Pharmacokinetics of Sodium and Calcium Salts of (6S)-5-Methyltetrahydrofolic Acid Compared to Folic Acid and Indirect Comparison of the Two Salts

(6S)-5-Methyltetrahydrofolic acid ((6S)-5-Methyl-THF) salts and folic acid may differ in their abilities to raise plasma (6S)-5-Methyl-THF levels. We compared the area under the curve (AUC), Cmax, and Tmax of plasma (6S)-5-Methyl-THF after intakes of (6S)-5-Methyl-THF-Na salt (Arcofolin®) and folic acid. Moreover, we compared the AUCs after intakes of (6S)-5-Methyl-THF-Na and the calcium salt, (6S)-5-Methyl-THF-Ca, that were tested against folic acid in two independent studies. The study was randomized, double blind, and cross over. Twenty-four adults (12 men and 12 women) received a single oral dose of 436 µg (6S)-5-Methyl-THF-Na and an equimolar dose of folic acid (400 µg) on two kinetic days with two weeks washout period in between. The plasma concentrations of (6S)-5-Methyl-THF were measured at 9 time points between 0 and 8 h. We found that the AUC0–8 h of plasma (6S)-5-Methyl-THF (mean (SD) = 126.0 (33.6) vs. 56.0 (25.3) nmol/L*h) and Cmax (36.8 (10.8) vs. 11.1 (4.1) nmol/L) were higher after administration of (6S)-5-Methyl-THF-Na than after the administration of folic acid (p < 0.001 for both). These differences were present in men and women. Only administration of folic acid resulted in a transient increase in plasma unmetabolized folic acid (2.5 (2.0) nmol/L after 0.5 h and 4.7 (2.9) nmol/L after 1 h). Intake of (6S)-5-Methyl-THF-Na was safe. The ratios of the AUC0–8 h for (6S)-5-Methyl-THF-Na and (6S)-5-Methyl-THF-Ca to the corresponding folic acid reference group and the delta of these AUC0–8 h did not differ between the studies. In conclusion, a single oral dose of (6S)-5-Methyl-THF-Na caused higher AUC0–8 h and Cmax of plasma (6S)-5-Methyl-THF compared to folic acid. The Na- and Ca- salts of (6S)-5-Methyl-THF are not likely to differ in their pharmacokinetics. Further studies may investigate whether supplementation of the compounds for a longer time will lead to differences in circulating or intracellular/tissue folate concentrations

Health Benefit Characterization of Dominant Lactobacilli in Traditional Doogh

The aim of our study was the characterization and evaluation of isolated lactic acid bacteria(LAB

Development of a high sensitivity label free waveguide interferometry instrument : a project of Creoptix GmbH with the center for Biochemistry ZHAW as main research partner

Creoptix GmbH has developed a novel and innovative technology for label-free detection of molecules based on grating-coupled interferometry (GCI). GCI is a proprietary technology characterized by a very high sensitivity at low technical complexity. One main application will be the measurement of binding affinities in research and development projects such as drug discovery. Goal of an interdisciplinary CTI project with the partners from ZHAW, FHNW and CSEM together with Creoptix is the development of a first GCI instrument including disposables and the optimization of its functionality, followed by field tests to pave the way to market introduction

Adhesion Class GPCRs (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Adhesion GPCRs are structurally identified on the basis of a large extracellular region, similar to the Class B GPCR, but which is linked to the 7TM region by a GPCR autoproteolysis-inducing (GAIN) domain [8] containing a GPCR proteolytic site. The N-terminus often shares structural homology with adhesive domains (e.g. cadherins, immunolobulin, lectins) facilitating inter- and matricellular interactions and leading to the term adhesion GPCR [82, 332]. Several receptors have been suggested to function as mechanosensors [254, 234, 315, 32]. The nomenclature of these receptors was revised in 2015 as recommended by NC-IUPHAR and the Adhesion GPCR Consortium [100]

Adhesion Class GPCRs in GtoPdb v.2023.1

Adhesion GPCRs are structurally identified on the basis of a large extracellular region, similar to the Class B GPCR, but which is linked to the 7TM region by a GPCR autoproteolysis-inducing (GAIN) domain [10] containing a GPCR proteolysis site (GPS). The N-terminal extracellular region often shares structural homology with adhesive domains (e.g. cadherins, immunolobulin, lectins) facilitating inter- and matricellular interactions and leading to the term adhesion GPCR [104, 418]. Several receptors have been suggested to function as mechanosensors [320, 288, 396, 38]. Cryo-EM structures of the 7-transmembrane domain of several adhesion GPCRs have been determined recently [292, 21, 403, 212, 300, 302, 431, 293]. The nomenclature of these receptors was revised in 2015 as recommended by NC-IUPHAR and the Adhesion GPCR Consortium [125]

