Evaluation of carbonate apatite blocks fabricated from dicalcium phosphate dihydrate blocks for reconstruction of rabbit femoral and tibial defects.

PubMed

Kanazawa, Masayuki; Tsuru, Kanji; Fukuda, Naoyuki; Sakemi, Yuta; Nakashima, Yasuharu; Ishikawa, Kunio

2017-06-01

This study aimed to evaluate in vivo behavior of a carbonate apatite (CO 3 Ap) block fabricated by compositional transformation via a dissolution-precipitation reaction using a calcium hydrogen phosphate dihydrate [DCPD: CaHPO 4 ·2H 2 O] block as a precursor. These blocks were used to reconstruct defects in the femur and tibia of rabbits, using sintered dense hydroxyapatite (HAp) blocks as the control. Both the CO 3 Ap and HAp blocks showed excellent tissue response and good osteoconductivity. HAp block maintained its structure even after 24 weeks of implantation, so no bone replacement of the implant was observed throughout the post-implantation period in either femoral or tibial bone defects. In contrast, CO 3 Ap was resorbed with increasing time after implantation and replaced with new bone. The CO 3 Ap block was resorbed approximately twice as fast at the metaphysis of the proximal tibia than at the epiphysis of the distal femur. The CO 3 Ap block was resorbed at an approximately linear change over time, with complete resorption was estimated by extrapolation of data at approximately 1-1.5 years. Hence, the CO 3 Ap block fabricated in this study has potential value as an ideal artificial bone substitute because of its resorption and subsequent replacement by bone.

Postnatal Loss of Hap1 Reduces Hippocampal Neurogenesis and Causes Adult Depressive-Like Behavior in Mice

PubMed Central

Xiang, Jianxing; Yan, Sen; Li, Shi-Hua; Li, Xiao-Jiang

2015-01-01

Depression is a serious mental disorder that affects a person’s mood, thoughts, behavior, physical health, and life in general. Despite our continuous efforts to understand the disease, the etiology of depressive behavior remains perplexing. Recently, aberrant early life or postnatal neurogenesis has been linked to adult depressive behavior; however, genetic evidence for this is still lacking. Here we genetically depleted the expression of huntingtin-associated protein 1 (Hap1) in mice at various ages or in selective brain regions. Depletion of Hap1 in the early postnatal period, but not later life, led to a depressive-like phenotype when the mice reached adulthood. Deletion of Hap1 in adult mice rendered the mice more susceptible to stress-induced depressive-like behavior. Furthermore, early Hap1 depletion impaired postnatal neurogenesis in the dentate gyrus (DG) of the hippocampus and reduced the level of c-kit, a protein expressed in neuroproliferative zones of the rodent brain and that is stabilized by Hap1. Importantly, stereotaxically injected adeno-associated virus (AAV) that directs the expression of c-kit in the hippocampus promoted postnatal hippocampal neurogenesis and ameliorated the depressive-like phenotype in conditional Hap1 KO mice, indicating a link between postnatal-born hippocampal neurons and adult depression. Our results demonstrate critical roles for Hap1 and c-kit in postnatal neurogenesis and adult depressive behavior, and also suggest that genetic variations affecting postnatal neurogenesis may lead to adult depression. PMID:25875952

Postnatal loss of hap1 reduces hippocampal neurogenesis and causes adult depressive-like behavior in mice.

PubMed

Xiang, Jianxing; Yan, Sen; Li, Shi-Hua; Li, Xiao-Jiang

2015-04-01

Depression is a serious mental disorder that affects a person's mood, thoughts, behavior, physical health, and life in general. Despite our continuous efforts to understand the disease, the etiology of depressive behavior remains perplexing. Recently, aberrant early life or postnatal neurogenesis has been linked to adult depressive behavior; however, genetic evidence for this is still lacking. Here we genetically depleted the expression of huntingtin-associated protein 1 (Hap1) in mice at various ages or in selective brain regions. Depletion of Hap1 in the early postnatal period, but not later life, led to a depressive-like phenotype when the mice reached adulthood. Deletion of Hap1 in adult mice rendered the mice more susceptible to stress-induced depressive-like behavior. Furthermore, early Hap1 depletion impaired postnatal neurogenesis in the dentate gyrus (DG) of the hippocampus and reduced the level of c-kit, a protein expressed in neuroproliferative zones of the rodent brain and that is stabilized by Hap1. Importantly, stereotaxically injected adeno-associated virus (AAV) that directs the expression of c-kit in the hippocampus promoted postnatal hippocampal neurogenesis and ameliorated the depressive-like phenotype in conditional Hap1 KO mice, indicating a link between postnatal-born hippocampal neurons and adult depression. Our results demonstrate critical roles for Hap1 and c-kit in postnatal neurogenesis and adult depressive behavior, and also suggest that genetic variations affecting postnatal neurogenesis may lead to adult depression.

Huntingtin-associated protein-1 (HAP1) regulates endocytosis and interacts with multiple trafficking-related proteins.

PubMed

Mackenzie, Kimberly D; Lim, Yoon; Duffield, Michael D; Chataway, Timothy; Zhou, Xin-Fu; Keating, Damien J

2017-07-01

Huntingtin-associated protein 1 (HAP1) was initially identified as a binding partner of huntingtin, mutations in which underlie Huntington's disease. Subcellular localization and protein interaction data indicate that HAP1 may be important in vesicle trafficking, cell signalling and receptor internalization. In this study, a proteomics approach was used for the identification of novel HAP1-interacting partners to attempt to shed light on the physiological function of HAP1. Using affinity chromatography with HAP1-GST protein fragments bound to Sepharose columns, this study identified a number of trafficking-related proteins that bind to HAP1. Interestingly, many of the proteins that were identified by mass spectrometry have trafficking-related functions and include the clathrin light chain B and Sec23A, an ER to Golgi trafficking vesicle coat component. Using co-immunoprecipitation and GST-binding assays the association between HAP1 and clathrin light chain B has been validated in vitro. This study also finds that HAP1 co-localizes with clathrin light chain B. In line with a physiological function of the HAP1-clathrin interaction this study detected a dramatic reduction in vesicle retrieval and endocytosis in adrenal chromaffin cells. Furthermore, through examination of transferrin endocytosis in HAP1 -/- cortical neurons, this study has determined that HAP1 regulates neuronal endocytosis. In this study, the interaction between HAP1 and Sec23A was also validated through endogenous co-immunoprecipitation in rat brain homogenate. Through the identification of novel HAP1 binding partners, many of which have putative trafficking roles, this study provides us with new insights into the mechanisms underlying the important physiological function of HAP1 as an intracellular trafficking protein through its protein-protein interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

The synergistic effect of micro/nano-structured and Cu2+-doped hydroxyapatite particles to promote osteoblast viability and antibacterial activity.

PubMed

Shi, Feng; Liu, Yumei; Zhi, Wei; Xiao, Dongqin; Li, Hongyu; Duan, Ke; Qu, Shuxin; Weng, Jie

2017-06-06

Microstructure and chemical constitution are important factors affecting the biological activity of biomaterials. This study aimed to fabricate hydroxyapatite (HAp) particles with both micro/nanohybrid structure and Cu 2+ doping to promote osteogenic differentiation and antibacterial property. In the presence of inositol hexakisphosphate (IP6), micro/nano-structured and Cu 2+ -doped HAp (HAp-IP6-Cu) microspheres were successfully fabricated via hydrothermal method. Morphological observation showed that HAp-IP6-Cu microspheres with a diameter of 3.1-4.1 μm were chrysanthemum-like and composed of nano-flakes approximately 50 nm in thickness. Compared with the HAp micro-rods or IP6 modified HAp (HAp-IP6) microspheres, HAp-IP6-Cu microspheres had a larger specific surface area, better hydrophilicity and stronger ability to adsorb bovine serum albumin. To evaluate the synergistic effects of micro/nanohybrid structure and Cu 2+ on cell behavior, rat calvarial osteoblasts (RCOs) were cultured on HAp-IP6-Cu, HAp-IP6 and HAp layers as well as their extracts, respectively. Results demonstrated that HAp-IP6-Cu layer promoted the adhesion, proliferation and osteogenic differentiation of RCOs. The cells grew on HAp-IP6-Cu and HAp-IP6 layers exhibited greater spreading than those on HAp layer. In addition, quantitative test by the agar disk diffusion technique found that HAp-IP6-Cu microspheres were effectively against S taphylococcus aureus and E scherichia coli. These results demonstrated that HAp-IP6-Cu microspheres may be a potential candidate as a bioactive and anti-infective biomaterial for bone regeneration.

The FOUR score and GCS as predictors of outcome after traumatic brain injury.

PubMed

McNett, Molly; Amato, Shelly; Gianakis, Anastasia; Grimm, Dawn; Philippbar, Sue Ann; Belle, Josie; Moran, Cristina

2014-08-01

The Glasgow Coma Scale (GCS) is a routine component of a neurological exam for critically ill traumatic brain injury (TBI) patients, yet has been criticized for not accurately depicting verbal status among intubated patients or including brain stem reflexes. Preliminary research on the Full Outline of UnResponsiveness (FOUR) Scale suggests it overcomes these limitations. Research is needed to determine correlations with patient outcomes. The aims of this study were to: (1) examine correlations between 24 and 72 h FOUR and GCS scores and functional/cognitive outcomes; (2) determine relationship between 24 and 72 h FOUR scores and mortality. Prospective cohort study. Data gathered on adult TBI patients at a Level I trauma center. FOUR scores assigned at 24, 72 h. Functional outcome measured by functional independence measure scores at rehabilitation discharge; cognitive status measured by Weschler Memory Scale scores 3 months post-injury. n = 136. Mean age 53.1. 72 h FOUR and GCS scores correlated with functional outcome (r s = 0.34, p = 0.05; r s = 0.39, p = 0.02), but not cognitive status. Receiver operating characteristic curves were comparable for FOUR and GCS at 24 and 72 h for functional status (24 h FOUR, GCS = 0.625, 0.602, respectively; 72 h FOUR, GCS = 0.640, 0.688), cognitive status (24 h FOUR, GCS = 0.703, 0.731; 72 h FOUR, GCS = 0.837, 0.674), and mortality (24 h FOUR, GCS = 0.913, 0.935; 72 h FOUR, GCS = 0.837, 0.884). FOUR is comparable to GCS in terms of predictive ability for functional status, cognitive outcome 3 months post-injury, and in-hospital mortality.

HapZipper: sharing HapMap populations just got easier.

PubMed

Chanda, Pritam; Elhaik, Eran; Bader, Joel S

2012-11-01

The rapidly growing amount of genomic sequence data being generated and made publicly available necessitate the development of new data storage and archiving methods. The vast amount of data being shared and manipulated also create new challenges for network resources. Thus, developing advanced data compression techniques is becoming an integral part of data production and analysis. The HapMap project is one of the largest public resources of human single-nucleotide polymorphisms (SNPs), characterizing over 3 million SNPs genotyped in over 1000 individuals. The standard format and biological properties of HapMap data suggest that a dedicated genetic compression method can outperform generic compression tools. We propose a compression methodology for genetic data by introducing HapZipper, a lossless compression tool tailored to compress HapMap data beyond benchmarks defined by generic tools such as gzip, bzip2 and lzma. We demonstrate the usefulness of HapZipper by compressing HapMap 3 populations to <5% of their original sizes. HapZipper is freely downloadable from https://bitbucket.org/pchanda/hapzipper/downloads/HapZipper.tar.bz2.

STMN1 Promotes Progesterone Production Via StAR Up-regulation in Mouse Granulosa Cells.

PubMed

Dou, Yun-De; Zhao, Han; Huang, Tao; Zhao, Shi-Gang; Liu, Xiao-Man; Yu, Xiao-Chen; Ma, Zeng-Xiang; Zhang, Yu-Chao; Liu, Tao; Gao, Xuan; Li, Lei; Lu, Gang; Chan, Wai-Yee; Gao, Fei; Liu, Hong-Bin; Chen, Zi-Jiang

2016-06-08

Stathmin 1 (STMN1) is a biomarker in several types of neoplasms. It plays an important role in cell cycle progression, mitosis, signal transduction and cell migration. In ovaries, STMN1 is predominantly expressed in granulosa cells (GCs). However, little is known about the role of STMN1 in ovary. In this study, we demonstrated that STMN1 is overexpressed in GCs in patients with polycystic ovary syndrome (PCOS). In mouse primary GCs, the overexpression of STMN1 stimulated progesterone production, whereas knockdown of STMN1 decreased progesterone production. We also found that STMN1 positively regulates the expression of Star (steroidogenic acute regulatory protein) and Cyp11a1 (cytochrome P450 family 11 subfamily A member 1). Promoter and ChIP assays indicated that STMN1 increased the transcriptional activity of Star and Cyp11a1 by binding to their promoter regions. The data suggest that STMN1 mediates the progesterone production by modulating the promoter activity of Star and Cyp11a1. Together, our findings provide novel insights into the molecular mechanisms of STMN1 in ovary GC steroidogenesis. A better understanding of this potential interaction between STMN1 and Star in progesterone biosynthesis in GCs will facilitate the discovery of new therapeutic targets in PCOS.

Microwave-induced production of boron-doped HAp (B-HAp) and B-HAp coated composite scaffolds.

PubMed

Tunçay, Ekin Ö; Demirtaş, T Tolga; Gümüşderelioğlu, Menemşe

2017-03-01

The aim of the present study is to produce boron (B) doped hydroxyapatite (B-HAp), which has an osteoinductive property, and investigate in-vitro osteogenesis potential of B-HAp coated chitosan (B-HAp/Ch) scaffolds. At first, B-HAp was produced by the interaction of ions within the concentrated synthetic body fluid containing boron (B-SBF) with microwave energy. Boron incorporation into HAp structure was performed by the substitution of borate ions with phosphate and hydroxyl ions. Experiments were carried out with different microwave powers and exposure times, and optimum conditions for the production of B-HAp were determined. B-HAp precipitated from B-SBF by 600W microwave power has 1.15±0.11% (w/w) B, 1.40 (w/w) Ca/P ratio, 4.30±0.07% (w/w) carbonate content, 30±4nm rod-like morphology and bone-like amorphous structure. Then, chitosan scaffolds that were prepared by freeze-drying were coated with B-HAp by performing microwave-assisted precipitation in the presence of scaffolds to improve their bioactivities and mechanical properties. The formation of apatite layer and the penetration of apatites into the pores were observed by scanning electron microscopy (SEM). Fourier Transform Infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD) analysis also confirmed the presence of B-HAp layer. As control, hydroxyapatite coated chitosan scaffolds (HAp/Ch) produced at the same conditions were used. The results of cell culture studies indicated that B releasing from scaffolds enhances proliferation and osteoblastic differentiation of MC3T3-E1 cells. This work emphasized the importance of the use of B within the scaffolds for enhancing in-vitro bone tissue engineering applications. Copyright © 2017 Elsevier GmbH. All rights reserved.

ESR investigation of ROS generated by H2O2 bleaching with TiO2 coated HAp.

PubMed

Saita, Makiko; Kobayashi, Kyo; Kobatashi, Kyou; Yoshino, Fumihiko; Hase, Hiriko; Nonami, Toru; Kimoto, Katsuhiko; Lee, Masaichi-Chang-il

2012-01-01

It is well known that clinical bleaching can be achieved with a solution of 30% hydrogen peroxide (H2O2) or H2O2/titanium dioxide (TiO2) combination. This study examined the hypothesis that TiO2 coated with hydroxyapatite (HAp-TiO2) can generate reactive oxygen species (ROS). ROS are generated via photocatalysis using electron spin resonance (ESR). The bleaching properties of HAp-TiO2 in the presence of H2O2 can be measured using hematoporphyrin litmus paper and extracted teeth. We demonstrate that superoxides (O2(•-)) and hydroxyl radicals (HO(•)) can be generated through excitation of anatase TiO2, rutile TiO2, anatase HAp-TiO2, and rutile HAp-TiO2 in the presence of H2O2. The combination of R HAp-TiO2 with H2O2 produced the highest level of HO(•) generation and the most marked bleaching effects of all the samples. The superior bleaching effects exhibited by R HAp-TiO2 with H2O2 suggest that this combination may lead to novel methods for the clinical application of bleaching treatments.

Molecular Characterization of Hap Complex Components Responsible for Methanol-Inducible Gene Expression in the Methylotrophic Yeast Candida boidinii

PubMed Central

Oda, Saori; Yurimoto, Hiroya; Nitta, Nobuhisa; Sasano, Yu

2015-01-01

We identified genes encoding components of the Hap complex, CbHAP2, CbHAP3, and CbHAP5, as transcription factors regulating methanol-inducible gene expression in the methylotrophic yeast Candida boidinii. We found that the Cbhap2Δ, Cbhap3Δ, and Cbhap5Δ gene-disrupted strains showed severe growth defects on methanol but not on glucose and nonfermentable carbon sources such as ethanol and glycerol. In these disruptants, the transcriptional activities of methanol-inducible promoters were significantly decreased compared to those of the wild-type strain, indicating that CbHap2p, CbHap3p, and CbHap5p play indispensable roles in methanol-inducible gene expression. Further molecular and biochemical analyses demonstrated that CbHap2p, CbHap3p, and CbHap5p localized to the nucleus and bound to the promoter regions of methanol-inducible genes regardless of the carbon source, and heterotrimer formation was suggested to be necessary for binding to DNA. Unexpectedly, distinct from Saccharomyces cerevisiae, the Hap complex functioned in methanol-specific induction rather than glucose derepression in C. boidinii. Our results shed light on a novel function of the Hap complex in methanol-inducible gene expression in methylotrophic yeasts. PMID:25595445

Evidence for participation of GCS1 in fertilization of the starlet sea anemone Nematostella vectensis: Implication of a common mechanism of sperm–egg fusion in plants and animals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ebchuqin, Eerdundagula; Yokota, Naoto; Yamada, Lixy

Highlights: • GCS1 is a sperm transmembrane protein that is essential for gamete fusion in flowering plants. • The GCS1 gene is present not only in angiosperms but also in unicellular organisms and animals. • NvGCS1 gene is expressed in the testis and GCS1 protein exists in sperm of a sea anemone. • Anti-GCS1 antibodies inhibited the fertilization, showing the participation in fertilization. - Abstract: It has been reported that GCS1 (Generative Cell Specific 1) is a transmembrane protein that is exclusively expressed in sperm cells and is essential for gamete fusion in flowering plants. The GCS1 gene is presentmore » not only in angiosperms but also in unicellular organisms and animals, implying the occurrence of a common or ancestral mechanism of GCS1-mediated gamete fusion. In order to elucidate the common mechanism, we investigated the role of GCS1 in animal fertilization using a sea anemone (Cnidaria), Nematostella vectensis. Although the existence of the GCS1 gene in N. vectensis has been reported, the expression of GCS1 in sperm and the role of GCS1 in fertilization are not known. In this study, we showed that the GCS1 gene is expressed in the testis and that GCS1 protein exists in sperm by in situ hybridization and proteomic analysis, respectively. Then we made four peptide antibodies against the N-terminal extracellular region of NvGCS1. These antibodies specifically reacted to NvGCS1 among sperm proteins on the basis of Western analysis and potently inhibited fertilization in a concentration-dependent manner. These results indicate that sperm GCS1 plays a pivotal role in fertilization, most probably in sperm–egg fusion, in a starlet sea anemone, suggesting a common gamete-fusion mechanism shared by eukaryotic organisms.« less

Intracellular colocalization of HAP1/STBs with steroid hormone receptors and its enhancement by a proteasome inhibitor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujinaga, Ryutaro; Takeshita, Yukio; Yoshioka, Kazuhiro

2011-07-15

The stigmoid body (STB) is a cytoplasmic inclusion containing huntingtin-associated protein 1 (HAP1), and HAP1/STB formation is induced by transfection of the HAP1 gene into cultured cells. In the present study, we examined the intracellular colocalization of HAP1/STBs with steroid hormone receptors (SHRs), including the androgen receptor (AR), estrogen receptor, glucocorticoid receptor (GR), and mineralocorticoid receptor, in COS-7 cells cotransfected with HAP1 and each receptor. We found that C-terminal ligand-binding domains of all SHRs had potential for colocalization with HAP1/STBs, whereas only AR and GR were clearly colocalized with HAP1/STBs when each full-length SHR was coexpressed with HAP1. In addition,more » it appeared that HAP1/STBs did not disrupt GR and AR functions because the receptors on HAP1/STBs maintained nuclear translocation activity in response to their specific ligands. When the cells were treated with a proteasome inhibitor, GR and AR localized outside HAP1/STBs translocated into the nucleus, whereas the receptors colocalized with HAP1/STBs persisted in their colocalization even after treatment with their ligands. Therefore, HAP1/STBs may be involved in cytoplasmic modifications of the nuclear translocation of GR and AR in a ubiquitin-proteasome system.« less

Development of an Intelligent Monitoring System for Geological Carbon Sequestration (GCS) Systems

NASA Astrophysics Data System (ADS)

Sun, A. Y.; Jeong, H.; Xu, W.; Hovorka, S. D.; Zhu, T.; Templeton, T.; Arctur, D. K.

2016-12-01

To provide stakeholders timely evidence that GCS repositories are operating safely and efficiently requires integrated monitoring to assess the performance of the storage reservoir as the CO2 plume moves within it. As a result, GCS projects can be data intensive, as a result of proliferation of digital instrumentation and smart-sensing technologies. GCS projects are also resource intensive, often requiring multidisciplinary teams performing different monitoring, verification, and accounting (MVA) tasks throughout the lifecycle of a project to ensure secure containment of injected CO2. How to correlate anomaly detected by a certain sensor to events observed by other devices to verify leakage incidents? How to optimally allocate resources for task-oriented monitoring if reservoir integrity is in question? These are issues that warrant further investigation before real integration can take place. In this work, we are building a web-based, data integration, assimilation, and learning framework for geologic carbon sequestration projects (DIAL-GCS). DIAL-GCS will be an intelligent monitoring system (IMS) for automating GCS closed-loop management by leveraging recent developments in high-throughput database, complex event processing, data assimilation, and machine learning technologies. Results will be demonstrated using realistic data and model derived from a GCS site.

HapMap filter 1.0: a tool to preprocess the HapMap genotypic data for association studies.

