A single Gly114Arg mutation stabilizes the hexameric subunit assembly and changes the substrate specificity of halo-archaeal nucleoside diphosphate kinase

AbstractNucleoside diphosphate kinase from extremely halophilic archaeon (HsNDK) requires above 2M NaCl concentration for in vitro refolding. Here an attempt was made to isolate mutations that allow HsNDK to refold in low salt media. Such a screening resulted in isolation of an HsNDK mutant, Gly114Arg, which efficiently refolded in the presence of 1M NaCl. This mutant, unlike the wild type enzyme, was expressed in Escherichia coli as an active form. The residue 114 is in close proximity to Glu155 of the neighboring subunit in the three dimensional hexameric structure of the HsNDK. It is thus possible that the attractive electrostatic interactions occur between Arg114 and Glu155 in the mutant HsNDK, stabilizing the hexameric subunit assembly

Deep Near-Infrared Imaging af an Embedded Cluster in the Extreme Outer Galaxy: Census of Supernovae Triggered Star Formation

While conducting a near-infrared (NIR) survey of ``Digel Clouds'', which are thought to be located in the extreme outer Galaxy (EOG), Kobayashi & Tokunaga found star formation activity in ``Cloud 2'', a giant molecular cloud at the Galactic radius of ~ 20 kpc. Additional infrared imaging showed two embedded young clusters at the densest regions of the molecular cloud. Because the molecular cloud is located in the vicinity of a supernova remnant (SNR) HI shell, GSH 138-01-94, it was suggested that the star formation activity in Cloud 2 was triggered by this expanding HI shell. We obtained deep J (1.25 um), H (1.65 um) and K (2.2 um) images of one of the embedded clusters in Cloud 2 with high spatial resolution (FWHM ~0".3) and high sensitivity (K ~ 20 mag, 10 sigma). We identified 52 cluster members. The estimated stellar density (~ 10 pc^{-2}) suggests that the cluster is a T-association. This is the deepest NIR imaging of an embedded cluster in the EOG. The observed K-band luminosity function (KLF) suggests that the underlying initial mass function (IMF) of the cluster down to the detection limit of ~ 0.1 M_sun is not significantly different from the typical IMFs in the field and in the near-by star clusters. The overall characteristics of this cluster appears to be similar to those of other embedded clusters in the far outer Galaxy. The estimated age of the cluster from the KLF, which is less than 1 Myr, is consistent with the view that the star formation was triggered by the HI shell whose age was estimated at 4.3 Myr (Stil & Irwin). The 3-dimensional geometry of SNR shell, molecular cloud and the embedded cluster, which is inferred from our data, as well as the cluster age strongly suggest that the star formation in Cloud 2 was triggered by the SNR shell.Comment: 19pages, 8 figures, 1 table, accepted to ApJ. Full paper (pdf) with high resolution figures available at http://www.ioa.s.u-tokyo.ac.jp/~ck_yasui/papers/Cloud2N_1.pd

HLA-VBSeq v2: improved HLA calling accuracy with full-length Japanese class-I panel

HLA-VBSeq is an HLA calling tool developed to infer the most likely HLA types from high-throughput sequencing data. However, there is still room for improvement in specific genetic groups because of the diversity of HLA alleles in human populations. Here, we present HLA-VBSeq v2, a software application that makes use of a new Japanese HLA reference panel to enhance calling accuracy for Japanese HLA class-I genes. Our analysis showed significant improvements in calling accuracy in all HLA regions, with prediction accuracies achieving over 99.0, 97.8, and 99.8% in HLA-A, B and C, respectively

Regional heritability mapping identifies several novel loci (STAT4, ULK4, and KCNH5) for primary biliary cholangitis in the Japanese population

原発性胆汁性胆管炎の新たな遺伝要因を同定 --ヒト全ゲノム領域へのRHM法による世界初の成果--. 京都大学プレスリリース. 2021-04-09.While the advent of GWAS more than a decade ago has ushered in remarkable advances in our understanding of complex traits, the limitations of single-SNP analysis have also led to the development of several other approaches. Simulation studies have shown that the regional heritability mapping (RHM) method, which makes use of multiple adjacent SNPs jointly to estimate the genetic effect of a given region of the genome, generally has higher detection power than single-SNP GWAS. However, thus far its use has been mostly limited to agricultural settings, and its potential for the discovery of new genes in human diseases is yet to be fully exploited. In this study, by applying the RHM method to primary biliary cholangitis (PBC) in the Japanese population, we identified three novel loci (STAT4, ULK4, and KCNH5) at the genome-wide significance level, two of which (ULK4 and KCNH5) have not been found associated with PBC in any population previously. Notably, these genes could not be detected by using conventional single-SNP GWAS, highlighting the potential of the RHM method for the detection of new susceptibility loci in human diseases. These findings thereby provide strong empirical evidence that RHM is an effective and practical complementary approach to GWAS in this context. Also, liver tissue mRNA microarray analysis revealed higher gene expression levels in ULK4 in PBC patients (P < 0.01). Lastly, we estimated the common SNP heritability of PBC in the Japanese population (0.210 ± 0.026)