Adhesion Class GPCRs in GtoPdb v.2021.3

Adhesion GPCRs are structurally identified on the basis of a large extracellular region, similar to the Class B GPCR, but which is linked to the 7TM region by a GPCR autoproteolysis-inducing (GAIN) domain [9] containing a GPCR proteolytic site. The N-terminus often shares structural homology with adhesive domains (e.g. cadherins, immunolobulin, lectins) facilitating inter- and matricellular interactions and leading to the term adhesion GPCR [101, 403]. Several receptors have been suggested to function as mechanosensors [309, 280, 383, 35]. The nomenclature of these receptors was revised in 2015 as recommended by NC-IUPHAR and the Adhesion GPCR Consortium [122]

A multidecadal simulation of Atlantic tropical cyclones using a variable‐resolution global atmospheric general circulation model

Using a variable‐resolution option within the National Center for Atmospheric Research/Department of Energy Community Atmosphere Model (CAM) Spectral Element (SE) global model, a refined nest at 0.25° (∼28 km) horizontal resolution located over the North Atlantic is embedded within a global 1° (∼111 km) grid. The grid is designed such that fine grid cells are located where tropical cyclones (TCs) are observed to occur during the Atlantic TC season (June–November). Two simulations are compared, one with refinement and one control case with no refinement (globally uniform 1° grid). Both simulations are integrated for 23 years using Atmospheric Model Intercomparison Protocols. TCs are tracked using an objective detection algorithm. The variable‐resolution simulation produces significantly more TCs than the unrefined simulation. Storms that do form in the refined nest are much more intense, with multiple storms strengthening to Saffir‐Simpson category 3 intensity or higher. Both count and spatial distribution of TC genesis and tracks in the variable‐resolution simulation are well matched to observations and represent significant improvements over the unrefined simulation. Some degree of interannual skill is noted, with the variable‐resolution grid able to reproduce the observed connection between Atlantic TCs and the El Niño‐Southern Oscillation (ENSO). It is shown that Genesis Potential Index (GPI) is well matched between the refined and unrefined simulations, implying that the introduction of variable‐resolution does not affect the synoptic environment. Potential “upscale” effects are noted in the variable‐resolution simulation, suggesting stronger TCs in refined nests may play a role in meridional transport of momentum, heat, and moisture. Key Points Variable‐resolution models can improve the representation of tropical cyclones CAM produces realistic Atlantic TC climatology at 0.25° resolution Addition of local refinement in CAM does not impact synoptic scalesPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109331/1/jame20104.pd

Objective tropical cyclone extratropical transition detection in high‐resolution reanalysis and climate model data

This paper describes an objective technique for detecting the extratropical transition (ET) of tropical cyclones (TCs) in high‐resolution gridded climate data. The algorithm is based on previous observational studies using phase spaces to define the symmetry and vertical thermal structure of cyclones. Storm tracking is automated, allowing for direct analysis of climate data. Tracker performance in the North Atlantic is assessed using 23 years of data from the variable‐resolution Community Atmosphere Model (CAM) at two different resolutions (ΔX∼55 km and 28 km), the Climate Forecast System Reanalysis (CFSR, ΔX∼38 km), and the ERA‐Interim Reanalysis (ERA‐I, ΔX∼80 km). The mean spatiotemporal climatologies and seasonal cycles of objectively detected ET in the observationally constrained CFSR and ERA‐I are well matched to previous observational studies, demonstrating the capability of the scheme to adequately find events. High‐resolution CAM reproduces TC and ET statistics that are in general agreement with reanalyses. One notable model bias, however, is significantly longer time between ET onset and ET completion in CAM, particularly for TCs that lose symmetry prior to developing a cold‐core structure and becoming extratropical cyclones, demonstrating the capability of this method to expose model biases in simulated cyclones beyond the tropical phase.Key PointsAn objective detection technique for tracking tropical cyclone extratropical transition in gridded climate data is describedObjectively calculated extratropical transition climatology in high‐resolution reanalyses closely match observational studiesTropical cyclones in CAM take too long to undergo extratropical transition highlighting model biases requiring further investigationPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136754/1/jame20355_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136754/2/jame20355.pd

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder