Family as One of the Key Determinants of Media Education of Young School-age Children

The attitude of parents influences formation of children’s attitude to life. It is even more noticeable when speaking about media. The proposed contribution shows partial results of research carried out as a part of VEGA project No. 1/0913/15: Media literacy of young school-age children in the context of family and school cooperation. The character of the empirical research was diagnostic and quantitative-qualitative. The aim of the research was to examine media education performed in formal and non-formal ways among young schoolaged children in Slovakia. 28 schools from all over Slovakia were examined in the presented research. The contribution focuses mainly on findings from questionnaires given to parents and other focus groups, i.e. pupils

Selective and potent proteomimetic inhibitors of intracellular protein–protein interactions

Inhibition of protein–protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. α-Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed “proteomimetics”, which can be assembled in a modular manner to reproduce the vectoral presentation of key side chains found on a helical motif from one partner within the PPI. In this work, it is demonstrated that by using a library of N-alkylated aromatic oligoamide helix mimetics, potent helix mimetics which reproduce their biophysical binding selectivity in a cellular context can be identified

Enriched environment ameliorates propagation of tau pathology and improves cognition in rat model of tauopathy

IntroductionThe typical symptoms of Alzheimer’s disease (AD) are cognitive impairment, disrupted spatial orientation, behavioral and psychiatric abnormalities, and later motor deficits. Neuropathologically, AD is characterized by deposits of pathological forms of endogenous proteins – amyloid-β, and neurofibrillary tau protein pathology. The latter closely correlates with brain atrophy and clinical impairment. Pharmacological therapies for these pathologies are largely absent, raising the question whether non-pharmacological interventions could be efficacious. Environmental factors can play a role in the manifestation of AD. It is unknown whether enriched environment (EE) can ameliorate the propagation of protein aggregates or their toxic components.MethodsWe injected insoluble tau extracts from human brains with AD (600 or 900 ng per animal) into hippocampi of SHR72 transgenic rats that express non-mutated truncated human tau 151-391/4R, but usually do not develop hippocampal tangles. The rats had either standard housing, or could access an EE 5×/week for 3 months. Behavioral analysis included the Morris Water Maze (MWM). Histological analysis was used to assess the propagation of tau pathology.ResultsAnimals exposed to EE performed better in the MWM (spatial acquisition duration and total distance, probe test); unexposed animals improved over the course of acquisition trials, but their mean performance remained below that of the EE group. Enriched environment abrogated tau propagation and hippocampal tangle formation in the 600 ng group; in the 900 ng group, tangle formation was ∼10-fold of the 600 ng group, and unaffected by EE.ConclusionEven a small difference in the amount of injected human AD tau can cause a pronounced difference in the number of resulting tangles. EE leads to a noticeably better spatial navigation performance of tau-injected animals. Furthermore, EE seems to be able to slow down tau pathology progression, indicating the possible utility of similar interventions in early stages of AD where tangle loads are still low

Complete 1H and 13C NMR assignments of a series of pergalloylated tannins

Tannins are secondary metabolites widely distributed in the plant kingdom.1 A common feature of tannins is their phenolic units, which can be linked together to form highly diverse chemical structures.2 Because these compounds constitute an important fraction of the food and beverage ingested,3 they have been thoroughly studied for their biological effects.4-6 Recently, we have performed a phytochemical study on Cornus canadensis, an abundant flowering plant growing wild in North America and giving edible fruits.7 A preliminary bioactivity screening was performed and revealed that an extract from C. canadensis was active toward Herpes simplex virus type 1.8 Following bioassay-guided fractionations, hydrolyzable tannins were identified.9 One of these compounds, namely, 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG), has been the subject of several pharmaceutical studies as recently reviewed by Zhang.10 The biological and medicinal properties of PGG are diverse and include anticancer, antioxidant, antimutagenic, anti-inflammatory, anti-allergic, hypocholesterolemic, anticoagulation, antinephrolithiasis, anticonvulsion, antiviral, and antibacterial activities. Furthermore, a series of PGG analogs were synthesized and found to be an optimal scaffold to stimulate glucose transport in adipocytes.11 Some of these compounds were also prepared in our laboratory in order to assess their antiherpetic activities. Because these analogs were only partially characterized by NMR,11 we would like to report herein the complete 1H and 13C assignments of pergalloylated D-glucose (1), D-mannose (2), D-galactose (3), D-xylose (4), L-ribose (5), L-arabinose (6), L-rhamnose (7), and D-fucose (8) by using a combination of one-dimensional and two-dimensional NMR experiments

An α-Helix-Mimicking 12,13-Helix: Designed α/β/γ-Foldamers as Selective Inhibitors of Protein-Protein Interactions

A major current challenge in bioorganic chemistry is the identification of effective mimics of protein secondary structures that act as inhibitors of protein–protein interactions (PPIs). In this work, trans-2-aminocyclobutanecarboxylic acid (tACBC) was used as the key β-amino acid component in the design of α/β/γ-peptides to structurally mimic a native α-helix. Suitably functionalized α/β/γ-peptides assume an α-helix-mimicking 12,13-helix conformation in solution, exhibit enhanced proteolytic stability in comparison to the wild-type α-peptide parent sequence from which they are derived, and act as selective inhibitors of the p53/hDM2 interaction

The structure of the KlcA and ArdB proteins reveals a novel fold and antirestriction activity against Type I DNA restriction systems in vivo but not in vitro

Plasmids, conjugative transposons and phage frequently encode anti-restriction proteins to enhance their chances of entering a new bacterial host that is highly likely to contain a Type I DNA restriction and modification (RM) system. The RM system usually destroys the invading DNA. Some of the anti-restriction proteins are DNA mimics and bind to the RM enzyme to prevent it binding to DNA. In this article, we characterize ArdB anti-restriction proteins and their close homologues, the KlcA proteins from a range of mobile genetic elements; including an ArdB encoded on a pathogenicity island from uropathogenic Escherichia coli and a KlcA from an IncP-1b plasmid, pBP136 isolated from Bordetella pertussis. We show that all the ArdB and KlcA act as anti-restriction proteins and inhibit the four main families of Type I RM systems in vivo, but fail to block the restriction endonuclease activity of the archetypal Type I RM enzyme, EcoKI, in vitro indicating that the action of ArdB is indirect and very different from that of the DNA mimics. We also present the structure determined by NMR spectroscopy of the pBP136 KlcA protein. The structure shows a novel protein fold and it is clearly not a DNA structural mimic

In Silico Improvement of beta(3)-Peptide Inhibitors of p53 center dot hDM2 and p53 center dot hDMX

There is great interest in molecules capable of inhibiting the interactions between p53 and its negative regulators hDM2 and hDMX, as these molecules have validated potential against cancers in which one or both oncoproteins are overexpressed. We reported previously that appropriately substituted β(3)-peptides inhibit these interactions and, more recently, that minimally cationic β(3)-peptides are sufficiently cell permeable to upregulate p53-dependent genes in live cells. These observations, coupled with the known stability of β-peptides in a cellular environment, and the recently reported structures of hDM2 and hDMX, motivated us to exploit computational modeling to identify β-peptides with improved potency and/or selectivity. This exercise successfully identified a new β(3)-peptide, β53-16, that possesses the highly desirable attribute of high affinity for both hDM2 as well as hDMX and identifies the 3,4-dichlorophenyl moiety as a novel determinant of hDMX affinity. [Image: see text