Characteristics of Highly Polymorphic Segmental Copy-Number Variations Observed in Japanese by BAC-Array-CGH

Segmental copy-number variations (CNVs) may contribute to genetic variation in humans. Reports of the existence and characteristics of CNVs in a large Japanese cohort are quite limited. We report the data from a large Japanese population. We conducted population screening for 213 unrelated Japanese individuals using comparative genomic hybridization based on a bacterial artificial chromosome microarray (BAC-aCGH). We summarize the data by focusing on highly polymorphic CNVs in ≥5.0% of the individual, since they may be informative for demonstrating the relationships between genotypes and their phenotypes. We found a total of 680 CNVs at 16 different BAC-regions in the genome. The majority of the polymorphic CNVs presented on BAC-clones that overlapped with regions of segmental duplication, and the majority of the polymorphic CNVs observed in this population had been previously reported in other publications. Some of the CNVs contained genes which might be related to phenotypic heterogeneity among individuals

Vertical structure and physical processes of the Madden-Julian oscillation: Linking hindcast fidelity to simulated diabatic heating and moistening

Many theories for the Madden-Julian oscillation (MJO) focus on diabatic processes, particularly the evolution of vertical heating and moistening. Poor MJO performance in weather and climate models is often blamed on biases in these processes and their interactions with the large-scale circulation. We introduce one of three components of a model-evaluation project, which aims to connect MJO fidelity in models to their representations of several physical processes, focusing on diabatic heating and moistening. This component consists of 20-day hindcasts, initialised daily during two MJO events in winter 2009-10. The 13 models exhibit a range of skill: several have accurate forecasts to 20 days' lead, while others perform similarly to statistical models (8-11 days). Models that maintain the observed MJO amplitude accurately predict propagation, but not vice versa. We find no link between hindcast fidelity and the precipitation-moisture relationship, in contrast to other recent studies. There is also no relationship between models' performance and the evolution of their diabatic-heating profiles with rain rate. A more robust association emerges between models' fidelity and net moistening: the highest-skill models show a clear transition from low-level moistening for light rainfall to mid-level moistening at moderate rainfall and upper-level moistening for heavy rainfall. The mid-level moistening, arising from both dynamics and physics, may be most important. Accurately representing many processes may be necessary, but not sufficient for capturing the MJO, which suggests that models fail to predict the MJO for a broad range of reasons and limits the possibility of finding a panacea

High-resolution simulation of the boreal summer intra-seasonal oscillation in Met Office unified model

The present study investigates the fidelity and resolution sensitivity of Met Office Unified Model Global Atmosphere 3.0 in simulating the intra-seasonal oscillation (ISO) of the East Asia and western North Pacific summer monsoon. Two sets of model simulations at horizontal resolutions of N216 (60km) and N96 (130km) forced by observed daily high-resolution sea surface temperature are examined and compared with the observations. Diagnostic results show that the model can well reproduce the gross spatio-temporal features of observed summer ISO over the East Asia and western North Pacific in terms of period, dominant REOF mode, variance, northward propagation, cycle evolution and vertical structure. The intra-seasonal change in intensity and position of western North Pacific Subtropical High and upper troposphere westerly jet associated with the northward propagating ISOs are also reasonably captured in the model. Moreover, increasing horizontal resolution improves most aspects of the ISO simulation, especially the intensity and northward propagation of the ISO-related convection and circulation systems. Further analysis indicates that the improvement as resolution increases is related to the weakening in background state of East Asian summer monsoon, which is due to the realistic simulation of land-sea thermal contrast at higher resolution model. This study suggests that enhanced model resolution can have some beneficial impacts on the ISO simulation

Mutational Analysis of Transmembrane Regions 3 and 4 of SecY, a Central Component of Protein Translocase

