New insights into P2X7 receptor regulation: Ca2+-calmodulin and GDP bind to the soluble P2X7 ballast domain.

P2X7 receptors are nonselective cation channels that are activated by extracellular ATP and play important roles in inflammation. They differ from other P2X family members by a large intracellular C-terminus that mediates diverse signaling processes that are little understood. A recent cryo-EM study revealed that the C-terminus of the P2X7 receptor forms a unique cytoplasmic ballast domain that possesses a GDP-binding site as well as a dinuclear Zn2+ site. However, the molecular basis for the regulatory function of the ballast domain as well as the interplay between the various ligands remain unclear. Here, we successfully expressed a soluble trimeric P2X7 ballast domain (P2X7BD) and characterized its ligand binding properties using a biophysical approach. We identified calmodulin (CaM)-binding regions within the ballast domain and found that binding of Ca2+-CaM and GDP to P2X7BD have opposite effects on its stability. Small-angle X-ray scattering experiments indicate that Ca2+-CaM binding disrupts the trimeric state of P2X7BD. Our results provide a possible framework for the intracellular regulation of the P2X7 receptor.

Linear nondisplaced skull fractures in children: who should be observed or admitted?

OBJECT: In this study the authors reviewed clinical management and outcomes in a large series of children with isolated linear nondisplaced skull fractures (NDSFs). Factors associated with hospitalization of these patients and costs of management were also reviewed. METHODS: After institutional review board approval, the authors retrospectively reviewed clinical records and imaging studies for patients between the ages of 0 and 16 years who were evaluated for NDSFs at a single children's hospital between January 2009 and December 2013. Patients were excluded if the fracture was open or comminuted. Additional exclusion criteria included intracranial hemorrhage, more than 1 skull fracture, or pneumocephalus. RESULTS: Three hundred twenty-six patients met inclusion criteria. The median patient age was 19 months (range 2 weeks to 15 years). One hundred ninety-three patients (59%) were male and 133 (41%) were female. One hundred eighty-four patients (56%) were placed under 23-hour observation, 87 (27%) were admitted to the hospital, and 55 patients (17%) were discharged from the emergency department. Two hundred seventy-eight patients (85%) arrived by ambulance, 36 (11%) arrived by car, and 12 (4%) were airlifted by helicopter. Two hundred fifty-seven patients (79%) were transferred from another institution. The mean hospital stay for patients admitted to the hospital was 46 hours (range 7-395 hours). The mean hospital stay for patients placed under 23-hour observation status was 18 hours (range 2-43 hours). The reasons for hospitalization longer than 1 day included Child Protective Services involvement in 24 patients and other injuries in 11 patients. Thirteen percent (n = 45) had altered mental status or loss of consciousness by history. No patient had any neurological deficits on examination, and none required neurosurgical intervention. Less than 16% (n = 50) had subsequent outpatient follow-up. These patients were all neurologically intact at the follow-up visit. CONCLUSIONS: Hospitalization is not necessary for many children with NDSFs. Patients with mental status changes, additional injuries, or possible nonaccidental injury may require observation.