Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Chirality-Induced Spin Selectivity (CISS) Effect: Magnetocurrent-Voltage Characteristics with Coulomb Interactions I

One of the manifestations of chirality-induced spin selectivity (CISS) is the appearance of a magnetocurrent. Magnetocurrent is the observation that the charge currents at finite bias in a two terminal device for opposite magnetizations of one of the leads differ. Magnetocurrents can only occur in the presence of interactions of the electrons either with vibrational modes or among themselves through the Coulomb interaction. In experiments on chiral molecules assembled in monolayers, the magnetocurrent seems to be dominantly cubic (odd) in bias voltage while theory finds a dominantly even bias voltage dependence. Thus far, theoretical work has predicted a magnetocurrent which is even bias. Here we analyze the bias voltage dependence of the magnetocurrent numerically and analytically involving the spin-orbit and Coulomb interactions (through the Hartree-Fock and Hubbard One approximations). For both approximations it is found that for strong Coulomb interactions the magnetocurrent is dominantly odd in bias voltage, confirming the symmetry observed in experiment.</p

Dynamic Wetting of CaO-Al2O3-SiO2-MgO Liquid Oxide on MgAl2O4 Spinel

Inclusion type and content in steel is critical in steelmaking, affecting both productivity through clogging, and downstream physical properties of the steel. They are normally removed from steel by reacting with a slag (liquid oxide) phase. For efficient inclusion removal, the inclusions must attach/bond with this liquid phase. The strength of the attachment can be in part characterized by the wettability of the liquid oxide on the inclusions. In this study, the dynamic wetting of liquid oxides of the CaO-Al2O3-SiO2-MgO system on a solid spinel (MgAl2O4) substrate with low porosity of 1.9 pct was measured at 1773 K (1500 °C) using a modified sessile drop technique. The dynamic contact angle between the liquid and solid spinel was determined for different CaO/Al2O3 mass percent ratios ranging from 0.98 to 1.55. Characteristic curves of wettability (θ) vs time showed a rapid decrease in wetting in the first 10 seconds tending to a plateau value at extended times. A mathematical model for spreading behavior of liquid oxides by Choi and Lee was adopted and shown to provide a reasonable representation of the spreading behavior with time. The chemical interaction at the interface between spinel (MgAl2O4) and slag was analyzed by carrying out detailed thermodynamic evaluation and characterization using scanning electron microscopy/energy dispersive spectroscopy. There is evidence of liquid penetrating the substrate via pores and along grain boundaries, forming a penetration layer in the substrate. The depth of the penetration layer was found to be a function of substrate porosity and sample cooling rate. It decreased from ~350 µm for 6.7 pct-porous substrate to ~190 µm for substrate with porosity of 1.9 pct and from ~190 µm to ~50 µm for a slow-cooled liquid oxide-spinel substrate sample in the furnace to a rapidly cooled liquid cooled-spinel substrate sample, respectively

Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error

10.1016/j.ajhg.2013.06.016American Journal of Human Genetics932264-277AJHG