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Nanostructured ZnO particles present in skin-care cosmetics and UVB/UVA sunscreen products generate strong oxidizing species (free radicals) when illuminated with UV radiation that can damages human skin and the horny layer. Damage to DNA by ZnO and other pigmentary ingredients in sunscreen formulations under artificial and solar UV exposure has been examined by Agarose gel electrophoresis using pUC 18 DNA plasmids (2686 base-pairs). Initial photoinduced oxidative damage done to DNA plasmids have been probed by nicking assays under in vitro conditions for ZnO. The effects of nanosize ZnO and CeO 2 particles, and the newly developed CaO-doped and SiO 2-coated CeO 2 pigment are compared when subjected to artificial (75-W Hg-lamp) and solar UV radiation. Supercoiled DNA plasmids undergo one nick to produce the relaxed form, followed by a second nick yielding the linear form of the plasmids. The DNA constituents deoxyadenosine-5'-monophosphate (dAMP), guanosine-5'monophosphate (GMP) and cytidine-5'-monophosphate (CMP) have been examined to assess the photooxidative damage done to these nucleotides under photocatalytic conditions using the cosmetic/sunscreen ZnO pigment. Adsorption of the nucleotide through the phosphate on the positively charged ZnO surface, followed by attack of the ribose/phosphate backbone by photogenerated •OH (and/or •OOH) radicals on the ZnO surface lead to the degradation of the dAMP's ribose moiety and subsequently to decomposition of the adenine base residue. About 90% mineralization of the ribose/phosphate backbone occurred as evidenced by formation of H 2 PO 4 ions after only 30 min of UV irradiation. The nitrogen atoms of the adenine base were converted to NO 3 and NH 4 + ions. About 45% of the organic carbons constituting the dAMP ribose backbone was mineralized to CO 2 within 8 h of UV irradiation occurring through formation of carboxylic acid intermediates (succinic, acetic and formic), with 85% of the remaining nucleobase ultimately mineralized after 48 h of UV irradiation. Similar occurrences were seen for the GMP and CMP

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Neurochondrin (NCDN) is a cytoplasmatic neural protein of importance for neural growth, glutamate receptor (mGluR) signaling, and synaptic plasticity. Conditional loss of Ncdn in mice neural tissue causes depressive-like behaviors, impaired spatial learning, and epileptic seizures. We report on NCDN missense variants in six affected individuals with variable degrees of developmental delay, intellectual disability (ID), and seizures. Three siblings were found homozygous for a NCDN missense variant, whereas another three unrelated individuals carried different de novo missense variants in NCDN. We assayed the missense variants for their capability to rescue impaired neurite formation in human neuroblastoma (SH-SY5Y) cells depleted of NCDN. Overexpression of wild-type NCDN rescued the neurite-phenotype in contrast to expression of NCDN containing the variants of affected individuals. Two missense variants, associated with severe neurodevelopmental features and epilepsy, were unable to restore mGluR5-induced ERK phosphorylation. Electrophysiological analysis of SH-SY5Y cells depleted of NCDN exhibited altered membrane potential and impaired action potentials at repolarization, suggesting NCDN to be required for normal biophysical properties. Using available transcriptome data from human fetal cortex, we show that NCDN is highly expressed in maturing excitatory neurons. In combination, our data provide evidence that bi-allelic and de novo variants in NCDN cause a clinically variable form of neurodevelopmental delay and epilepsy, highlighting a critical role for NCDN in human brain development.

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