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Molecular similarity is an impressively broad topic with many implications in several areas of chemistry. Its roots lie in the paradigm that 'similar molecules have similar properties'. For this reason, methods for determining molecular similarity find wide application in pharmaceutical companies, e.g., in the context of structure-activity relationships. The similarity evaluation is also used in the field of chemical legislation, specifically in the procedure to judge if a new molecule can obtain the status of orphan drug with the consequent financial benefits. For this procedure, the European Medicines Agency uses experts' judgments. It is clear that the perception of the similarity depends on the observer, so the development of models to reproduce the human perception is useful. In this paper, we built models using both 2D fingerprints and 3D descriptors, i.e., molecular shape and pharmacophore descriptors. The proposed models were also evaluated by constructing a dataset of pairs of molecules which was submitted to a group of experts for the similarity judgment. The proposed machine-learning models can be useful to reduce or assist human efforts in future evaluations. For this reason, the new molecules dataset and an online tool for molecular similarity estimation have been made freely available. [ABSTRACT FROM AUTHOR]

A detailed Valence Bond‐Spin Coupled analysis of a series of halogenated molecules is here reported, allowing to get a rigorous ab initio demonstration of the qualitative models previously proposed to explain the origin of halogen bonding. The concepts of σ‐hole and negative belt observed around the halogen atoms in the electrostatic potential maps are here interpreted by analysis of the relevant Spin Coupled orbitals. [ABSTRACT FROM AUTHOR]

A 168-bp amplification product was obtained in RT-PCR experiments using a degenerate oligonucleotide designed on a five-amino acid sequence of IN, a 7-kDa protein, previously characterized as a PKC inhibitor. It was included in the coding ORF of the 1530-bp-long IMAGE clone ID 38900 (accession numbers R51337 and R51448) that produces a translation product of 6.5 kDa. The translation of the ORF conceptual reading frame allowed the preparation of the synthetic protein PKI55, which was found to inhibit and degrade both untreated nPKC d isozymes and activated cPKC isozymes. The PKI55 gene is localized in chromosome 2q35. The Repeat Maskers output showed a 533-bp-long LTR32/ERVL segment that included the PKI55 coding sequence and a complete regulatory region. The coding sequence and the structure of PKI55 were detected in a brain cDNA of Macaca fascicularis (diverged from human lineages about 25 Myr ago). Three other human genes with over 60% identities with PKI55 were identified in three different loci (i.e., chromosomes 10, 15, and 20.) Synthesis of PKI55 was stimulated by PKC activation. A feedback loop of inhibition is established. When the PKCs are overactivated, PKI55 induces degradation of the enzyme and prevents the isozyme overexpression implicated in a number of important diseases including cancer, diabetes, and disorders of the immune system. The presence of the PKI55 sequence in Macaca fascicularis as well as in human chromosomes 10, 15, and 20 indicates a selective advantage for the PKI55 sequence and the adaptive value of the feedback mechanism. [ABSTRACT FROM AUTHOR]

A case of partial trisomy 9 is described in a mentally retarded and dysmorphic child, confirming that this chromosome unbalance results in a characteristic clinical entity. This trisomy arose through aberrant segregation of translocation chromosome during meiosis in the patient's mother, who is a balanced heterozygote for a complex translocation involving chromosomes 9, 21 and 22. The phenotypically normal sister of the propositus is also carrier of the same complex translocation. [ABSTRACT FROM AUTHOR]

Centric fission of chromosome No. 4 was found in the healthy mother of two children with trisomy 4p. The two telocentrics derived are stable and show no evidence of fusing again. the 2:3 ratio of unbalanced offsprings born to the proposita indicates that, contrary to the evidence emerging from studies in other species, the risk for the production of unbalanced gametes is high. [ABSTRACT FROM AUTHOR]