Journal: bioRxiv

Article Title: A revised mechanism of action of hyperaldosteronism-linked mutations in cytosolic domains of GIRK4 (KCNJ5)

doi: 10.1101/866202

Figure Lengend Snippet: Oocytes expressed GIRK4 mutants and GIRK4 WT , with or without Gβγ. Cells were exposed to 4 concentrations of VU0529331 (1, 5, 20, and 60 μM). Only GIRK4 WT and GIRK4 G247R mutant responded to VU0529331. (A) I basal of GIRK4 WT and GIRK4 G247R . GIRK4 WT and GIRK4 G247R react similarly to VU0529331. (B) I βγ of GIRK4 WT and GIRK4 G247R . GIRK4 WT had larger current at 0 μM VU0529931, while GIRK4 G247R did not show any response to concentrations lower than 20 μM VU0529331. (C) Normalized I basal (I/I control ). GIRK4 WT and GIRK4 G247R were activated similarly by VU0529331. (D) I/I control of I βγ show that GIRK4 G247R was activated by VU0529331 stronger than GIRK4 WT , in relative terms. (E) I-V relationship of GIRK4 WT (top) and GIRK4 G247R (bottom) without Gβγ. (F) I-V relationship of GIRK4 WT (top) and GIRK4 G247R (bottom) with Gβγ.

Article Snippet: VU0529331 (Alomone Labs; V-155), an opener of homotetrameric GIRK2 and GIRK4 channels, was dissolved in 100% DMSO to a final concentration of 25 mM.

Techniques: Mutagenesis

Journal: Molecular Metabolism

Article Title: Whole-brain activation signatures of weight-lowering drugs

doi: 10.1016/j.molmet.2021.101171

Figure Lengend Snippet: 3D mapping and quantification of whole-brain c-Fos responses to acute treatment with various weight-loss promoting compounds . Quantification and statistical analysis of c-Fos expression was performed in 308 brain regions. (A) Lorcaserin (7 mg/kg, i.p.), (B) rimonabant (10 mg/kg, i.p.), (C) bromocriptine (10 mg/kg, i.p.), (D) sibutramine (10 mg/kg, p.o.), (E) semaglutide (0.04 mg/kg, s.c.) and (F) setmelanotide (4 mg/kg, s.c.). All samples were registered into an LSFM-based mouse brain atlas. Heatmaps (dorsal view) depict vehicle-subtracted average whole-brain c-Fos expression (n = 7-8 mice per group) responses to the individual drug. Brain areas with statistically significant changes in c-Fos expression (p < 0.05; Dunnett's test negative binomial generalised linear model, FDR < 0.05 for p-value adjustment) are delineated in red (upregulation) or blue (downregulation) compared to corresponding vehicle controls. Coronal slice-by-slice fly-through of the heatmaps can be found in the G3DE imaging viewer. Bar plots show the differences in total numbers of c-Fos+ cells detected in compound and corresponding vehicle-dosed mice (∗p <0.05, ∗∗∗p < 0.001; Dunnett's test negative binomial generalised linear model). (G) Principal component analysis (PCA) of whole-brain c-Fos expression. The PCA plot illustrates the degree of separation between individual drug effects on global c-Fos expression patterns (large markers indicate group average). (H) PCA loading plot depicting the coefficients of the top 15 most influential brain regions driving the clustering of data points in PCA plot. Abbreviations : Vehicle IP1, 0.1% Tween-80 in saline (intraperitoneal); Vehicle IP2, 5% DMSO + 5% chremophor in saline (intraperitoneal); Vehicle PO, 0.5% hydroxypropyl methylcellulose (peroral); Vehicle SC, 0.1% bovine serum albumin in phosphate-buffered saline (PBS, subcutaneous); PARN , parvicellular reticular nucleus; MDRNd , dorsal medullary reticular nucleus; MY-mot , motor-related part of medulla; PB , parabrachial nucleus; NTS , nucleus of the solitary tract; IRN , intermediate reticular nucleus; IMD , intermediodorsal nucleus of the thalamus, LP , lateral posterior nucleus of the thalamus; DG , dentate gyrus; LGv , ventral part of the lateral geniculate complex; APN , anterior pretectal nucleus; PPT , posterior pretectal nucleus; HIP , hippocampal region; SCm , motor-related superior colliculus; CA3 , field CA3 of the Ammon's horn.

Article Snippet: Compounds included lorcaserin hydrochloride hemihydrate (Adooq Bioscience, Irvine, CA); rimonabant hydrochloride (Chemos GmbH, Regenstauf, Germany); bromocriptine mesylate (Toronto Research Chemicals, Toronto, ON, Canada); sibutramine (AH Diagnostics, Aarhus, Denmark); semaglutide (Hoersholm Pharmacy, Hoersholm, Denmark) and setmelanotide hydrochloride (MetChemExpress, Monmouth Junction, NJ).

Techniques: Expressing, Imaging, Saline