c), did not show antiallodynic effect.
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| 3. |
- Aas, Wenche, et al.
(författare)
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Equilibria and dynamics in binary and ternary uranyl oxalate and acetate/fluoride complexes
- 1999
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Ingår i: Journal of the Chemical Society - Dalton Transactions. - : Royal Society of Chemistry (RSC). - 0300-9246 .- 1364-5447. ; :8, s. 1311-1317
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Tidskriftsartikel (refereegranskat)abstract
- The formation of ternary UO2(ac)pFq2-p-q (p = 1 or 2 and q = 1-3) complexes, and their equilibrium constants were investigated by potentiometric titrations and 19F NMR spectroscopy. The equilibrium constants have been determined from the emf data in a NaClO4 medium at constant sodium concentration, [Na+] = 1.00 M at 25°C, except for the UO2(ac)F32- complex where 19F NMR at -5°C was used. The magnitude of the equilibrium constant for the stepwise addition of fluoride indicates that prior co-ordination of acetate has only a small effect on the subsequent bonding of fluoride. The acetate exchange in the ternary UO2(ac)F32- complex was studied using 19F NMR. Through magnetisation transfer experiments, it was possible to confirm the provisional mechanism from a previous study and also the consistency of the rate constants for the five different exchange pathways required to describe the fluoride exchange. The exchange takes place via the intermediate UO2F3(H2O)2-, indicating that the acetate exchange follows an interchange mechanism with solvent participation in the transition state. The rates and mechanisms of the ligand exchange reactions in UO2(ox)2(H2O)2- and UO2(ac)2(H2O) have been studied using 13C NMR techniques at -5°C. The rate law is v = k-[complex][ligand], and the second order rate constant and the activation parameters for both systems have been determined. The reactions most likely take place through an Eigen-Wilkins type of mechanism, where the first step is a pre-equilibrium of an outer-sphere complex followed by a rate determining exchange of water. The rate constants for the water exchange reactions are very similar to that in UO2(H2O)52+. The information from the binary oxalate system rules out the formation of UO2(ox)2(H2O)2- as an intermediate in the exchange reactions in the previously studied UO2(ox)2F3-, also in this case confirming a previously suggested exchange mechanism. The H+/D+ isotope effects and a linear free energy relationship suggest that the main catalytic effect of H+ on ligand exchange rates is due to the formation of a protonated precursor. Hence, the catalytic effect depends on the basicity of the ligand and the site for the proton attack.
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| 4. |
- Ahn, Henrik Casimir, 1949-, et al.
(författare)
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A New Total Artificial Heart Concept Allowing Replacement or Support of the Native Heart
- 2018
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Ingår i: Journal of Clinical & Experimental Cardiology. - Los Angeles, United States : Omics Publishing Group. - 2155-9880. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- A total artificial heart (TAH) is typically used to bridge the time to heart transplantation. A device designed by Robert Jarvik has been improved through the years and under the name of Syncardia™ this has been the most successful commercially available TAH so far. Since 2008 the Carmat™ heart has been under development in Europe. The Scandinavian Real Heart™ is based on a unique physiological concept where the atrio-ventricular valve plane is of utmost importance in the pumping function of the heart. It consists of two identical parts driven separately by independent motors and in this first animal study we have used one part as a left ventricular assist device. This new concept makes the device flexible as it may be used not only as a TAH but also as a separate pump for left or right ventricular assist.
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| 5. |
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| 6. |
- Augustin, Jakob, 1976, et al.
