3-Thio-3,4,5-trisubstituted-1,2,4-triazoles: high affinity somatostatin receptor-4 agonist synthesis and structure-activity relationships.

Somatostatin receptor-4 (SST) is a therapeutic target for several conditions, including Alzheimer's disease, seizures, neuropsychiatric disorders, and pain. Our previous work on 1,2,4-triazole derivatives led to enhanced SST binding affinity, selectivity, and functional activity. Herein we report the discovery of 3-thio-1,2,4-triazole series as selective and high affinity SST agonists.

Late Pleistocene onset of mutualistic human/canid ( spp.) relationships in subarctic Alaska.

Large canids (wolves, dogs, and coyote) and people form a close relationship in northern (subarctic and arctic) socioecological systems. Here, we document the antiquity of this bond and the multiple ways it manifested in interior Alaska, a region key to understanding the peopling of the Americas and early northern lifeways. We compile original and existing genomic, isotopic, and osteological canid data from archaeological, paleontological, and modern sites.

The role of the dopamine D1 receptor in anticipatory pleasure and social play.

Social play is a highly rewarding activity seen across mammalian species that is vital for neurobehavioural development. Dysfunctions in social play are seen across psychiatric and neurodevelopmental disorders positing the importance of understanding the neurobiological mechanisms underlying social play. A multitude of neurotransmitter systems have been implicated in social play, with the present study focused on the role of dopamine, specifically the dopamine D1 receptor.