Molecular docking of danuglipron uncovers potential crossovers between GLP-1R and the endocannabinoid system.

The targeting of the G-protein coupled receptor (GPCRs) glucagon-like-peptide-1-receptor (GLP-1R) by weight loss medications has become extremely prevalent due to the effectiveness of a class of GLP-1R agonists. Also, interest in cannabinoids, such as delta-9-tetrahydrocannabinol (THC), has risen independently of GLP's newfound fame due to the relaxation of legal hurdles across the nation to recreational cannabis usage. THC interacts with receptors in the endocannabinoid system, with the major ones being cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), both GPCRs.

Detection of driver mutations and genomic signatures in endometrial cancers using artificial intelligence algorithms.

Analyzed endometrial cancer (EC) genomes have allowed for the identification of molecular signatures, which enable the classification, and sometimes prognostication, of these cancers. Artificial intelligence algorithms have facilitated the partitioning of mutations into driver and passenger based on a variety of parameters, including gene function and frequency of mutation. Here, we undertook an evaluation of EC cancer genomes deposited on the Catalogue of Somatic Mutations in Cancers (COSMIC), with the goal to classify all mutations as either driver or passenger.

Protein Arginine Methyltransferase 5 (PRMT5) Mutations in Cancer Cells.

Arginine methylation is a form of posttranslational modification that regulates many cellular functions such as development, DNA damage repair, inflammatory response, splicing, and signal transduction, among others. Protein arginine methyltransferase 5 (PRMT5) is one of nine identified methyltransferases, and it can methylate both histone and non-histone targets. It has pleiotropic functions, including recruitment of repair machinery to a chromosomal DNA double strand break (DSB) and coordinating the interplay between repair and checkpoint activation.

Study of -Quinone Methide Precursors toward the Realkylation of Aged Acetylcholinesterase.

Acetylcholinesterase (AChE) is an essential enzyme that can be targeted by organophosphorus (OP) compounds, including nerve agents. Following exposure to OPs, AChE becomes phosphylated (inhibited) and undergoes a subsequent aging process where the OP-AChE adduct is dealkylated. The aged AChE is unable to hydrolyze acetylcholine, resulting in accumulation of the neurotransmitter in the central nervous system (CNS) and elsewhere.

Efforts toward treatments against aging of organophosphorus-inhibited acetylcholinesterase.

Aging is a dealkylation reaction of organophosphorus (OP)-inhibited acetylcholinesterase (AChE). Despite many studies to date, aged AChE cannot be reactivated directly by traditional pyridinium oximes. This review summarizes strategies that are potentially valuable in the treatment against aging in OP poisoning.

The prospect of selective recognition of nerve agents with modular basket-like hosts. A structure-activity study of the entrapment of a series of organophosphonates in aqueous media.

We designed, prepared, and characterized three cup-shaped cavitands 1-3 for trapping organophosphonates (O═PR(OR')2, 118-197 Å(3)) whose shape and size correspond to G-type chemical warfare agents (132-186 Å(3)). With the assistance of computational (molecular dynamics) and experimental ((1)H NMR spectroscopy) methods, we found that host [1-H3](3+) orients its protonated histamine residues at the rim outside the cavity, in bulk water. In this unfolded form, the cavitand traps a series of organophosphonates 5-13 (K(app) = 87 ± 1 to 321 ± 6 M(-1) at 298.

Method for the preparation of derivatives of heptiptycene: toward dual-cavity baskets.

We have developed a novel synthetic method that enables the preparation of functional derivatives of heptiptycene, i.e., cavitands with two juxtaposed cavities.

Phylogenomic evidence for a common ancestor of mitochondria and the SAR11 clade.

Mitochondria share a common ancestor with the Alphaproteobacteria, but determining their precise origins is challenging due to inherent difficulties in phylogenetically reconstructing ancient evolutionary events. Nonetheless, phylogenetic accuracy improves with more refined tools and expanded taxon sampling. We investigated mitochondrial origins with the benefit of new, deeply branching genome sequences from the ancient and prolific SAR11 clade of Alphaproteobacteria and publicly available alphaproteobacterial and mitochondrial genome sequences.

Hal: an automated pipeline for phylogenetic analyses of genomic data.

The rapid increase in genomic and genome-scale data is resulting in unprecedented levels of discrete sequence data available for phylogenetic analyses. Major analytical impasses exist, however, prior to analyzing these data with existing phylogenetic software. Obstacles include the management of large data sets without standardized naming conventions, identification and filtering of orthologous clusters of proteins or genes, and the assembly of alignments of orthologous sequence data into individual and concatenated super alignments.

Self-efficacy and resource allocation: support for a nonmonotonic, discontinuous model.

Self-regulation theories are paving the way to integrating motivational theories of behavior. However, a review of the motivation literature reveals several possible relationships between self-efficacy and motivation. Past findings were reduced to 4 empirical models, which were compared within a single study using undergraduates playing a computer task.