Background: Apela, a newly identified peptide hormone, is important during zebrafish embryogenesis. Results: Apela binds directly to APJ and acts through the Gi pathway. Apela is expressed exclusively in adult kidney and regulates fluid homeostasis. Conclusion: Apela regulates fluid homeostasis through Gi signaling pathway. Significance: Apela is a kidney ligand more potent than apelin in regulating fluid homeostasis.
[1] Satellite remote sensing offers one of the best spatial and temporal observational approaches. However, well-validated satellite imagery has remained elusive for Lake Superior. Lake Superior's optical properties are highly influenced by colored dissolved organic matter (CDOM), which has hindered the retrieval of chlorophyll concentration through band-ratio algorithms. This study evaluated seven existing inversion algorithms. The top-performing inversion algorithm was tuned to a Lake Superior optical data set and applied to satellite imagery. The retrieval of chlorophyll concentration via inversion algorithms was not possible due to errors in derived CDOM absorption being greater than phytoplankton absorption values and the very small contribution of phytoplankton absorption to the overall absorption budget. However, the retrieval of absorption due to CDOM from satellite imagery was encouraging. To ensure that the best satellite remotely sensed reflectance estimates were used in the retrieval of absorption due to CDOM, several atmospheric correction schemes were evaluated. The absorption due to CDOM was greatest in the western arm of Lake Superior and near river mouths and decreased with distance offshore. The absorption due to CDOM had a bimodal distribution over the annual cycle with the greatest peak in fall and a smaller peak in spring.
G protein–coupled receptors (GPCRs) play an important role in physiology and disease and represent the most productive drug targets. Orphan GPCRs, with their endogenous ligands unknown, were considered a source of drug targets and consequently attract great interest to identify their endogenous cognate ligands for deorphanization. However, a contrary view to the ubiquitous existence of endogenous ligands for every GPCR is that there might be a significant overlooked fraction of orphan GPCRs that function constitutively in a ligand-independent manner only. Here, we investigated the evolution of the bombesin receptor–ligand family in vertebrates in which one member—bombesin receptor subtype-3 (BRS3)—is a potential orphan GPCR. With analysis of 17 vertebrate BRS3 structures and 10 vertebrate BRS3 functional data, our results demonstrated that nonplacental vertebrate BRS3 still connects to the original ligands—neuromedin B (NMB) and gastrin-releasing peptide (GRP)—because of adaptive evolution, with significantly changed protein structure, especially in three altered key residues (Q127R, P205S, and R294H) originally involved in ligand binding/activation, whereas the placental mammalian BRS3 lost the binding affinity to NMB/GRP and constitutively activates Gs/Gq/G12 signaling in a ligand-independent manner. Moreover, the N terminus of placental mammalian BRS3 underwent positive selection, exhibiting significant structural differences compared to nonplacental vertebrate BRS3, and this domain plays an important role in constitutive activity of placental mammalian BRS3. In conclusion, constitutively active BRS3 is a genuinely orphan GPCR in placental mammals, including human. To our knowledge, this study identified the first example that might represent a new group of genuinely orphan GPCRs that will never be deorphanized by the discovery of a natural ligand and provided new perspectives in addition to the current ligand-driven GPCR deorphanization.
The storage of anomalous heat and carbon in the Southern Ocean in response to increasing greenhouse gases greatly mitigates atmospheric warming and exerts a large impact on the marine ecosystem. However, the mechanisms driving the ocean storage patterns are uncertain. Here using recent hydrographic observations, we compare for the first time the spatial patterns of heat and carbon storage, which show substantial differences in the Southern Ocean, in contrast with the conventional view of simple passive subduction into the thermocline. Using an eddy‐rich global climate model, we demonstrate that redistribution of the preindustrial temperature field is the dominant control on the heat storage pattern, whereas carbon storage largely results from passive transport of anthropogenic carbon uptake at the surface. Lastly, this study highlights the importance of realistic representation of wind and surface buoyancy flux in climate models to improve future projection of circulation change and thus heat and carbon storage.
Based on year-round biogeochemical measurements with profiling floats that resolve the seasonal cycle, recent work has identified a larger than previously estimated release of carbon dioxide (CO 2 ) from the Southern Ocean to the atmosphere during austral winter (black line in Figure 1; Bushinsky et al., 2019;Gray et al., 2018). While there has been a broad consensus that the region south of about 50°S releases old, pre-industrial CO 2 to the atmosphere (
Alu elements contribute considerably to gene regulation and genome evolution in primates. The generation of new exons from Alu elements has been found in various human genes, and the regulatory function of the Alu exon has been investigated in many studies. However, the functionalization of Alu elements in protein coding regions remains unknown. Here, we reported that an Alu-J element exonized in the glycoprotein hormone alpha (GPHA) gene and encoded an additional N-terminal peptide (Alu-J encoding peptide) of the mature GPHA peptide, leading to a splicing variant of Alu-GPHA in anthropoid primates ∼35 Ma. Interestingly, adaptive evolution of the Alu-J exon occurred in the human and ape lineages during anthropoid evolution. The Alu-J encoding peptide is found to be a new biomarker in human early pregnancy and prolongs the serum half-life of human chorionic gonadotropin (HCG) circulation. Moreover, Alu-J encoding peptide enhances the bioactivity of HCG protein, both in vivo and in vitro. Our study reveals the first example of an Alu element functioning as the encoding peptide to increase the whole protein stability and provides insight into the potential multi-functionalization of the Alu exon in the protein coding regions. Furthermore, with the chorionic gonadotropin linking with hemochorial placentation, the exonization and functionalization of the Alu-J exon in GPHA gene represent a novel mechanism to the evolution of hemochorial placentation in primates.
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