Expanding the clinical spectrum of biallelic ZNF335 variants.

ZNF335 plays an essential role in neurogenesis and biallelic variants in ZNF335 have been identified as the cause of severe primary autosomal recessive microcephaly in 2 unrelated families. We describe, herein, 2 additional affected individuals with biallelic ZNF335 variants, 1 individual with a homozygous c.1399 T > C, p.(Cys467Arg) variant, and a second individual with compound heterozygous c.2171_2173delTCT, p.(Phe724del) and c.3998A > G, p.(Glu1333Gly) variants with the latter variant predicted to affect splicing. Whereas the first case presented with early death and a severe phenotype characterized by anterior agyria with prominent extra-axial spaces, absent basal ganglia, and hypoplasia of the brainstem and cerebellum, the second case had a milder clinical presentation with hypomyelination and otherwise preserved brain structures on MRI. Our findings expand the clinical spectrum of ZNF335-associated microcephaly.

Nucleation, growth and characterization of semiorganic nonlinear optical crystal sodium acetate doped L-tyrosine.

Sodium acetate doped L-tyrosine single crystal with dimensions 47×15×8 mm(3) was grown by slow evaporation solution growth technique. Nucleation kinetics of the growth of the material was studied to optimize the growth conditions. The grown doped crystal was then characterized using single crystal XRD, UV-vis-NIR, FTIR, NMR, SEM-EDAX and NLO studies. XRD study reveals that the grown crystal belongs to monoclinic system with space group P21. Lattice parameters of the grown crystals are found to be a=5.096 Å, b=8.966 Å, c=11.088 Å, α=ß=90° and γ=92.035°. The transparent range of the grown crystal was measured as 260-1100 nm with 260 nm as lower cut off wavelength using UV-vis-NIR absorption spectrum and the optical band gap was evaluated as 3.24 eV from the Tauc's plot. The various functional groups were identified using FTIR spectral analysis. The thermal behavior of the title compound has been analyzed using TGA/DTA and DSC thermal curves. From the thermal study, the material is found to possess thermal stability up to 158°C. The microstructure of the grown crystal and the presence of various elements in the crystal were analyzed using SEM and EDAX techniques. NMR spectral analysis confirms the molecular structure of the grown compound. The nonlinear optical property was tested using Kurtz Perry powder technique and SHG efficiency was measured nearly same as that of KDP.

Synthesis, growth, structural and optical studies of organic nonlinear optical material--piperazine-1,4-diium bis 2,4,6-trinitrophenolate.

Piperazine-1,4-diium bis 2,4,6-trinitrophenolate is one of the useful organic materials with nonlinear optical (NLO) and pharmaceutical applications. The material was grown by slow evaporation solution growth method at room temperature. The crystal system and lattice parameters were identified by single crystal XRD analysis. The grown material crystallizes in monoclinic system with P21/n space group. The main functional groups NH2, NO2, CN, CC, and phenolic 'O' atom were identified using FTIR analysis. The protons and carbons of grown crystal with various chemical environments were studied by 1H and 13C NMR spectroscopy to confirm the molecular structure. The optical properties of the crystal were studied by UV-vis-NIR spectroscopy and the transmission 100% range starts from 532 nm onwards. The optical band gap was measured as 2.63 eV from the plot of (αhν)2 versus hν. The thermal stability was detected at 304.1°C using TG-DTA analysis. The dielectric studies of the sample were carried out at different temperatures in the frequency range from 50 Hz to 5 MHz to establish the dielectric nature of the crystal. Photoconductivity measurements were carried out on the grown crystal. The Second Harmonic Generation (SHG) of the crystal was tested to confirm the nonlinear optical property.

Growth and optical, thermal, mechanical and surface morphology studies of semiorganic nonlinear optical material: Dichlorobis (l-proline) zinc (II) crystal.

The organometallic nonlinear optical material Dichlorobis (l-proline) zinc (II) (DCBPZ) was crystallized using solution growth technique. XRD data reveal that the grown crystal belongs to orthorhombic system with space group P212121. The crystals were characterized using UV-vis-NIR, FTIR and NMR spectral studies, SEM-EDAX analysis and Atomic force microscopy (AFM), thermal and microhardness studies. Photoconductivity measurements were made to understand the response of the grown material to the visible light. The SHG efficiency of DCBPZ was also measured using Kurtz and Perry powder technique. It is observed that the NLO activity of DCBPZ is found to be twice that of KDP due to improved linear and nonlinear optical properties of the material.

Increased phosphorylation of neurofilament subunits in PC12 cells and rat dorsal root ganglion neurons treated with N-Acetyl-Leu-Leu-norleucinal.

Treatment of PC12 cells or dorsal root ganglion neurons with the protease inhibitor, N-Acetyl-Leu-Leu-norleucinal, stimulated phosphorylation of the mid-sized and heavy neurofilament subunits and caused the heavy subunit in the perikarya of dorsal root ganglion neurons to become hyperphosphorylated. The closely related inhibitor, N-Acetyl-Leu-Leu-methioninal, did not produce a similar effect. Okadaic acid increased the phosphorylation state of the heavy neurofilament subunit in PC12 cells in a fashion similar to N-Acetyl-Leu-Leu-norleucinal and the effect of both compounds together was greater than for either one alone. There was no increase in cyclin-dependent kinase 5-immunoprecipitable histone H1 kinase activity in PC12 cells treated with N-Acetyl-Leu-Leu-norleucinal despite the presence of enzyme protein. The present study demonstrates that a protease inhibitor can induce the hyperphosphorylation of neurofilament subunits to a level normally seen only in axons. This suggests that perturbations in intracellular proteolysis may lead to the accumulation of phosphorylated neurofilament epitopes in neuronal perikarya in certain pathological states. The results also show that the carboxy-terminal tail domains of the two largest neurofilament subunits are phosphorylated even when cyclin dependent kinase 5 is inactive, indicating that other neuronal kinases are involved in the phosphorylation of Lys-Ser-Pro repeats.