PubMed

Zhang, Wei; Duan, Shiwei; Dolan, M Eileen

2008-05-13

The International HapMap Project provides a resource of genotypic data on single nucleotide polymorphisms (SNPs), which can be used in various association studies to identify the genetic determinants for phenotypic variations. Prior to the association studies, the HapMap dataset should be preprocessed in order to reduce the computation time and control the multiple testing problem. The less informative SNPs including those with very low genotyping rate and SNPs with rare minor allele frequencies to some extent in one or more population are removed. Some research designs only use SNPs in a subset of HapMap cell lines. Although the HapMap website and other association software packages have provided some basic tools for optimizing these datasets, a fast and user-friendly program to generate the output for filtered genotypic data would be beneficial for association studies. Here, we present a flexible, straight-forward bioinformatics program that can be useful in preparing the HapMap genotypic data for association studies by specifying cell lines and two common filtering criteria: minor allele frequencies and genotyping rate. The software was developed for Microsoft Windows and written in C++. The Windows executable and source code in Microsoft Visual C++ are available at Google Code (http://hapmap-filter-v1.googlecode.com/) or upon request. Their distribution is subject to GNU General Public License v3.

Software quality assurance plan for GCS

NASA Technical Reports Server (NTRS)

Duncan, Stephen E.; Bailey, Elizabeth K.

1990-01-01

The software quality assurance (SQA) function for the Guidance and Control Software (GCS) project which is part of a software error studies research program is described. The SQA plan outlines all of the procedures, controls, and audits to be carried out by the SQA organization to ensure adherence to the policies, procedures, and standards for the GCS project.

Glucocorticoids promote Von Hippel Lindau degradation and Hif-1α stabilization

PubMed Central

Greenald, David; Wilson, Garrick K.; Peron, Margherita; Markham, Eleanor; Sinnakaruppan, Mathavan; Matthews, Laura C.; McKeating, Jane A.; Argenton, Francesco; van Eeden, Fredericus J. M.

2017-01-01

Glucocorticoid (GC) and hypoxic transcriptional responses play a central role in tissue homeostasis and regulate the cellular response to stress and inflammation, highlighting the potential for cross-talk between these two signaling pathways. We present results from an unbiased in vivo chemical screen in zebrafish that identifies GCs as activators of hypoxia-inducible factors (HIFs) in the liver. GCs activated consensus hypoxia response element (HRE) reporters in a glucocorticoid receptor (GR)-dependent manner. Importantly, GCs activated HIF transcriptional responses in a zebrafish mutant line harboring a point mutation in the GR DNA-binding domain, suggesting a nontranscriptional route for GR to activate HIF signaling. We noted that GCs increase the transcription of several key regulators of glucose metabolism that contain HREs, suggesting a role for GC/HIF cross-talk in regulating glucose homeostasis. Importantly, we show that GCs stabilize HIF protein in intact human liver tissue and isolated hepatocytes. We find that GCs limit the expression of Von Hippel Lindau protein (pVHL), a negative regulator of HIF, and that treatment with the c-src inhibitor PP2 rescued this effect, suggesting a role for GCs in promoting c-src–mediated proteosomal degradation of pVHL. Our data support a model for GCs to stabilize HIF through activation of c-src and subsequent destabilization of pVHL. PMID:28851829

Mechanical properties and corrosion behavior of Mg-HAP composites.

PubMed

Campo, R Del; Savoini, B; Muñoz, A; Monge, M A; Garcés, G

2014-11-01

Mg and Mg-HAP composites containing 5, 10 and 15 wt% of hydroxyapatite have been produced following a powder metallurgy route that consists of mixing raw powders and consolidation by extrusion. The microstructure, texture, mechanical behavior and resistance to corrosion under a PBS solution have been studied. Addition of HAP increases the microhardness of the composites, however the yield strength under compression slightly decreases. Texture analyses reveal a fiber texture for pure Mg that is weakened increasing the HAP fraction. This texture promotes twinning and softening of Mg and Mg-5HAP during the initial deformation stages. Mg-10HAP and Mg-15HAP present a strain-hardening dependence showing no softening. The volume fraction of HAP particles weakens the texture and favors the activation of secondary slip systems. Corrosion experiments in PBS solution have shown that Mg-5HAP exhibits the best resistance to corrosion. Texture and porosity appear to be the main material features controlling the corrosion rates of Mg-HAP composites under the present conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

GCS plan for software aspects of certification

NASA Technical Reports Server (NTRS)

Shagnea, Anita M.; Lowman, Douglas S.; Withers, B. Edward

1990-01-01

As part of the Guidance and Control Software (GCS) research project being sponsored by NASA to evaluate the failure processes of software, standard industry software development procedures are being employed. To ensure that these procedures are authentic, the guidelines outlined in the Radio Technical Commission for Aeronautics (RTCA/DO-178A document entitled, software considerations in airborne systems and equipment certification, were adopted. A major aspect of these guidelines is proper documentation. As such, this report, the plan for software aspects of certification, was produced in accordance with DO-178A. An overview is given of the GCS research project, including the goals of the project, project organization, and project schedules. It also specifies the plans for all aspects of the project which relate to the certification of the GCS implementations developed under a NASA contract. These plans include decisions made regarding the software specification, accuracy requirements, configuration management, implementation development and verification, and the development of the GCS simulator.

A positive feedback loop between progesterone and microsomal prostaglandin E synthase-1-mediated PGE2 promotes production of both in mouse granulosa cells.

PubMed

Tamura, Kazuhiro; Naraba, Hiroaki; Hara, Takahiko; Nakamura, Kota; Yoshie, Mikihiro; Kogo, Hiroshi; Tachikawa, Eiichi

2016-03-01

Microsomal prostaglandin E synthase-1 (mPGES-1) is primarily expressed in granulosa cells (GCs) in the preovulatory follicle. Both prostaglandin E2 (PGE2) and progesterone (P4) are implicated in various reproductive functions. Here, we demonstrate that mPges-1 may be a direct downstream target gene of the P4 receptor and P4-stimulated PGE2 secretion can stimulate P4 production in a newly generated mouse GC line (GtsT). Treatment of GtsT cells with a P4 receptor agonist, norgestrel, markedly increased mPGES-1 expression detected by RT-PCR analysis. PGE2 secretion measured by an enzyme-linked immunosorbent assay was enhanced by P4 treatment. Luciferase assays revealed that the proximal promoter region of the mPges-1 gene was responsible for the effects of P4 treatment. Conversely, PGE2 treatment stimulated P4 secretion, which coordinated with mRNA expression of steroidogenic acute regulatory protein. Taken together, P4 may regulate mPGES-1 expression to increase PGE2 secretion and in turn P4 production. An autocrine loop between P4 and PGE2 might function to maintain the increased levels of both in GCs. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic value of FOUR and GCS scores in determining mortality in patients with traumatic brain injury.

PubMed

Saika, Amrit; Bansal, Sonia; Philip, Mariamma; Devi, Bhagavatula Indira; Shukla, Dhaval P

2015-09-01

The Glasgow Coma Scale (GCS) is considered the gold standard for assessment of unconsciousness in patients with traumatic brain injury (TBI) against which other scales are compared. To overcome the disadvantages of GCS, the Full Outline Of Unresponsiveness (FOUR) score was proposed. We aimed to compare the predictability of FOUR score and GCS for early mortality, after moderate and severe TBI. This is a prospective observational study of patients with moderate and severe TBI. Both FOUR and GCS scores were determined at admission. The primary outcome was mortality at the end of 2 weeks of injury. A total of 138 (117 males) patients were included in the study. Out of these, 17 (12.3 %) patients died within 2 weeks of injury. The mean GCS and FOUR scores were 9.5 (range, 3-13) and 11 (0-16), respectively. The total GCS and FOUR scores were significantly lower in patients who did not survive. At a cut-off score of 7 for FOUR score, the AUC was 0.97, with sensitivity of 97.5 and specificity of 88.2 % (p < 0.0001). For GCS score, AUC was 0.95, with sensitivity of 98.3 % and specificity of 82.4 % with cut-off score of 6 (p < 0.0001). The correlation coefficient was 0.753 (p < 0.001) between the GCS and FOUR scores. The predictive value of the FOUR score on admission of patients with TBI is no better than the GCS score.

Peat Water Purification by Hydroxyapatite (HAp) Synthesized from Waste Pensi (Corbicula moltkiana) Shells

NASA Astrophysics Data System (ADS)

Fajri Alif, Matlal; Aprillia, Wandha; Arief, Syukri

2018-01-01

Hydroxyapatite (HAP) were synthesized from Pensi (Corbicula moltkiana) sheels by hydrothermal method and used as adsorbent for peat water purification. Batch adsorption experiments were performed to investigate the effects of various factors such as contact time, adsorbent dosage, and pH. The obtained materials were characterized by powder X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscope (SEM). Results showed that HAP calcined at 900°C (HAP900) and 1000°C (HAP1000) have a poorly crystalline shape. HAP900 also contain Tetracalsium Phosphate (TTCP) with a Ca/P molar ratio 2.18, while HAP 1000 contain HAp with a Ca/P molar ratio 1.67. Optimum condition for peat water purification with HAP900 and HAP1000 were both achieved at 1 hours, 1 grams adsorben mass at pH 2. SEM micrographs show that after purification, the surface of HAP were covered by organic compounds from peat water.

Transactivation of micrornA-320 by microRNA-383 regulates granulosa cell functions by targeting E2F1 and SF-1 proteins.

PubMed

Yin, Mianmian; Wang, Xiaorong; Yao, Guidong; Lü, Mingrong; Liang, Meng; Sun, Yingpu; Sun, Fei

2014-06-27

Our previous studies have shown that microRNA-320 (miR-320) is one of the most down-regulated microRNAs (miRNA) in mouse ovarian granulosa cells (GCs) after TGF-β1 treatment. However, the underlying mechanisms of miR-320 involved in GC function during follicular development remain unknown. In this study, we found that pregnant mare serum gonadotropin treatment resulted in the suppression of miR-320 expression in a time-dependent manner. miR-320 was mainly expressed in GCs and oocytes of mouse ovarian follicles in follicular development. Overexpression of miR-320 inhibited estradiol synthesis and proliferation of GCs through targeting E2F1 and SF-1. E2F1/SF-1 mediated miR-320-induced suppression of GC proliferation and of GC steroidogenesis. FSH down-regulated the expression of miR-320 and regulated the function of miR-320 in mouse GCs. miR-383 promoted the expression of miR-320 and enhanced miR-320-mediated suppression of GC proliferation. Injection of miR-320 into the ovaries of mice partially promoted the production of testosterone and progesterone but inhibited estradiol release in vivo. Moreover, the expression of miR-320 and miR-383 was up-regulated in the follicular fluid of polycystic ovarian syndrome patients, although the expression of E2F1 and SF-1 was down-regulated in GCs. These data demonstrated that miR-320 regulates the proliferation and steroid production by targeting E2F1 and SF-1 in the follicular development. Understanding the regulation of miRNA biogenesis and function in the follicular development will potentiate the usefulness of miRNA in the treatment of reproduction and some steroid-related disorders. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

24 CFR 891.560 - HAP contract.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false HAP contract. 891.560 Section 891... Assistance § 891.560 HAP contract. (a) HAP contract. The housing assistance payments contract sets forth.... (b) HAP contract execution. (1) Upon satisfactory completion of the project, the Borrower and HUD...

Chromosomal Expression of the Haemophilus influenzae Hap Autotransporter Allows Fine-Tuned Regulation of Adhesive Potential via Inhibition of Intermolecular Autoproteolysis

PubMed Central

Fink, Doran L.; St. Geme III, Joseph W.

2003-01-01

The Haemophilus influenzae Hap autotransporter is a nonpilus adhesin that promotes adherence to respiratory epithelial cells and selected extracellular matrix proteins and facilitates bacterial aggregation and microcolony formation. Hap consists of a 45-kDa outer membrane translocator domain called Hapβ and a 110-kDa extracellular passenger domain called HapS. All adhesive activity resides within HapS, which also contains protease activity and directs its own secretion from the bacterial cell surface via intermolecular autoproteolysis. In the present study, we sought to determine the relationship between the magnitude of Hap expression, the efficiency of Hap autoproteolysis, and the level of Hap-mediated adherence and aggregation. We found that a minimum threshold of Hap precursor was required for autoproteolysis and that this threshold approximated expression of Hap from a chromosomal allele, as occurs in H. influenzae clinical isolates. Chromosomal expression of wild-type Hap was sufficient to promote significant adherence to epithelial cells and extracellular matrix proteins, and adherence was enhanced substantially by inhibition of autoproteolysis. In contrast, chromosomal expression of Hap was sufficient to promote bacterial aggregation only when autoproteolysis was inhibited, indicating that the threshold for Hap-mediated aggregation is above the threshold for autoproteolysis. These results highlight the critical role of autoproteolysis and an intermolecular mechanism of cleavage in controlling the diverse adhesive activities of Hap. PMID:12591878

Hospital-acquired pneumonia is an independent predictor of poor global outcome in severe traumatic brain injury up to 5 years after discharge.

PubMed

Kesinger, Matthew Ryan; Kumar, Raj G; Wagner, Amy K; Puyana, Juan Carlos; Peitzman, Andrew P; Billiar, Timothy R; Sperry, Jason L

2015-02-01

Long-term outcomes following traumatic brain injury (TBI) correlate with initial head injury severity and other acute factors. Hospital-acquired pneumonia (HAP) is a common complication in TBI. Limited information exists regarding the significance of infectious complications on long-term outcomes after TBI. We sought to characterize risks associated with HAP on outcomes 5 years after TBI. This study involved data from the merger of an institutional trauma registry and the Traumatic Brain Injury Model Systems outcome data. Individuals with severe head injuries (Abbreviated Injury Scale [AIS] score ≥ 4) who survived to rehabilitation were analyzed. Primary outcome was Glasgow Outcome Scale-Extended (GOSE) at 1, 2, and 5 years. GOSE was dichotomized into low (GOSE score < 6) and high (GOSE score ≥ 6). Logistic regression was used to determine adjusted odds of low GOSE score associated with HAP after controlling for age, sex, head and overall injury severity, cranial surgery, Glasgow Coma Scale (GCS) score, ventilation days, and other important confounders. A general estimating equation model was used to analyze all outcome observations simultaneously while controlling for within-patient correlation. A total of 141 individuals met inclusion criteria, with a 30% incidence of HAP. Individuals with and without HAP had similar demographic profiles, presenting vitals, head injury severity, and prevalence of cranial surgery. Individuals with HAP had lower presenting GCS score. Logistic regression demonstrated that HAP was independently associated with low GOSE scores at follow-up (1 year: odds ratio [OR], 6.39; 95% confidence interval [CI], 1.76-23.14; p = 0.005) (2 years: OR, 7.30; 95% CI, 1.87-27.89; p = 0.004) (5-years: OR, 6.89; 95% CI, 1.42-33.39; p = 0.017). Stratifying by GCS score of 8 or lower and early intubation, HAP remained a significant independent predictor of low GOSE score in all strata. In the general estimating equation model, HAP continued to be an

Heteroaryldihydropyrimidine (HAP) and Sulfamoylbenzamide (SBA) Inhibit Hepatitis B Virus Replication by Different Molecular Mechanisms

PubMed Central

Zhou, Zheng; Hu, Taishan; Zhou, Xue; Wildum, Steffen; Garcia-Alcalde, Fernando; Xu, Zhiheng; Wu, Daitze; Mao, Yi; Tian, Xiaojun; Zhou, Yuan; Shen, Fang; Zhang, Zhisen; Tang, Guozhi; Najera, Isabel; Yang, Guang; Shen, Hong C.; Young, John A. T.; Qin, Ning

2017-01-01

Heteroaryldihydropyrimidine (HAP) and sulfamoylbenzamide (SBA) are promising non-nucleos(t)ide HBV replication inhibitors. HAPs are known to promote core protein mis-assembly, but the molecular mechanism of abnormal assembly is still elusive. Likewise, the assembly status of core protein induced by SBA remains unknown. Here we show that SBA, unlike HAP, does not promote core protein mis-assembly. Interestingly, two reference compounds HAP_R01 and SBA_R01 bind to the same pocket at the dimer-dimer interface in the crystal structures of core protein Y132A hexamer. The striking difference lies in a unique hydrophobic subpocket that is occupied by the thiazole group of HAP_R01, but is unperturbed by SBA_R01. Photoaffinity labeling confirms the HAP_R01 binding pose at the dimer-dimer interface on capsid and suggests a new mechanism of HAP-induced mis-assembly. Based on the common features in crystal structures we predict that T33 mutations generate similar susceptibility changes to both compounds. In contrast, mutations at positions in close contact with HAP-specific groups (P25A, P25S, or V124F) only reduce susceptibility to HAP_R01, but not to SBA_R01. Thus, HAP and SBA are likely to have distinctive resistance profiles. Notably, P25S and V124F substitutions exist in low-abundance quasispecies in treatment-naïve patients, suggesting potential clinical relevance. PMID:28205569

The Haemophilus influenzae Hap Autotransporter Binds to Fibronectin, Laminin, and Collagen IV

PubMed Central

Fink, Doran L.; Green, Bruce A.; St. Geme III, Joseph W.

2002-01-01

Nontypeable Haemophilus influenzae (NTHI) initiates infection by colonizing the upper respiratory tract mucosa. NTHI disease frequently occurs in the context of respiratory tract inflammation, where organisms encounter damaged epithelium and exposed basement membrane. In this study, we examined interactions between the H. influenzae Hap adhesin and selected extracellular matrix proteins. Hap is an autotransporter protein that undergoes autoproteolytic cleavage, with release of the adhesive passenger domain, Haps, from the bacterial cell surface. We found that Hap promotes bacterial adherence to purified fibronectin, laminin, and collagen IV and that Hap-mediated adherence is enhanced by inhibition of autoproteolysis. Adherence is inhibited by pretreatment of bacteria with a polyclonal antiserum recognizing Haps. Purified Haps binds with high affinity to fibronectin, laminin, and collagen IV but not to collagen II. Binding of Haps to fibronectin involves interaction with the 45-kDa gelatin-binding domain but not the 30-kDa heparin-binding domain of fibronectin. Taken together, these observations suggest that interactions between Hap and extracellular matrix proteins may play an important role in NTHI colonization of the respiratory tract. PMID:12183535

40 CFR Table 1 to Subpart III of... - HAP ABA Formulation Limitations Matrix for New Sources [see § 63.1297(d)(2)

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 11 2010-07-01 2010-07-01 true HAP ABA Formulation Limitations Matrix for New Sources [see § 63.1297(d)(2)] 1 Table 1 to Subpart III of Part 63 Protection of Environment... Formulation Limitations Matrix for New Sources [see § 63.1297(d)(2)] ER07OC98.010 ...

Household air pollution (HAP), microenvironment and child health: Strategies for mitigating HAP exposure in urban Rwanda

NASA Astrophysics Data System (ADS)

Das, Ipsita; Pedit, Joseph; Handa, Sudhanshu; Jagger, Pamela

2018-04-01

Exposure to household air pollution (HAP) from cooking and heating with solid fuels is a major risk factor for morbidity and mortality in sub-Saharan Africa. Children under five are particularly at risk for acute lower respiratory infection. We use baseline data from a randomized controlled trial evaluating a household energy intervention in Gisenyi, Rwanda to investigate the role of the microenvironment as a determinant of children’s HAP-related health symptoms. Our sample includes 529 households, with 694 children under five. We examine the association between likelihood of HAP-related health symptom prevalence and characteristics of the microenvironment including: dwelling and cooking area structure; distance to nearest road; and tree cover. We find that children residing in groups of enclosed dwellings, in households that cook indoors, and in households proximate to tree cover, are significantly more likely to experience symptoms of respiratory infection, illness with cough and difficulty breathing. On the other hand, children in households with cemented floors and ventilation holes in the cooking area, are significantly less likely to experience the same symptoms. Our findings suggest that in addition to promoting increased access to clean cooking technologies, there are important infrastructure and microenvironment-related interventions that mitigate HAP exposure.

Household air pollution (HAP), microenvironment and child health: Strategies for mitigating HAP exposure in urban Rwanda

PubMed Central

Das, Ipsita; Pedit, Joseph; Handa, Sudhanshu; Jagger, Pamela

2018-01-01

Exposure to household air pollution (HAP) from cooking and heating with solid fuels is major risk factor for morbidity and mortality in sub-Saharan Africa. Children under five are particularly at risk for acute lower respiratory infection. We use baseline data from randomized controlled trial evaluating a household energy intervention in Gisenyi, Rwanda to investigate the role of the microenvironment as a determinant of children’s HAP-related health symptoms. Our sample includes 529 households, with 694 children under five. We examine the association between likelihood of HAP-related health symptom prevalence and characteristics of the microenvironment including: dwelling and cooking area structure; distance to nearest road; and tree cover. We find that children residing in groups of enclosed dwellings, in households that cook indoors, and in households proximate to tree cover, are significantly more likely to experience symptoms of respiratory infection, illness with cough and difficulty breathing. On the other hand, children in households with cemented floors and ventilation holes in the cooking area, are significantly less likely to experience the same symptoms. Our findings suggest that in addition to promoting increased access to clean cooking technologies, there are important infrastructure and micro-environment related interventions that mitigate HAP exposure. PMID:29682002

Recombinant C-terminal 311 amino acids of HapS adhesin as a vaccine candidate for nontypeable Haemophilus influenzae: A study on immunoreactivity in Balb/C mouse.

PubMed

Tabatabaee Bafroee, Akram Sadat; Siadat, Seyed Davar; Mousavi, Seyed Fazlollah; Aghasadeghi, Mohammad Reza; Khorsand, Hashem; Nejati, Mehdi; Sadat, Seyed Mehdi; Mahdavi, Mehdi

2016-09-01

Hap, an auto-transporter protein, is an antigenically conserved adhesion protein which is present on both typeable and nontypeable Haemophilus influenzae. This protein has central role in bacterial attachment to respiratory tract epithelial cells. A 1000bp C-terminal fragment of Hap passenger domain (HapS) from nontypeable Haemophilus influenzae was cloned into a prokaryotic expression vector, pET-24a. BALB/c mice were immunized subcutaneously with purified rC-HapS. Serum IgG responses to purified rC-HapS, serum IgG subclasses were determined by ELISA and functional activity of antibodies was examined by Serum Bactericidal Assay. The output of rC-HapS was approximately 62% of the total bacterial proteins. Serum IgG responses were significantly increased in immunized group with rC-HapS mixed with Freund's adjuvant in comparison with control groups. Analysis of the serum IgG subclasses showed that the IgG1 subclass was predominant after subcutaneous immunization in BALB/c mice (IgG2a/IgG1 < 1). The sera from rC-HapS immunized animals were strongly bactericidal against nontypeable Haemophilus influenzae. These results suggest that rC-HapS may be a potential vaccine candidate for nontypeable Haemophilus influenzae. Copyright © 2016 Elsevier Ltd. All rights reserved.

