A phosphorylated form of Mel-18 targets the Ring1B histone H2A ubiquitin ligase to chromatin

Recent studies have shown that PRC1-like Polycomb repressor complexes monoubiquity-late chromatin on histone H2A at lysine residue 119. Here we have analyzed the function of the polycomb protein Mel-18. Using affinity-tagged human MEL-18, we identify a polycomb-like complex, melPRC1, containing the core PRC1 proteins, RING1/2, HPH2, and CBX8. We show that, in ES cells, melPRC1 can functionally substitute for other PRC1-like complexes in Hox gene repression. A reconstituted subcomplex containing only Ring1B and Mel-18 functions as an efficient ubiquitin E3 ligase. This complex ubiquitylates free histone substrates nonspecifically but is highly specific for histone H2A lysine 119 in the context of nucleosomes. Mutational analysis demonstrates that while Ring1B is required for E3 function, Mel-18 directs this activity to H2A lysine 119 in chromatin. Moreover, this substrate-targeting function of Mel-18 is dependent on its prior phosphorylation at multiple residues, providing a direct link between chromatin modification and cell signaling pathways.     

A genome‐wide association study of coping behaviors suggests FBXO45 is associated with emotional expression

Individuals use coping behaviors to deal with unpleasant daily events. Such behaviors can moderate or mediate the pathway between psychosocial stress and health‐related outcomes. However, few studies have examined the associations between coping behaviors and genetic variants. We conducted a genome‐wide association study (GWAS) on coping behaviors in 14088 participants aged 35 to 69 years as part of the Japan Multi‐Institutional Collaborative Cohort Study. Five coping behaviors (emotional expression, emotional support seeking, positive reappraisal, problem solving and disengagement) were measured and analyzed. A GWAS analysis was performed using a mixed linear model adjusted for study area, age and sex. Variants with suggestive significance in the discovery phase (N = 6403) were further examined in the replication phase (N = 7685). We then combined variant‐level association evidence into gene‐level evidence using a gene‐based analysis. The results showed a significant genetic contribution to emotional expression and disengagement, with an estimation that the 19.5% and 6.6% variance in the liability‐scale was explained by common variants. In the discovery phase, 12 variants met suggestive significance (P < 1 × 10^?6) for association with the coping behaviors and perceived stress. However, none of these associations were confirmed in the replication stage. In gene‐based analysis, FBXO45, a gene with regulatory roles in synapse maturation, was significantly associated with emotional expression after multiple corrections (P < 3.1 × 10^?6). In conclusion, our results showed the existence of up to 20% genetic contribution to coping behaviors. Moreover, our gene‐based analysis using GWAS data suggests that genetic variations in FBXO45 are associated with emotional expression.     

Taxonomic Richness of Yeasts in Japan within Subtropical and Cool Temperate Areas

Background

An understanding of the role of yeasts in the environment has been uncertain because estimates of population size and diversity have often been based on species identifications that were determined from a limited number of phenotypic characteristics. DNA-based species identification has now become widely used, allowing an accurate assessment of species in different habitats. However, there are still problems in classification because some genera are polyphyletic. Consequently, the identification of yeasts and measurement of their diversity at the genus level remains difficult, as does assignment of genera to higher taxonomic ranks.

Methodology/Principal Findings

A total of 1021 yeast strains was isolated from soil samples and plant materials collected from Japan’s subtropical Iriomote Island and the cool temperate Rishiri Island. Based on sequence analyses of the D1/D2 domain of the LSU rRNA gene, these 1021 strains were tentatively classified into 183 species, with apparent new species accounting for approximately half of the total species isolated (60 and 46, Iriomote and Rishiri, respectively). The yeast species composition was statistically different between the two sites with only 15 species in common. Rarefaction curves of respective sources/areas gave distinctive patterns when the threshold of sequence identity became broader, indicating that the yeast diversity was distinct at the different taxonomic levels compared.

Conclusions/Significance

Our isolation study of yeasts in Japan has enabled us to expand the inventory of species diversity because a large number of new species was observed in the sampling areas. Further, we propose use of a particular diversity threshold as an “indicator” to recognize species, genera and higher taxonomic ranks.     

