PRRT2 missense mutations cluster near C-terminus and frequently lead to protein mislocalization.

OBJECTIVE: Variants in human PRRT2 cause paroxysmal kinesigenic dyskinesia (PKD) and other neurological disorders. Most reported variants resulting in truncating proteins failed to localize to cytoplasmic membrane. The present study identifies novel PRRT2 variants in PKD and epilepsy patients and evaluates the functional consequences of PRRT2 missense variations. METHODS: We investigated two families with PKD and epilepsies using Sanger sequencing and a multiple gene panel. Subcellular localization of mutant proteins was investigated using confocal microscopy and cell surface biotinylation assay in Prrt2-transfected cells. RESULTS: Two novel PRRT2 variants, p.His232Glnfs*10 and p.Leu298Pro, were identified, and functional study revealed impaired localization of both mutant proteins to the plasma membrane. Further investigation of other reported missense variants revealed decreased protein targeting to the plasma membrane in eight of the 13 missense variants examined (p.Trp281Arg, p.Ala287Thr, p.Ala291Val, p.Arg295Gln, p.Leu298Pro, p.Ala306Asp, p.Gly324Glu, and p.Gly324Arg). In contrast, all benign variants we tested exhibited predominant localization to the plasma membrane similar to wild-type Prrt2. Most likely pathogenic variants were located at conserved amino acid residues near the C-terminus, whereas truncating variants spread throughout the gene. SIGNIFICANCE: PRRT2 missense variants clustering at the C-terminus often lead to protein mislocalization. Failure in protein targeting to the plasma membrane by PRRT2 variants may be a key mechanism in causing PKD and related neurological disorders.

Single-cell transcriptomic analysis reveals diversity within mammalian spinal motor neurons.

Spinal motor neurons (MNs) integrate sensory stimuli and brain commands to generate movements. In vertebrates, the molecular identities of the cardinal MN types such as those innervating limb versus trunk muscles are well elucidated. Yet the identities of finer subtypes within these cell populations that innervate individual muscle groups remain enigmatic. Here we investigate heterogeneity in mouse MNs using single-cell transcriptomics. Among limb-innervating MNs, we reveal a diverse neuropeptide code for delineating putative motor pool identities. Additionally, we uncover that axial MNs are subdivided into three molecularly distinct subtypes, defined by mediolaterally-biased Satb2, Nr2f2 or Bcl11b expression patterns with different axon guidance signatures. These three subtypes are present in chicken and human embryos, suggesting a conserved axial MN expression pattern across higher vertebrates. Overall, our study provides a molecular resource of spinal MN types and paves the way towards deciphering how neuronal subtypes evolved to accommodate vertebrate motor behaviors.

Synthesis, structures, and physical properties of benzo[k]fluoranthene-based linear acenes.

This work describes the syntheses, crystal structures, photophysical properties, and electro-chemical analyses of benzo[k]fluoranthene-based linear acenes, together with ab initio density functional theory computations on them. The molecules were prepared in generally moderate to good yields through Pd-catalyzed cycloadditions between 1,8-diethynylnaphthalene derivatives and aryl iodides. This protocol is simpler and more efficient than conventional methods. The scope and limitations of this reaction were examined. The structures of compounds 4hb, 15ac, 17ab, 19ac, and 24je were determined by X-ray analysis; they are either bent or twisted, rather than planar. The photophysical and electrochemical properties of these cycloadducts were also investigated and compared with computational predictions based on density functional theory.

High-performance p-channel organic semiconducting candidates based on benzo[1,2-k;4,5-k']difluoranthene derivatives.

Orbital promises: Frontier orbital analyses showed that the small lambda(+) value of 8,17-di-n-hexylbenzo[1,2-k;4,5-k']difluoranthene (DH-BDF) is owed to the nonbonding character of the BDF framework. The calculated adiabatic ionic potential and hole mobility indicates that this compound is a p-type air-stable organic field-effect transistor, which promises to be a soluble, stable and high-performance p-type organic semiconductor.

Photocatalysis and Hydrogen Evolution of Al- and Zn-Doped TiO2 Nanotubes Fabricated by Atomic Layer Deposition.

