Proapoptotic modification of substituted isoindolinones as MDM2-p53 inhibitors

A series of novel amino acid ester derivatives of 2,3-substituted isoindolinones was synthesized and evaluated for p53-mediated apoptotic activity. The rationale for augmentation of the target activity of 2,3-substituted isoindolinones was based on the introduction of new fragments in the structure of the inhibitor that would provide additional binding sites in the hydrophobic cavity of MDM2. To select for the anticipated modifications we employed molecular docking. Synthesized molecules were evaluated for their ability to induce apoptosis in two cancer cell lines and their derivatives with different status of p53 (colorectal HCT116 and osteosarcoma U2OS cells) by Annexin V staining. The target activity was estimated using high-content imaging system Operetta. Valine and phenylglycine ester derivatives were identified as potentially active MDM2-p53 inhibitors.     

Mitochondria-targeted plastoquinone antioxidant SkQR1 decreases trauma-induced neurological deficit in rat

A protective effect of a mitochondria-targeted antioxidant, a cationic rhodamine derivative linked to a plastoquinone molecule (10-(6′-plastoquinonyl)decylrhodamine-19, SkQR1) was studied in the model of open focal trauma of rat brain sensorimotor cortex. It was found that daily intraperitoneal injections of SkQR1 (100 nmol/kg) for 4 days after the trauma improved performance in a test characterizing neurological deficit and decreased the volume of the damaged cortical area. Our results suggest that SkQR1 exhibits profound neuroprotective effect, which may be explained by its antioxidative activity.     

Studies on the possible role of protein phosphorylation in the transduction of the ethylene signal

Previous work in our laboratory has demonstrated the existence of high affinity binding sites for the plant growth regulator ethylene. The ethylene binding protein (EBP), from Phaseolus cotyledons, shows many of the characteristics of a functional receptor for ethylene, has been purified on SDS-PAGE and polyclonal antibodies raised in rabbits. Current work involves the investigation of the ethylene transduction signal in a number of ethylene-responsive tissues.In peas, it has been shown that ethylene promotes the phosphorylation of specific proteins of similar molecular weight to the EBP from Phaseolus. Such ethylene-induced phosphorylation can be inhibited by the ethylene antagonist, 2,5-NBD. The antibodies raised to the EBP from Phaseolus have been shown to immunoprecipitate ³²P-labelled proteins from membrane protein preparations obtained from pea tissue. Studies on ethylene binding in pea have also shown that the binding of ethylene may be regulated by phosphorylation. Thus, under conditions which promote phosphorylation, binding is inhibited, whereas the reverse is true under conditions which enhance dephosphorylation.Further work is described which examines the effect of protein kinase, protein phosphatase and calcium channel inhibitors on ethylene-induced phosphorylation in peas, together with wild-type (WT) and ethylene insensitive (eti) mutants of Arabidopsis thaliana. The effects of these treatments can be monitored in vivo using the ethylene-induced triple response as a screen. Furthermore, the protein profiles of such treated seedlings can then be compared by labelling protein extracts with ³²P and subjecting the samples to SDS-PAGE followed by autoradiography.     

Hyper-Resistance of the Bacillus licheniformis 24 Strain to Oxidative Stress Is Associated with Overexpression of Enzymatic Antioxidant System Genes

Molecular Biology - At the International Space Station (ISS), artificial living conditions are created and maintained to satisfy human needs, these conditions are also favorable for the growth of...     

Protein quantification

Protein quantification is an integral part of any investigation related to protein isolation, purification, characterization, and analysis. Although the methods considered in this lecture have multi-year history and applied widely in the laboratory practice, there are some crucial points, which must be taken into consideration while choosing the method permitting reliably and with a high specificity and reproducibility to quantify protein.     

Influence of climatypes of Scots pine on certain chemical and microbiological characteristics of soils

By using multivariate statistical analysis, the influence of Scots pine climatypes on a set of chemical and microbiological properties of soil, i.e., soil C/N, C_mic/C_org, and C_mic/N_mic, was revealed in a series of long-term (ca. 30 years) field experiments, which were carried out according to the same scheme under contrasting environmental and soil conditions of Siberian forestries.     

Relationships between EEG θ and α spectral amplitudes and cognitive ability in preschool children

Relationships between individual θ and α EEG amplitudes and intelligence were studied in five- to six-year-old children. EEG was recorded in 83 children in three functional states: eyes closed, sustained visual attention, and attention to adult’s speech. Intelligence was assessed using Kaufman’s K-ABC test. Relationships between the EEG parameters and intelligence were studied using correlational and regression analyses. The results suggest that stable individual differences in local spectral amplitudes (SA) in the EEG θ and α bands predict reliably (when the covariant proportions of their variances is controlled) the level of simultaneous data processing in children under the conditions of sustained attention but not at rest. Thus, the individual features of the limbic thalamocortical and corticothalamic attentional systems are expected to influence cognitive abilities at the preschool age.