Structural determinants of the interaction between the Haemophilus influenzae Hap autotransporter and fibronectin.

PubMed

Spahich, Nicole A; Kenjale, Roma; McCann, Jessica; Meng, Guoyu; Ohashi, Tomoo; Erickson, Harold P; St Geme, Joseph W

2014-06-01

Haemophilus influenzae is a Gram-negative cocco-bacillus that initiates infection by colonizing the upper respiratory tract. Hap is an H. influenzae serine protease autotransporter protein that mediates adherence, invasion and microcolony formation in assays with human epithelial cells and is presumed to facilitate the process of colonization. Additionally, Hap mediates adherence to fibronectin, laminin and collagen IV, extracellular matrix (ECM) proteins that are present in the respiratory tract and are probably important targets for H. influenzae colonization. The region of Hap responsible for adherence to ECM proteins has been localized to the C-terminal 511 aa of the Hap passenger domain (HapS). In this study, we characterized the structural determinants of the interaction between HapS and fibronectin. Using defined fibronectin fragments, we established that Hap interacts with the fibronectin repeat fragment called FNIII(1-2). Using site-directed mutagenesis, we found a series of motifs in the C-terminal region of HapS that contribute to the interaction with fibronectin. Most of these motifs are located on the F1 and F3 faces of the HapS structure, suggesting that the F1 and F3 faces may be responsible for the HapS-fibronectin interaction. © 2014 The Authors.

Structural determinants of the interaction between the Haemophilus influenzae Hap autotransporter and fibronectin

PubMed Central

Spahich, Nicole A.; Kenjale, Roma; McCann, Jessica; Meng, Guoyu; Ohashi, Tomoo; Erickson, Harold P.

2014-01-01

Haemophilus influenzae is a Gram-negative cocco-bacillus that initiates infection by colonizing the upper respiratory tract. Hap is an H. influenzae serine protease autotransporter protein that mediates adherence, invasion and microcolony formation in assays with human epithelial cells and is presumed to facilitate the process of colonization. Additionally, Hap mediates adherence to fibronectin, laminin and collagen IV, extracellular matrix (ECM) proteins that are present in the respiratory tract and are probably important targets for H. influenzae colonization. The region of Hap responsible for adherence to ECM proteins has been localized to the C-terminal 511 aa of the Hap passenger domain (HapS). In this study, we characterized the structural determinants of the interaction between HapS and fibronectin. Using defined fibronectin fragments, we established that Hap interacts with the fibronectin repeat fragment called FNIII(1–2). Using site-directed mutagenesis, we found a series of motifs in the C-terminal region of HapS that contribute to the interaction with fibronectin. Most of these motifs are located on the F1 and F3 faces of the HapS structure, suggesting that the F1 and F3 faces may be responsible for the HapS–fibronectin interaction. PMID:24687948

Oxygen-Dependent Transcriptional Regulator Hap1p Limits Glucose Uptake by Repressing the Expression of the Major Glucose Transporter Gene RAG1 in Kluyveromyces lactis▿

PubMed Central

Bao, Wei-Guo; Guiard, Bernard; Fang, Zi-An; Donnini, Claudia; Gervais, Michel; Passos, Flavia M. Lopes; Ferrero, Iliana; Fukuhara, Hiroshi; Bolotin-Fukuhara, Monique

2008-01-01

The HAP1 (CYP1) gene product of Saccharomyces cerevisiae is known to regulate the transcription of many genes in response to oxygen availability. This response varies according to yeast species, probably reflecting the specific nature of their oxidative metabolism. It is suspected that a difference in the interaction of Hap1p with its target genes may explain some of the species-related variation in oxygen responses. As opposed to the fermentative S. cerevisiae, Kluyveromyces lactis is an aerobic yeast species which shows different oxygen responses. We examined the role of the HAP1-equivalent gene (KlHAP1) in K. lactis. KlHap1p showed a number of sequence features and some gene targets (such as KlCYC1) in common with its S. cerevisiae counterpart, and KlHAP1 was capable of complementing the hap1 mutation. However, the KlHAP1 disruptant showed temperature-sensitive growth on glucose, especially at low glucose concentrations. At normal temperature, 28°C, the mutant grew well, the colony size being even greater than that of the wild type. The most striking observation was that KlHap1p repressed the expression of the major glucose transporter gene RAG1 and reduced the glucose uptake rate. This suggested an involvement of KlHap1p in the regulation of glycolytic flux through the glucose transport system. The ΔKlhap1 mutant showed an increased ability to produce ethanol during aerobic growth, indicating a possible transformation of its physiological property to Crabtree positivity or partial Crabtree positivity. Dual roles of KlHap1p in activating respiration and repressing fermentation may be seen as a basis of the Crabtree-negative physiology of K. lactis. PMID:18806211

Enhanced bone regeneration composite scaffolds of PLLA/β-TCP matrix grafted with gelatin and HAp.

PubMed

Wang, Jie-Lin; Chen, Qian; Du, Bei-Bei; Cao, Lu; Lin, Hong; Fan, Zhong-Yong; Dong, Jian

2018-06-01

The composite polylactide PLLA/β-TCP scaffolds were fabricated by solution casting and were coated with gelatin/hydroxyapatite (Gel/HAp) to improve the biological properties of the composite scaffolds. The Gel/HAp mixture was prepared using an in situ reaction, and a grafting-coating method was used to increase the efficiency of coating the PLLA/β-TCP matrix with Gel/HAp. First, free amino groups were introduced by 1,6-hexanediamine to aminolyze the PLLA/β-TCP matrix surface. Second, glutaraldehyde was coupled to Gel/HAp as a crosslinking agent. The structure and properties of Gel/HAp-modified PLLA/β-TCP films were characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and water contact angle measurements (WCA). The experimental results show that 23 wt% HAp was uniformly dispersed in the gelatin coating by in situ synthesis. The Gel/HAp composite coating was successfully immobilized on the aminolyzed PLLA/β-TCP surface via a chemical grafting method, which promoted a lower degradation rate and was more hydrophilic than a physical grafting method. The Gel/HAp composite coating adhered tightly and homogeneously to the hydrophobic PLLA/β-TCP surface. Moreover, mouse embryo osteoblast precursor (MC3T3-E1) cells grown on the scaffolds were behaviorally and morphologically characterized. The results indicated that the Gel/HAp composite coating was favorable for the attachment and proliferation of preosteoblasts and that Gel/HAp-NH-PLLA/β-TCP would be a candidate scaffold for bone repair. Copyright © 2018 Elsevier B.V. All rights reserved.

ptr-MIR169 is a posttranscriptional repressor of PtrHAP2 during vegetative bud dormancy period of aspen (Populus tremuloides) trees

DOE Office of Scientific and Technical Information (OSTI.GOV)

Potkar, Rewati; Recla, Jill; Busov, Victor, E-mail: vbusov@mtu.edu

2013-02-15

Highlights: ► We show a novel microRNA-mediated mechanism for control of bud dormancy in trees. ► ptr-MIR169a and PtrHAP2–5 gene showed inverse expression during dormancy period. ► The PtrHAP2–5 decline in abundance correlated with high ptr-MIR169a levels. ► PtrHAP2–5 cleavage occurred at the miR169 site during PtrHAP2–5 transcript decline. ► Our results show that miR169 attenuates PtrHAP2–5 transcript during dormancy. -- Abstract: Dormancy is a mechanism evolved in woody perennial plants to survive the winter freezing and dehydration stress via temporary suspension of growth. We have identified two aspen microRNAs (ptr-MIR169a and ptr-MIR169h) which were highly and specifically expressed inmore » dormant floral and vegetative buds. ptr-MIR169a and its target gene PtrHAP2–5 showed inverse expression patterns during the dormancy period. ptr-MIR169a transcript steadily increased through the first half of the dormancy period and gradually declined with the approach of active growing season. PtrHAP2–5 abundance was higher in the beginning of the dormancy period but rapidly declined thereafter. The decline of PtrHAP2–5 correlated with the high levels of ptr-MIR169a accumulation, suggesting miR169-mediated attenuation of the target PtrHAP2–5 transcript. We experimentally verified the cleavage of PtrHAP2–5 at the predicted miR169a site at the time when PtrHAP2–5 transcript decline was observed. HAP2 is a subunit of a nuclear transcription factor Y (NF-Y) complex consisting of two other units, HAP3 and HAP5. Using digital expression profiling we show that poplar HAP2 and HAP5 are preferentially detected in dormant tissues. Our study shows that microRNAs play a significant and as of yet unknown and unstudied role in regulating the timing of bud dormancy in trees.« less

A Simplified GCS-DCSK Modulation and Its Performance Optimization

NASA Astrophysics Data System (ADS)

Xu, Weikai; Wang, Lin; Chi, Chong-Yung

2016-12-01

In this paper, a simplified Generalized Code-Shifted Differential Chaos Shift Keying (GCS-DCSK) whose transmitter never needs any delay circuits, is proposed. However, its performance is deteriorated because the orthogonality between substreams cannot be guaranteed. In order to optimize its performance, the system model of the proposed GCS-DCSK with power allocations on substreams is presented. An approximate bit error rate (BER) expression of the proposed model, which is a function of substreams’ power, is derived using Gaussian Approximation. Based on the BER expression, an optimal power allocation strategy between information substreams and reference substream is obtained. Simulation results show that the BER performance of the proposed GCS-DCSK with the optimal power allocation can be significantly improved when the number of substreams M is large.

Effect of stearic acid modified HAp nanoparticles in different solvents on the properties of Pickering emulsions and HAp/PLLA composites.

PubMed

Zhang, Ming; Wang, Ai-Juan; Li, Jun-Ming; Song, Na

2017-10-01

Stearic acid (Sa) was used to modify the surface properties of hydroxyapatite (HAp) in different solvents (water, ethanol or dichloromethane(CH 2 Cl 2 )). Effect of different solvents on the properties of HAp particles (activation ratio, grafting ratio, chemical properties), emulsion properties (emulsion stability, emulsion type, droplet morphology) as well as the cured materials (morphology, average pore size) were studied. FT-IR and XPS results confirmed the interaction occurred between stearic acid and HAp particles. Stable O/W and W/O type Pickering emulsions were prepared using unmodified and Sa modified HAp nanoparticles respectively, which indicated a catastrophic inversion of the Pickering emulsion happened possibly because of the enhanced hydrophobicity of HAp particles after surface modification. Porous materials with different structures and pore sizes were obtained using Pickering emulsion as the template via in situ evaporation solvent method. The results indicated the microstructures of cured samples are different form each other when HAp was surface modified in different solvents. HAp particles fabricated using ethanol as solvent has higher activation ratio and grafting ratio. Pickering emulsion with higher stability and cured porous materials with uniform morphology were obtained compared with samples prepared using water and CH 2 Cl 2 as solvents. In conclusion, surface modification of HAp in different solvents played a very important role for its stabilized Pickering emulsion as well as the microstructure of cured samples. It is better to use ethanol as the solvent for Sa modified HAp particles, which could increase the stability of Pickering emulsion and obtain cured samples with uniform pore size. Copyright © 2017 Elsevier B.V. All rights reserved.

Parallel nano-assembling of a multifunctional GO/HapNP coating on ultrahigh-purity magnesium for biodegradable implants

NASA Astrophysics Data System (ADS)

Santos, C.; Piedade, C.; Uggowitzer, P. J.; Montemor, M. F.; Carmezim, M. J.

2015-08-01

This work reports the one-step fabrication of a novel coating on ultra high purity magnesium using a parallel nano assembling process. The multifunctional biodegradable surface was obtained by adding hydroxyapatite nanoparticles (HapNP) plus graphene oxide (GO). The coating was characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffractometer (XRD), micro-Raman spectroscopy. The thin phosphate coating (thickness of 1 μm) reveals a uniform coverage with cypress like structures. The incorporation of HapNP and GO promotes the hydrophilic behavior of the coating surface. The results revealed that the proposed coating can be used to tailor the surface properties such as wettability by adjusting the contents of HapNP and GO. The in vitro degradation rate of the coated magnesium suggests that the presence of HapNP and GO/HapNP in the phosphate coating decreased the current density compared to the single phosphate coating and uncoated magnesium. This study also reveals the HapNP/GO/phosphate coating induces apatite formation, showing suitable degradability that makes it a promising coating candidate for enhanced bone regeneration.

Age at onset in Huntington's disease: replication study on the association of HAP1.

PubMed

Karadima, Georgia; Dimovasili, Christina; Koutsis, Georgios; Vassilopoulos, Demetris; Panas, Marios

2012-11-01

In recent years two association studies investigating the HAP1 T441M (rs4523977) polymorphism as a potential modifying factor of the age at onset (AAO) of Huntington's disease (HD), have been reported. Initially evidence for association was found between the M441 risk allele and the AAO. Subsequently, a second study, although failing to replicate these findings, found evidence for association between the same risk allele and AAO of motor symptoms (mAAO). In the present study, the role of the HAP1 T441M polymorphism as a modifier of the AAO in HD was investigated in a cohort of 298 Greek HD patients. In this cohort the CAG repeat number accounted for 55% of the variance in AAO. No association was found between the HAP1 T441M polymorphism and the AAO of HD. © 2012 Elsevier Ltd. All rights reserved.

Characterization of derived natural hydroxyapatite (HAp) obtained from different types of tilapia fish bones and scales

NASA Astrophysics Data System (ADS)

Fara, A. N. K. A.; Abdullah, H. Z.

2015-07-01

Hydroxyapatite, (HAp), Ca10(PO4)6(OH)2, is recognised as a biomaterial that is widely used for bone implant due to its chemical and structural similarity to the mineral components in human bone and enamel. The elements of HAp are primarily composed of calcium and phosphorus molar ratio of calcium to phosphorous is 1.67 capable to promote bone in-growth into prosthetic implant. Enormous amounts of by-product waste produced from fish factories generated an undesirable environmental impact. Thus, this study was conducted to obtain natural biological HAp from different types of tilapia fish bones and scales from fishery waste. Therefore, fish bones and scales can be as cheap source to produce biological HAp for medical applications. For this purpose, fish bones and scales of tilapia fish were boiled at 100°C to remove adhering meat and other impurities. Later, fish bones and scales were separated into several groups and subjected to different calcination temperatures of 800° C and 900° C for 3h respectively. Afterward, all calcined samples were crushed to form a fine powder. The XRD result revealed the presence of derived Hapfrom the samples powder and were identical with standard Hap. Thermo Gravimetric Analysis was carried out to show the thermal stability of the HAp powder from different types of fish bones and scales. SEM results show porous structure appeared in calcined samples compared to raw samples. The findings are the promising alternative to produce calcium and phosphorus from fishery wastes that beneficial to medical applications.

24 CFR 983.204 - When HAP contract is executed.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false When HAP contract is executed. 983... When HAP contract is executed. (a) PHA inspection of housing. (1) Before execution of the HAP contract... into a HAP contract for any contract unit until the PHA has determined that the unit complies with the...

40 CFR Appendix: Table 1 to... - List of Hazardous Air Pollutants (HAP) for Subpart HHH

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 11 2010-07-01 2010-07-01 true List of Hazardous Air Pollutants (HAP) for Subpart HHH Table Appendix: Table 1 to Subpart HHH of Part 63 Protection of Environment... HHH of Part 63—List of Hazardous Air Pollutants (HAP) for Subpart HHH CAS Number a Chemical name 75070...

GCS programmer's manual

NASA Technical Reports Server (NTRS)

Lowman, Douglas S.; Withers, B. Edward; Shagnea, Anita M.; Dent, Leslie A.; Hayhurst, Kelly J.

1990-01-01

A variety of instructions to be used in the development of implementations of software for the Guidance and Control Software (GCS) project is described. This document fulfills the Radio Technical Commission for Aeronautics RTCA/DO-178A guidelines, 'Software Considerations in Airborne Systems and Equipment Certification' requirements for document No. 4, which specifies the information necessary for understanding and programming the host computer, and document No. 12, which specifies the software design and implementation standards that are applicable to the software development and testing process. Information on the following subjects is contained: activity recording, communication protocol, coding standards, change management, error handling, design standards, problem reporting, module testing logs, documentation formats, accuracy requirements, and programmer responsibilities.

Magnetophysiologic and echocardiographic comparison of blocked atrial bigeminy and 2:1 atrioventricular block in the fetus.

PubMed

Wiggins, Delonia L; Strasburger, Janette F; Gotteiner, Nina L; Cuneo, Bettina; Wakai, Ronald T

2013-08-01

Blocked atrial bigeminy (BAB) and second-degree atrioventricular block with 2:1 conduction block (2:1 AVB) both present as ventricular bradycardia and can be difficult to distinguish by echocardiography. Since the prognosis and clinical management of these rhythms are different, an accurate diagnosis is essential. To identify magnetic and mechanical heart rate and rhythm parameters that could reliably distinguish BAB from 2:1 AVB. A retrospective study of ten BAB and seven 2:1 AVB subjects was performed, using fMCG and pulsed Doppler ultrasound. Distinguishing BAB from 2:1 AVB by using fMCG was relatively straightforward because in BAB the ectopic P wave (P') occurred early, resulting in a bigeminal (short-long) atrial rhythm. The normalized coupling interval of the ectopic beat (PP' of the blocked beat to PP of the conducted beat) was 0.29 ± 0.03. In contrast, the echocardiographic assessment of inflow-outflow gave a normalized mechanical coupling interval (AA'/AA) near 0.5, which made it difficult to distinguish BAB from 2:1 AVB. Heart rate distinguished most subjects with BAB from those with 2:1 AVB (82 ± 5.7 beats/min vs 69 ± 4.2 beats/min), but was not a completely reliable indicator. In most subjects, BAB alternated with sinus rhythm or other rhythms, resulting in complex heart rate and rhythm patterns. Fetal BAB and 2:1 AV block can be difficult to distinguish using echocardiography because in many fetuses with BAB the mechanical rhythm does not accurately reflect the magnetic rhythm. fMCG provides a more reliable means of making a differential diagnosis. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

The temperate marine phage PhiHAP-1 of Halomonas aquamarina possesses a linear plasmid-like prophage genome.

PubMed

Mobberley, Jennifer M; Authement, R Nathan; Segall, Anca M; Paul, John H

2008-07-01

A myovirus-like temperate phage, PhiHAP-1, was induced with mitomycin C from a Halomonas aquamarina strain isolated from surface waters in the Gulf of Mexico. The induced cultures produced significantly more virus-like particles (VLPs) (3.73 x 10(10) VLP ml(-1)) than control cultures (3.83 x 10(7) VLP ml(-1)) when observed with epifluorescence microscopy. The induced phage was sequenced by using linker-amplified shotgun libraries and contained a genome 39,245 nucleotides in length with a G+C content of 59%. The PhiHAP-1 genome contained 46 putative open reading frames (ORFs), with 76% sharing significant similarity (E value of <10(-3)) at the protein level with other sequences in GenBank. Putative functional gene assignments included small and large terminase subunits, capsid and tail genes, an N6-DNA adenine methyltransferase, and lysogeny-related genes. Although no integrase was found, the PhiHAP-1 genome contained ORFs similar to protelomerase and parA genes found in linear plasmid-like phages with telomeric ends. Southern probing and PCR analysis of host genomic, plasmid, and PhiHAP-1 DNA indicated a lack of integration of the prophage with the host chromosome and a difference in genome arrangement between the prophage and virion forms. The linear plasmid prophage form of PhiHAP-1 begins with the protelomerase gene, presumably due to the activity of the protelomerase, while the induced phage particle has a circularly permuted genome that begins with the terminase genes. The PhiHAP-1 genome shares synteny and gene similarity with coliphage N15 and vibriophages VP882 and VHML, suggesting an evolutionary heritage from an N15-like linear plasmid prophage ancestor.

Synthesis of carboxylic block copolymers via reversible addition fragmentation transfer polymerization for tooth erosion prevention.

PubMed

Lei, Y; Wang, T; Mitchell, J W; Qiu, J; Kilpatrick-Liverman, L

2014-12-01

Dental professionals are seeing a growing population of patients with visible signs of dental erosion. The approach currently being used to address the problem typically leverages the enamel protection benefits of fluoride. In this report, an alternative new block copolymer with a hydrophilic polyacrylic acid (PAA) block and a hydrophobic poly(methyl methacrylate) (PMMA) block was developed to similarly reduce the mineral loss from enamel under acidic conditions. This series of PMMA-b-PAA block copolymers was synthesized by reversible addition fragmentation transfer (RAFT) polymerization. Their structures were characterized by gel permeation chromatography (GPC) and (1)H nuclear magnetic resonance (NMR) spectra. The molar fractions of acrylic acid (AA) in the final block copolymer were finely controlled from 0.25 to 0.94, and the molecular weight (Mn) of PMMA-b-PAA was controlled from 10 kDa to 90 kDa. The binding capability of the block copolymer with hydroxyapatite (HAP) was investigated by ultraviolet-visible spectroscopy (UV-Vis) and Fourier transform infrared (FTIR) spectroscopy. FTIR spectra confirmed that the PMMA-b-PAA block copolymer could bind to HAP via bridging bidentate bonds. Both UV-Vis and FTIR spectra additionally indicated that a high polymer concentration and low solution pH favored the polymer binding to HAP. The erosion-preventing efficacy of the PMMA-b-PAA block copolymer in inhibiting HAP mineral loss was quantitatively evaluated by atomic absorption spectroscopy (AAS). Based on the results, polymer treatment reduced the amount of calcium released by 27% to 30% in comparison with the unprotected samples. Scanning electron microscope (SEM) observations indicated that PMMA-b-PAA polymer treatment protected enamel from acid erosion. This new amphiphilic block copolymer has significant potential to be integrated into dentifrices or mouthrinses as an alternative non-fluoride ingredient to reduce tooth erosion. © International & American

Synthesis of Carboxylic Block Copolymers via Reversible Addition Fragmentation Transfer Polymerization for Tooth Erosion Prevention

PubMed Central

Lei, Y.; Wang, T.; Mitchell, J.W.; Qiu, J.; Kilpatrick-Liverman, L.

