| 1. |
- Gusarova, Viktoria, et al.
(författare)
-
Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes
- 2018
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9, s. 1-11
-
Tidskriftsartikel (refereegranskat)abstract
- Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10-10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.
|
|
| 2. |
- Groenewald, David P., et al.
(författare)
-
Unique trackway on Permian Karoo shoreline provides evidence of temnospondyl locomotory behaviour
- 2023
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:3
-
Tidskriftsartikel (refereegranskat)abstract
- Large-bodied temnospondyl amphibians were the dominant predators in non-marine aquatic ecosystems from the Carboniferous to the Middle Triassic. In the Permian-aged lower Beaufort Group ofthe main Karoo Basin, South Africa, temnospondyls are represented exclusively by the family Rhinesuchidae and are well represented by body fossils, whereas trace fossils are scarce. Accordingly, most interpretations of the behaviour of this family are based on skeletal morphology and histological data. Here we document the sedimentology and palaeontology of a late Permian palaeosurface situated immediately below the palaeoshoreline ofthe Ecca Sea (transition from the Ecca Group to the Beaufort Group) near the town of Estcourt in KwaZulu-Natal Province. The surface preserves numerous ichnofossils, including tetrapod footprints and fish swim-trails, but most striking are seven body impressions and associated swim trails that we attribute to amedium-sized (~1.9 mlong) rhinesuchid temnospondyl. These provide valuable insight into the behaviour of these animals. The sinuous shape ofsome of the traces suggest that the tracemaker swam with continuous sub-undulatory propulsion of the tail.
|
|
| 3. |
- Handley, Dean A., et al.
(författare)
-
Biological actions of formoterol isomers
- 2002
-
Ingår i: Pulmonary Pharmacology & Therapeutics. - : Elsevier BV. - 1094-5539 .- 1522-9629. ; 15:2, s. 135-145
-
Tidskriftsartikel (refereegranskat)abstract
- Racemic β2 agonists, composed of equal amounts of (R)- and (S)-isomers, can display anomalous actions that compromise their effectiveness as asthma therapies. Loss of efficacy during regular use is characteristic of isoprenaline, albuterol and terbutaline and has in part been attributed to the biological effects of the (S)-isomer. This hypothesis was applied to the (R,R)- and (S,S)-isomers of formoterol. (R,R)-formoterol had 1000-times greater affinity (2.9 nm) to the human β2 adrenoceptor than (S,S)-formoterol (3100 nm), with receptor binding modulating intracellular cAMP levels. The minimum lethal intravenous (IV) dose was determined to be 100 mg/kg for (R,R)- and 50 mg/kg for (S,S)-formoterol, suggesting that the toxicity of (S,S)-formoterol may not be related to the binding of β2 adrenoceptors. In tissues pretreated with (S,S)-formoterol but not with (R,R)- or racemic formoterol contractions to high concentrations of carbachol were exaggerated. In vivo experiments with sensitized guinea pigs demonstrated that (R,R)-formoterol inhibited both histamine and antigen-induced bronchoconstriction with greater potency than (R,R/S,S)-formoterol while (S,S)-formoterol was ineffective. Metabolic radiolabeling experiments of (R,R)-, (S,S)- or (R,R/S,S)-formoterol with crude human liver phenolsulfotransferase (PST) determined the Vmax/Km values to be (0.151), (0.74) and (0.143), respectively. The reciprocal plot illustrates a 2-fold reduction in sulfation rate when (R,R)-formoterol is present as a single isomer. The data presented here suggest that (R,R)-formoterol binds to the β2 adrenoceptor and inhibits the contraction of bronchial tissues by spasmogens. However, (S,S)-formoterol exhibits properties inconsistent as an asthma therapeutic and may antagonize the actions of (R,R)-formoterol.
|
|
| 4. |
|
|
| 5. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
