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There are five muscarinic receptor subtypes expressed in the human heart. The main subtype is the M 2 -muscarinic receptor. We hypothesized that overexpression of the M 2 -muscarinic receptor should augment any contractile effects that are M 2 -muscarinic receptor–mediated. Therefore, we generated a transgenic mouse with overexpression of the human M 2 -muscarinic receptor under the control of the heart-specific α-myosin heavy...
Positive inotropic effects of glucose-dependent insulinotropic polypeptide in the human atrium and the mouse atriumNARA Subscribed
Glucose-dependent insulinotropic polypeptide formerly called gastrin inhibitory peptide (GIP), a peptide composed of 42 amino acids, is formed in duodenal and jejunal cells. GIP acts via GIP receptors (GIPR). GIPR can stimulate adenylyl cyclases (AC) and increase intracellular cyclic adenosine-3´,5´-monophosphate (cAMP) levels. The physiological role of GIPR in the human heart is not fully understood. Thence, force of contract...
Predicting the geometrical evolution of the pore space in geological formations due to fluid–solid interactions has applications in reservoir engineering, oil recovery, and geological storage of carbon dioxide. However, modeling frameworks that combine fluid flow with physical and chemical processes at a rock’s pore scale are scarce. Here, we report a method for modeling a rock’s pore space as a network of connected capillarie...
Genome-wide association study of Fuchs’ endothelial corneal dystrophy in the German populationNARA Subscribed
The genetic etiology of Fuchs Endothelial Corneal Dystrophy (FECD) is not yet fully elucidated. While the disease is widespread and the leading indication for corneal transplantation in the Western world, the concurrent shortage of corneal transplants underscores the urgent need for further research into the underlying mechanisms. Such investigations could enable the development of innovative therapeutic strategies. Therefore,...
Cantharidin and sodium fluoride inhibit the activity of serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A) and increase the force of contraction in human atrial preparations. R-phenylisopropyl adenosine (R-PIA) acts as an agonist at A 1 -adenosine receptors. R-PIA exerts a negative inotropic effect on human atria. The effect of R-PIA—and its various manifestations—are currently explained as a function of the inhibitio...
Contractile effects of stimulation of D1-dopamine receptors in the isolated human atriumNARA Subscribed
Dopamine receptors have been claimed not to directly increase contractility in the human heart. Therefore, we performed contraction experiments in isolated electrically driven human atrial preparations (HAP). For comparison, we performed contraction experiments with left atrial preparations of transgenic mice which harbor a cardiac overexpression of human D 1 -dopamine receptors (D 1 -TG). In D 1 -TG, first we noted that dopam...
Congenital adrenal hyperplasia (CAH) is characterized by impaired adrenal cortisol production. Hydrocortisone (synthetic cortisol) is the drug-of-choice for cortisol replacement therapy, aiming to mimic physiological cortisol circadian rhythm. The hypothalamic-pituitary-adrenal (HPA) axis controls cortisol production through the pituitary adrenocorticotropic hormone (ACTH) and feedback mechanisms. The aim of this study was to...
Studies on the mechanisms of action of MR33317NARA Subscribed
MR33317 was synthesized as an acetylcholinesterase-inhibitor and an agonist at brain 5-HT 4 -receptors. MR33317 might be used to treat Morbus Alzheimer. This therapeutic action of MR33317 might be based on MR33317´s dual synergistic activity. We tested the hypothesis that MR33317 also stimulates 5-HT 4 -receptors in the heart. MR33317 (starting at 10 nM) increased force of contraction and beating rate in isolated atrial prepar...
The Toxicology Investigators Consortium 2023 Annual ReportNARA Subscribed
Healthy environments for athleTes (HEAT): environmental conditions along a 90 km ultra-marathon event, South AfricaNARA Subscribed
This paper provides an overview of the HEAT (Healthy Environments for AthleTes) project, which aims to understand the impact of environmental conditions on athlete health and performance during major sporting events such as long-distance running, cycling, and triathlons. In collaboration with the SAFER (Strategies to reduce Adverse medical events For the ExerciseR) initiative, the HEAT project carried out a field campaign at t...
Initial characterization of a transgenic mouse with overexpression of the human D1-dopamine receptor in the heartNARA Subscribed
Dopamine can exert effects in the mammalian heart via five different dopamine receptors. There is controversy whether dopamine receptors increase contractility in the human heart. Therefore, we have generated mice that overexpress the human D 1 -dopamine receptor in the heart (D 1 -TG) and hypothesized that dopamine increases force of contraction and beating rate compared to wild-type mice (WT). In D 1 -TG hearts, we ascertain...
Persistent net release of carbon dioxide and methane from an Alaskan lowland boreal peatland complexNARA Subscribed
Permafrost degradation in peatlands is altering vegetation and soil properties and impacting net carbon storage. We studied four adjacent sites in Alaska with varied permafrost regimes, including a black spruce forest on a peat plateau with permafrost, two collapse scar bogs of different ages formed following thermokarst, and a rich fen without permafrost. Measurements included year‐round eddy covariance estimates of net carbo...