2014-01-01

Dental professionals are seeing a growing population of patients with visible signs of dental erosion. The approach currently being used to address the problem typically leverages the enamel protection benefits of fluoride. In this report, an alternative new block copolymer with a hydrophilic polyacrylic acid (PAA) block and a hydrophobic poly(methyl methacrylate) (PMMA) block was developed to similarly reduce the mineral loss from enamel under acidic conditions. This series of PMMA-b-PAA block copolymers was synthesized by reversible addition fragmentation transfer (RAFT) polymerization. Their structures were characterized by gel permeation chromatography (GPC) and 1H nuclear magnetic resonance (NMR) spectra. The molar fractions of acrylic acid (AA) in the final block copolymer were finely controlled from 0.25 to 0.94, and the molecular weight (Mn) of PMMA-b-PAA was controlled from 10 kDa to 90 kDa. The binding capability of the block copolymer with hydroxyapatite (HAP) was investigated by ultraviolet–visible spectroscopy (UV-Vis) and Fourier transform infrared (FTIR) spectroscopy. FTIR spectra confirmed that the PMMA-b-PAA block copolymer could bind to HAP via bridging bidentate bonds. Both UV-Vis and FTIR spectra additionally indicated that a high polymer concentration and low solution pH favored the polymer binding to HAP. The erosion-preventing efficacy of the PMMA-b-PAA block copolymer in inhibiting HAP mineral loss was quantitatively evaluated by atomic absorption spectroscopy (AAS). Based on the results, polymer treatment reduced the amount of calcium released by 27% to 30% in comparison with the unprotected samples. Scanning electron microscope (SEM) observations indicated that PMMA-b-PAA polymer treatment protected enamel from acid erosion. This new amphiphilic block copolymer has significant potential to be integrated into dentifrices or mouthrinses as an alternative non-fluoride ingredient to reduce tooth erosion. PMID:25248611

A comparison of the Full Outline of UnResponsiveness (FOUR) score and Glasgow Coma Score (GCS) in predictive modelling in traumatic brain injury.

PubMed

Kasprowicz, Magdalena; Burzynska, Malgorzata; Melcer, Tomasz; Kübler, Andrzej

2016-01-01

To compare the performance of multivariate predictive models incorporating either the Full Outline of UnResponsiveness (FOUR) score or Glasgow Coma Score (GCS) in order to test whether substituting GCS with the FOUR score in predictive models for outcome in patients after TBI is beneficial. A total of 162 TBI patients were prospectively enrolled in the study. Stepwise logistic regression analysis was conducted to compare the prediction of (1) in-ICU mortality and (2) unfavourable outcome at 3 months post-injury using as predictors either the FOUR score or GCS along with other factors that may affect patient outcome. The areas under the ROC curves (AUCs) were used to compare the discriminant ability and predictive power of the models. The internal validation was performed with bootstrap technique and expressed as accuracy rate (AcR). The FOUR score, age, the CT Rotterdam score, systolic ABP and being placed on ventilator within day one (model 1: AUC: 0.906 ± 0.024; AcR: 80.3 ± 4.8%) performed equally well in predicting in-ICU mortality as the combination of GCS with the same set of predictors plus pupil reactivity (model 2: AUC: 0.913 ± 0.022; AcR: 81.1 ± 4.8%). The CT Rotterdam score, age and either the FOUR score (model 3) or GCS (model 4) equally well predicted unfavourable outcome at 3 months post-injury (AUC: 0.852 ± 0.037 vs. 0.866 ± 0.034; AcR: 72.3 ± 6.6% vs. 71.9%±6.6%, respectively). Adding the FOUR score or GCS at discharge from ICU to predictive models for unfavourable outcome increased significantly their performances (AUC: 0.895 ± 0.029, p = 0.05; AcR: 76.1 ± 6.5%; p < 0.004 when compared with model 3; and AUC: 0.918 ± 0.025, p < 0.05; AcR: 79.6 ± 7.2%, p < 0.009 when compared with model 4), but there was no benefit from substituting GCS with the FOUR score. Results showed that FOUR score and GCS perform equally well in multivariate predictive modelling in TBI.

Plk1 relieves centriole block to reduplication by promoting daughter centriole maturation

PubMed Central

Shukla, Anil; Kong, Dong; Sharma, Meena; Magidson, Valentin; Loncarek, Jadranka

2015-01-01

Centrosome overduplication promotes mitotic abnormalities, invasion and tumorigenesis. Cells regulate the number of centrosomes by limiting centriole duplication to once per cell cycle. The orthogonal orientation between a mother and a daughter centriole, established at the time of centriole duplication, is thought to block further duplication of the mother centriole. Loss of orthogonal orientation (disengagement) between two centrioles during anaphase is considered a licensing event for the next round of centriole duplication. Disengagement requires the activity of Polo-like kinase 1 (Plk1), but how Plk1 drives this process is not clear. Here we employ correlative live/electron microscopy and demonstrate that Plk1 induces maturation and distancing of the daughter centriole, allowing reduplication of the mother centriole even if the original daughter centriole is still orthogonal to it. We find that mother centrioles can undergo reduplication when original daughter centrioles are only ∼80 nm apart, which is the distance centrioles normally reach during prophase. PMID:26293378

40 CFR Table 2 to Subpart Uuu of... - Operating Limits for Metal HAP Emissions From Catalytic Cracking Units

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 13 2014-07-01 2014-07-01 false Operating Limits for Metal HAP Emissions From Catalytic Cracking Units 2 Table 2 to Subpart UUU of Part 63 Protection of Environment... Units Pt. 63, Subpt. UUU, Table 2 Table 2 to Subpart UUU of Part 63—Operating Limits for Metal HAP...

40 CFR Table 2 to Subpart Uuu of... - Operating Limits for Metal HAP Emissions From Catalytic Cracking Units

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 13 2012-07-01 2012-07-01 false Operating Limits for Metal HAP Emissions From Catalytic Cracking Units 2 Table 2 to Subpart UUU of Part 63 Protection of Environment... Units Pt. 63, Subpt. UUU, Table 2 Table 2 to Subpart UUU of Part 63—Operating Limits for Metal HAP...

40 CFR Table 2 to Subpart Uuu of... - Operating Limits for Metal HAP Emissions From Catalytic Cracking Units

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 13 2013-07-01 2012-07-01 true Operating Limits for Metal HAP Emissions From Catalytic Cracking Units 2 Table 2 to Subpart UUU of Part 63 Protection of Environment... Units Pt. 63, Subpt. UUU, Table 2 Table 2 to Subpart UUU of Part 63—Operating Limits for Metal HAP...

40 CFR Figure 1 to Subpart Tttt of... - Example Logs for Recording Leather Finish Use and HAP Content

Code of Federal Regulations, 2010 CFR

2010-07-01

... Finishing Operations Part 63, Subpt. TTTT, Fig. 1 Figure 1 to Subpart TTTT of Part 63—Example Logs for Recording Leather Finish Use and HAP Content Month:______Year:______ Finish Inventory Log Finish type Finish usage(pounds) HAP Content(mass fraction) Date and time Operator's name Product process operation Monthly...

[Optimized isolation and purification of non-typeable Haemophilus influenzae Haps protein].

PubMed

Li, Wan-yi; Kuang, Yu; Li, Ming-yuan; Yang, Yuan; Jiang, Zhong-hua; Yao, Feng; Chen, Chang-chun

2007-12-01

To optimize the isolation and purification conditions for Hap(s) protein of non-typeable Haemophilus influenzae. Hap(s) protein was purified by ammonium sulfate precipitation, dialysis desalting and Hitrap weak cation exchange columns of CM Sepharose Fast Flow. The condition of the elution was optimized for pH and ionic strength, the absorbance at 280 nm of the elution samples were detected, and the targeted protein band in the collected samples was observed by SDS-PAGE electrophoresis. The Hitrap ion exchange column was eluted with buffer 1, which resulted in a baseline distribution of absorbance at 280 nm. Buffer 2 elution of the column resulted in the presence of peak absorbance with trails, which was identified to be constituted by some low molecular weight bands by subsequent SDS-PAGE. In serial column elution with buffer 3 with different ionic strength, a peak absorbance was observed with the ionic strength of 100 mmol/L NaCl, and SDS-PAGE confirmed that the peak was generated by the target protein. No obvious peaks or bands in SDS-PAGE occurred with the other ionic strengths. The pH of the buffer only affect the elution of the irrelevant proteins rather than the Hap(s) protein, and elution with the buffer containing 100 mmol/L NaCl can be optimal for eluting the Hap(s) protein.

Progranulin compensates for blocked IGF-1 signaling to promote myotube hypertrophy in C2C12 myoblasts via the PI3K/Akt/mTOR pathway.

PubMed

Hu, Shao-Yang; Tai, Chen-Chen; Li, Yen-Hsing; Wu, Jen-Leih

2012-09-21

It is well known that growth hormone (GH)-induced IGF-1 signaling plays a dominant role in postnatal muscle growth. Our previous studies have identified a growth factor, progranulin (PGRN), that is co-induced with IGF-1 upon GH administration. This result prompted us to explore the function of PGRN and its association with IGF-1. In the present study, we demonstrated that, similar to IGF-1, PGRN can promote C2C12 myotube hypertrophy via the PI(3)K/Akt/mTOR pathway. Moreover, PGRN can rescue the muscle atrophy phenotypes in C2C12 myotube when IGF-1 signaling is blocked. This result shows that PGRN can substitute for IGF-1 signaling in the regulation of muscle growth. Our findings provide new insights into IGF-1-modulated complicated networks that regulate muscle growth. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Anticancer activity of bacteriophage T4 and its mutant HAP1 in mouse experimental tumour models.

PubMed

Dabrowska, Krystyna; Opolski, Adam; Wietrzyk, Joanna; Switala-Jelen, Kinga; Godlewska, Joanna; Boratynski, Janusz; Syper, Danuta; Weber-Dabrowska, Beata; Gorski, Andrzej

2004-01-01

Previously, we have shown the ability of the bacteriophage T4 and its substrain HAP1 (selected for a higher affinity to melanoma cells) to reveal antimetastatic activity in a mouse melanoma model. Here, we investigated the potential phage anticancer activity in primary tumour models. Mice were inoculated subcutaneously with B16 or LLC cells (collected from in vitro culture). Bacteriophages T4 and HAP1 were injected intraperitoneally daily (8 x 10(8)pfu/mouse, except the experiment concerning the dose-dependence). Treatment with purified preparations of bacteriophage T4 resulted in significant reduction of tumour size, the effect being dose-dependent. HAP1 was more effective than T4 and its activity was also dose-dependent. Parallel experiments with non-purified bacteriophage lysates resulted in significant stimulation of tumour growth. These data suggest that purified bacteriophages may inhibit tumour growth, a phenomenon with potentially important clinical implications in oncology.

Low-affinity spermine block mediating outward currents through Kir2.1 and Kir2.2 inward rectifier potassium channels

PubMed Central

Ishihara, Keiko; Yan, Ding-Hong

2007-01-01

The outward component of the strong inward rectifier K+ current (IKir) plays a pivotal role in polarizing the membranes of excitable and non-excitable cells and is regulated by voltage-dependent channel block by internal cations. Using the Kir2.1 channel, we previously showed that a small fraction of the conductance susceptible only to a low-affinity mode of block likely carries a large portion of the outward current. To further examine the relevance of the low-affinity block to outward IKir and to explore its molecular mechanism, we studied the block of the Kir2.1 and Kir2.2 channels by spermine, which is the principal Kir2 channel blocker. Current–voltage relations of outward Kir2.2 currents showed a peak, a plateau and two peaks in the presence of 10, 1 and 0.1 μm spermine, respectively, which was explained by the presence of two conductances that differ in their susceptibility to spermine block. When the current–voltage relations showed one peak, like those of native IKir, outward Kir2.2 currents were mediated mostly by the conductance susceptible to the low-affinity block. They also flowed in a narrower range than the corresponding Kir2.1 currents, because of 3- to 4-fold greater susceptibility to the low-affinity block than in Kir2.1. Reducing external [K+] shifted the voltage dependences of both the high- and low-affinity block of Kir2.1 in parallel with the shift in the reversal potential, confirming the importance of the low-affinity block in mediating outward IKir. When Kir2.1 mutants known to have reduced sensitivity to internal blockers were examined, the D172N mutation in the transmembrane pore region made almost all of the conductance susceptible only to low-affinity block, while the E224G mutation in the cytoplasmic pore region reduced the sensitivity to low-affinity block without markedly altering that to the high-affinity block or the high/low conductance ratio. The effects of these mutations support the hypothesis that Kir2 channels exist in

Effect of Massage Therapy on Vital Signs and GCS Scores of ICU Patients: A Randomized Controlled Clinical Trial.

PubMed

Vahedian-Azimi, Amir; Ebadi, Abbas; Asghari Jafarabadi, Mohammad; Saadat, Soheil; Ahmadi, Fazlollah

2014-08-01

Unalleviated complications related to hospitalization, including stress, anxiety, and pain, can easily influence different structures, like the neural system, by enhancing the stimulation of sympathetic nervous pathways and causing unstable vital signs and deterioration in the level of consciousness. The purpose of this study was to determine the effects of massage therapy by family members on vital signs and Glasgow Coma Scale Score (GCS) of patients hospitalized in the Intensive Care Unit (ICU). This randomized controlled clinical trial was conducted at the ICU of the Shariati Hospital during 2012; 45 ICU patients and 45 family members in the experimental group and the same number of patients and family members in the control group were consecutively selected . The data collection instrument consisted of two parts. The first part included demographic data (age, marital status and Body Mass Index) and the second part included a checklist to record the patient's vital signs (systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR), pulse rate (PR)) and GCS. All measurements were done at the same time in both groups before the intervention (full body massage therapy), and 1 hour, 2 hours, 3 hours, and 4 hours after intervention. The patients were provided with a 60-minute full body massage The massage protocol included static, surface tension, stretching, superficial lymph unload, transverse friction, and myofacial releasing techniques. Significant differences were observed between experimental and control groups in the SBP at 1 hour, SBP 2 hours, and SBP 3 hours, and also in GCS at 1 hour to GCS at 4 hours (P < 0.05). Multivariate analysis revealed a significant difference between experimental and control groups in SBP at all time points (P < 0.05). Massage via family members had several positive effects on the patients' clinical conditions, and therefore, it should be recognized as one of the most important clinical considerations in

The Healthy Activity Program (HAP), a lay counsellor-delivered brief psychological treatment for severe depression, in primary care in India: a randomised controlled trial.

PubMed

Patel, Vikram; Weobong, Benedict; Weiss, Helen A; Anand, Arpita; Bhat, Bhargav; Katti, Basavraj; Dimidjian, Sona; Araya, Ricardo; Hollon, Steve D; King, Michael; Vijayakumar, Lakshmi; Park, A-La; McDaid, David; Wilson, Terry; Velleman, Richard; Kirkwood, Betty R; Fairburn, Christopher G

2017-01-14

Although structured psychological treatments are recommended as first-line interventions for depression, only a small fraction of people globally receive these treatments because of poor access in routine primary care. We assessed the effectiveness and cost-effectiveness of a brief psychological treatment (Healthy Activity Program [HAP]) for delivery by lay counsellors to patients with moderately severe to severe depression in primary health-care settings. In this randomised controlled trial, we recruited participants aged 18-65 years scoring more than 14 on the Patient Health Questionnaire 9 (PHQ-9) indicating moderately severe to severe depression from ten primary health centres in Goa, India. Pregnant women or patients who needed urgent medical attention or were unable to communicate clearly were not eligible. Participants were randomly allocated (1:1) to enhanced usual care (EUC) alone or EUC combined with HAP in randomly sized blocks (block size four to six [two to four for men]), stratified by primary health centre and sex, and allocation was concealed with use of sequential numbered opaque envelopes. Physicians providing EUC were masked. Primary outcomes were depression symptom severity on the Beck Depression Inventory version II and remission from depression (PHQ-9 score of <10) at 3 months in the intention-to-treat population, assessed by masked field researchers. Secondary outcomes were disability, days unable to work, behavioural activation, suicidal thoughts or attempts, intimate partner violence, and resource use and costs of illness. We assessed serious adverse events in the per-protocol population. This trial is registered with the ISRCTN registry, number ISRCTN95149997. Between Oct 28, 2013, and July 29, 2015, we enrolled and randomly allocated 495 participants (247 [50%] to the EUC plus HAP group [two of whom were subsequently excluded because of protocol violations] and 248 [50%] to the EUC alone group), of whom 466 (95%) completed the 3 month

Overexpression of pig selenoprotein S blocks OTA-induced promotion of PCV2 replication by inhibiting oxidative stress and p38 phosphorylation in PK15 cells.

PubMed

Gan, Fang; Hu, Zhihua; Huang, Yu; Xue, Hongxia; Huang, Da; Qian, Gang; Hu, Junfa; Chen, Xingxiang; Wang, Tian; Huang, Kehe

2016-04-12

Porcine circovirus type 2 (PCV2) is the primary cause of porcine circovirus disease, and ochratoxin A (OTA)-induced oxidative stress promotes PCV2 replication. In humans, selenoprotein S (SelS) has antioxidant ability, but it is unclear whether SelS affects viral infection. Here, we stably transfected PK15 cells with pig pCDNA3.1-SelS to overexpress SelS. Selenium (Se) at 2 or 4 μM and SelS overexpression blocked the OTA-induced increases of PCV2 DNA copy number and infected cell numbers. SelS overexpression also increased glutathione (GSH), NF-E2-related factor 2 (Nrf2) mRNA, and γ-glutamyl-cysteine synthetase mRNA levels; decreased reactive oxygen species (ROS) levels; and inhibited p38 phosphorylation in PCV2-infected PK15 cells, regardless of OTA treatment. Buthionine sulfoximine reversed all of the above SelS-induced changes. siRNA-mediated SelS knockdown decreased Nrf2 mRNA and GSH levels, increased ROS levels, and promoted PCV2 replication in OTA-treated PK15 cells. These data indicate that pig SelS blocks OTA-induced promotion of PCV2 replication by inhibiting the oxidative stress and p38 phosphorylation in PK15 cells.

Overexpression of pig selenoprotein S blocks OTA-induced promotion of PCV2 replication by inhibiting oxidative stress and p38 phosphorylation in PK15 cells

PubMed Central

Gan, Fang; Hu, Zhihua; Huang, Yu; Xue, Hongxia; Huang, Da; Qian, Gang; Hu, Junfa; Chen, Xingxiang; Wang, Tian; Huang, Kehe

2016-01-01

Porcine circovirus type 2 (PCV2) is the primary cause of porcine circovirus disease, and ochratoxin A (OTA)-induced oxidative stress promotes PCV2 replication. In humans, selenoprotein S (SelS) has antioxidant ability, but it is unclear whether SelS affects viral infection. Here, we stably transfected PK15 cells with pig pCDNA3.1-SelS to overexpress SelS. Selenium (Se) at 2 or 4 μM and SelS overexpression blocked the OTA-induced increases of PCV2 DNA copy number and infected cell numbers. SelS overexpression also increased glutathione (GSH), NF-E2-related factor 2 (Nrf2) mRNA, and γ-glutamyl-cysteine synthetase mRNA levels; decreased reactive oxygen species (ROS) levels; and inhibited p38 phosphorylation in PCV2-infected PK15 cells, regardless of OTA treatment. Buthionine sulfoximine reversed all of the above SelS-induced changes. siRNA-mediated SelS knockdown decreased Nrf2 mRNA and GSH levels, increased ROS levels, and promoted PCV2 replication in OTA-treated PK15 cells. These data indicate that pig SelS blocks OTA-induced promotion of PCV2 replication by inhibiting the oxidative stress and p38 phosphorylation in PK15 cells. PMID:26943035

Absolute Ages and Distances of 22 GCs Using Monte Carlo Main-sequence Fitting

NASA Astrophysics Data System (ADS)

O'Malley, Erin M.; Gilligan, Christina; Chaboyer, Brian

2017-04-01

The recent Gaia Data Release 1 of stellar parallaxes provides ample opportunity to find metal-poor main-sequence stars with precise parallaxes. We select 21 such stars with parallax uncertainties better than σ π /π ≤ 0.10 and accurate abundance determinations suitable for testing metal-poor stellar evolution models and determining the distance to Galactic globular clusters (GCs). A Monte Carlo analysis was used, taking into account uncertainties in the model construction parameters, to generate stellar models and isochrones to fit to the calibration stars. The isochrones that fit the calibration stars best were then used to determine the distances and ages of 22 GCs with metallicities ranging from -2.4 dex to -0.7 dex. We find distances with an average uncertainty of 0.15 mag and absolute ages ranging from 10.8 to 13.6 Gyr with an average uncertainty of 1.6 Gyr. Using literature proper motion data, we calculate orbits for the clusters, finding six that reside within the Galactic disk/bulge, while the rest are considered halo clusters. We find no strong evidence for a relationship between age and Galactocentric distance, but we do find a decreasing age-[Fe/H] relation.

Ultra-fine structures of Pd-Ag-HAp nanoparticle deposition on protruded TiO2 barrier layer for dental implant

NASA Astrophysics Data System (ADS)

Jang, Jae-Myung; Kim, Seung-Dai; Park, Tae-Eon; Choe, Han-Cheol

2018-02-01

The biocompatibility structure of an implant surface is of great importance to the formation of new bone tissue around the dental implant and also has a significant chemical reaction in the osseointegration process. Thus, ultra-fine Pd-Ag-HAp nanoparticles have been electrodeposited on protruded TiO2 barrier layer in mixed electrolyte solutions. Unusual protrusions patterns, which are assigned to Pd-Ag-HAp nanoparticles, can be clearly differentiated from a TiO2 nanotube oxide layer formed by an anodizing process. In the chemical bonding state, the surface characteristics of Pd/Ag/HAp compounds have been investigated by FE-SEM, EDS mapping analysis, and XPS analysis. The mapping dots of the elements including Ti, Ca, Pd, Ag, and P showed a homogeneous distribution throughout the entire surface when deposited onto the protruded TiO2 barrier layer. The XPS spectra of Ti-2p, O-1S, Pd-3d, and Ag-3d have been investigated, with the major XPS peak indicating Pd-3d. The Ag-3d level was clearly observed with further scanning of the Ca-2p region. Based on the results of the chemical states, the structural properties of the protrusion patterns were also examined after being deposited onto the barrier oxide film, resulting in the representative protrusion patterns being mainly composed of Pd-Ag-HAp compounds. The results of the soaking evaluation showed that the protrusion patterns and the protruded TiO2 barrier layer were all effective in regards to biocompatibility.

