Structure of the FHA1 domain of yeast Rad53 and identification of binding sites for both FHA1 and its target protein Rad9

Forkhead-associated (FHA) domains have been shown to recognize both pThr and pTyr-peptides. The solution structures of the FHA2 domain of Rad53 from Saccharomyces cerevisiae, and its complex with a pTyr peptide, have been reported recently. We now report the solution structure of the other FHA domain of Rad53, FHA1 (residues 14-164), and identification of binding sites of FHA1 and its target protein Rad9. The FHA1 structure consists of 11 beta-strands, which form two large twisted anti-parallel beta-sheets folding into a beta-sandwich. Three short alpha-helices were also identified. The beta-strands are linked by several loops and turns. These structural features of free FHA1 are similar to those of free FHA2, but there are significant differences in the loops. Screening of a peptide library [XXX(pT)XXX] against FHA1 revealed an absolute requirement for Asp at the +3 position and a preference for Ala at the +2 position. These two criteria are met by a pThr motif (192)TEAD(195) in Rad9. Surface plasmon resonance analysis showed that a pThr peptide containing this motif, (188)SLEV(pT)EADATFVQ(200) from Rad9, binds to FHA1 with a K(d) value of 0.36 microM. Other peptides containing pTXXD sequences also bound to FHA1, but less tightly (K(d)=4-70 microM). These results suggest that Thr192 of Rad9 is the likely phosphorylation site recognized by the FHA1 domain of Rad53. The tight-binding peptide was then used to identify residues of FHA1 involved in the interaction with the pThr peptide. The results are compared with the interactions between the FHA2 domain and a pTyr peptide derived from Rad9 reported previously.     

Variability of the EEG autocorrelation structure in adolescents with schizophrenia spectrum disorders

Quantitative analysis of changes in the autocorrelation structure of EEG short segments (in the range of several seconds) was performed in healthy adolescents (n = 39) and adolescents with schizophrenia spectrum disorders (n = 39). The variability of the EEG autocorrelation structure was shown to be higher in patients with the greatest trend in the frontal leads. It is suggested that psychopathology of the schizophrenia spectrum is accompanied by a break in the mutual determination of cortical neural networks with predominant localization of this process in the frontal areas of the brain cortex.     

Complete mitochondrial genome of the bullhead torrent catfish, Liobagrus obesus (Siluriformes, Amblycipididae): Genome description and phylogenetic considerations inferred from the Cyt b and 16S rRNA genes

Mitochondrial DNA (mtDNA) from the bullhead torrent catfish, Liobagrus obesus, was isolated by long-polymerase chain reaction (Long-PCR) with universal primers and was fully sequenced by primer working using flanking sequences. The complete mtDNA from L. obesus was 16,531 bp in length and contained 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a control region, demonstrating a structure very similar to that of other bony fish. An analysis of the protein-coding genes revealed a statistically substantiated bias in (T+C): (A+G) content, supporting earlier findings regarding this peculiarity. As indicated by a chi-square test, the observed scores for pyrimidine and purine content were different from those expected assuming a 50:50 ratio: chi(2)=41.63, d.f.=5, p<0.000001 for three categories, including the 1st, 2nd, and 3rd codon positions. Further, there was a difference in nucleotide content between ND6 and the other 12 protein-coding genes in L. obesus. The values of p-distances, as summarized for different scales of evolutionary history at the Cyt b gene, revealed a clear pattern of increased nucleotide diversity at four levels: (1) intraspecies, (2) intragenus, (3) intrafamily, and (4) intraorder. Scores of average p-distances of the four categories in catfish were (1) 1.59+/-0.54%, (2) 5.28+/-1.72% (3) 16.37+/-1.26%, and (4) 19.81+/-0.14%, respectively. These data support the hypothesis that speciation in the order Siluriformes, in most cases, follows a geographic mode through the accumulation of a numerous small genetic changes over a long time period. A phylogenetic tree for the bullhead torrent catfish and several other fish species belonging to the order Siluriformes was developed on the basis of respective Cyt b sequences (1138 bp); the analysis revealed a monophyletic origin for the five examined families. A species-specific clustering of sequences from single species was obtained, supporting additionally basic phylogenetic information for the catfish and the barcoding suitability of Cyt b sequence data. Lastly, one of the well-supported properties of our phylogenetic tree (99% repetition level in our analysis) was the monophyletic placement of all catfish (order Siluriformes) among other ray-finned fish of the class Actinopterigii. Also discussed herein are the aspects of phylogeny based on the 16S rRNA gene.     