(författare)
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No evidence of genetic benefits from extra-pair fertilisations in female sand martins (Riparia riparia)
- 2007
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Ingår i: Journal of Ornithology. - : Springer Science and Business Media LLC. - 2193-7192 .- 2193-7206. ; 148:2, s. 189-198
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Tidskriftsartikel (refereegranskat)abstract
- Genetic parentage studies of socially monogamous birds reveal a widespread prevalence of extra-pair paternity. Variation in extra-pair paternity among individuals may depend on how different individuals benefit from extra-pair fertilisations and on the opportunity to pursue extra-pair copulations. A long-term study of sand martins (Riparia riparia) in Hungary allowed us to examine patterns of extra-pair fertilisations in a large colony of over 3,000 breeding pairs with many known age individuals. We used multi-locus DNA fingerprinting to determine whether extra-pair fertilisations occur when females are paired to (1) presumably low quality mates, or (2) genetically similar or dissimilar mates, and whether extra-pair fertilisations result in offspring of higher quality. Extra-paternal young were found in 38% of 47 broods and comprised 19% of 190 offspring. Males that lost paternity did not differ significantly from others in age or body condition. Social mates of broods containing extra-pair offspring did not differ in genetic similarity from pairs without extra-pair offspring. Furthermore, there was no significant difference in body condition between extra-pair young and their maternal half-siblings. We were unable to assign paternity and therefore cannot exclude the possibility that extra-pair males differed from the within-pair males they cuckolded, in age, body condition or genetic similarity with the female. We found a positive relationship between paternity losses and breeding density, suggesting that low breeding density may constrain opportunities for seeking extra-pair copulations.
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| 7. |
- Batta, Gy., et al.
(författare)
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C‐19 configurational assignments in some morphine derivatives by homonuclear NOE
- 1992
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Ingår i: Magnetic Resonance in Chemistry. - : Wiley. - 0749-1581 .- 1097-458X. ; 30:13, s. S96-S104
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Tidskriftsartikel (refereegranskat)abstract
- Azidolysis‐thermolysis of C‐19 diastereomer tosyl esters of morphine derivatives resulted in the formation of a new substituted 4‐azatetracyclo [4.4.02,4.03,8] decane ring system. As the course of such transformations depends on the chirality of C‐19, its relative configuration was determined both in the starting materials and in the new compounds. To this end a semiquantitative 1H{1H} NOE interpretation was combined with MMX molecular mechanics. Interestingly, both in the starting materials with a rotating C‐7—C‐19 bond and in the fairly rigid aziridine ring‐containing products, the same (H‐8α{19‐Me}) NOE effects were the most informative on the stereochemistry. In addition full a priori 1H and 13C assignments of 13 compounds are presented.
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| 8. |
- Birch Tyrberg, Rasmus, et al.
(författare)
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Students’ and teachers’ attitudes towards PBL-curriculum components in a medical programme : a follow-up study
- 2021
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Ingår i: MedEdPublish. - : Association for Medical Education in Europe. - 2312-7996. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to explore students' and teachers' attitudes towards horizontal and vertical integration and other components of the curriculum, and to compare these results with data from a study at our medical school published in 2002.Methods: A questionnaire with 17 questions regarding different components of our curriculum was sent to students and staff at our medical school. They were asked to rate the importance of different components on a Likert scale from 1-6. We compared the answers between the two groups, and also compared them with the results from 2002.Results: Horizontal and vertical integration were rated as very important components (Teachers (n=283) median 5 and 5, Students (n=596) 6 and 5 respectively). Students valued lectures and clinical rotations more highly than teachers. Teachers considered laboratory training, training in searching scientific literature, scientific projects, basic education in ethics, reading and discussion of fictional literature, interprofessional components and examinations as significantly more important than the students did.Conclusions: Attitudes have remained positive towards horizontal and vertical integration despite major changes in the curriculum. The majority of the components of our curriculum were well appreciated, indicating that our curriculum is robust, but some components warrant inspection and possible revision.
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| 9. |
- Bodor, A., et al.
