A
bstract
We embed Nelson’s theory of stochastic quantization in the Schwartz-Meyer second order geometry framework. The result is a non-perturbative theory of quantum mechanics on ...(pseudo-)Riemannian manifolds. Within this approach, we derive stochastic differential equations for massive spin-0 test particles charged under scalar potentials, vector potentials and gravity. Furthermore, we derive the associated Schrödinger equation. The resulting equations show that massive scalar particles must be conformally coupled to gravity in a theory of quantum gravity. We conclude with a discussion of some prospects of the stochastic framework.
We calculate quantum gravitational corrections to the entropy of black holes using the Wald entropy formula within an effective field theory approach to quantum gravity. The corrections to the ...entropy are calculated to second order in curvature and we calculate a subset of those at third order. We show that, at third order in curvature, interesting issues appear that had not been considered previously in the literature. The fact that the Schwarzschild metric receives corrections at this order in the curvature expansion has important implications for the entropy calculation. Indeed, the horizon radius and the temperature receive corrections. These corrections need to be carefully considered when calculating the Wald entropy.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
In this letter, we show that quantum gravity leads to lower and upper bounds on the masses of dark matter candidates. These bounds depend on the spins of the dark matter candidates and the nature of ...interactions in the dark matter sector. For example, for singlet scalar dark matter, we find a mass range 10−3 eV≲mϕ≲107 eV. The lower bound comes from limits on fifth force type interactions and the upper bound from the lifetime of the dark matter candidate.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In this paper we consider very weakly interacting and ultra light scalar and pseudoscalar dark matter candidates. We show that quantum gravity has important implications for such models and that the ...masses of the singlet scalar and pseudoscalar fields must be heavier than
3
×
10
-
3
eV. However, if they are gauged, their masses could be much lighter and as light as
10
-
22
eV
. The existence of new gauge forces in the dark matter sector can thus be probed by atomic clocks or quantum sensors experiments.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bile acids and their signaling pathways are increasingly recognized as potential therapeutic targets for cholestatic and metabolic liver diseases. This review summarizes new insights in bile acid ...physiology, focusing on regulatory roles of bile acids in the control of immune regulation and on effects of pharmacological modulators of bile acid signaling pathways in human liver disease. Recent mouse studies have highlighted the importance of the interactions between bile acids and gut microbiome. Interfering with microbiome composition may be beneficial for cholestatic and metabolic liver diseases by modulating formation of secondary bile acids, as different bile acid species have different signaling functions. Bile acid receptors such as FXR, VDR, and TGR5 are expressed in a variety of cells involved in innate as well as adaptive immunity, and specific microbial bile acid metabolites positively modulate immune responses of the host. Identification of Cyp2c70 as the enzyme responsible for the generation of hydrophilic mouse/rat-specific muricholic acids has allowed the generation of murine models with a human-like bile acid composition. These novel mouse models will aid to accelerate translational research on the (patho)physiological roles of bile acids in human liver diseases .
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Institut Pasteur de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 545, and Université de Lille 2, Faculté des Sciences Pharmaceutiques et Biologiques et Faculté de ...Médecine, Lille; INSERM, U 915, Université de Nantes, Faculté de Médecine, and Clinique d'Endocrinologie, Institut du Thorax, Nantes, France; and Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Medical Center Groningen, Groningen, The Netherlands
The incidence of the metabolic syndrome has taken epidemic proportions in the past decades, contributing to an increased risk of cardiovascular disease and diabetes. The metabolic syndrome can be defined as a cluster of cardiovascular disease risk factors including visceral obesity, insulin resistance, dyslipidemia, increased blood pressure, and hypercoagulability. The farnesoid X receptor (FXR) belongs to the superfamily of ligand-activated nuclear receptor transcription factors. FXR is activated by bile acids, and FXR -deficient ( FXR –/– ) mice display elevated serum levels of triglycerides and high-density lipoprotein cholesterol, demonstrating a critical role of FXR in lipid metabolism. In an opposite manner, activation of FXR by bile acids (BAs) or nonsteroidal synthetic FXR agonists lowers plasma triglycerides by a mechanism that may involve the repression of hepatic SREBP-1c expression and/or the modulation of glucose-induced lipogenic genes. A cross-talk between BA and glucose metabolism was recently identified, implicating both FXR-dependent and FXR-independent pathways. The first indication for a potential role of FXR in diabetes came from the observation that hepatic FXR expression is reduced in animal models of diabetes. While FXR –/– mice display both impaired glucose tolerance and decreased insulin sensitivity, activation of FXR improves hyperglycemia and dyslipidemia in vivo in diabetic mice. Finally, a recent report also indicates that BA may regulate energy expenditure in a FXR-independent manner in mice, via activation of the G protein-coupled receptor TGR5. Taken together, these findings suggest that modulation of FXR activity and BA metabolism may open new attractive pharmacological approaches for the treatment of the metabolic syndrome and type 2 diabetes.
Dysbiosis has been implemented in the etiologies of obesity-related chronic diseases such as type 2 diabetes, NAFLD and cardiovascular diseases. Bile acids, a class of amphipathic steroids produced ...in the liver and extensively modified by the microbiome, are increasingly recognized as actors in onset and progression of these diseases. Indeed, human obesity is associated with altered bile acid metabolism. Bile acids facilitate intestinal fat absorption but also exert hormone-like functions through activation of nuclear and membrane-bound receptors and thereby modulate glucose, lipid and energy metabolism, intestinal integrity and immunity. Bile acid-signaling pathways have thus been identified as potential pharmacological targets for obesity-related diseases. Interfering with microbiome composition may also be considered, as liver- and microbiome-derived bile acid species have different signaling functions. This review summarizes recent developments in this rapidly expanding field of research and addresses potential clinical prospects of interference with bile acid signaling pathways in human diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
The gut microbiome is an ecosystem that involves complex interactions. Currently, our knowledge about the role of the gut microbiome in health and disease relies mainly on differential ...microbial abundance, and little is known about the role of microbial interactions in the context of human disease. Here, we construct and compare microbial co-abundance networks using 2,379 metagenomes from four human cohorts: an inflammatory bowel disease (IBD) cohort, an obese cohort and two population-based cohorts. We find that the strengths of 38.6% of species co-abundances and 64.3% of pathway co-abundances vary significantly between cohorts, with 113 species and 1,050 pathway co-abundances showing IBD-specific effects and 281 pathway co-abundances showing obesity-specific effects. We can also replicate these IBD microbial co-abundances in longitudinal data from the IBD cohort of the integrative human microbiome (iHMP-IBD) project. Our study identifies several key species and pathways in IBD and obesity and provides evidence that altered microbial abundances in disease can influence their co-abundance relationship, which expands our current knowledge regarding microbial dysbiosis in disease.
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