Hospital Acquired Pneumonia is an Independent Predictor of Poor Global Outcome in Severe Traumatic Brain Injury up to 5 Years after Discharge

PubMed Central

Kesinger, Matthew R.; Kumar, Raj G.; Wagner, Amy K.; Puyana, Juan C.; Peitzman, Andrew P.; Billiar, Timothy R.; Sperry, Jason L.

2016-01-01

Objectives Long-term outcomes following traumatic brain injury (TBI) correlate with initial head injury severity and other acute factors. Hospital-acquired pneumonia (HAP) is a common complication in TBI. Little information exists regarding the significance of infectious complications on long-term outcomes post-TBI. We sought to characterize risks associated with HAP on outcomes 5 years post-TBI. Methods Ddata from the merger of an institutional trauma registry and the TBI Model Systems outcome data. Individuals with severe head injuries (Abbreviated Injury Scale≥4), who survived to rehabilitation were analyzed. Primary outcome was Glasgow Outcome Scaled-Extended (GOSE) at 1, 2, and 5 years. GOSE was dichotomized into LOW (GOSE<6) and HIGH (GOSE≥6). Logistic regression was utilized to determine adjusted odds of LOW-GOSE associated with HAP after controlling for age, sex, head and overall injury severity, cranial surgery, Glasgow Coma Scale (GCS), ventilation days, and other important confounders. A general estimating equation (GEE) model was used to analyze all outcome observations simultaneously while controlling for within-patient correlation. Results A total of 141 individuals met inclusion criteria, with a 30% incidence of HAP. Individuals with and without HAP had similar demographic profiles, presenting vitals, head injury severity, and prevalence of cranial surgery. Individuals with HAP had lower presenting GCS. Logistic regression demonstrated that HAP was independently associated with LOW-GOSE scores at follow-up (1year: OR=6.39, 95%CI: 1.76-23.14, p=0.005; 2-years: OR=7.30, 95%CI 1.87-27.89, p=0.004; 5-years: OR=6.89, 95%CI: 1.42-33.39, p=0.017). Stratifying by GCS≤8 and early intubation, HAP remained a significant independent predictor of LOW-GOSE in all strata. In the GEE model, HAP continued to be an independent predictor of LOW-GOSE (OR: 4.59; 95%CI: 1.82-11.60′ p=0.001). Conclusion HAP is independently associated with poor outcomes in severe

VizieR Online Data Catalog: Carbon in red giants in GCs and dSph galaxies (Kirby+, 2015)

NASA Astrophysics Data System (ADS)

Kirby, E. N.; Guo, M.; Zhang, A. J.; Deng, M.; Cohen, J. G.; Guhathakurta, P.; Shetrone, M. D.; Lee, Y. S.; Rizzi, L.

2015-07-01

We obtained Keck/DEIMOS spectra of the carbon G band in red giants in Milky Way (MW) globular clusters (GCs) and dwarf spheroidal galaxies (dSphs) between 2011 Jul 29 and 2012 Mar 19. The GCs are NGC 2419, NGC 4590 (M68), and NGC 7078 (M15). The dSphs are Sculptor, Fornax, Ursa Minor, and Draco. See table 1. (3 data files).

Ab initio simulation of elastic and mechanical properties of Zn- and Mg-doped hydroxyapatite (HAP).

PubMed

Aryal, Sitaram; Matsunaga, Katsuyuki; Ching, Wai-Yim

2015-07-01

Hydroxyapatite (HAP) is an important bioceramic which constitutes the mineral components of bones and hard tissues in mammals. It is bioactive and used as bioceramic coatings for metallic implants and bone fillers. HAP readily absorbs a large amount of impurities. Knowledge on the elastic and mechanical properties of impurity-doped HAP is a subject of great importance to its potential for biomedical applications. Zn and Mg are the most common divalent cations HAP absorbs. Using density function theory based ab initio methods, we have carried out a large number of ab initio calculations to obtain the bulk elastic and mechanical properties of HAP with Zn or Mg doped in different concentration at the Ca1 and Ca2 sites using large 352-atom supercells. Detailed information on their dependece on the concetraion of the substitued impurity is obtained. Our results show that Mg enhances overall elastic and bulk mechanical properties whereas Zn tends to degrade except at low concentrations. At a higher concentration, the mechanical properties of Zn and Mg doped HAP also depend significantly on impurity distribution between the Ca1 and Ca2 sites. There is a strong evidence that Zn prefers Ca2 site for substituion whereas Mg has no such preference. These results imply that proper control of dopant concentration and their site preference must carefully considered in using doped HAP for specific biomedical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

The length of glycine-rich linker in DNA-binding domain is critical for optimal functioning of quorum-sensing master regulatory protein HapR.

PubMed

Singh, Naorem Santa; Kachhap, Sangita; Singh, Richa; Mishra, Rahul Chandra; Singh, Balvinder; Raychaudhuri, Saumya

2014-12-01

HapR is a quorum-sensing master regulatory protein in Vibrio cholerae. Though many facts are known regarding its structural and functional aspects, much still can be learnt from natural variants of this wild-type protein. While unraveling the underlying cause of functional inertness of a natural variant (HapRV2), the significance of a conserved glycine residue at position 39 in a glycine-rich linker in DNA-binding domain comes into light. This work aims at investigating how the length of glycine-rich linker (R(33)GIGRGG(39)) bridging helices α1 and α2 modulates the functionality of HapR. In pursuit of our interest, glycine residues were inserted after terminal glycine (G39) of the linker in a sequential manner. To evaluate functionality, all the glycine linker variants were subjected to a battery of performance tests under various conditions. Combined in vitro and in vivo results clearly demonstrated a gradual functional impairment of HapR linker variants coupled with increasing length of glycine-rich linker and finally, linker variant harboring four glycine residues resulted in a functionally compromised protein with significant loss of communication with cognate DNAs. Molecular dynamics studies of modeled HapR linker variants in complex with cognate promoter region show that residues namely Ser50, Thr53 and Asn56 are involved in varying degree of interactions with different nucleotides of HapR-DNA complex. The diminished functionality between variants and DNA appears to result from reduced or no interactions between Phe55 and nucleotides of cognate DNA as observed during simulations.

The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess

PubMed Central

Gsaller, Fabio; Hortschansky, Peter; Beattie, Sarah R; Klammer, Veronika; Tuppatsch, Katja; Lechner, Beatrix E; Rietzschel, Nicole; Werner, Ernst R; Vogan, Aaron A; Chung, Dawoon; Mühlenhoff, Ulrich; Kato, Masashi; Cramer, Robert A; Brakhage, Axel A; Haas, Hubertus

2014-01-01

Balance of physiological levels of iron is essential for every organism. In Aspergillus fumigatus and other fungal pathogens, the transcription factor HapX mediates adaptation to iron limitation and consequently virulence by repressing iron consumption and activating iron uptake. Here, we demonstrate that HapX is also essential for iron resistance via activating vacuolar iron storage. We identified HapX protein domains that are essential for HapX functions during either iron starvation or high-iron conditions. The evolutionary conservation of these domains indicates their wide-spread role in iron sensing. We further demonstrate that a HapX homodimer and the CCAAT-binding complex (CBC) cooperatively bind an evolutionary conserved DNA motif in a target promoter. The latter reveals the mode of discrimination between general CBC and specific HapX/CBC target genes. Collectively, our study uncovers a novel regulatory mechanism mediating both iron resistance and adaptation to iron starvation by the same transcription factor complex with activating and repressing functions depending on ambient iron availability. PMID:25092765

Lysophosphatidic Acid Promotes Cell Migration through STIM1- and Orai1-Mediated Ca2+i Mobilization and NFAT2 Activation

PubMed Central

Jans, Ralph; Mottram, Laura; Johnson, Darren L; Brown, Anna M; Sikkink, Stephen; Ross, Kehinde; Reynolds, Nick J

2013-01-01

Lysophosphatidic acid (LPA) enhances cell migration and promotes wound healing in vivo, but the intracellular signaling pathways regulating these processes remain incompletely understood. Here we investigated the involvement of agonist-induced Ca2+ entry and STIM1 and Orai1 proteins in regulating nuclear factor of activated T cell (NFAT) signaling and LPA-induced keratinocyte cell motility. As monitored by Fluo-4 imaging, stimulation with 10 μℳ LPA in 60 μℳ Ca2+o evoked Ca2+i transients owing to store release, whereas addition of LPA in physiological 1.2 mℳ Ca2+o triggered store release coupled to extracellular Ca2+ entry. Store-operated Ca2+ entry (SOCE) was blocked by the SOCE inhibitor diethylstilbestrol (DES), STIM1 silencing using RNA interference (RNAi), and expression of dominant/negative Orai1R91W. LPA induced significant NFAT activation as monitored by nuclear translocation of green fluorescent protein-tagged NFAT2 and a luciferase reporter assay, which was impaired by DES, expression of Orai1R91W, and inhibition of calcineurin using cyclosporin A (CsA). By using chemotactic migration assays, LPA-induced cell motility was significantly impaired by STIM1, CsA, and NFAT2 knockdown using RNAi. These data indicate that in conditions relevant to epidermal wound healing, LPA induces SOCE and NFAT activation through Orai1 channels and promotes cell migration through a calcineurin/NFAT2-dependent pathway. PMID:23096711

Similarities between GCS and human motor cortex: complex movement coordination

NASA Astrophysics Data System (ADS)

Rodríguez, Jose A.; Macias, Rosa; Molgo, Jordi; Guerra, Dailos

2014-07-01

The "Gran Telescopio de Canarias" (GTC1) is an optical-infrared 10-meter segmented mirror telescope at the ORM observatory in Canary Islands (Spain). The GTC control system (GCS), the brain of the telescope, is is a distributed object & component oriented system based on RT-CORBA and it is responsible for the management and operation of the telescope, including its instrumentation. On the other hand, the Human motor cortex (HMC) is a region of the cerebrum responsible for the coordination of planning, control, and executing voluntary movements. If we analyze both systems, as far as the movement control of their mechanisms and body parts is concerned, we can find extraordinary similarities in their architectures. Both are structured in layers, and their functionalities are comparable from the movement conception until the movement action itself: In the GCS we can enumerate the Sequencer high level components, the Coordination libraries, the Control Kit library and the Device Driver library as the subsystems involved in the telescope movement control. If we look at the motor cortex, we can also enumerate the primary motor cortex, the secondary motor cortices, which include the posterior parietal cortex, the premotor cortex, and the supplementary motor area (SMA), the motor units, the sensory organs and the basal ganglia. From all these components/areas we will analyze in depth the several subcortical regions, of the the motor cortex, that are involved in organizing motor programs for complex movements and the GCS coordination framework, which is composed by a set of classes that allow to the high level components to transparently control a group of mechanisms simultaneously.

40 CFR Table 2c to Subpart Zzzz of... - Requirements for Existing Compression Ignition Stationary RICE Located at a Major Source of HAP...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Ignition Stationary RICE Located at a Major Source of HAP Emissions and Existing Spark Ignition Stationary RICE ⤠500 HP Located at a Major Source of HAP Emissions 2c Table 2c to Subpart ZZZZ of Part 63... Stationary RICE Located at a Major Source of HAP Emissions and Existing Spark Ignition Stationary RICE ≤ 500...

HDM2 promotes WIP1-mediated medulloblastoma growth

PubMed Central

Buss, Meghan C.; Read, Tracy-Ann; Schniederjan, Matthew J.; Gandhi, Khanjan; Castellino, Robert C.

2012-01-01

Medulloblastoma is the most common malignant childhood brain tumor. The protein phosphatase and oncogene WIP1 is over-expressed or amplified in a significant number of primary human medulloblastomas and cell lines. In the present study, we examine an important mechanism by which WIP1 promotes medulloblastoma growth using in vitro and in vivo models. Human cell lines and intracerebellar xenografted animal models were used to study the role of WIP1 and the major TP53 regulator, HDM2, in medulloblastoma growth. Stable expression of WIP1 enhances growth of TP53 wild-type medulloblastoma cells, compared with cells with stable expression of an empty-vector or mutant WIP1. In an animal model, WIP1 enhances proliferation and reduces the survival of immunodeficient mice bearing intracerebellar xenografted human medulloblastoma cells. Cells with increased WIP1 expression also exhibit increased expression of HDM2. HDM2 knockdown or treatment with the HDM2 inhibitor Nutlin-3a, the active enantomer of Nutlin-3, specifically inhibits the growth of medulloblastoma cells with increased WIP1 expression. Nutlin-3a does not affect growth of medulloblastoma cells with stable expression of an empty vector or of mutant WIP1. Knockdown of WIP1 or treatment with the WIP1 inhibitor CCT007093 results in increased phosphorylation of known WIP1 targets, reduced HDM2 expression, and reduced growth specifically in WIP1 wild-type and high-expressing medulloblastoma cells. Combined WIP1 and HDM2 inhibition is more effective than WIP1 inhibition alone in blocking growth of WIP1 high-expressing medulloblastoma cells. Our preclinical study supports a role for therapies that target WIP1 and HDM2 in the treatment of medulloblastoma. PMID:22379189

Effect of Massage Therapy on Vital Signs and GCS Scores of ICU Patients: A Randomized Controlled Clinical Trial

PubMed Central

Vahedian-Azimi, Amir; Ebadi, Abbas; Asghari Jafarabadi, Mohammad; Saadat, Soheil; Ahmadi, Fazlollah

2014-01-01

Background: Unalleviated complications related to hospitalization, including stress, anxiety, and pain, can easily influence different structures, like the neural system, by enhancing the stimulation of sympathetic nervous pathways and causing unstable vital signs and deterioration in the level of consciousness. Objectives: The purpose of this study was to determine the effects of massage therapy by family members on vital signs and Glasgow Coma Scale Score (GCS) of patients hospitalized in the Intensive Care Unit (ICU). Patients and Methods: This randomized controlled clinical trial was conducted at the ICU of the Shariati Hospital during 2012; 45 ICU patients and 45 family members in the experimental group and the same number of patients and family members in the control group were consecutively selected . The data collection instrument consisted of two parts. The first part included demographic data (age, marital status and Body Mass Index) and the second part included a checklist to record the patient’s vital signs (systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR), pulse rate (PR)) and GCS. All measurements were done at the same time in both groups before the intervention (full body massage therapy), and 1 hour, 2 hours, 3 hours, and 4 hours after intervention. The patients were provided with a 60-minute full body massage The massage protocol included static, surface tension, stretching, superficial lymph unload, transverse friction, and myofacial releasing techniques. Results: Significant differences were observed between experimental and control groups in the SBP at 1 hour, SBP 2 hours, and SBP 3 hours, and also in GCS at 1 hour to GCS at 4 hours (P < 0.05). Multivariate analysis revealed a significant difference between experimental and control groups in SBP at all time points (P < 0.05). Conclusions: Massage via family members had several positive effects on the patients’ clinical conditions, and therefore, it should

The activity of the artemisinic aldehyde Δ11(13) reductase promoter is important for artemisinin yield in different chemotypes of Artemisia annua L.

PubMed

Yang, Ke; Monfared, Sajad Rashidi; Monafared, Rashidi Sajad; Wang, Hongzhen; Lundgren, Anneli; Brodelius, Peter E

2015-07-01

The artemisinic aldehyde double bond reductase (DBR2) plays an important role in the biosynthesis of the antimalarial artemisinin in Artemisia annua. Artemisinic aldehyde is reduced into dihydroartemisinic aldehyde by DBR2. Artemisinic aldehyde can also be oxidized by amorpha-4,11-diene 12-hydroxylase and/or aldehyde dehydrogenase 1 to artemisinic acid, a precursor of arteannuin B. In order to better understand the effects of DBR2 expression on the flow of artemisinic aldehyde into either artemisinin or arteannuin B, we determined the content of dihydroartemisinic aldehyde, artemisinin, artemisinic acid and arteannuin B content of A. annua varieties sorted into two chemotypes. The high artemisinin producers (HAPs), which includes the '2/39', 'Chongqing' and 'Anamed' varieties, produce more artemisinin than arteannuin B; the low artemisinin producers (LAPs), which include the 'Meise', 'Iran#8', 'Iran#14', 'Iran#24' and 'Iran#47' varieties, produce more arteannuin B than artemisinin. Quantitative PCR showed that the relative expression of DBR2 was significantly higher in the HAP varieties. We cloned and sequenced the promoter of the DBR2 gene from varieties of both the LAP and the HAP groups. There were deletions/insertions in the region just upstream of the ATG start codon in the LAP varities, which might be the reason for the different promoter activities of the HAP and LAP varieties. The relevance of promoter variation, DBR2 expression levels and artemisinin biosynthesis capabilities are discussed and a selection method for HAP varieties with a DNA marker is suggested. Furthermore, putative cis-acting regulatory elements differ between the HAP and LAP varieties.

40 CFR 63.2465 - What requirements must I meet for process vents that emit hydrogen halide and halogen HAP or HAP...

Code of Federal Regulations, 2014 CFR

2014-07-01

... process vents that emit hydrogen halide and halogen HAP or HAP metals? 63.2465 Section 63.2465 Protection... hydrogen halide and halogen HAP or HAP metals? (a) You must meet each emission limit in Table 3 to this...) of this section. (b) If any process vents within a process emit hydrogen halide and halogen HAP, you...

40 CFR 63.2465 - What requirements must I meet for process vents that emit hydrogen halide and halogen HAP or HAP...

Code of Federal Regulations, 2013 CFR

2013-07-01

... process vents that emit hydrogen halide and halogen HAP or HAP metals? 63.2465 Section 63.2465 Protection... hydrogen halide and halogen HAP or HAP metals? (a) You must meet each emission limit in Table 3 to this...) of this section. (b) If any process vents within a process emit hydrogen halide and halogen HAP, you...

40 CFR 63.2465 - What requirements must I meet for process vents that emit hydrogen halide and halogen HAP or HAP...

Code of Federal Regulations, 2012 CFR

2012-07-01

... process vents that emit hydrogen halide and halogen HAP or HAP metals? 63.2465 Section 63.2465 Protection... hydrogen halide and halogen HAP or HAP metals? (a) You must meet each emission limit in Table 3 to this...) of this section. (b) If any process vents within a process emit hydrogen halide and halogen HAP, you...

40 CFR Table 3 to Subpart Ggg of... - Soluble HAP

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 11 2010-07-01 2010-07-01 true Soluble HAP 3 Table 3 to Subpart GGG of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... HAP Compound 1,1-Dimethylhydrazine. 1,4-Dioxane. Acetonitrile. Acetophenone. Diethyl sulfate. Dimethyl...

The natural compound cantharidin induces cancer cell death through inhibition of heat shock protein 70 (HSP70) and Bcl-2-associated athanogene domain 3 (BAG3) expression by blocking heat shock factor 1 (HSF1) binding to promoters.

PubMed

Kim, Joo Ae; Kim, Youngmi; Kwon, Byoung-Mog; Han, Dong Cho

2013-10-04

Heat shock factor 1 (HSF1) enhances the survival of cancer cells under various stresses. The knock-out of HSF1 impairs cancer formation and progression, suggesting that HSF1 is a promising therapeutic target. To identify inhibitors of HSF1 activity, we performed cell-based screening with a library of marketed and experimental drugs and identified cantharidin as an HSF1 inhibitor. Cantharidin is a potent antitumor agent from traditional Chinese medicine. Cantharidin inhibited heat shock-induced luciferase activity with an IC50 of 4.2 μm. In contrast, cantharidin did not inhibit NF-κB luciferase reporter activity, demonstrating that cantharidin is not a general transcription inhibitor. When the HCT-116 colorectal cancer cells were exposed to heat shock in the presence of cantharidin, the induction of HSF1 downstream target proteins, such as HSP70 and BAG3 (Bcl-2-associated athanogene domain 3), was suppressed. HSP70 and its co-chaperone BAG3 have been reported to protect cells from apoptosis by stabilizing anti-apoptotic Bcl-2 family proteins. As expected, treating HCT-116 cancer cells with cantharidin significantly decreased the amounts of BCL-2, BCL-xL, and MCL-1 protein and induced apoptotic cell death. Chromatin immunoprecipitation analysis showed that cantharidin inhibited the binding of HSF1 to the HSP70 promoter and subsequently blocked HSF1-dependent p-TEFb recruitment. Therefore, the p-TEFb-dependent phosphorylation of the C-terminal domain of RNA polymerase II was blocked, arresting transcription at the elongation step. Protein phosphatase 2A inhibition with PP2CA siRNA or okadaic acid did not block HSF1 activity, suggesting that cantharidin inhibits HSF1 in a protein phosphatase 2A-independent manner. We show for the first time that cantharidin inhibits HSF1 transcriptional activity.

40 CFR 63.5340 - How do I determine the allowable HAP loss?

Code of Federal Regulations, 2010 CFR

2010-07-01

... appropriate HAP emission limit, expressed in pounds of HAP loss per 1,000 square feet of leather processed... the annual total of leather processed in 1,000's of square feet for each product process operation in... of square feet of leather processed in the previous 12 months in product process operation “i”. HAP...

40 CFR 63.5340 - How do I determine the allowable HAP loss?

Code of Federal Regulations, 2011 CFR

2011-07-01

... appropriate HAP emission limit, expressed in pounds of HAP loss per 1,000 square feet of leather processed... the annual total of leather processed in 1,000's of square feet for each product process operation in... of square feet of leather processed in the previous 12 months in product process operation “i”. HAP...

Hilson Adolescent Profile (HAP): Hilson Research Abstracts.

