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- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 2. |
- Eap, C. B., et al.
(författare)
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Tools for optimising pharmacotherapy in psychiatry (therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests) : focus on antidepressants
- 2021
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Ingår i: World Journal of Biological Psychiatry. - : Taylor & Francis Group. - 1562-2975 .- 1814-1412. ; 22:8, s. 561-628
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Forskningsöversikt (refereegranskat)abstract
- Objectives: More than 40 drugs are available to treat affective disorders. Individual selection of the optimal drug and dose is required to attain the highest possible efficacy and acceptable tolerability for every patient. Methods: This review, which includes more than 500 articles selected by 30 experts, combines relevant knowledge on studies investigating the pharmacokinetics, pharmacodynamics and pharmacogenetics of 33 antidepressant drugs and of 4 drugs approved for augmentation in cases of insufficient response to antidepressant monotherapy. Such studies typically measure drug concentrations in blood (i.e. therapeutic drug monitoring) and genotype relevant genetic polymorphisms of enzymes, transporters or receptors involved in drug metabolism or mechanism of action. Imaging studies, primarily positron emission tomography that relates drug concentrations in blood and radioligand binding, are considered to quantify target structure occupancy by the antidepressant drugs in vivo. Results: Evidence is given that in vivo imaging, therapeutic drug monitoring and genotyping and/or phenotyping of drug metabolising enzymes should be an integral part in the development of any new antidepressant drug. Conclusions: To guide antidepressant drug therapy in everyday practice, there are multiple indications such as uncertain adherence, polypharmacy, nonresponse and/or adverse reactions under therapeutically recommended doses, where therapeutic drug monitoring and cytochrome P450 genotyping and/or phenotyping should be applied as valid tools of precision medicine.
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| 3. |
- Petersen, N., et al.
(författare)
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Targeting the Gut in Obesity: Signals from the Inner Surface
- 2022
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is caused by prolonged energy surplus. Current anti-obesity medications are mostly centralized around the energy input part of the energy balance equation by increasing satiety and reducing appetite. Our gastrointestinal tract is a key organ for regulation of food intake and supplies a tremendous number of circulating signals that modulate the activity of appetite-regulating areas of the brain by either direct interaction or through the vagus nerve. Intestinally derived messengers are manifold and include absorbed nutrients, microbial metabolites, gut hormones and other enterokines, collectively comprising a fine-tuned signalling system to the brain. After a meal, nutrients directly interact with appetite-inhibiting areas of the brain and induce satiety. However, overall feeding behaviour also depends on secretion of gut hormones produced by highly specialized and sensitive enteroendocrine cells. Moreover, circulating microbial metabolites and their interactions with enteroendocrine cells further contribute to the regulation of feeding patterns. Current therapies exploiting the appetite-regulating properties of the gut are based on chemically modified versions of the gut hormone, glucagon-like peptide-1 (GLP-1) or on inhibitors of the primary GLP-1 inactivating enzyme, dipeptidyl peptidase-4 (DPP-4). The effectiveness of these approaches shows that that the gut is a promising target for therapeutic interventions to achieve significant weigh loss. We believe that increasing understanding of the functionality of the intestinal epithelium and new delivery systems will help develop selective and safe gut-based therapeutic strategies for improved obesity treatment in the future. Here, we provide an overview of the major homeostatic appetite-regulating signals generated by the intestinal epithelial cells and how these signals may be harnessed to treat obesity by pharmacological means. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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