In vivo and in vitro studies of Mgs1 suggest a link between genome instability and Okazaki fragment processing

The non-essential MGS1 gene of Saccharomyces cerevisiae is highly conserved in eukaryotes and encodes an enzyme containing both DNA-dependent ATPase and DNA annealing activities. MGS1 appears to function in post-replicational repair processes that contribute to genome stability. In this study, we identified MGS1 as a multicopy suppressor of the temperature-sensitive dna2Δ405N mutation, a DNA2 allele lacking the N-terminal 405 amino acid residues. Mgs1 stimulates the structure-specific nuclease activity of Rad27 (yeast Fen1 or yFen1) in an ATP-dependent manner. ATP binding but not hydrolysis was sufficient for the stimulatory effect of Mgs1, since non-hydrolyzable ATP analogs are as effective as ATP. Suppression of the temperature-sensitive growth defect of dna2Δ405N required the presence of a functional copy of RAD27, indicating that Mgs1 suppressed the dna2Δ405N mutation by increasing the activity of yFen1 (Rad27) in vivo. Our results provide in vivo and in vitro evidence that Mgs1 is involved in Okazaki fragment processing by modulating Fen1 activity. The data presented raise the possibility that the absence of MGS1 may impair the processing of Okazaki fragments, leading to genomic instability

Methano­ldinitrato[N-(2-pyridylmethyl­ene)aniline]copper(II)

The Cu atom in the title compound, [Cu(NO3)2(C12H10N2)(CH3OH)], adopts a square-pyramidal geometry, being ligated by two N atoms of the bidentate N-(2-pyridylmethyl­ene)­aniline (ppma) ligand, two O atoms of NO3 ligands and one O atom of a methanol molecule, which occupies the apical position. The phenyl ring on the ppma ligand is twisted out of the pyridine plane, forming a dihedral angle of 42.9 (1)°. In the crystal, inter­molecular O—H⋯O hydrogen bonds between methanol and NO3 ligands form an extensive one-dimensional network extending parallel to [100]

Echo Path Transfer Function Estimation for Spectral Subtraction-based Acoustic Echo Suppression

In this study, we propose a novel technique for spectral subtraction (SS)-based acoustic echo suppression (AES). Conventional AES methods based on SS apply fixed weights to the estimated echo path transfer function (EPTF) at the current signal segment and to the EPTF estimated until the previous time interval. We propose a new EPTF estimation approach that adaptively updates the weight parameters in response to abrupt changes in the acoustic environment. From the experiments, we conclude that the developed techniques can be successfully used for the SS-based AES systems

Correlation of hypoxia inducible transcription factor in breast cancer and SUVmax of F-18 FDG PET/CT

BACKGROUND: Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in patients with invasive ductal cancer (IDC) of the breast and the possible correlation with the maximum standardized uptake value of the primary tumor (pSUVmax) as well as other biological parameters. Prognostic significance of pSUVmax and expression of HIF-1a for the prediction of progression-free survival (PFS) was also assessed. MATERIAL AND METHODS: Two-hundred seven female patients with IDC who underwent pretreatment fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) were enrolled. The pSUVmax was compared with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), axillary lymph node (LN) metastasis, stage and HIF-1a expression. The prognostic value of pSUVmax for PFS was assessed using the Kaplan-Meier method. RESULTS: pSUVmax was significantly higher in patients with HIF-1a expression ≥ 2 compared to patients with HIF-1a expression < 2 (5.2 ± 4.5 vs. 3.7 ± 3.1, p = 0.008). pSUVmax was also significantly higher in higher stage (p < 0.000001), ER-negative tumors (p < 0.0001), PR-negative tumors (p = 0.0011) and positive LN metastasis (p = 0.0013). pSUVmax was significantly higher in patients with progression compared to patients who were disease-free (6.8 ± 4.4 vs. 4.1 ± 3.7, p = 0.0005). A receiver-operating characteristic curve demonstrated a pSUVmax of 6.51 to be the optimal cutoff for predicting PFS (sensitivity: 53.6%, specificity: 86.0%). Patients with high pSUVmax (> 6.5) had significantly shorter PFS compared to patients with low pSUVmax (p < 0.0001). CONCLUSIONS: pSUVmax on pretreatment F-18 FDG PET/ CT reflect expression of HIF-1a and can be used as a good surrogate marker for the prediction of progression in patients with IDC. The amount of FDG uptake is determined by the presence of glucose metabolism and hypoxia in breast cancer cell

High-Throughput Genotyping in Metastatic Esophageal Squamous Cell Carcinoma Identifies Phosphoinositide-3-Kinase and BRAF Mutations

