Examination of acid-base properties and structural parameters of thiobarbituric acid

The stepwise proton-ligand stability constant of thiobarbituric acid anion was determined in an aqueous solution via pH-potentiometry at ionic strength I=0,1 and temperature T=20°C. Based on the absorption spectra analysis of thiobarbituric acid (H[2]L, H[2]thioBar) solutions in the UV-region at different pH values, it was shown that H[2]thioBar could exist in di-, mono-, and deprotonated forms. This latter fact is reflected in the particle yield H[2]L diagrams as a function of the aqueous solution pH. Besides, some geometric and physico-chemical characteristics of H2thioBar were described by means of quantum chemical calculations

Chromatin profiling of cortical neurons identifies individual epigenetic signatures in schizophrenia

Both heritability and environment contribute to risk for schizophrenia. However, the molecular mechanisms of interactions between genetic and non-genetic factors remain unclear. Epigenetic regulation of neuronal genome may be a presumable mechanism in pathogenesis of schizophrenia. Here, we performed analysis of open chromatin landscape of gene promoters in prefrontal cortical (PFC) neurons from schizophrenic patients. We cataloged cell-type-based epigenetic signals of transcriptional start sites (TSS) marked by histone H3-K4 trimethylation (H3K4me3) across the genome in PFC from multiple schizophrenia subjects and age-matched control individuals. One of the top-ranked chromatin alterations was found in the major histocompatibility (MHC) locus on chromosome 6 highlighting the overlap between genetic and epigenetic risk factors in schizophrenia. The chromosome conformation capture (3C) analysis in human brain cells revealed the architecture of multipoint chromatin interactions between the schizophrenia-associated genetic and epigenetic polymorphic sites and distantly located HLA-DRB5 and BTNL2 genes. In addition, schizophrenia-specific chromatin modifications in neurons were particularly prominent for non-coding RNA genes, including an uncharacterized LINC01115 gene and recently identified BNRNA_052780. Notably, protein-coding genes with altered epigenetic state in schizophrenia are enriched for oxidative stress and cell motility pathways. Our results imply the rare individual epigenetic alterations in brain neurons are involved in the pathogenesis of schizophrenia

Novel Environment and GABA Agonists Alter Event-Related Potentials in N-Methyl-d-aspartate NR1 Hypomorphic and Wild-Type Mice

Clinical and experimental data suggest dysregulation of N-methyl-d-aspartate receptor (NMDAR)-mediated glutamatergic pathways in schizophrenia. The interaction between NMDAR-mediated abnormalities and the response to novel environment has not been studied. Mice expressing 5 to 10% of normal N-methyl-d-aspartate receptor subunit 1 (NR1) subunits [NR1neo(−/−)] were compared with wild-type littermates for positive deflection at 20 ms (P20) and negative deflection at 40 ms (N40) auditory event-related potentials (ERPs). Groups were tested for habituation within and across five testing sessions, with novel environment tested during a sixth session. Subsequently, we examined the effects of a GABAA positive allosteric modulator (chlordiazepoxide) and a GABAB receptor agonist (baclofen) as potential interventions to normalize aberrant responses. There was a reduction in P20, but not N40 amplitude within each habituation day. Although there was no amplitude or gating change across habituation days, there was a reduction in P20 and N40 amplitude and gating in the novel environment. There was no difference between genotypes for N40. Only NR1neo(−/−) mice had reduced P20 in the novel environment. Chlordiazepoxide increased N40 amplitude in wild-type mice, whereas baclofen increased P20 amplitude in NR1neo(−/−) mice. As noted in previous publications, the pattern of ERPs in NR1neo(−/−) mice does not recapitulate abnormalities in schizophrenia. In addition, reduced NR1 expression does not influence N40 habituation but does affect P20 in a novel environment. Thus, the pattern of P50 (positive deflection at 50 ms) but not N100 (negative deflection at 100 ms) in human studies may relate to subjects’ reactions to unfamiliar environments. In addition, NR1 reduction decreased GABAA receptor-mediated effects on ERPs while causing increased GABAB receptor-mediated effects. Future studies will examine changes in GABA receptor subunits after reductions in NR1 expression

За кадры. 1988. № 47 (2773)

7 октября - День конституции СССРКаким быть парткому? / Э. Н. КамышевПартгрупоргНаш многонациональный дом / Г. В. ЯловскаяПервые вожаки комсомола / Е. ПершинаНа закладке овощейЧто за тонной и гектаром? / А. ЯковлевБыстрое чтениеОсенний десант в Чаинск / В. ЯнковскийРаботают рядомСуметь понять другогоТак держать! / Т. ПоляковаНужны энтузиасты / Д. МайоровНакануне новоселья / А. ТаенковНе смешно! / В. Краснокутски