The Orphan GPCR Receptor, GPR88, Interacts with Nuclear Protein Partners in the Cerebral Cortex.

GPR88 is an orphan G-protein-coupled receptor (GPCR) highly expressed in striatal medium spiny neurons (MSN), also found in cortical neurons at low level. In MSN, GPR88 has a canonical GPCR plasma membrane/cytoplasmic expression, whereas in cortical neurons, we previously reported an atypical intranuclear localization. Molecular size analysis suggests that GPR88, expressed in plasma membrane of MSN or in nuclear compartment of cortical neurons, corresponds to the full-length protein. By transfection of cortical neurons, we showed that GPR88 fluorescent chimeras exhibit a nuclear localization. This localization is contingent on the third intracytoplasmic loop and C-terminus domains, even though these domains do not contain any known nuclear localization signals (NLS). Using yeast two-hybrid screening with these domains, we identified the nuclear proteins ATRX, TOP2B, and BAZ2B, all involved in chromatin remodeling, as potential protein partners of GPR88. We also validated the interaction of GPR88 with these nuclear proteins by proximity ligation assay on cortical neurons in culture and coimmunoprecipitation experiments on cortical extracts from GPR88 wild-type (WT) and knockout (KO) mice. The identification of GPR88 subcellular partners may provide novel functional insights for nonclassical modes of GPCR action that could be relevant in the maturating process of neocortical neurons.

Unmet Need for Emergency Medical Services in Hanoi, Vietnam.

Low- and middle-income countries urgently need to improve emergency medical services (EMSs) as a component of their healthcare systems. Here, we detailed EMS resources and their provision in Hanoi, Vietnam, and discussed necessary policies to upgrade EMSs. Between 2013 and 2018, EMS resources, measured as provider-to-population and ambulance-to-population ratios, decreased, whereas service provision, measured as the number of patients transported by ambulance per population, increased. EMS resources and their provision in Hanoi are far below the standards of high-income countries or figures in neighboring Asian countries. Therefore, it is imperative to upgrade health policies for the appropriate allocation of healthcare resources to EMSs and hospital services.