ABSTRACT. Dimensionality of a relatively big data set (95 compounds) observed for toxicity (mutagenicity) was explored in order to compute QSAR models. Distinct molecular descriptors were used. Dimensionality of data, using PCA, correlation plots and clustering, was evaluated. Analyzing data dimensionality allowed model optimization. Docking studies and PCA were used in order to expand data dimensionality. Pearson correlation coefficient (r 2 ) values, obtained for both perceptive and predictive models, were satisfactory.

The protrusion domain (P-domain; MrNVPd) of Macrobrachium rosenbergii nodavirus (MrNV) exists in two conformations, parallel and X-shaped. We have performed a theoretical study to gain insight into the nature of the dimeric interactions involving the dimeric interfaces within parallel and X-shaped conformations of MrNVPd by applying the quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses in the framework of the density functional theory (DFT) approach. The results reveal that the dimer–dimer interfaces of MrNVPd have hydrogen bonds of common types. Leu255–Lys287, Tyr257–Lys287, Lys287–Ser253, Met294–Cys328, Asp295–Lys327, Ser298–Ser324, Ile326–Asp295, and Cys328–Met294 are the key residue pairs of the dimer–dimer interfaces to maintain the dimer–dimer structures of MrNVPd through charge–charge, charge–dipole, dipole–dipole, hydrophobic, and hydrogen bonding interactions. The strengths of these intermolecular dimer–dimer interactions in the parallel conformation are much greater than those in the X-shaped conformation. The parallel trimeric interface is held basically by electrostatic and hydrophobic interactions. The electrostatic interactions accompanying a strong hydrogen bond of Oγ1–Hγ1···Oγ1 in the Thr276 A–Thr276 D pair maintain the intermolecular interface of two X-shaped MrNVPd dimers.

Neuroblastoma (NBL) and medulloblastoma (MB) are aggressive pediatric cancers which can benefit from therapies targeting gangliosides. Therefore, we compared the ganglioside profile of 9 MB and 14 NBL samples by thin layer chromatography and mass spectrometry. NBL had the highest expression of GD2 (median 0.54 nmol GD2/mg protein), and also expressed complex gangliosides. GD2-low samples expressed GD1a and were more differentiated. MB mainly expressed GD2 (median 0.032 nmol GD2/mg protein) or GM3. Four sonic hedgehog-activated (SHH) as well as one group 4 and one group 3 MBs were GD2-positive. Two group 3 MB samples were GD2-negative but GM3-positive. N-glycolyl neuraminic acid-containing GM3 was neither detected in NBL nor MB by mass spectrometry. Furthermore, a GD2-phenotype predicting two-gene signature (ST8SIA1 and B4GALNT1) was applied to RNA-Seq datasets, including 86 MBs and validated by qRT-PCR. The signature values were decreased in group 3 and wingless-activated (WNT) compared to SHH and group 4 MBs. These results suggest that while NBL is GD2-positive, only some MB patients can benefit from a GD2-directed therapy. The expression of genes involved in the ganglioside synthesis may allow the identification of GD2-positive MBs. Finally, the ganglioside profile may reflect the differentiation status in NBL and could help to define MB subtypes.

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