Structural basis of ligand recognition and self-activation of orphan GPR52.

GPR52 is a class-A orphan G-protein-coupled receptor that is highly expressed in the brain and represents a promising therapeutic target for the treatment of Huntington's disease and several psychiatric disorders1,2. Pathological malfunction of GPR52 signalling occurs primarily through the heterotrimeric Gs protein2, but it is unclear how GPR52 and Gs couple for signal transduction and whether a native ligand or other activating input is required. Here we present the high-resolution structures of human GPR52 in three states: a ligand-free state, a Gs-coupled self-activation state and a potential allosteric ligand-bound state. Together, our structures reveal that extracellular loop 2 occupies the orthosteric binding pocket and operates as a built-in agonist, conferring an intrinsically high level of basal activity to GPR523. A fully active state is achieved when Gs is coupled to GPR52 in the absence of an external agonist. The receptor also features a side pocket for ligand binding. These insights into the structure and function of GPR52 could improve our understanding of other self-activated GPCRs, enable the identification of endogenous and tool ligands, and guide drug discovery efforts that target GPR52.

Analysis of temporal and spatial dynamics and driving factors in the aquaculture industry of Fuding City, China.

Background: The sustainable development of aquaculture is a crucial determinant of food security, the well-being of aquaculture practitioners, and economic growth within coastal regions. Considering the existing gap in research regarding spatial and temporal development of aquaculture, this study investigates the progression of aquaculture practices over time and across various locations in Fuding City, China. Methods: We retrospectively collected temporal and spatial data on aquaculture, as well as demographic, social, and economic data for Fuding City from 2010 to 2020. By employing 3D kernel density analysis, we illustrated the temporal and spatial changes in aquaculture. Furthermore, we utilized Ordinary Least Squares regression to investigate the driving factors behind the spatial changes in the aquaculture industry. Results: Over the past decades, we observed that in Fuding City, both the number of fishing rafts and aquaculture households initially decreased and then increased. The spatial distribution of aquaculture experienced a shift from the west (inner bay area) to the east (coastal area). Additionally, the type of fishing rafts also varied by region, with traditional rafts dominating the western inner bay and plastic rafts prevalent in the eastern offshore areas. Analysis of driving factors revealed that at least six factors have a significant positive correlation with the eastward shift of the aquaculture industry's center, including the proportion of migrant population, proportion of aquaculture to total fishery output, average temperature, investment in aquaculture technology, total fish sales, and GDP of Fuding City. Conclusion: This study examines the spatial and temporal dynamics of aquaculture in Fuding City from 2010 to 2020, proposing an innovative approach to spatial optimization that integrates both horizontal and vertical strategies. These insights aim to guide the development of coastal aquaculture policies and support sustainable regional development, fostering a balanced coexistence between human activities and marine environments.

Biochemical model of glucose induced enhanced biological phosphorus removal under anaerobic condition.

Enhanced biological phosphorus removal (EBPR) is playing an increasingly important role in controlling the eutrophication phenomenon in natural waters. It is believed that substrates other than acetate exert significant effects on the EBPR process. In this research, it was found that glucose could be used as the dominant substrate to induce and maintain a successful EBPR process. However, compared to the conventional EBPR process using acetate as the dominant substrate, it was found that less PO4-P was released into the medium and 3-hydroxyvalerate (3-HV) enriched poly-beta-hydroxyalkanoate (PHA), rather than 3-hydroxybutyrate (3-HB) enriched PHA, was accumulated during the anaerobic condition. According to the experimental results, a new biochemical model is hypothesized for the anaerobic metabolism of glucose. It is reasoned that the predominance of 3-HV enriched PHA is employed to balance the internal redox during the anaerobic condition. The Entner-Doudoroff (ED) pathway is likely used for anaerobic glucose metabolism when the bacteria demonstrate good EBPR performance, because the ED pathway necessitates the use of polyphosphate for energy purposes.