Background: Given the high incidence of metastatic esophageal squamous cell carcinoma, especially in Asia, we screened for the presence of somatic mutations using OncoMap platform with the aim of defining subsets of patients who may be potential candidate for targeted therapy. Methods and Materials We analyzed 87 tissue specimens obtained from 80 patients who were pathologically confirmed with esophageal squamous cell carcinoma and received 5-fluoropyrimidine/platinum-based chemotherapy. OncoMap 4.0, a mass-spectrometry based assay, was used to interrogate 471 oncogenic mutations in 41 commonly mutated genes. Tumor specimens were prepared from primary cancer sites in 70 patients and from metastatic sites in 17 patients. In order to test the concordance between primary and metastatic sites from the patient for mutations, we analyzed 7 paired (primary-metastatic) specimens. All specimens were formalin-fixed paraffin embedded tissues and tumor content was >70%. Results: In total, we have detected 20 hotspot mutations out of 80 patients screened. The most frequent mutation was PIK3CA mutation (four E545K, five H1047R and one H1047L) (N = 10, 11.5%) followed by MLH1 V384D (N = 7, 8.0%), TP53 (R306, R175H and R273C) (N = 3, 3.5%), BRAF V600E (N = 1, 1.2%), CTNNB1 D32N (N = 1, 1.2%), and EGFR P733L (N = 1, 1.2%). Distributions of somatic mutations were not different according to anatomic sites of esophageal cancer (cervical/upper, mid, lower). In addition, there was no difference in frequency of mutations between primary-metastasis paired samples. Conclusions: Our study led to the detection of potentially druggable mutations in esophageal SCC which may guide novel therapies in small subsets of esophageal cancer patients

Plasmacytoid Dendritic Cells Contribute to the Protective Immunity Induced by Intranasal Treatment with Fc-fused Interleukin-7 against Lethal Influenza Virus Infection

Developing a novel vaccine that can be applied against multiple strains of influenza virus is of utmost importance to human health. Previously, we demonstrated that the intranasal introduction of Fc-fused IL-7 (IL-7-mFc), a long-acting cytokine fusion protein, confers long-lasting prophylaxis against multiple strains of influenza A virus (IAV) by inducing the development of lung-resident memory-like T cells, called TRM-like cells. Here, we further investigated the mechanisms of IL-7-mFc-mediated protective immunity to IAVs. First, we found that IL-7-mFc treatment augments the accumulation of pulmonary T cells in 2 ways: recruiting blood circulating T cells into the lung and expanding T cells at the lung parenchyma. Second, the blockade of T cell migration from the lymph nodes (LNs) with FTY720 treatment was not required for mounting the protective immunity to IAV with IL-7-mFc, suggesting a more important role of IL-7 in T cells in the lungs. Third, IL-7-mFc treatment also recruited various innate immune cells into the lungs. Among these cells, plasmacytoid dendritic cells (pDCs) play an important role in IL-7-mFc-mediated protective immunity through reducing the immunopathology and increasing IAV-specific cytotoxic T lymphocyte (CTL) responses. In summary, our results show that intranasal treatment with IL-7-mFc modulates pulmonary immune responses to IAV, affecting both innate and adaptive immune cells. ? 2017. The Korean Association of Immunologists.112Ysciescopuskc

Dichlorido[N,N-diethyl-N′-(2-pyridyl­methyl­ene)ethane-1,2-diamine]mercury(II)

The Hg atom in the title compound, [HgCl2(C12H19N3)], adopts a distorted trigonal-bipyramidal geometry, being ligated by two Cl atoms and three N atoms of the N,N-diethyl-N′-(2-pyridylmethyl­ene)ethane-1,2-diamine ligand. The dihedral angle between the HgN3 and HgCl2 least-squares planes is 88.6 (1)°. The Hg—N distances including the pyridine N and the ammonium N atom are about 0.20 Å longer than the Hg—N distance including the imino N atom

Sinus bone graft and simultaneous vertical ridge augmentation: case series study

Background This study aims to examine the outcome of simultaneous maxillary sinus lifting, bone grafting, and vertical ridge augmentation through retrospective studies. Methods From 2005 to 2010, patients with exhibited severe alveolar bone loss received simultaneous sinus lifting, bone grafting, and vertical ridge augmentations were selected. Fifteen patients who visited in Seoul National University Bundang Hospital were analyzed according to clinical records and radiography. Postoperative complications; success and survival rate of implants; complications of prosthesis; implant stability quotient (ISQ); vertical resorption of grafted bone after 1, 2, and 3 years after surgery; and final observation and marginal bone loss were evaluated. Results The average age of the patients was 54.2 years. Among the 33 implants, six failed to survive and succeed, resulting in an 81.8% survival rate and an 81.8% success rate. Postoperative complications were characterized by eight cases of ecchymosis, four cases of exposure of the titanium mesh or membrane, three cases of peri-implantitis, three cases of hematoma, two cases of sinusitis, two cases of fixture fracture, one case of bleeding, one case of numbness, one case of trismus, and one case of fixture loss. Prosthetic complications involved two instances of screw loosening, one case of abutment fracture, and one case of food impaction. Resorption of grafted bone material was 0.23 mm after 1 year, 0.47 mm after 2 years, 0.41 mm after 3 years, and 0.37 mm at the final observation. Loss of marginal bone was 0.12 mm after 1 year, and 0.20 mm at final observation. Conclusions When sinus lifting, bone grafting, and vertical ridge augmentation were performed simultaneously, postoperative complications increased, and survival rates were lower. For positive long-term prognosis, it is recommended that a sufficient recovery period be needed before implant placement to ensure good bone formation, and implant placement be delayed