ERIC Educational Resources Information Center

Hilson Research Inc., Kew Gardens, NY.

Abstracts and bibliographic citations are given for the following documents concerned with the use and characteristics of the Hilson Adolescent Profile (HAP): (1) "Use of the Hilson Adolescent Profile To Compare Juvenile Offenders with Junior and Senior High School Students" (R. E. Inwald and K. E. Brobst); (2) "The Effectiveness of…

IL-4 production by group 2 innate lymphoid cells promotes food allergy by blocking regulatory T-cell function.

PubMed

Noval Rivas, Magali; Burton, Oliver T; Oettgen, Hans C; Chatila, Talal

2016-09-01

Food allergy is a major health issue, but its pathogenesis remains obscure. Group 2 innate lymphoid cells (ILC2s) promote allergic inflammation. However their role in food allergy is largely unknown. We sought to investigate the role of ILC2s in food allergy. Food allergy-prone mice with a gain-of-function mutation in the IL-4 receptor α chain (Il4raF709) were orally sensitized with food allergens, and the ILC2 compartment was analyzed. The requirement for ILC2s in food allergy was investigated by using Il4raF709, IL-33 receptor-deficient (Il1rl1(-/-)), IL-13-deficient (Il13(-/-)), and IL-4-deficient (Il4(-/-)) mice and by adoptive transfer of in vitro-expanded ILC2s. Direct effects of ILC2s on regulatory T (Treg) cells and mast cells were analyzed in coculture experiments. Treg cell control of ILC2s was assessed in vitro and in vivo. Il4raF709 mice with food allergy exhibit increased numbers of ILC2s. IL-4 secretion by ILC2s contributes to the allergic response by reducing allergen-specific Treg cell and activating mast cell counts. IL-33 receptor deficiency in Il4raF709 Il1rl1(-/-) mice protects against allergen sensitization and anaphylaxis while reducing ILC2 induction. Adoptive transfer of wild-type and Il13(-/-) but not Il4(-/-) ILC2s restored sensitization in Il4raF709 Il1rl1(-/-) mice. Treg cells suppress ILC2s in vitro and in vivo. IL-4 production by IL-33-stimulated ILC2s blocks the generation of allergen-specific Treg cells and favors food allergy. Strategies to block ILC2 activation or the IL-33/IL-33 receptor pathway can lead to innovative therapies in the treatment of food allergy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Hazardous air pollutant (HAP) emission characterization of sewage treatment facilities in Korea.

PubMed

Kang, Kyoung-Hee; Dong, Jong-In

2010-04-01

Until recently, nearly all sewage treatment-related regulations and researches have focused on the removal of the conventional and toxic pollutants from liquid effluents. The discharge of toxic compounds to the atmosphere has been implicitly regarded as a way of removal or destruction. During sewage treatment, the fate mechanism of volatilization/stripping, sorption and biotransformation primarily determines the fate of volatile HAPs. The objectives of this study are to investigate the emission characteristics of HAPs, which are generated from the liquid surface of sewage treatment facilities, by using an emission isolation flux chamber. HAP emissions increased at the inlet of the aerobic chamber during summer due to the relatively high atmospheric temperature. The percent ratio of flux for toluene reached its peak in winter, accounting for 33.6-34.2% of the total, but decreased to 25.1-28.6% in summer. In autumn, trichloroethene (TCE) was the highest, recording 17.6-18.1%, with chloroform and toluene showing similar levels. It seems that the ratio of chlorinated hydrocarbons increases in both summer and autumn because the chamber temperature during that time is higher than winter. This study is the initial study to investigate the emission characteristics of volatile HAPs emitted from domestic sewage treatment facilities to the air in Korea. Therefore, the isolation flux chamber will be used as an emission estimations tool to measure HAPs from sewage treatment facilities and may be applied to develop the emission factor and national source inventory of HAPs.

Calcein represses human papillomavirus 16 E1-E2 mediated DNA replication via blocking their binding to the viral origin of replication.

PubMed

Das, Dipon; Smith, Nathan W; Wang, Xu; Richardson, Stacie L; Hartman, Matthew C T; Morgan, Iain M

2017-08-01

Human papillomaviruses are causative agents in several human diseases ranging from genital warts to ano-genital and oropharyngeal cancers. Currently only symptoms of HPV induced disease are treated; there are no antivirals available that directly target the viral life cycle. Previously, we determined that the cellular protein TopBP1 interacts with the HPV16 replication/transcription factor E2. This E2-TopBP1 interaction is essential for optimal E1-E2 DNA replication and for the viral life cycle. The drug calcein disrupts the interaction of TopBP1 with itself and other host proteins to promote cell death. Here we demonstrate that calcein blocks HPV16 E1-E2 DNA replication via blocking the viral replication complex forming at the origin of replication. This occurs at non-toxic levels of calcein and demonstrates specificity as it does not block the ability of E2 to regulate transcription. We propose that calcein or derivatives could be developed as an anti-HPV therapeutic. Copyright © 2017 Elsevier Inc. All rights reserved.

40 CFR 63.5335 - How do I determine the actual HAP loss?

Code of Federal Regulations, 2013 CFR

2013-07-01

... and the mass fraction of HAP in each solvent/finish. (1) Measure Finish as Applied. Use a finish... and the mass fraction of HAP in each applied finish. Figure 1 of this subpart shows an example log for... each finish applied to the leather; (iii) Mass fraction of HAP in each applied finish; (iv) Date of the...

40 CFR 63.5335 - How do I determine the actual HAP loss?

Code of Federal Regulations, 2012 CFR

2012-07-01

... and the mass fraction of HAP in each solvent/finish. (1) Measure Finish as Applied. Use a finish... and the mass fraction of HAP in each applied finish. Figure 1 of this subpart shows an example log for... each finish applied to the leather; (iii) Mass fraction of HAP in each applied finish; (iv) Date of the...

40 CFR 63.5335 - How do I determine the actual HAP loss?

Code of Federal Regulations, 2014 CFR

2014-07-01

... and the mass fraction of HAP in each solvent/finish. (1) Measure Finish as Applied. Use a finish... and the mass fraction of HAP in each applied finish. Figure 1 of this subpart shows an example log for... each finish applied to the leather; (iii) Mass fraction of HAP in each applied finish; (iv) Date of the...

40 CFR Table 2 to Subpart Ooo of... - Known Organic Hazardous Air Pollutants (HAP) From the Manufacture of Amino/Phenolic Resins

Code of Federal Regulations, 2011 CFR

2011-07-01

... (HAP) From the Manufacture of Amino/Phenolic Resins 2 Table 2 to Subpart OOO of Part 63 Protection of... Pollutant Emissions: Manufacture of Amino/Phenolic Resins Pt. 63, Subpt. OOO, Table 2 Table 2 to Subpart OOO of Part 63—Known Organic Hazardous Air Pollutants (HAP) From the Manufacture of Amino/Phenolic Resins...

40 CFR Table 2 to Subpart Ooo of... - Known Organic Hazardous Air Pollutants (HAP) From the Manufacture of Amino/Phenolic Resins

Code of Federal Regulations, 2010 CFR

2010-07-01

... (HAP) From the Manufacture of Amino/Phenolic Resins 2 Table 2 to Subpart OOO of Part 63 Protection of... Pollutant Emissions: Manufacture of Amino/Phenolic Resins Pt. 63, Subpt. OOO, Table 2 Table 2 to Subpart OOO of Part 63—Known Organic Hazardous Air Pollutants (HAP) From the Manufacture of Amino/Phenolic Resins...

24 CFR 891.580 - HAP contract administration.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false HAP contract administration. 891... Handicapped-Section 8 Assistance § 891.580 HAP contract administration. HUD is responsible for the administration of the HAP contract. ...

40 CFR Table 2d to Subpart Zzzz of... - Requirements for Existing Stationary RICE Located at Area Sources of HAP Emissions

Code of Federal Regulations, 2011 CFR

2011-07-01

... RICE Located at Area Sources of HAP Emissions 2d Table 2d to Subpart ZZZZ of Part 63 Protection of... 2d Table 2d to Subpart ZZZZ of Part 63—Requirements for Existing Stationary RICE Located at Area... requirements for existing stationary RICE located at area sources of HAP emissions: For each . . . You must...

Pollution prevention and the use of low-VOC/HAP coatings at wood furniture manufacturing facilities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marshall, A.M.; Spaight, J.L.; Jones, J.W.

1999-07-01

Midwest Research Institute, under a cooperative agreement with the Air Pollution Prevention and Control Division of the U.S. Environmental Protection Agency's (EPA's) National Risk Management Research Laboratory, is conducting a study to identify wood furniture and cabinet manufacturing facilities that have converted to low-volatile organic compound/hazardous air pollutant (VOC/HAP) coatings and to develop case studies for those facilities. The case studies include: (1) a discussion of the types of products each facility manufactures; (2) the types of low-VOC/HAP coatings each facility is using; (3) problems encountered in converting to low-VOC/HAP coatings; (4) equipment changes that were required; (5) the costsmore » associated with the conversion process, including capital costs associated with equipment purchases, research and development costs, and operating costs such as operator training in new application techniques; (6) advantages/disadvantages of the low-VOC/HAP coatings; and (7) customer feedback on products finished with the low-VOC/HAP coatings. The primary goals of the project are (1) to demonstrate that low-VOC/HAP coatings can be used successfully by many wood furniture manufacturing facilities, and (2) to assist other wood furniture manufacturing facilities in their conversion to low-VOC/HAP coatings, in particular facilities that do not have the resources to devote to extensive coatings research. This paper discusses the progress of the project and pollution prevention options at wood furniture manufacturing facilities and the regulatory requirements (e.g., the National Emissions Standards for Hazardous Air Pollutants [NESHAP] for Wood Furniture Manufacturing Operations) that these facilities face.« less

The role of fructose‑1,6‑bisphosphatase 1 in abnormal development of ovarian follicles caused by high testosterone concentration.

PubMed

Liu, Tao; Zhao, Han; Wang, Jianfeng; Shu, Xin; Gao, Yuan; Mu, Xiaoli; Gao, Fei; Liu, Hongbin

2017-11-01

The present study aimed to identify the molecular mechanisms underlying the effects of the fructose‑1,6‑bisphosphatase 1 (FBP1) signaling pathway within normal follicle development and in hyperandrogenism‑induced abnormal follicle growth. To achieve this, murine primary follicles, granulosa cells (GCs) and theca‑interstitial cells (TICs) were isolated, cultured in vitro and treated with a high concentration of androgens. A concentration of 1x10‑5 mol/l testosterone was considerable to induce hyperandrogenism by MTT assay. All cells were divided into four groups, as follows: Control group, testosterone group, androgen receptor antagonist‑flutamide group and flutamide + testosterone group. Flutamide was used in the present study as it blocks the effects of the androgen receptor. The mRNA expression levels of FBP1 were detected using reverse transcription‑quantitative polymerase chain reaction. The expression levels and localization of FBP1 were analyzed by western blot analysis and immunofluorescence staining. The experimental results demonstrated that androgen presence stimulated follicle development, whereas excessive testosterone inhibited development. FBP1 was identified as being mainly expressed in follicles; FBP1 protein was significantly expressed in GCs of the 14‑day‑cultured follicle, as well as in the cytoplasm and nuclei of GCs and TICs in vitro. Testosterone increased FBP1 expression during a specific range of testosterone concentrations. Testosterone increased the expression of FBP1 within GCs. Furthermore, FBP1 and phosphoenolpyruvate carboxykinase 1 (PCK1) mRNA expression was increased in GCs treated with testosterone, whereas forkhead box protein O1 (FOXO1) and peroxisome proliferator‑activated receptor γ coactivator‑1α mRNA expression was significantly decreased in the testosterone group. In TICs, testosterone and flutamide inhibited the mRNA expression levels of FOXO1 and glucose‑6‑phosphatase enzyme, and promoted

24 CFR 983.202 - Purpose of HAP contract.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Purpose of HAP contract. 983.202... DEVELOPMENT PROJECT-BASED VOUCHER (PBV) PROGRAM Housing Assistance Payments Contract § 983.202 Purpose of HAP contract. (a) Requirement. The PHA must enter into a HAP contract with the owner. The HAP contract must be...

P2Y2 Receptor and EGFR Cooperate to Promote Prostate Cancer Cell Invasion via ERK1/2 Pathway.

PubMed

Li, Wei-Hua; Qiu, Ying; Zhang, Hong-Quan; Tian, Xin-Xia; Fang, Wei-Gang

2015-01-01

As one member of G protein-coupled P2Y receptors, P2Y2 receptor can be equally activated by extracellular ATP and UTP. Our previous studies have proved that activation of P2Y2 receptor by extracellular ATP could promote prostate cancer cell invasion and metastasis in vitro and in vivo via regulating the expressions of some epithelial-mesenchymal transition/invasion-related genes (including IL-8, E-cadherin, Snail and Claudin-1), and the most significant change in expression of IL-8 was observed after P2Y2 receptor activation. However, the signaling pathway downstream of P2Y2 receptor and the role of IL-8 in P2Y2-mediated prostate cancer cell invasion remain unclear. Here, we found that extracellular ATP/UTP induced activation of EGFR and ERK1/2. After knockdown of P2Y2 receptor, the ATP -stimulated phosphorylation of EGFR and ERK1/2 was significantly suppressed. Further experiments showed that inactivation of EGFR and ERK1/2 attenuated ATP-induced invasion and migration, and suppressed ATP-mediated IL-8 production. In addition, knockdown of IL-8 inhibited ATP-mediated invasion and migration of prostate cancer cells. These findings suggest that P2Y2 receptor and EGFR cooperate to upregulate IL-8 production via ERK1/2 pathway, thereby promoting prostate cancer cell invasion and migration. Thus blocking of the P2Y2-EGFR-ERK1/2 pathway may provide effective therapeutic interventions for prostate cancer.

24 CFR 891.565 - Term of HAP contract.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Term of HAP contract. 891.565... 8 Assistance § 891.565 Term of HAP contract. The term of the HAP contract for assisted units shall be 20 years. If the project is completed in stages, the term of the HAP contract for assisted units...

24 CFR 983.203 - HAP contract information.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false HAP contract information. 983.203... DEVELOPMENT PROJECT-BASED VOUCHER (PBV) PROGRAM Housing Assistance Payments Contract § 983.203 HAP contract information. The HAP contract must specify: (a) The total number of contract units by number of bedrooms; (b...

Erythrocyte plasma membrane-bound ERK1/2 activation promotes ICAM-4-mediated sickle red cell adhesion to endothelium.

PubMed

Zennadi, Rahima; Whalen, Erin J; Soderblom, Erik J; Alexander, Susan C; Thompson, J Will; Dubois, Laura G; Moseley, M Arthur; Telen, Marilyn J

2012-02-02

The core pathology of sickle cell disease (SCD) starts with the erythrocyte (RBC). Aberration in MAPK/ERK1/2 signaling, which can regulate cell adhesion, occurs in diverse pathologies. Because RBCs contain abundant ERK1/2, we predicted that ERK1/2 is functional in sickle (SS) RBCs and promotes adherence, a hallmark of SCD. ERK1/2 remained active in SS but not normal RBCs. β(2)-adrenergic receptor stimulation by epinephrine can enhance ERK1/2 activity only in SS RBCs via PKA- and tyrosine kinase p72(syk)-dependent pathways. ERK signaling is implicated in RBC ICAM-4 phosphorylation, promoting SS RBC adhesion to the endothelium. SS RBC adhesion and phosphorylation of both ERK and ICAM-4 all decreased with continued cell exposure to epinephrine, implying that activation of ICAM-4-mediated SS RBC adhesion is temporally associated with ERK1/2 activation. Furthermore, recombinant ERK2 phosphorylated α- and β-adducins and dematin at the ERK consensus motif. Cytoskeletal protein 4.1 also showed dynamic phosphorylation but not at the ERK consensus motif. These results demonstrate that ERK activation induces phosphorylation of cytoskeletal proteins and the adhesion molecule ICAM-4, promoting SS RBC adhesion to the endothelium. Thus, blocking RBC ERK1/2 activation, such as that promoted by catecholamine stress hormones, could ameliorate SCD pathophysiology.

Shifting the fermentative/oxidative balance in Saccharomyces cerevisiae by transcriptional deregulation of Snf1 via overexpression of the upstream activating kinase Sak1p.

PubMed

Raab, Andreas M; Hlavacek, Verena; Bolotina, Natalia; Lang, Christine

2011-03-01

With the aim to reduce fermentation by-products and to promote respiratory metabolism by shifting the fermentative/oxidative balance, we evaluated the constitutive overexpression of the SAK1 and HAP4 genes in Saccharomyces cerevisiae. Sak1p is one of three kinases responsible for the phosphorylation, and thereby the activation, of the Snf1p complex, while Hap4p is the activator subunit of the Hap2/3/4/5 transcriptional complex. We compared the physiology of a SAK1-overexpressing strain with that of a strain overexpressing the HAP4 gene in wild-type and sdh2 deletion (respiratory-deficient) backgrounds. Both SAK1 and HAP4 overexpressions led to the upregulation of glucose-repressed genes and to reduced by-product formation rates (ethanol and glycerol). SAK1 overexpression had a greater impact on growth rates than did HAP4 overexpression. Elevated transcript levels of SAK1, but not HAP4, resulted in increased biomass yields in batch cultures grown on glucose (aerobic and excess glucose) as well as on nonfermentable carbon sources. SAK1 overexpression, but not the combined overexpression of SAK1 and HAP4 or the overexpression of HAP4 alone, restored growth on ethanol in an sdh2 deletion strain. In glucose-grown shake flask cultures, the sdh2 deletion strain with SAK1 and HAP4 overexpression produced succinic acid at a titer of 8.5 g liter(-1) and a yield of 0.26 mol (mol glucose)(-1) within 216 h. We here report for the first time that a constitutively high level of expression of SAK1 alleviates glucose repression and shifts the fermentative/oxidative balance under both glucose-repressed and -derepressed conditions.

E(y)2/Sus1 is required for blocking PRE silencing by the Wari insulator in Drosophila melanogaster.

PubMed

Erokhin, Maksim; Parshikov, Alexander; Georgiev, Pavel; Chetverina, Darya

2010-06-01

Chromatin insulators affect interactions between promoters and enhancers/silencers and function as barriers to the spread of repressive chromatin. Recently, we have found an insulator, named Wari, located on the 3' side of the white gene. Here, we show that the previously identified 368-bp core of this insulator is sufficient for blocking Polycomb response element-mediated silencing. Although Wari does not contain binding sites for known insulator proteins, the E(y)2 and CP190 proteins bind to Wari as well as to the Su(Hw)-containing insulators in vivo. It may well be that these proteins are recruited to the insulator by as yet unidentified DNA-binding protein. Partial inactivation of E(y)2 in a weak e(y)2 ( u1 ) mutation impairs only the anti-silencing but not the enhancer-blocking activity of the Wari insulator. Thus, the E(y)2 protein in different Drosophila insulators serves to protect gene expression from silencing.

Intersystem Interference Reduction for Overlaid HAPS-Terrestrial CDMA System

NASA Astrophysics Data System (ADS)

Huang, Jeng-Ji; Wang, Wei-Ting; Li, Mingfu; Shiung, David; Ferng, Huei-Wen

In this letter, we propose that directional antennas, combined with power management, be incorporated to reduce intersystem interference in a shared band overlaid high altitude platform station (HAPS)-terrestrial code division multiple access (CDMA) system. To eliminate the HAPS to terrestrial interference, the HAPS is accessed only via directional antennas under the proposed scheme. By doing so, the uplink power to the HAPS can accordingly be increased, so that the terrestrial to HAPS interference is also effectively suppressed.

P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions

PubMed Central

Giroud, Charline; Marin, Mariana; Hammonds, Jason; Spearman, Paul

2015-01-01

ABSTRACT HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. IMPORTANCE Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1

P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions.

PubMed

Giroud, Charline; Marin, Mariana; Hammonds, Jason; Spearman, Paul; Melikyan, Gregory B

2015-09-01

HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1 receptor antagonist, NF

Relative Contribution of P5 and Hap Surface Proteins to Nontypable Haemophilus influenzae Interplay with the Host Upper and Lower Airways

PubMed Central

Viadas, Cristina; Ruiz de los Mozos, Igor; Valle, Jaione; Bengoechea, José Antonio; Garmendia, Junkal

2015-01-01

Nontypable Haemophilus influenzae (NTHi) is a major cause of opportunistic respiratory tract disease, and initiates infection by colonizing the nasopharynx. Bacterial surface proteins play determining roles in the NTHi-airways interplay, but their specific and relative contribution to colonization and infection of the respiratory tract has not been addressed comprehensively. In this study, we focused on the ompP5 and hap genes, present in all H. influenzae genome sequenced isolates, and encoding the P5 and Hap surface proteins, respectively. We employed isogenic single and double mutants of the ompP5 and hap genes generated in the pathogenic strain NTHi375 to evaluate P5 and Hap contribution to biofilm growth under continuous flow, to NTHi adhesion, and invasion/phagocytosis on nasal, pharyngeal, bronchial, alveolar cultured epithelial cells and alveolar macrophages, and to NTHi murine pulmonary infection. We show that P5 is not required for bacterial biofilm growth, but it is involved in NTHi interplay with respiratory cells and in mouse lung infection. Mechanistically, P5NTHi375 is not a ligand for CEACAM1 or α5 integrin receptors. Hap involvement in NTHi375-host interaction was shown to be limited, despite promoting bacterial cell adhesion when expressed in H. influenzae RdKW20. We also show that Hap does not contribute to bacterial biofilm growth, and that its absence partially restores the deficiency in lung infection observed for the ΔompP5 mutant. Altogether, this work frames the relative importance of the P5 and Hap surface proteins in NTHi virulence. PMID:25894755

Senataxin Mutation Reveals How R-Loops Promote Transcription by Blocking DNA Methylation at Gene Promoters.