Rational Core–Shell Design of Open Air Low Temperature In Situ Processable CsPbI3 Quasi‐Nanocrystals for Stabilized p‐i‐n Solar Cells

As a promising alternative, inorganic perovskite nanocrystals allow reinforced stability of photovoltaic device. Unfortunately, directly assembling these nanocrystals into film is uncontrollable. Instead, in situ assembling technology under low temperature in open air is attractive but limited due to the tendency of nonperovskite transition. The adverse shell ligands and unstable core lattices are known as the fundamental problems. In order to address this issue, here proposed is a rational core–shell design: 1) with respect to ligands, a new one, 4‐fluorophenethylammonium iodide, is used to enhance bonding force and charge coupling between ligands and nanocrystals; 2) with respect to lattices, a novel compound H₂PbI₄ is employed to assist divalent ion (Mn²⁺) doping into perovskite lattices. By low temperature in situ processing CsPbI₃ quasi‐nanocrystal film, the highest power conversion efficiency of 13.4% for p‐i‐n solar cells is achieved, which retains 92% after 500 h in ambient air. The current study underlines the significance of rational hierarchical design of inorganic perovskite nanocrystals, especially for low temperature in situ processable electronic devices.     

Relationship between Television Viewing and Language Delay in Toddlers: Evidence from a Korea National Cross-Sectional Survey

Purpose

This study investigated the relationship between 2-year-old children’s exposure to TV and language delay.

Methods

The subjects of this study were 1,778 toddlers (906 males and 872 females) who participated in the Panel Study on Korean Children conducted in 2010. The linguistic ability of the toddlers was measured with the K-ASQ (Korean-Ages and Stages Questionnaire). The relationship between the amount of young children’s exposure to TV and language delay was analyzed with Poisson regression.

Results

The average daily TV watching time of 2-year-old Korean toddlers in this study was 1.21 hours. After all confounding variables were adjusted, toddlers with over 2 hours and less than 3 hours of TV watching time had 2.7 times more risk (RR = 2.74, 95% CI: 1.13–6.65) of language delay than those with less than 1 hour of TV watching time. Those with more than 3 hours of TV watching time had approximately 3 times (RR = 3.03, 95% CI: 1.12–8.21) more risk (p<0.05). In addition, the risk of language delay increased proportionately with the increase in toddlers’ TV watching time (p = 0.004).

Conclusion

Two-year-old Korean toddlers’ average daily TV watching time of more than 2 hours was related with language delay.     

An archaeal NADH oxidase causes damage to both proteins and nucleic acids under oxidative stress

NADH oxidases (NOXs) catalyze the two-electron reduction of oxygen to H₂O₂ or four-electron reduction of oxygen to H₂O. In this report, we show that an NADH oxidase from Thermococcus profundus (NOXtp) displays two forms: a native dimeric protein under physiological conditions and an oxidized hexameric form under oxidative stress. Native NOXtp displays high NADH oxidase activity, and oxidized NOXtp can accelerate the aggregation of partially unfolded proteins. The aggregates formed by NOXtp have characteristics similar to β-amyloid and Lewy bodies in neurodegenerative diseases, including an increase of β-sheet content. Oxidized NOXtp can also bind nucleic acids and cause their degradation by oxidizing NADH to produce H₂O₂. Furthermore, Escherichia coli cells expressing NOXtp are less viable than cells not expressing NOXtp after treatment with H₂O₂. As NOXtp shares similar features with eukaryotic cell death isozymes and life may have originated from hyperthermophiles, we suggest that NOXtp may be an ancestor of cell death proteins.     

The point mutation A34F causes dimerization of GB1

The immunoglobulin-binding domain B1 of streptococcal protein G (GB1), a very stable, small, single-domain protein, is one of the most extensively used models in the area of protein folding and design. Variants derived from a library of randomized hydrophobic core residues previously revealed alternative folds, namely a completely intertwined tetramer (Frank et al., Nat Struct Biol 2002;9:877-885) and a domain-swapped dimer (Byeon et al., J Mol Biol 2003;333:141-152). Here, we report the NMR structure of the single amino acid mutant Ala-34-Phe which exists as side-by-side dimer. The dimer dissociation constant is 27 +/- 4 microM. The dimer interface comprises two structural elements: First, the beta-sheets of the two monomers pair in an antiparallel arrangement, thereby forming an eight-stranded beta-sheet. Second, the alpha-helix is shortened, ending in a loop that engages in intermolecular contacts. The largest difference between the monomer unit in the A34F dimer and the monomeric wild-type GB1 is the dissolution of the C-terminal half of the alpha-helix associated with a pronounced slow conformational motion of the interface loop. This involves a large movement of the Tyr-33 side chain that swings out from the monomer to engage in dimer contacts.