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Although the nonselective β‐blocker, propranolol, improves bone density with parathyroid hormone (PTH) treatment in mice, the mechanism of this effect is unclear. To address this, we used a combination of in vitro and in vivo approaches to address how propranolol influences bone remodeling in the context of PTH treatment. In female C57BL/6J mice, intermittent PTH and propranolol administration had complementary effects in the trabecular bone of the distal femur and fifth lumbar vertebra (L5), with combination treatment achieving microarchitectural parameters beyond that of PTH alone. Combined treatment improved the serum bone formation marker, procollagen type 1 N propeptide (P1NP), but did not impact other histomorphometric parameters relating to osteoblast function at the L5. In vitro, propranolol amplified the acute, PTH‐induced, intracellular calcium signal in osteoblast‐like cells. The most striking finding, however, was suppression of PTH‐induced bone resorption. Despite this, PTH‐induced receptor activator of nuclear factor κ‐B ligand (RANKL) mRNA and protein levels were unaltered by propranolol, which led us to hypothesize that propranolol could act directly on osteoclasts. Using in situ methods, we found Adrb2 expression in osteoclasts in vivo, suggesting β‐blockers may directly impact osteoclasts. Consistent with this, we found propranolol directly suppresses osteoclast differentiation in vitro. Taken together, this work suggests a strong anti‐osteoclastic effect of nonselective β‐blockers in vivo, indicating that combining propranolol with PTH could be beneficial to patients with extremely low bone density. © 2022 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Sensation seeking is a multifaceted, heritable trait which predicts the development of substance use and abuse in humans; similar phenomena have been observed in rodents. Genetic correlations among sensation seeking and substance use indicate shared biological mechanisms, but the genes and networks underlying these relationships remain elusive. Here, we used a systems genetics approach in the BXD recombinant inbred mouse panel to identify shared genetic mechanisms underlying substance use and preference for sensory stimuli, an intermediate phenotype of sensation seeking. Using the operant sensation seeking (OSS) paradigm, we quantified preference for sensory stimuli in 120 male and 127 female mice from 62 BXD strains and the C57BL/6J and DBA/2J founder strains. We used relative preference for the active and inactive levers to dissociate preference for sensory stimuli from locomotion and exploration phenotypes. We identified genomic regions on chromosome 4 (155.236‐155.742 Mb) and chromosome 13 (72.969‐89.423 Mb) associated with distinct behavioral components of OSS. Using publicly available behavioral data and mRNA expression data from brain regions involved in reward processing, we identified (a) genes within these behavioral QTL exhibiting genome‐wide significant cis‐eQTL and (b) genetic correlations among OSS phenotypes, ethanol phenotypes and mRNA expression. From these analyses, we nominated positional candidates for behavioral QTL associated with distinct OSS phenotypes including Gnb1 and Mef2c. Genetic covariation of Gnb1 expression, preference for sensory stimuli and multiple ethanol phenotypes suggest that heritable variation in Gnb1 expression in reward circuitry partially underlies the widely reported relationship between sensation seeking and substance use. We used a systems genetics approach in the BXD recombinant inbred mouse panel to identify shared genetic mechanisms underlying substance use and preference for sensory stimuli, an intermediate phenotype of sensation seeking. Using the operant sensation seeking (OSS) paradigm, we quantified preference for sensory stimuli in mice from 62 BXD strains and the C57BL/6J and DBA/2J founder strains. We identified QTL associated with distinct behavioral components of OSS and used a systems genetics approach to prioritize positional candidates for these QTL including Gnb1 and Mef2c. Genetic covariation of Gnb1 expression, preference for sensory stimuli and multiple ethanol phenotypes suggest that heritable variation in Gnb1 expression in reward circuitry may underlie the widely reported relationship between sensation seeking and substance use. [ABSTRACT FROM AUTHOR]

2,4-dichlorophenoxy acetic acid (2,4-D) and 1,1-dimethyl-4,4-bipiridinium chloride (paraquat) are among the most widely used herbicides and are known to be toxic. Fabrication of green adsorbents which are capable of removing both herbicides remains a challenge. Here, we fabricate a novel adsorbent from tropical waste wood and use a facile, chitosan-mediated N-heteroatom functionalization technique to augment surface nitrogen and improve specific surface area. The addition of 20 wt% chitosan to the waste wood feedstock prior to activation, increased specific surface area by 300 m 2 /g (∼25%) and nitrogen content by 7-fold. This functionalized material removed 69% of 2,4-D and 82% of paraquat at initial concentrations of 4 ppm and 40 ppm from model solutions at pH 7. It also removed 39% 2,4-D and 93% paraquat from binary mixtures demonstrating its versatility. 2,4-D adsorption increased with chitosan addition suggesting synergistic effects between protonated amine functions and the anionic herbicide form. Paraquat adsorption was negatively correlated with chitosan addition, implying antagonistic interaction between protonated amine functions and quaternary nitrogen atoms on herbicide molecules. Adsorption of both herbicides was spontaneous, entropically favored and exothermic with ΔG °: 19.2 kJ/mol and -28.8 kJ/mol; ΔS °: 7.42 and 28.6 J/Kmol and ΔH °: 17.0 kJ/mol and -20.1 kJ/mol for 2,4-D and paraquat respectively. Chitosan addition therefore provides a facile and green alternative for N-heteroatom functionalization, and these nitrogen-doped materials are promising candidates for the removal of multiple herbicides from aqueous systems., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Hamant E. France reports financial support was provided by Sustainable Guyana Program a partnership between Trent University and the University of Guyana funded by CGX Energy Inc. and Frontera Energy Corporation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)