PubMed

Grunseich, Christopher; Wang, Isabel X; Watts, Jason A; Burdick, Joshua T; Guber, Robert D; Zhu, Zhengwei; Bruzel, Alan; Lanman, Tyler; Chen, Kelian; Schindler, Alice B; Edwards, Nancy; Ray-Chaudhury, Abhik; Yao, Jianhua; Lehky, Tanya; Piszczek, Grzegorz; Crain, Barbara; Fischbeck, Kenneth H; Cheung, Vivian G

2018-02-01

R-loops are three-stranded nucleic acid structures found abundantly and yet often viewed as by-products of transcription. Studying cells from patients with a motor neuron disease (amyotrophic lateral sclerosis 4 [ALS4]) caused by a mutation in senataxin, we uncovered how R-loops promote transcription. In ALS4 patients, the senataxin mutation depletes R-loops with a consequent effect on gene expression. With fewer R-loops in ALS4 cells, the expression of BAMBI, a negative regulator of transforming growth factor β (TGF-β), is reduced; that then leads to the activation of the TGF-β pathway. We uncovered that genome-wide R-loops influence promoter methylation of over 1,200 human genes. DNA methyl-transferase 1 favors binding to double-stranded DNA over R-loops. Thus, in forming R-loops, nascent RNA blocks DNA methylation and promotes further transcription. Hence, our results show that nucleic acid structures, in addition to sequences, influence the binding and activity of regulatory proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

An Ecological Approach to the Design of UAV Ground Control Station (GCS) Status Displays

NASA Technical Reports Server (NTRS)

Dowell, Susan; Morphew, Ephimia; Shively, Jay

2003-01-01

Use of UAVs in military and commercial applications will continue to increase. However, there has been limited research devoted to UAV GCS design. The current study employed an ecological approach to interfac e design. Ecological Interface Design (EID) can be characterized as r epresenting the properties of a system, such that an operator is enco uraged to use skill-based behavior when problem solving. When more ef fortful cognitive processes become necessary due to unfamiliar situations, the application of EID philosophy supports the application of kn owledge-based behavior. With advances toward multiple UAV command and control, operators need GCS interfaces designed to support understan ding of complex systems. We hypothesized that use of EID principles f or the display of UAV status information would result in better opera tor performance and situational awareness, while decreasing workload. Pilots flew a series of missions with three UAV GCS displays of statu s information (Alphanumeric, Ecological, and Hybrid display format). Measures of task performance, Situational Awareness, and workload dem onstrated the benefits of using an ecological approach to designing U AV GCS displays. The application of ecological principles to the design of UAV GCSs is a promising area for improving UAV operations.

HAP-PRO USER'S MANUAL (FOR USE WITH VERSION 1.0)

EPA Science Inventory

The primary purpose of the Hazardous Air Pollutant Program (HAP-PRO) is to assist permit engineers in reviewing applications for control of air toxics by calculating the capital and annual costs for 6 volatile organic compound (VOC) and 3 different particulate control devices, i...

The Haemophilus influenzae Hap autotransporter mediates microcolony formation and adherence to epithelial cells and extracellular matrix via binding regions in the C-terminal end of the passenger domain.

PubMed

Fink, Doran L; Buscher, Amy Z; Green, Bruce; Fernsten, Phillip; St Geme, Joseph W

2003-03-01

The pathogenesis of non-typable Haemophilus influenzae disease begins with colonization of the nasopharynx and is facilitated by bacterial adherence to respiratory mucosa. The H. influenzae Hap autotransporter is a non-pilus adhesin that promotes adherence to epithelial cells and selected extracellular matrix proteins and mediates bacterial aggregation and microcolony formation. In addition, Hap has serine protease activity. Hap contains a 110 kDa internal passenger domain called HapS and a 45 kDa C-terminal translocator domain called Hapbeta. In the present study, we sought to define the structural basis for Hap adhesive activities. Based on experiments using a panel of monoclonal antibodies against HapS, a deletion derivative lacking most of HapS and a purified fragment of HapS, we established that adherence to epithelial cells is mediated by sequences within the C-terminal 311 residues of HapS. In additional experiments, we discovered that bacterial aggregation is also mediated by sequences within the C-terminal 311 residues of HapS and occurs via HapS-HapS interaction between molecules on neighbouring organisms. Finally, we found that adherence to fibronectin, laminin and collagen IV is mediated in part by sequences within the C-terminal 311 residues of HapS and in full by sequences within the C-terminal 511 residues of HapS. Taken together, these results demonstrate that all Hap adhesive activities reside in the C-terminal portion of HapS. Coupled with earlier observations, the current results establish that HapS adhesive activities and HapS protease activity are contained in separate modules of the protein.

24 CFR 891.590 - Notice upon HAP contract expiration.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Notice upon HAP contract expiration... Handicapped-Section 8 Assistance § 891.590 Notice upon HAP contract expiration. (a) Notice required. The HAP contract will provide that the Borrower will, at least one year before the end of the HAP contract term...

A dual role for glucocorticoid-induced leucine zipper in glucocorticoid function: tumor growth promotion or suppression?

PubMed

Ayroldi, Emira; Cannarile, Lorenza; Delfino, Domenico V; Riccardi, Carlo

2018-04-26

Glucocorticoids (GCs), important therapeutic tools to treat inflammatory and immunosuppressive diseases, can also be used as part of cancer therapy. In oncology, GCs are used as anticancer drugs for lymphohematopoietic malignancies, while in solid neoplasms primarily to control the side effects of chemo/radiotherapy treatments. The molecular mechanisms underlying the effects of GCs are numerous and often overlapping, but not all have been elucidated. In normal, cancerous, and inflammatory tissues, the response to GCs differs based on the tissue type. The effects of GCs are dependent on several factors: the tumor type, the GC therapy being used, the expression level of the glucocorticoid receptor (GR), and the presence of any other stimuli such as signals from immune cells and the tumor microenvironment. Therefore, GCs may either promote or suppress tumor growth via different molecular mechanisms. Stress exposure results in dysregulation of the hypothalamic-pituitary-adrenal axis with increased levels of endogenous GCs that promote tumorigenesis, confirming the importance of GCs in tumor growth. Most of the effects of GCs are genomic and mediated by the modulation of GR gene transcription. Moreover, among the GR-induced genes, glucocorticoid-induced leucine zipper (GILZ), which was cloned and characterized primarily in our laboratory, mediates many GC anti-inflammatory effects. In this review, we analyzed the possible role for GILZ in the effects GCs have on tumors cells. We also suggest that GILZ, by affecting the immune system, tumor microenvironment, and directly cancer cell biology, has a tumor-promoting function. However, it may also induce apoptosis or decrease the proliferation of cancer cells, thus inhibiting tumor growth. The potential therapeutic implications of GILZ activity on tumor cells are discussed here.

40 CFR Table 2d to Subpart Zzzz of... - Requirements for Existing Compression Ignition Stationary RICE Located at Area Sources of HAP...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Ignition Stationary RICE Located at Area Sources of HAP Emissions 2d Table 2d to Subpart ZZZZ of Part 63... Stationary RICE Located at Area Sources of HAP Emissions As stated in §§ 63.6600 and 63.6640, you must comply with the following emission and operating limitations for existing compression ignition stationary RICE...

E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Zejun; Gong, Chaoju; Liu, Hong

2015-08-21

As the ribonucleotide reductase small subunit, the high expression of ribonucleotide reductase small subunit M2 (RRM2) induces cancer and contributes to tumor growth and invasion. In several colorectal cancer (CRC) cell lines, we found that the expression levels of RRM2 were closely related to the transcription factor E2F1. Mechanistic studies were conducted to determine the molecular basis. Ectopic overexpression of E2F1 promoted RRM2 transactivation while knockdown of E2F1 reduced the levels of RRM2 mRNA and protein. To further investigate the roles of RRM2 which was activated by E2F1 in CRC, CCK-8 assay and EdU incorporation assay were performed. Overexpression ofmore » E2F1 promoted cell proliferation in CRC cells, which was blocked by RRM2 knockdown attenuation. In the migration and invasion tests, overexpression of E2F1 enhanced the migration and invasion of CRC cells which was abrogated by silencing RRM2. Besides, overexpression of RRM2 reversed the effects of E2F1 knockdown partially in CRC cells. Examination of clinical CRC specimens demonstrated that both RRM2 and E2F1 were elevated in most cancer tissues compared to the paired normal tissues. Further analysis showed that the protein expression levels of E2F1 and RRM2 were parallel with each other and positively correlated with lymph node metastasis (LNM), TNM stage and distant metastasis. Consistently, the patients with low E2F1 and RRM2 levels have a better prognosis than those with high levels. Therefore, we suggest that E2F1 can promote CRC proliferation, migration, invasion and metastasis by regulating RRM2 transactivation. Understanding the role of E2F1 in activating RRM2 transcription will help to explain the relationship between E2F1 and RRM2 in CRC and provide a novel predictive marker for diagnosis and prognosis of the disease. - Highlights: • E2F1 promotes RRM2 transactivation in CRC cells. • E2F1 promotes the proliferation of CRC cells by activating RRM2. • E2F1 promotes the migration

HDPE-Al2O3-HAp composites for biomedical applications: processing and characterizations.

PubMed

Nath, Shekhar; Bodhak, Subhadip; Basu, Bikramjit

2009-01-01

The objective of this work is to demonstrate how the stiffness, hardness, as well as the biocompatibility property, of bioinert high-density polyethylene (HDPE) can be significantly improved by the combined addition of both bioinert and bioactive ceramic fillers. For this purpose, different volume fractions of hydroxyapatite and alumina, limited to a total of 40 vol %, have been incorporated in HDPE matrix. All the hybrid composites and monolithic HDPE were developed under optimized hot pressing condition (130 degrees C, 0.5 h, 92 MPa pressure). The results of the mechanical property characterization reveal that higher elastic modulus (6.2 GPa) and improved hardness (226.5 MPa) could be obtained in the developed HDPE-20 vol %-HAp-20 vol % Al(2)O(3) composite. Under the selected fretting conditions against various counterbody materials (steel, Al(2)O(3), and ZrO(2)), an extremely low COF of (0.07-0.11) and higher wear resistance (order of 10(-6) mm(3)/Nm) are obtained with the HDPE/20 vol % HAp/20 vol % Al(2)O(3) composite in both air and simulated body fluid environment. Importantly, in-vitro cell culture study using L929 fibroblast cells confirms favorable cell adhesion properties in the developed hybrid composite. (c) 2008 Wiley Periodicals, Inc.

Time-dependent cytokine expression in bone of experimental animals after hydroxyapatite (Hap) implantation

NASA Astrophysics Data System (ADS)

Pilmane, M.; Salms, G.; Salma, I.; Skagers, A.; Locs, J.; Loca, D.; Berzina-Cimdina, L.

2011-06-01

Proinflammatory cytokines mediate bone loss around the implants in patients with peri-implant disease. However, there is no complete data about the expression of cytokines into the bone around the implants. The aim of this work was to investigate the distribution and appearance of inflammatory cytokines and anti-inflammatory proteins in the bone of jaw of experimental rabbits in different time periods after HAp implantation. Material was obtained from 8 rabbits in lower jaw 6 and 8 months after HAp implants were placed. Tissues were processed for immunohistochemical detection of tumor necrosis factor alfa (TNFα), Interleukin 1, 6, 8, 10 (IL-1, IL-6, IL-8, IL-10) and defensin 2. Results demonstrated practically unchanged expression of IL-6 and IL-10 between both - experimental and control side 6 months after implantation, while IL-1 and IL-8 notably increased in control side. IL-1 and IL-10 expression did not change in either the experimental side nor the controle side after 8 months HAP implantation, but IL-6 and IL-8 demonstrated a decrease in the control sites. Only IL-8 was elevated with time in experimental sites, while IL-10 showed individual variations in 2 cases.

Poisoning severity score, APACHE II and GCS: effective clinical indices for estimating severity and predicting outcome of acute organophosphorus and carbamate poisoning.

PubMed

Sam, Kishore Gnana; Kondabolu, Krishnakanth; Pati, Dipanwita; Kamath, Asha; Pradeep Kumar, G; Rao, Padma G M

2009-07-01

Self-poisoning with organophosphorus (OP) compounds is a major cause of morbidity and mortality across South Asian countries. To develop uniform and effective management guidelines, the severity of acute OP poisoning should be assessed through scientific methods and a clinical database should be maintained. A prospective descriptive survey was carried out to assess the utility of severity scales in predicting the outcome of 71 organophosphate (OP) and carbamate poisoning patients admitted during a one year period at the Kasturba Hospital, Manipal, India. The Glasgow coma scale (GCS) scores, acute physiology and chronic health evaluation II (APACHE II) scores, predicted mortality rate (PMR) and Poisoning severity score (PSS) were estimated within 24h of admission. Significant correlation (P<0.05) between PSS and GCS and APACHE II and PMR scores were observed with the PSS scores predicting mortality significantly (P< or =0.001). A total of 84.5% patients improved after treatment while 8.5% of the patients were discharged with severe morbidity. The mortality rate was 7.0%. Suicidal poisoning was observed to be the major cause (80.2%), while other reasons attributed were occupational (9.1%), accidental (6.6%), homicidal (1.6%) and unknown (2.5%) reasons. This study highlights the application of clinical indices like GCS, APACHE, PMR and severity scores in predicting mortality and may be considered for planning standard treatment guidelines.

Structural insights into activation and inhibition of histo-aspartic protease (HAP) from Plasmodium falciparum

PubMed Central

Bhaumik, Prasenjit; Xiao, Huogen; Hidaka, Koushi; Gustchina, Alla; Kiso, Yoshiaki; Yada, Rickey Y.; Wlodawer, Alexander

2012-01-01

Histo-aspartic protease (HAP) from Plasmodium falciparum offers a promising target for the development of novel antimalarial drugs. HAP exhibits high sequence similarity to pepsin-like aspartic proteases, but one of the two catalytic aspartates, Asp32, is replaced by histidine. Crystal structures of the truncated zymogen of HAP and of the complex of the mature enzyme with inhibitor KNI-10395 have been determined at 2.1 and 2.5 Å resolution, respectively. As in other proplasmepsins, the propeptide of the zymogen interacts with the C-terminal domain of the enzyme, forcing the N- and C- terminal domains apart, thereby separating His32 and Asp215 and preventing formation of the mature active site. In the inhibitor complex the enzyme forms a tight domain-swapped dimer, not previously seen in any aspartic proteases. The inhibitor is found in an unprecedented conformation resembling the letter “U”, stabilized by two intramolecular hydrogen bonds. Surprisingly, the location and conformation of the inhibitor are similar to the fragment of helix 2 comprising residues 34p–38p in the prosegments of the zymogens of gastric aspartic proteases; a corresponding helix assumes a vastly different orientation in proplasmepsins. Each inhibitor molecule is in contact with two molecules of HAP, interacting with the carboxylate group of the catalytic Asp215 of one HAP protomer through a water molecule, while also making a direct hydrogen bond to Glu278A′ of the other protomer. A comparison of the shifts in the positions of the catalytic residues in the inhibitor complex presented here with those published previously gives further hints regarding the enzymatic mechanism of HAP. PMID:21928835

The C-Terminal Fragment of the Internal 110-Kilodalton Passenger Domain of the Hap Protein of Nontypeable Haemophilus influenzae Is a Potential Vaccine Candidate

PubMed Central

Liu, Dai-Fang; Mason, Kathryn W.; Mastri, Maria; Pazirandeh, Mehran; Cutter, David; Fink, Doran L.; St. Geme, Joseph W.; Zhu, Duzhang; Green, Bruce A.

2004-01-01

Nontypeable Haemophilus influenzae is a major causative agent of bacterial otitis media in children. H. influenzae Hap autotransporter protein is an adhesin composed of an outer membrane Hapβ region and a moiety of an extracellular internal 110-kDa passenger domain called HapS. The HapS moiety promotes adherence to human epithelial cells and extracellular matrix proteins, and it also mediates bacterial aggregation and microcolony formation. A recent work (D. L. Fink, A. Z. Buscher, B. A. Green, P. Fernsten, and J. W. St. Geme, Cell. Microbiol. 5:175-186, 2003) demonstrated that HapS adhesive activity resides within the C-terminal 311 amino acids (the cell binding domain) of the protein. In this study, we immunized mice subcutaneously with recombinant proteins corresponding to the C-terminal region of HapS from H. influenzae strains N187, P860295, and TN106 and examined the resulting immune response. Antisera against the recombinant proteins from all three strains not only recognized native HapS purified from strain P860295 but also inhibited H. influenzae Hap-mediated adherence to Chang epithelial cells. Furthermore, when mice immunized intranasally with recombinant protein plus mutant cholera toxin CT-E29H were challenged with strain TN106, they were protected against nasopharyngeal colonization. These observations demonstrate that the C-terminal region of HapS is capable of eliciting cross-reacting antibodies that reduce nasopharyngeal colonization, suggesting utility as a vaccine antigen for the prevention of nontypeable H. influenzae diseases. PMID:15557618

40 CFR Table 2c to Subpart Zzzz of... - Requirements for Existing Compression Ignition Stationary Rice Located at Major Sources of HAP...

Code of Federal Regulations, 2010 CFR

2010-07-01

..., non-black start CI 500 HP a. Limit concentration of CO in the stationary RICE exhaust to 23 ppmvd or... Ignition Stationary Rice Located at Major Sources of HAP Emissions 2c Table 2c to Subpart ZZZZ of Part 63... Stationary Rice Located at Major Sources of HAP Emissions As stated in §§ 63.6600 and 63.6640, you must...

Antenna Beam Pattern Characteristics of HAPS User Terminal

NASA Astrophysics Data System (ADS)

Ku, Bon-Jun; Oh, Dae Sub; Kim, Nam; Ahn, Do-Seob

High Altitude Platform Stations (HAPS) are recently considered as a green infrastructure to provide high speed multimedia services. The critical issue of HAPS is frequency sharing with satellite systems. Regulating antenna beam pattern using adaptive antenna schemes is one of means to facilitate the sharing with a space receiver for fixed satellite services on the uplink of a HAPS system operating in U bands. In this letter, we investigate antenna beam pattern characteristics of HAPS user terminals with various values of scan angles of main beam, null position angles, and null width.

Study on the removal of organic micropollutants from aqueous and ethanol solutions by HAP membranes with tunable hydrophilicity and hydrophobicity.

PubMed

He, Junyong; Li, Yulian; Cai, Xingguo; Chen, Kai; Zheng, Hejing; Wang, Chengming; Zhang, Kaisheng; Lin, Dongyue; Kong, Lingtao; Liu, Jinhuai

2017-05-01

A biocompatible and uniquely defined hydroxyapatite (HAP) adsorption membrane with a sandwich structure was developed for the removal of organic micropollutants for the first time. Both the adsorption and membrane technique were used for the removal of organic micropollutants. The hydrophilicity and hydrophobicity of the HAP adsorbent and membrane were tunable by controlling the surface structure of HAP. The adsorption of organic micropollutants on the HAP adsorbent was studied in batch experiments. The adsorption process was fit with the Freundlich model, while the adsorption kinetics followed the pseudo-second-order model. The HAP membrane could remove organic micropollutants effectively by dynamic adsorption in both aqueous and ethanol solutions. The removal efficiencies of organic micropollutants depended on the solution composition, membrane thickness and hydrophilicity, flow rate, and the initial concentration of organic micropollutants. The adsorption capacities of the HAP membrane with a sandwich structure (membrane thickness was 0.3 mm) were 6700, 6510, 6310, 5960, 5490, 5230, 4980 and 4360 L m -2 for 1-naphthyl amine, 2-naphthol, bisphenol S, propranolol hydrochloride, metolachlor, ethinyl oestradiol, 2,4-dichlorophenol and bisphenol A, respectively, when the initial concentration was 3.0 mg L -1 . The biocompatible HAP adsorption membrane can be easily regenerated by methanol and was thus demonstrated to be a novel concept for the removal of organic micropollutants from both aqueous and organic solutions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hair Follicle-Associated Pluripotent (HAP) Stem Cells in Gelfoam® Histoculture for Use in Spinal Cord Repair.

PubMed

Liu, Fang; Hoffman, Robert M

2018-01-01

The stem cell marker, nestin, is expressed in the hair follicle, both in cells in the bulge area (BA) and the dermal papilla (DP). Nestin-expressing hair follicle-associated-pluripotent (HAP) stem cells of both the BA and DP have been previously shown to be able to form neurons, heart muscle cells, and other non-follicle cell types. The ability of the nestin-expressing HAP stem cells from the BA and DP to repair spinal cord injury was compared. Nestin-expressing HAP stem cells from both the BA and DP grew very well on Gelfoam ® . The HAP stem cells attached to the Gelfoam ® within 1 h. They grew along the grids of the Gelfoam ® during the first 2 or 3 days. Later they spread into the Gelfoam ® . After transplantation of Gelfoam ® cultures of nestin-expressing BA or DP HAP stem cells into the injured spinal cord (including the Gelfoam ® ) nestin-expressing BA and DP cells were observed to be viable over 100 days post-surgery. Hematoxylin and eosin (H&E) staining showed connections between the transplanted cells and the host spine tissue. Immunohistochemistry showed many Tuj1-, Isl 1/2, and EN1-positive cells and nerve fibers in the transplanted area of the spinal cord after BA Gelfoam ® or DP Gelfoam ® cultures were transplanted to the spine. The spinal cord of mice was injured to effect hind-limb paralysis. Twenty-eight days after transplantation with BA or DP HAP stem cells on Gelfoam ® to the injured area of the spine, the mice recovered normal locomotion.

40 CFR Table 2 to Subpart Tttt of... - Leather Finishing HAP Emission Limits for Determining the Allowable HAP Loss

Code of Federal Regulations, 2012 CFR

2012-07-01

...)(ii)(H) Application for approval Type and quantity of HAP, operating parameters No All sources emit... listed below. § 63.6(e)(3) Operation and maintenance requirements Startup, shutdown, and malfunction plan requirements No Subpart TTTT does not have any startup, shutdown, and malfunction plan requirements. § 63.6(f...

40 CFR Table 2 to Subpart Tttt of... - Leather Finishing HAP Emission Limits for Determining the Allowable HAP Loss

Code of Federal Regulations, 2014 CFR

2014-07-01

...)(ii)(H) Application for approval Type and quantity of HAP, operating parameters No All sources emit... listed below. § 63.6(e)(3) Operation and maintenance requirements Startup, shutdown, and malfunction plan requirements No Subpart TTTT does not have any startup, shutdown, and malfunction plan requirements. § 63.6(f...