Association of the physical and chemical properties and the cytotoxicity of metal oxide nanoparticles: metal ion release, adsorption ability and specific surface area

Association of cellular influences and physical and chemical properties were examined for 24 kinds of industrial metal oxide nanoparticles: ZnO, CuO, NiO, Sb(2)O(3), CoO, MoO(3), Y(2)O(3), MgO, Gd(2)O(3), SnO(2), WO(3), ZrO(2), Fe(2)O(3), TiO(2), CeO(2), Al(2)O(3), Bi(2)O(3), La(2)O(3), ITO, and cobalt blue pigments. We prepared a stable medium dispersion for each nanoparticle and examined the influence on cell viability and oxidative stress together with physical and chemical characterizations. ZnO, CuO, NiO, MgO, and WO(3) showed a large amount of metal ion release in the culture medium. The cellular influences of these soluble nanoparticles were larger than insoluble nanoparticles. TiO(2), SnO(2), and CeO(2) nanoparticles showed strong protein adsorption ability; however, cellular influences of these nanoparticles were small. The primary particle size and the specific surface area seemed unrelated to cellular influences. Cellular influences of metal oxide nanoparticles depended on the kind and concentrations of released metals in the solution. For insoluble nanoparticles, the adsorption property was involved in cellular influences. The primary particle size and specific surface area of metal oxide nanoparticles did not affect directly cellular influences. In conclusion the most important cytotoxic factor of metal oxide nanoparticles was metal ion release.     

Phylogenetic analyses of the dinoflagellate Noctiluca scintillans based on beta-tubulin and Hsp90 genes

The noctilucid dinoflagellate Noctiluca scintillans is an unarmed heterotrophic protist that inhabits the world's oceans and is sometimes responsible for harmful red tides. The phylogenetic position of the noctilucids has been widely disputed because of two alternative views based on morphological characters and phylogenetic analyses using SSU rDNA. Specifically, noctilucids are either placed in a basal position within the dinoflagellates or they are seen as evolutionarily recent derivations descended from unarmored dinoflagellates in the order Gymnodiniales. Thus, the precise relationship of noctilucids to other dinoflagellates is still uncertain. In this study, we isolated β-tubulin and heat shock protein 90 genes from N. scintillans to examine this relationship further. The deduced amino acid sequences share commonly substituted amino acids and a deletion with other dinoflagellates, but not with Perkinsus marinus or other alveolates. Although Hsp90 analysis did not give robust support, β-tubulin analysis including an AU test, as well as combined analysis of these two amino acid sequences showed that N. scintillans is the next earliest branch after Oxyrrhis marina, within the dinoflagellates. Given the phylogenetic position of N. scintillans, its extremely specialized diploid trophont, and the primitive dinoflagellate-like characteristics of its haploid zoospore, we propose that noctilucids are a possible evolutionary link between ancestral diploid dinoflagellates and haploid core dinoflagellates. This implies that the transition from diploidy to haploidy in trophonts probably occurred via neoteny of a noctilucid-like zoospore.     

Temperature-sensitive reaction intermediate of F1-ATPase

F(1)-ATPase is a rotary molecular motor that makes 120 degrees stepping rotations, with each step being driven by a single-ATP hydrolysis. In this study, a new reaction intermediate of F(1)-ATPase was discovered at a temperature below 4 degrees C, which makes a pause at the same angle in its rotation as when ATP binds. The rate constant of the intermediate reaction was strongly dependent on temperature with a Q(10) factor of 19, implying that the intermediate reaction accompanies a large conformational change. Kinetic analyses showed that the intermediate state does not correspond to ATP binding or hydrolysis. The addition of ADP to the reaction mixture did not alter the angular position of the intermediate state, but specifically lengthened the time constant of this state. Conversely, the addition of inorganic phosphate caused a pause at an angle of +80 degrees from that of the intermediate state. These observations strongly suggest that the newly found reaction intermediate is an ADP-releasing step.