Klitlauridsen9827

BACKGROUND & AIMS G protein-coupled receptor 55 (GPR55) is a putative cannabinoid receptor, and l-α-lysophosphatidylinositol (LPI) is its only known endogenous ligand. Although GPR55 has been linked to energy homeostasis in different organs, its specific role in lipid metabolism in the liver and its contribution to the pathophysiology of non-alcoholic fatty liver disease (NAFLD) remains unknown. APPROACH & RESULTS We measured 1) GPR55 expression in the liver of patients with NAFLD, compared with non-obese individuals without liver disease, as well as animal models with steatosis and non-alcoholic steatohepatitis (NASH); and 2) the effects of LPI and genetic disruption of GPR55 in mice, human hepatocytes and human hepatic stellate cells. Notably, we found that circulating LPI and liver expression of GPR55 were upregulated in patients with NASH. LPI induced- AMP-activated protein kinase (AMPK) activation of acetyl-CoA carboxylase (ACC) and increased lipid content in human hepatocytes and in the liver of treated mice by inducing de novo lipogenesis and decreasing beta oxidation. The inhibition of GPR55 and ACCα blocked the effects of LPI, and the in vivo knockdown of GPR55 was sufficient to improve liver damage in mice fed a high fat diet and mice fed a methionine-choline-deficient diet. Finally, LPI promoted the initiation of hepatic stellate cells activation by stimulating GPR55 and activation of ACC. CONCLUSIONS The LPI/GPR55 system plays a role in the development of of NAFLD and NASH by activating ACC. This article is protected by copyright. All rights reserved.Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy (1). Acute FPIES is typical and characterized by repetitive and often incoercible emesis starting 1-4 h after ingestion of the culprit food (1). Severe forms may result in dehydration or hypovolemic shock (1). In the absence of biomarkers, the diagnosis of FPIES is based on clinical presentation (1). Symptoms improve after exclusion of the culprit foods and acute FPIES occurs at re-exposure. FPIES generally resolves during the first years of life and an oral food challenge (OFC) is performed to assess tolerance, generally 12-18 months after the last reaction (1). find more This article is protected by copyright. All rights reserved.Recruitment is a primary determinant of the long-term dynamics of plant populations in changing environments. However, little information is known about the effects of anthropogenic environmental changes on reproductive ecology of trees. We evaluated the impact of experimentally induced 18 yr of drought on reproduction of three contrasting forest trees Quercus ilex, Phillyrea latifolia and Arbutus unedo. Rainfall reduction did not decrease tree fecundity. Drought, however, affected the allocation of resources in Q. ilex and A. unedo but not the more drought tolerant P. latifolia. Larger crop production by Q. ilex and A. unedo was associated with a stronger decrease in growth in the rainfall-reduction plots compared with the control plots, suggesting that these species were able to maintain their fecundity by shifting their allocation of resources away from growth. Our results indicated resistance to change in tree fecundity in Mediterranean-type forest subjected to an average 15% decrease in the amount of soil moisture, suggesting that these ecosystems may adapt to a progressive increase in arid conditions. However, the species-specific reductions in growth may indirectly affect future fecundity and ultimately shift community composition, even without immediate direct effects of drought on tree fecundity. © 2020 The Authors. New Phytologist © 2020 New Phytologist Trust.INTRODUCTION MRI has been increasingly used in radiation therapy to facilitate tumor and organ delineation and assess treatment response. Diffusion MRI can provide cellularity information and may enable functional-based treatment planning and adaptation. However, strong distortion associated with the conventional diffusion-weighted single-shot echo-planar imaging (DW-ssEPI) sequence is problematic for accurate target delineation. The goal of this work is to propose a 3D diffusion sequence with minimal distortion for radiation therapy applications. METHODS A 3D diffusion-prepared magnitude-stabilized balanced steady-state free precession sequence (DP-MS-bSSFP) was developed. A 2D navigator was acquired during the linear catalyzation stage of the bSSFP readout to estimate the phase, which was then used in a plane-by-plane low-rank constrained reconstruction to correct the shot-to-shot k-space inconsistency. A diffusion phantom was scanned to evaluate and compare the geometric reliability and ADC accuracy with tn the phantom. The mean TRE decreased from 2.09 mm to 0.70 mm. The percentage difference of the ADC values between the two diffusion sequences were less than 5.5% and 7% for the 0 °C and room temperature study, respectively. The DW-ssEPI had strong distortion and susceptibility-related artifacts at tissue air boundary, whereas distortion was minimal in DP-MS images. Overall, the mean/max TRE was over 2 mm/7 mm in the volunteers for DW-ssEPI, whereas less than 0.8 mm/2 mm for DP-MS. Good ADC agreement was observed for the white matter, the cerebellum, and the CSF based on the Bland-Altman plots. CONCLUSION A 3D diffusion sequence was developed and validated. It provided high-resolution diffusion imaging with mean distortion less than 1 mm at 1.5T, and is a promising imaging technique for treatment planning and adaptive radiotherapy. This article is protected by copyright. All rights reserved.BACKGROUND Numerous non-meat ingredients such as hydrocolloids, starches, and fibers have been studied to improve texture characteristics and increase the ability to bind water in low-fat meat products. In this sense, pulses flours (lentil, chickpea, pea, and bean) were studied at two levels and various water/flour ratios to replace 10-44 % pork meat in low-fat burgers and determine the effect on their sensory and technological properties (cooking yield, expressible liquid, diameter reduction, and color and texture profile). RESULTS All pork-meat burgers that included pulse flour showed higher cooking yields, lower diameter reductions, and expressible liquids than all-meat burgers which displayed better oil and water retention. Higher water additions resulted in burgers with less hardness. Burgers with 80 g kg -1 lentil flour in all water/flour ratios presented the lowest total color difference (ΔE) compared to the commercial control. Burgers with the higher level of all pulse flour tested and medium water levels showed acceptable sensory scores.