(författare)
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F-19 NMR study of the equilibria and dynamics of the Al3+/F- system
- 2000
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 39:12, s. 2530-2537
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Tidskriftsartikel (refereegranskat)abstract
- A careful reinvestigation by high-field F-19 NMR (470 MHz) spectroscopy has been made of the Al3+/F- system in aqueous solution under carefully controlled conditions of pH, concentration, ionic strength (I), and temperature. The F-19 NMR spectra show five distinct signals at 278 K and I = 0.6 M (TMACl) which have been attributed to the complexes AlFi(3-i)+(aq) with i less than or equal to 5. There was no need to invoke AlFi(OH)(j)((3-i-j)+) mixed complexes in the model under our experimental conditions (pH less than or equal to 6.5), nor was any evidence obtained for the formation of AlF63-(aq) at very high ratios of F-/Al3+. The stepwise equilibrium constants obtained for the complexes by integration of the F-19 signals are in good agreement with literature data given the differences in medium and temperature. In I = 0.6 M TMACl at 278 K and in I = 3 M KCl at 298 K the log K-i values are 6.42, 5.31, 3.99, 2.50, and 0.84 (for species i = 1-5) and 6.35, 5.25, and 4.11 (for species i = 1-3), respectively. Disappearance of the F-19 NMR signals under certain conditions was shown to be due to precipitation. Certain 19F NMR signals exhibit temperature- and concentration-dependent exchange broadening. Detailed line shape analysis of the spectra and magnetization transfer measurements indicate that the kinetics are dominated by F- exchange rather than complex formation. The detected reactions and their rate constants are AlF22+ + *F- reversible arrow AIF*F2+ + F- (k(02) = (1.8 +/- 0.3) x 10(6) M-1 s(-1)), AlF30 + *F- reversible arrow (AlF2F0)-F-* + F- (k(03) = (3.9 +/- 0.9) x 10(6) M-1 s(-1)), and AlF30 + H*F reversible arrow AlF2*F-0 + HF (k(03)(H) = (6.6 +/- 0.5) x 10(4) M-1 s(-1)). The rates of these exchange reactions increase markedly with increasing F- substitution. Thus, the reactions of AlF2+(aq) were too inert to be detected even on the T-1 NMR time scale, while some of the reactions of AlF30(aq) were fast, causing large line broadening. The ligand exchange appears to follow an associative interchange mechanism. The cis-trans isomerization of AlF2+(aq), consistent with octahedral geometry for that complex, is slowed sufficiently to be observed at temperatures around 270 R. Difference between the Al3+/F- system and the much studied Al3+/OH- system are briefly commented on.
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| 10. |
- Chang-Chun, Chen, et al.
(författare)
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Nucleoside transport inhibition mediates lidoflazine-induced cardioprotection during intermittent aortic crossclamping
- 1992
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier. - 0022-5223 .- 1097-685X. ; 104:6, s. 1602-1609
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Tidskriftsartikel (refereegranskat)abstract
- The effects of pretreatment with the nucleoside transport inhibitor lidoflazine on repeated ischemia-reperfusion injury induced by normothermic intermittent aortic crossclamping were studied in canine hearts. Eighteen mongrel dogs were allocated to three groups: placebo (n = 6), lidoflazine (1 mg/kg) (n = 6), and lidoflazine (1 mg/kg) plus the adenosine receptor blocker aminophylline (7 mg/kg) (n = 6). Pretreatment was performed intravenously during 15 minutes before extracorporeal circulation. All hearts were subjected to four intervals of 15 minutes of global ischemia each followed by 10 minutes of reperfusion. After weaning from extracorporeal circulation, functional recovery was followed for 1 hour. In the lidoflazine group, myocardial adenosine content (0.25 +/- 0.06 mumol/gm dry weight) was 3.5 times higher than that in the control group (0.07 +/- 0.03 mumol/gm dry weight; p < 0.05) at the end of the last aortic crossclamping. The release of adenosine from the myocardium during each reperfusion period was significantly higher than that in the control group (p < 0.05). Myocardial extraction of lactate was normalized at every reperfusion interval in the lidoflazine group but not in the control group (p < 0.05). In the lidoflazine group functional recovery was significantly better than that in the control group. Positive rate of rise of pressure, negative rate of rise of pressure, and cardiac output recovered to, respectively, 150% +/- 19%, 82% +/- 8%, and 131% +/- 15% in the lidoflazine group versus, respectively, 37% +/- 9%, 23% +/- 7%, and 29% +/- 8% in the control group (p < 0.001) at 1 hour after extracorporeal circulation. When the adenosine receptor blocker aminophylline was administered in association with lidoflazine, protection dropped significantly: positive and negative rate of rise of pressure and cardiac output were, respectively, 58% +/- 8%, 46% +/- 9%, and 67% +/- 16% at 1 hour after extracorporeal circulation (p < 0.05 versus lidoflazine alone). These results suggest that the cardioprotective effects of lidoflazine are at least in part mediated by adenosine receptor stimulation via nucleoside transport inhibition-induced accumulation of endogenous adenosine in the myocardium.
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