Crystal Structures of the HslVU Peptidase–ATPase Complex Reveal an ATP-Dependent Proteolysis Mechanism

AbstractBackground: The bacterial heat shock locus HslU ATPase and HslV peptidase together form an ATP-dependent HslVU protease. Bacterial HslVU is a homolog of the eukaryotic 26S proteasome. Crystallographic studies of HslVU should provide an understanding of ATP-dependent protein unfolding, translocation, and proteolysis by this and other ATP-dependent proteases.Results: We present a 3.0 Å resolution crystal structure of HslVU with an HslU hexamer bound at one end of an HslV dodecamer. The structure shows that the central pores of the ATPase and peptidase are next to each other and aligned. The central pore of HslU consists of a GYVG motif, which is conserved among protease-associated ATPases. The binding of one HslU hexamer to one end of an HslV dodecamer in the 3.0 Å resolution structure opens both HslV central pores and induces asymmetric changes in HslV.Conclusions: Analysis of nucleotide binding induced conformational changes in the current and previous HslU structures suggests a protein unfolding–coupled translocation mechanism. In this mechanism, unfolded polypeptides are threaded through the aligned pores of the ATPase and peptidase and translocated into the peptidase central chamber

Clinical effect of IRT-5 probiotics on immune modulation of autoimmunity or alloimmunity in the eye

Background: Although the relation of the gut microbiota to a development of autoimmune and inflammatory diseases has been investigated in various animal models, there are limited studies that evaluate the effect of probiotics in the autoimmune eye disease. Therefore, we aimed to investigate the effect of IRT-5 probiotics consisting of Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus reuteri, Bifidobacterium bifidum, and Streptococcus thermophilus on the autoimmunity of uveitis and dry eye and alloimmunity of corneal transplantation. Methods: Experimental autoimmune uveitis was induced by subcutaneous immunization with interphotoreceptor-binding protein and intraperitoneal injection of pertussis toxin in C57BL/6 (B6) mice. For an autoimmune dry eye model, 12-weeks-old NOD.B10.H2b mice were used. Donor cornea of B6 mice was transplanted into BALB/C mice. IRT-5 probiotics or phosphate buffered saline (PBS) were administered for three weeks immediately after induction of uveitis or transplantation. The inflammation score of the retinal tissues, dry eye manifestations (corneal staining and tear secretion), and graft survival were measured in each model. The changes of T cells were evaluated in drainage lymph nodes using fluorescence-activated cell sorting. Results: Retinal histology score in IRT-5 group of uveitis was lower than that in PBS group (p = 0.045). Ocular staining score was lower (p < 0.0001) and tear secretion was higher (p < 0.0001) in the IRT-5 group of NOD.B10.H2b mice than that in the PBS group. However, the graft survival in the IRT-5 group was not different from those of PBS group. The percentage of regulatory T cells was increased in the IRT-5-treated dry eye models (p = 0.032). The percentage of CD8+IL-17hi (p = 0.027) and CD8+ interferon gamma (IFN��)hi cells (p = 0.022) were significantly decreased in the IRT-5-treated uveitis models and the percentage of CD8+IFN��hi cells was markedly reduced (p = 0.036) in IRT-5-treated dry eye model. Conclusion: Our results suggest that administration of IRT-5 probiotics may modulate clinical manifestations of autoimmunity in the eye, but not on alloimmunity of corneal transplantation. ? 2017 by the authors.112Nsciescopu

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data

Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants

Adhesion and leakage current characteristics of selective CVD tungsten films on the silicon substrate

In this study we investigated the effects of SF6 and CF4 plasma pretreatments on the adhesion and junction leakage characteristics of the selective CVD W films by SiH4 reduction of WF6 on the Si substrate. The SF6 plasma pretreatment performed in situ prior to W deposition to remove the polymer films in contact holes results in enhancement of the adhesion of W films to the Si substrate but degradation of junction leakages due to vertical and lateral Si consumptions. The CF4 plasma pretreatment performed as the last step of the reactive ion etching for contact window opening produced the W/Si contacts of good adhesion, low contact resistances and low junction leakages for thin W films, while it produced the W/Si contacts of poor adhesion and high contact resistances for thick W films. The selective CVD W films deposited by the three step process of SiH4 reduction/ in situ annealing / SiH4 reduction was found to have both good adhesion and low junction leakage characteristics

Mutation of ten-eleven translocation-2 is associated with increased risk of autoimmune disease in patients with myelodysplastic syndrome

Background/Aims: Myelodysplastic syndrome (MDS) is caused by genetic and epigenetic alteration of hematopoietic precursors and immune dysregulation. Approximately 20% of patients with MDS develop an autoimmune disease (AID). Here, we investigated whether particular genetic mutations are associated with AID in patients with MDS. Methods: Eighty-eight genetic mutations associated with myeloid malignancy were sequenced in 73 MDS patients. The association between these mutations and AID was then analyzed. Results: The median age of the 73 MDS patients was 70 years (interquartile range, 56 to 75), and 49 (67.1%) were male. AID was observed in 16 of 73 patients (21.9%). Mutations were detected in 57 (78.1%) patients. The percentage (68.8% vs. 80.7%, p = 0.32) and the mean number of mutations (1.8 ± 1.6 vs. 2.2 ± 1.8, p = 0.34) in MDS patients with or without AID were similar. However, the ten-eleven translocation-2 (TET2) mutation rate was significantly higher in patients with AID than in those without (31.3% vs. 5.3%, respectively; p = 0.001). All TET2 mutations were variants of strong clinical significance. Conclusions: Mutation of TET2 in patients with MDS may be associated with increased risk of developing AID.We thank Professor Eun Bong Lee for critical review of the manuscript. This research was supported by Basic Science Research Program through the Nation-al Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT and Future Planning (NRF-2017R1A2A1A17069780)

Corrigendum to "Statistical TiO2/dye-mass dependence and dye-regeneration efficiency on dye-sensitized solar cells" [Nano Energy 16 (2015) 383-388]

The authors would like to amend the authorship and acknowledgment as follows: 1. Co-authors, ‘Jongdeok An’, ‘Dajung Kim’, and ‘Chan Im’ made significant contributions to this work, but their efforts have not been recognized. Therefore, these three contributors should be included as co-authors by the listing of their names and affiliations. 2. We would also like to acknowledge and add the financial supporting as follows: “Acknowledgment: This research was supported by Seoul R&BD Program (WR090671). This research was also supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013R1A6A3A03021144)”. 3. First author now have two affiliations and the order of affiliations rearranged. All authors sincerely apologize for these corrections and any inconvenience to readers