The SecYEG heterotrimeric membrane protein complex functions as a channel for protein translocation across the Escherichia coli cytoplasmic membrane. SecY is the central subunit of the SecYEG complex and contains 10 transmembrane segments (TM1 to TM10). Previous mutation studies suggested that TM3 and TM4 are particularly important for SecY function. To further characterize TM3 and TM4, we introduced a series of cysteine-scanning mutations into these segments. With one exception (an unstable product), all the mutant proteins complemented the cold-sensitive growth defect of the secY39 mutant. A combination of this secY mutation and the secG deletion resulted in synthetic lethality, and the TM3 and TM4 SecY cysteine substitution mutations were examined for their ability to complement this lethality. Although they were all positive for complementation, some of the complemented cells exhibited significant retardation of protein export. The substitution-sensitive residues in TM3 can be aligned to one side of the alpha-helix, and those in TM4 revealed a tendency for residues closer to the cytosolic side of the membrane to be more severely affected. Disulfide cross-linking experiments identified a specific contact point for TM3 and SecG TM2 as well as for TM4 and SecG TM1. Thus, although TM3 and TM4 do not contain any single residue that is absolutely required, they include functionally important helix surfaces and specific contact points with SecG. These results are discussed in light of the structural information available for the SecY complex

Copy-Number Variations Observed in a Japanese Population by BAC Array CGH: Summary of Relatively Rare CNVs

Copy-number variations (CNVs) may contribute to genetic variation in humans. Reports regarding existence and characteristics of CNVs in a large apparently healthy Japanese cohort are quite limited. We report the data from a screening of 213 unrelated Japanese individuals using comparative genomic hybridization based on a bacterial artificial chromosome microarray (BAC aCGH). In a previous paper, we summarized the data by focusing on highly polymorphic CNVs (in ≥5.0 % of the individuals). However, rare variations have recently received attention from scientists who espouse a hypothesis called “common disease and rare variants.” Here, we report CNVs identified in fewer than 10 individuals in our study population. We found a total of 126 CNVs at 52 different BAC regions in the genome. The CNVs observed at 27 of the 52 BAC-regions were found in only one unrelated individual. The majority of CNVs found in this study were not identified in the Japanese who were examined in the other studies. Family studies were conducted, and the results demonstrated that the CNVs were inherited from one parent in the families

Characterization of T cell receptors in a novel murine model of nickel-induced intraoral metal contact allergy.

Nickel is a component of several alloy types that are widely used in our environment, including several dental alloy types that cause intraoral metal contact allergy. However, metal-specific immune responses in the oral mucosa have not been elucidated because a suitable animal model has not been established. In this study, we established a novel murine model of nickel-induced intraoral metal contact allergy and aimed to elucidate the immune response in terms of T-cell receptor repertoire and cytokine profiles in inflamed oral mucosa. The intraoral metal contact allergy model was induced by two sensitizations of nickel plus lipopolysaccharide solution into the postauricular skin followed by a single nickel challenge of the buccal mucosa. Cytokine expression profiles and T-cell phenotypes were determined by quantitative polymerase chain reaction. T cells accumulated in the cervical lymph nodes and inflamed oral mucosa were characterized by analyzing their T-cell receptor α- and β-chain repertoires, and the nucleotide sequences of complementary determining region 3. Significant swelling and pathological features were histologically evident at 1 day after challenge in mice with nickel allergy. At 1 day after the challenge, CD8-positive T cells producing high levels of T helper 1 type cytokines had accumulated in the allergic oral mucosa. At 7 days after the challenge, excessive nickel allergy in the oral mucosa was suppressed by regulatory T cells. Characterization of the T-cell receptor repertoire in nickel allergic mice revealed the presence of natural killer T cells and T cells bearing Trav6-6-Traj57 at 1 day after the challenge. Our murine model of nickel-induced intraoral metal contact allergy showed that natural killer T cells and T cells bearing Trav6-6-Traj57 might be involved in the immune responses of nickel-induced intraoral metal contact allergy