Highly homogeneous Al- and Zn-doped TiO2 nanotubes were fabricated by atomic layer deposition (ALD) via nanolaminated stacks of binary layers of TiO2/Al2O3 and TiO2/ZnO, respectively. The bilayers were alternately deposited on the polycarbonate (PC) membrane template by ALD with various cyclic sequences. The nanotubes in a length of 20 µm and a diameter of 220 nm were obtained after removal of the PC membrane by annealing at 450 °C. The effects of doping composition on the photocatalytic and photoelectrochemical (PEC) activities were investigated. Increasing the Al doping reduced the photocatalytic activity of TiO2 due to formation of charge recombination sites and reduction of hydroxide radicals. In contrast, there was an optimal range of Zn doping to get enhanced photocatalytic activity and higher PEC efficiency. With a doping ratio of 0.01, the hydrogen production rate from water splitting was 6 times higher than that of commercial P25 TiO2. The energy-band diagram of Zn-doped TiO2 determined by ultraviolet photoelectron spectroscopy revealed shift up of the Fermi level to provide more electrons to the conduction band. The photoinduced trapped electrons and holes were detected in Zn-doped TiO2 by in situ electron paramagnetic resonance spectroscopy, which revealed that Ti3+ sites on the surface and surface oxygen vacancies played a key role in promoting the photocatalytic process.

Fabrication of TiO2 on porous g-C3N4 by ALD for improved solar-driven hydrogen evolution.

Porous graphitic carbon nitride (P-g-C3N4) thin sheets were fabricated by a one-step calcination of a mixture of urea, melamine, and ammonia chloride at 550 °C. P-g-C3N4 showed 48% higher photocatalytic H2 production from methanol aqueous solution than conventional urea-derived graphitic carbon nitride (g-C3N4) because the existence of numerous pores reduces the recombination rate of charge carriers. In order to further enhance the photocatalytic activity, TiO2 was uniformly deposited on P-g-C3N4 by 60-300 cycles of atomic layer deposition (ALD) to form the TiO2@P-g-C3N4 composite. They exhibited much higher photocatalytic hydrogen production rates than both TiO2 and P-g-C3N4. Among all composites, the sample deposited with 180 ALD cycles of TiO2 showed the highest H2 production because of optimal diffusion length for electrons and holes. It also performed better than the sample of g-C3N4 deposited with 180 cycles of TiO2.

Uniform coating of Ta2O5 on vertically aligned substrate: A prelude to forced flow atomic layer deposition.

Uniform tantalum oxide thin films, with a growth rate of 0.6 Å/cycle, were fabricated on vertically aligned, 10 cm-long, silicon substrates using an innovative atomic layer deposition (ALD) design. The ALD system, with a reaction chamber depth of 13.3 cm and 18 vertical enclosed channels (inner diameter 1.3 cm), was coupled with a shower-head type precursor conduit plate bearing 6 radial channels. This design enabled deposition on 6 silicon substrates at a time. The degrees of non-uniformity of deposits along the length of the silicon wafer and across different positions in the ALD chamber were found to be 1.77%-6.21% and 3.27%-5.45%, respectively. A further advantage of the design is that the conduit plate may be modified and the number of channels increased to process 18 substrates simultaneously, thus moving toward efficient and expedited ALD systems.

Aggregation of stabilized TiO2 nanoparticle suspensions in the presence of inorganic ions.

The present study aims to evaluate the effect of inorganic ions on the aggregation kinetics of stabilized titanium dioxide (TiO(2) ) nanoparticle (NP) suspension, an NP mode widely used in consumer goods and in aquatic environments. The point of zero charge of stabilized TiO(2) NPs was approximately pH 6.5. The particle size of the stabilized TiO(2) NP suspensions increased with the increase in salt concentrations. The additional salts caused the shift of zeta potentials of TiO(2) suspensions to a lower value. The TiO(2) NPs aggregated more obviously in the presence of anions than cations, and the effect of divalent anions was larger than that of monovalent anions. The critical coagulation concentration (CCC) values for commercial TiO(2) NP suspensions with positive surfaces were estimated as 290 and 2.3 meq/L for Cl(-) and SO 42-, respectively. These CCC values of stabilized TiO(2) NP suspensions are higher than those of TiO(2) NP powders, indicating greater stability of the commercial stabilized TiO(2) NP suspensions. The effects of commercial TiO(2) NP suspensions still need to be explored and defined. Derjaguin-Landau-Verwey-Overbeek (DLVO) analysis can explain the aggregation behaviors of stabilized TiO(2) NP suspensions. Such an understanding can facilitate the prediction of NP fate in the environment.