A large topographic feature on the surface of the trans-Neptunian object (307261) 2002 MS4_4 measured from stellar occultations

This work aims at constraining the size, shape, and geometric albedo of the dwarf planet candidate 2002 MS4 through the analysis of nine stellar occultation events. Using multichord detection, we also studied the object's topography by analyzing the obtained limb and the residuals between observed chords and the best-fitted ellipse. We predicted and organized the observational campaigns of nine stellar occultations by 2002 MS4 between 2019 and 2022, resulting in two single-chord events, four double-chord detections, and three events with three to up to sixty-one positive chords. Using 13 selected chords from the 8 August 2020 event, we determined the global elliptical limb of 2002 MS4. The best-fitted ellipse, combined with the object's rotational information from the literature, constrains the object's size, shape, and albedo. Additionally, we developed a new method to characterize topography features on the object's limb. The global limb has a semi-major axis of 412 $\pm$ 10 km, a semi-minor axis of 385 $\pm$ 17 km, and the position angle of the minor axis is 121 $^\circ$ $\pm$ 16$^\circ$. From this instantaneous limb, we obtained 2002 MS4's geometric albedo and the projected area-equivalent diameter. Significant deviations from the fitted ellipse in the northernmost limb are detected from multiple sites highlighting three distinct topographic features: one 11 km depth depression followed by a 25$^{+4}_{-5}$ km height elevation next to a crater-like depression with an extension of 322 $\pm$ 39 km and 45.1 $\pm$ 1.5 km deep. Our results present an object that is $\approx$138 km smaller in diameter than derived from thermal data, possibly indicating the presence of a so-far unknown satellite. However, within the error bars, the geometric albedo in the V-band agrees with the results published in the literature, even with the radiometric-derived albedo

Gain-of-function and loss-of-function variants in GRIA3 lead to distinct neurodevelopmental phenotypes

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) mediate fast excitatory neurotransmission in the brain. AMPARs form by homo- or heteromeric assembly of subunits encoded by the GRIA1-GRIA4 genes, of which only GRIA3 is X-chromosomal. Increasing numbers of GRIA3 missense variants are reported in patients with neurodevelopmental disorders (NDD), but only a few have been examined functionally. Here, we evaluated the impact on AMPAR function of one frameshift and 43 rare missense GRIA3 variants identified in patients with NDD by electrophysiological assays. Thirty-one variants alter receptor function and show loss-of-function or gain-of-function properties, whereas 13 appeared neutral. We collected detailed clinical data from 25 patients (from 23 families) harbouring 17 of these variants. All patients had global developmental impairment, mostly moderate (9/25) or severe (12/25). Twelve patients had seizures, including focal motor (6/12), unknown onset motor (4/12), focal impaired awareness (1/12), (atypical) absence (2/12), myoclonic (5/12) and generalized tonic-clonic (1/12) or atonic (1/12) seizures. The epilepsy syndrome was classified as developmental and epileptic encephalopathy in eight patients, developmental encephalopathy without seizures in 13 patients, and intellectual disability with epilepsy in four patients. Limb muscular hypotonia was reported in 13/25, and hypertonia in 10/25. Movement disorders were reported in 14/25, with hyperekplexia or non-epileptic erratic myoclonus being the most prevalent feature (8/25). Correlating receptor functional phenotype with clinical features revealed clinical features for GRIA3-associated NDDs and distinct NDD phenotypes for loss-of-function and gain-of-function variants. Gain-of-function variants were associated with more severe outcomes: patients were younger at the time of seizure onset (median age: 1 month), hypertonic and more often had movement disorders, including hyperekplexia. Patients with loss-of-function variants were older at the time of seizure onset (median age: 16 months), hypotonic and had sleeping disturbances. Loss-of-function and gain-of-function variants were disease-causing in both sexes but affected males often carried de novo or hemizygous loss-of-function variants inherited from healthy mothers, whereas affected females had mostly de novo heterozygous gain-of-function variants.</p