40 CFR Table 2 to Subpart Tttt of... - Leather Finishing HAP Emission Limits for Determining the Allowable HAP Loss

Code of Federal Regulations, 2013 CFR

2013-07-01

...)(ii)(H) Application for approval Type and quantity of HAP, operating parameters No All sources emit... listed below. § 63.6(e)(3) Operation and maintenance requirements Startup, shutdown, and malfunction plan requirements No Subpart TTTT does not have any startup, shutdown, and malfunction plan requirements. § 63.6(f...

Genotype imputation for African Americans using data from HapMap phase II versus 1000 genomes projects.

PubMed

Sung, Yun J; Gu, C Charles; Tiwari, Hemant K; Arnett, Donna K; Broeckel, Ulrich; Rao, Dabeeru C

2012-07-01

Genotype imputation provides imputation of untyped single nucleotide polymorphisms (SNPs) that are present on a reference panel such as those from the HapMap Project. It is popular for increasing statistical power and comparing results across studies using different platforms. Imputation for African American populations is challenging because their linkage disequilibrium blocks are shorter and also because no ideal reference panel is available due to admixture. In this paper, we evaluated three imputation strategies for African Americans. The intersection strategy used a combined panel consisting of SNPs polymorphic in both CEU and YRI. The union strategy used a panel consisting of SNPs polymorphic in either CEU or YRI. The merge strategy merged results from two separate imputations, one using CEU and the other using YRI. Because recent investigators are increasingly using the data from the 1000 Genomes (1KG) Project for genotype imputation, we evaluated both 1KG-based imputations and HapMap-based imputations. We used 23,707 SNPs from chromosomes 21 and 22 on Affymetrix SNP Array 6.0 genotyped for 1,075 HyperGEN African Americans. We found that 1KG-based imputations provided a substantially larger number of variants than HapMap-based imputations, about three times as many common variants and eight times as many rare and low-frequency variants. This higher yield is expected because the 1KG panel includes more SNPs. Accuracy rates using 1KG data were slightly lower than those using HapMap data before filtering, but slightly higher after filtering. The union strategy provided the highest imputation yield with next highest accuracy. The intersection strategy provided the lowest imputation yield but the highest accuracy. The merge strategy provided the lowest imputation accuracy. We observed that SNPs polymorphic only in CEU had much lower accuracy, reducing the accuracy of the union strategy. Our findings suggest that 1KG-based imputations can facilitate discovery of

EEG and ERP profiles in the high alcohol preferring (HAP) and low alcohol preferring (LAP) mice: relationship to ethanol preference.

PubMed

Slawecki, Craig J; Grahame, Nicholas J; Roth, Jennifer; Katner, Simon N; Ehlers, C L

2003-01-31

Neurophysiological measures, such as decreased P300 amplitude and altered EEG alpha activity, have been associated with increased alcoholism risk. The purpose of the present study was to extend the assessment of the neurophysiological indices associated with alcohol consumption to a recently developed mouse model of high ethanol consumption, the first replicate line of high alcohol preferring (HAP-1) and low alcohol preferring (LAP-1) mice. Male HAP-1, LAP-1, and HS mice from the Institute for Behavioral Genetics at the University of Colorado Health Science Center (i.e., HS/Ibg mice) were implanted with cortical electrodes. EEG activity, and event related potentials (ERPs) were then examined. Following electrophysiological assessment, ethanol preference was assessed to examine the relationship between neurophysiological indices and ethanol consumption. EEG analyses revealed that HAPs and HS/Ibgs had greater peak frequency in the 2-4-Hz band and lower peak frequency in the 6-8- and 1-50-Hz bands of the cortical EEG compared to LAPs. Compared to HAPs, LAPs and HS/Ibgs had decreased peak EEG frequency in the 8-16-Hz band. Decreased parietal cortical power from 8 to 50 Hz was associated with high initial ethanol preference in HAP mice. In regards to ERPs, P1 amplitude was greater in HAPs compared to both LAPs and HS/Ibgs and the P3 latency in LAPs was decreased compared to both HAPs and HS/Ibgs. As expected, HAPs consumed more ethanol and had higher ethanol preference than LAPs and HS/Ibgs. There were no significant differences in ethanol intake or preference between HS/Ibgs and LAPs. These data indicate that selective breeding of the HAP and LAP lines has resulted in the divergence of EEG and ERP phenotypes. The differences observed suggest that increased cortical P1 amplitude and altered cortical EEG activity in the 8-50-Hz frequency range may be neurophysiological 'risk factors' associated with high ethanol consumption in mice. Decreased P3 latency in LAPs compared

40 CFR 63.2465 - What requirements must I meet for process vents that emit hydrogen halide and halogen HAP or HAP...

Code of Federal Regulations, 2011 CFR

2011-07-01

... process vents that emit hydrogen halide and halogen HAP or HAP metals? 63.2465 Section 63.2465 Protection... Compliance Requirements § 63.2465 What requirements must I meet for process vents that emit hydrogen halide... section. (b) If any process vents within a process emit hydrogen halide and halogen HAP, you must...

HapMap tagSNP transferability in multiple populations: general guidelines

PubMed Central

Xing, Jinchuan; Witherspoon, David J.; Watkins, W. Scott; Zhang, Yuhua; Tolpinrud, Whitney; Jorde, Lynn B.

2008-01-01

This PDF receipt will only be used as the basis for generating PubMed Central (PMC) documents. PMC documents will be made available for review after conversion (approx. 2–3 weeks time). Any corrections that need to be made will be done at that time. No materials will be released to PMC without the approval of an author. Only the PMC documents will appear on PubMed Central -- this PDF Receipt will not appear on PubMed Central. Linkage disequilibrium (LD) has received much recent attention because of its value in localizing disease-causing genes. Due to the extensive LD between neighboring loci in the human genome, it is believed that a subset of the single nucleotide polymorphisms in a region (tagSNPs) can be selected to capture most of the remaining SNP variants. In this study, we examined LD patterns and HapMap tagSNP transferability in more than 300 individuals. A South Indian and an African Mbuti Pygmy population sample were included to evaluate the performance of HapMap tagSNPs in geographically distinct and genetically isolated populations. Our results show that HapMap tagSNPs selected with r2 >= 0.8 can capture more than 85% of the SNPs in populations that are from the same continental group. Combined tagSNPs from HapMap CEU and CHB+JPT serve as the best reference for the Indian sample. The HapMap YRI are a sufficient reference for tagSNP selection in the Pygmy sample. In addition to our findings, we reviewed over 25 recent studies of tagSNP transferability and propose a general guideline for selecting tagSNPs from HapMap populations. PMID:18482828

40 CFR 63.5340 - How do I determine the allowable HAP loss?

Code of Federal Regulations, 2013 CFR

2013-07-01

... select the appropriate HAP emission limit, expressed in pounds of HAP loss per 1,000 square feet of... months. Next, determine the annual total of leather processed in 1,000's of square feet for each product... Total of Leather Processed = 1,000's of square feet of leather processed in the previous 12 months in...

40 CFR 63.5340 - How do I determine the allowable HAP loss?

Code of Federal Regulations, 2014 CFR

2014-07-01

... select the appropriate HAP emission limit, expressed in pounds of HAP loss per 1,000 square feet of... months. Next, determine the annual total of leather processed in 1,000's of square feet for each product... Total of Leather Processed = 1,000's of square feet of leather processed in the previous 12 months in...

["Habitual" left branch block alternating with 2 "disguised" bracnch block].

PubMed

Lévy, S; Jullien, G; Mathieu, P; Mostefa, S; Gérard, R

1976-10-01

Two cases of alternating left bundle branch block and "masquerading block" (with left bundle branch morphology in the stnadard leads and right bundle branch block morphology in the precordial leads) were studied by serial tracings and his bundle electrocardiography. In case 1 "the masquerading" block was associated with a first degree AV block related to a prolongation of HV interval. This case is to our knowledge the first cas of alternating bundle branch block in which his bundle activity was recorded in man. In case 2, the patient had atrial fibrilation and His bundle recordings were performed while differents degrees of left bundle branch block were present: The mechanism of the alternation and the concept of "masquerading" block are discussed. It is suggested that this type of block represents a right bundle branch block associated with severe lesions of the "left system".

40 CFR Table 2 to Subpart II of... - Volatile Organic HAP (VOHAP) Limits for Marine Coatings

Code of Federal Regulations, 2013 CFR

2013-07-01

... for Marine Coatings 2 Table 2 to Subpart II of Part 63 Protection of Environment ENVIRONMENTAL... (Surface Coating) Pt. 63, Subpt. II, Table 2 Table 2 to Subpart II of Part 63—Volatile Organic HAP (VOHAP) Limits for Marine Coatings Coating category VOHAP limits a,b,c Grams/liter coating (minus water and...

40 CFR Table 2 to Subpart II of... - Volatile Organic HAP (VOHAP) Limits for Marine Coatings

Code of Federal Regulations, 2012 CFR

2012-07-01

... for Marine Coatings 2 Table 2 to Subpart II of Part 63 Protection of Environment ENVIRONMENTAL... (Surface Coating) Pt. 63, Subpt. II, Table 2 Table 2 to Subpart II of Part 63—Volatile Organic HAP (VOHAP) Limits for Marine Coatings Coating category VOHAP limits a,b,c Grams/liter coating (minus water and...

40 CFR Table 2 to Subpart II of... - Volatile Organic HAP (VOHAP) Limits for Marine Coatings

Code of Federal Regulations, 2014 CFR

2014-07-01

... for Marine Coatings 2 Table 2 to Subpart II of Part 63 Protection of Environment ENVIRONMENTAL... (Surface Coating) Pt. 63, Subpt. II, Table 2 Table 2 to Subpart II of Part 63—Volatile Organic HAP (VOHAP) Limits for Marine Coatings Coating category VOHAP limits a b c Grams/liter coating (minus water and...

40 CFR Table 2 to Subpart II of... - Volatile Organic HAP (VOHAP) Limits for Marine Coatings

Code of Federal Regulations, 2010 CFR

2010-07-01

... for Marine Coatings 2 Table 2 to Subpart II of Part 63 Protection of Environment ENVIRONMENTAL... (Surface Coating) Pt. 63, Subpt. II, Table 2 Table 2 to Subpart II of Part 63—Volatile Organic HAP (VOHAP) Limits for Marine Coatings Coating category VOHAP limits a,b,c Grams/liter coating (minus water and...

40 CFR Table 2 to Subpart II of... - Volatile Organic HAP (VOHAP) Limits for Marine Coatings

Code of Federal Regulations, 2011 CFR

2011-07-01

... for Marine Coatings 2 Table 2 to Subpart II of Part 63 Protection of Environment ENVIRONMENTAL... (Surface Coating) Pt. 63, Subpt. II, Table 2 Table 2 to Subpart II of Part 63—Volatile Organic HAP (VOHAP) Limits for Marine Coatings Coating category VOHAP limits a,b,c Grams/liter coating (minus water and...

The dipeptide Pro-Asp promotes IGF-1 secretion and expression in hepatocytes by enhancing JAK2/STAT5 signaling pathway.

PubMed

Wang, Songbo; Wang, Guoqing; Zhang, Mengyuan; Zhuang, Lu; Wan, Xiaojuan; Xu, Jingren; Wang, Lina; Zhu, Xiaotong; Gao, Ping; Xi, Qianyun; Zhang, Yongliang; Shu, Gang; Jiang, Qingyan

2016-11-15

It has been implicated that IGF-1 secretion can be regulated by dietary protein. However, whether the dipeptides, one of digested products of dietary protein, have influence on IGF-1 secretion remain largely unknown. Our study aimed to investigate the effects of the dipeptide Pro-Asp on IGF-1 secretion and expression in hepatocytes and to explore the possible underlying mechanisms. Our findings demonstrated that Pro-Asp promoted the secretion and gene expression of IGF-1 in HepG2 cells and primary porcine hepatocytes. Meanwhile, Pro-Asp activated the ERK and Akt signaling pathways, downstream of IGF-1. In addition, Pro-Asp enhanced GH-mediated JAK2/STAT5 signaling pathway, while inhibition of JAK2/STAT5 blocked the promotive effect of Pro-Asp on IGF-1 secretion and expression. Moreover, acute injection of Pro-Asp stimulated IGF-1 expression and activated JAK2/STAT5 signaling pathway in mice liver. Together, these results suggested that the dipeptide Pro-Asp promoted IGF-1 secretion and expression in hepatocytes by enhancing GH-mediated JAK2/STAT5 signaling pathway. Copyright © 2016. Published by Elsevier Ireland Ltd.

40 CFR Table 3 to Subpart Ffff of... - Emission Limits for Hydrogen Halide and Halogen HAP Emissions or HAP Metals Emissions From...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 12 2011-07-01 2009-07-01 true Emission Limits for Hydrogen Halide and... to Subpart FFFF of Part 63—Emission Limits for Hydrogen Halide and Halogen HAP Emissions or HAP... following table that applies to your process vents that contain hydrogen halide and halogen HAP emissions or...

40 CFR Table 3 to Subpart Ffff of... - Emission Limits for Hydrogen Halide and Halogen HAP Emissions or HAP Metals Emissions From...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Emission Limits for Hydrogen Halide and... to Subpart FFFF of Part 63—Emission Limits for Hydrogen Halide and Halogen HAP Emissions or HAP... following table that applies to your process vents that contain hydrogen halide and halogen HAP emissions or...

Crystal structure of the Haemophilus influenzae Hap adhesin reveals an intercellular oligomerization mechanism for bacterial aggregation

PubMed Central

Meng, Guoyu; Spahich, Nicole; Kenjale, Roma; Waksman, Gabriel; St Geme, Joseph W

2011-01-01

Bacterial biofilms are complex microbial communities that are common in nature and are being recognized increasingly as an important determinant of bacterial virulence. However, the structural determinants of bacterial aggregation and eventual biofilm formation have been poorly defined. In Gram-negative bacteria, a major subgroup of extracellular proteins called self-associating autotransporters (SAATs) can mediate cell–cell adhesion and facilitate biofilm formation. In this study, we used the Haemophilus influenzae Hap autotransporter as a prototype SAAT to understand how bacteria associate with each other. The crystal structure of the H. influenzae HapS passenger domain (harbouring the SAAT domain) was determined to 2.2 Å by X-ray crystallography, revealing an unprecedented intercellular oligomerization mechanism for cell–cell interaction. The C-terminal SAAT domain folds into a triangular-prism-like structure that can mediate Hap–Hap dimerization and higher degrees of multimerization through its F1–F2 edge and F2 face. The intercellular multimerization can give rise to massive buried surfaces that are required for overcoming the repulsive force between cells, leading to bacterial cell–cell interaction and formation of complex microcolonies. PMID:21841773

24 CFR 982.603 - SRO: Lease and HAP contract.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false SRO: Lease and HAP contract. 982... Types Single Room Occupancy (sro) § 982.603 SRO: Lease and HAP contract. For SRO housing, there is a separate lease and HAP contract for each assisted person. ...

VizieR Online Data Catalog: UKIDSS-DR8 LAS, GCS and DXS Surveys (Lawrence+ 2012)

NASA Astrophysics Data System (ADS)

Lawrence, A.; Warren, S. J.; Almaini, O.; Edge, A. C.; Hambly, N. C.; Jameson, R. F.; Lucas, P.; Casali, M.; Adamson, A.; Dye, S.; Emerson, J. P.; Foucaud, S.; Hewett, P.; Hirst, P.; Hodgkin, S. T.; Irwin, M. J.; Lodieu, N.; McMahon, R. G.; Simpson, C.; Smail, I.; Mortlock, D.; Folger, M.

2012-03-01

The UKIRT Infrared Deep Sky Survey (UKIDSS) is a large-scale near-IR survey which aim is to cover 7500 square degrees of the Northern sky. The survey is carried out using the Wide Field Camera (WFCAM), with a field of view of 0.21 square degrees, mounted on the 3.8m United Kingdom Infra-red Telescope (UKIRT) in Hawaii. The project comprises five surveys (LAS, GCS, DXS, GPS and UDS). The Large Area Survey (LAS) covers an area of 4000 square degrees in high Galactic latitudes (extragalactic) in the four bands Y(1.0um) J(1.2um) H(1.6um) and K(2.2um) to a depth of K=18.4. The Galactic Clusters Survey (GCS) aims to survey ten large open star clusters and star formation associations, covering a total of 1067 square degrees in the five bands Z (0.9um), Y(1.0um) J(1.2um) H(1.6um) and K(2.2um), plus a second pass in K for proper motions, to a depth of Z=20.4, Y=20.3, J=19.5, H=18.6, K=18.6. The Deep Extragalactic Survey (DXS) aims to map 35 square degrees of sky to a 5-σ point-source sensitivity of J=22.3 and K=20.8 in four carefully selected, multi-wavelength survey areas. The central regions of each field will also be mapped to H=21.8. The primary aim of the survey is to produce a photometric galaxy sample at a redshift of 1-2, within a volume comparable to that of the SDSS, selected in the same passband (rest frame optical). Details of the surveys can be found in the in the paper by Lawrence et al. (2007MNRAS.379.1599L), and at the UKIDSS Surveys site (http://www.ukidss.org/surveys/surveys.html). The data described here represent a subset of the UKIDSS data, limited to the public data and most representative columns. In the "Byte-by-byte Description" below the original names of the columns are given as bracketed names. (3 data files).

Evaluation of model-predicted hazardous air pollutants (HAPs) near a mid-sized U.S. airport

NASA Astrophysics Data System (ADS)

Vennam, Lakshmi Pradeepa; Vizuete, William; Arunachalam, Saravanan

2015-10-01

Accurate modeling of aircraft-emitted pollutants in the vicinity of airports is essential to study the impact on local air quality and to answer policy and health-impact related issues. To quantify air quality impacts of airport-related hazardous air pollutants (HAPs), we carried out a fine-scale (4 × 4 km horizontal resolution) Community Multiscale Air Quality model (CMAQ) model simulation at the T.F. Green airport in Providence (PVD), Rhode Island. We considered temporally and spatially resolved aircraft emissions from the new Aviation Environmental Design Tool (AEDT). These model predictions were then evaluated with observations from a field campaign focused on assessing HAPs near the PVD airport. The annual normalized mean error (NME) was in the range of 36-70% normalized mean error for all HAPs except for acrolein (>70%). The addition of highly resolved aircraft emissions showed only marginally incremental improvements in performance (1-2% decrease in NME) of some HAPs (formaldehyde, xylene). When compared to a coarser 36 × 36 km grid resolution, the 4 × 4 km grid resolution did improve performance by up to 5-20% NME for formaldehyde and acetaldehyde. The change in power setting (from traditional International Civil Aviation Organization (ICAO) 7% to observation studies based 4%) doubled the aircraft idling emissions of HAPs, but led to only a 2% decrease in NME. Overall modeled aircraft-attributable contributions are in the range of 0.5-28% near a mid-sized airport grid-cell with maximum impacts seen only within 4-16 km from the airport grid-cell. Comparison of CMAQ predictions with HAP estimates from EPA's National Air Toxics Assessment (NATA) did show similar annual mean concentrations and equally poor performance. Current estimates of HAPs for PVD are a challenge for modeling systems and refinements in our ability to simulate aircraft emissions have made only incremental improvements. Even with unrealistic increases in HAPs aviation emissions the model

24 CFR 982.455 - Automatic termination of HAP contract.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Automatic termination of HAP contract. 982.455 Section 982.455 Housing and Urban Development Regulations Relating to Housing and Urban... Payments Contract and Owner Responsibility § 982.455 Automatic termination of HAP contract. The HAP...

The HAP Complex Governs Fumonisin Biosynthesis and Maize Kernel Pathogenesis in Fusarium verticillioides.

PubMed

Ridenour, John B; Smith, Jonathon E; Bluhm, Burton H

2016-09-01

Contamination of maize ( Zea mays ) with fumonisins produced by the fungus Fusarium verticillioides is a global concern for food safety. Fumonisins are a group of polyketide-derived secondary metabolites linked to esophageal cancer and neural tube birth defects in humans and numerous toxicoses in livestock. Despite the importance of fumonisins in global maize production, the regulation of fumonisin biosynthesis during kernel pathogenesis is poorly understood. The HAP complex is a conserved, heterotrimeric transcriptional regulator that binds the consensus sequence CCAAT to modulate gene expression. Recently, functional characterization of the Hap3 subunit linked the HAP complex to the regulation of secondary metabolism and stalk rot pathogenesis in F. verticillioides . Here, we determine the involvement of HAP3 in fumonisin biosynthesis and kernel pathogenesis. Deletion of HAP3 suppressed fumonisin biosynthesis on both nonviable and live maize kernels and impaired pathogenesis in living kernels. Transcriptional profiling via RNA sequencing indicated that the HAP complex regulates at least 1,223 genes in F. verticillioides , representing nearly 10% of all predicted genes. Disruption of the HAP complex caused the misregulation of biosynthetic gene clusters underlying the production of secondary metabolites, including fusarins. Taken together, these results reveal that the HAP complex is a central regulator of fumonisin biosynthesis and kernel pathogenesis and works as both a positive and negative regulator of secondary metabolism in F. verticillioides .

24 CFR 891.595 - HAP contract extension or renewal.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false HAP contract extension or renewal... Handicapped-Section 8 Assistance § 891.595 HAP contract extension or renewal. Upon expiration of the term of the HAP contract, HUD and the Borrower may agree (subject to available funds) to extend the term of...

Synthesis of HAP nano rods and processing of nano-size ceramic reinforced poly(L)lactic acid composites

NASA Astrophysics Data System (ADS)

Flanigan, Kyle Yusef

2000-09-01

montmorillonite galleries were successfully intercalated and exfoliated. Gallery spacings increased as much as 30A with ODA. NMR results demonstrated that the ODA in the galleries of the highly loaded clay is in an extended trans-configuration at lower temperatures. Furthermore the alkyl chains are nano-constrained and have limited mobility. These configurations influence the gallery spacing. The appearance of two crystalline melts (DSC) may indicate that the desired physicochemical modification of the PLLA at the clay nano-reinforcement interface was achieved. For the growth of HAP nano-rods a hydrothermal synthesis route was developed. A kinetics study revealed several unique features of the method of growth. TEM analysis indicates that the synthesis procedure was successful in generating rod-like HAP structures of 100nm length and 10 nm in width. The effect of synthesis conditions on the phase purity and the morphology of the precipitates was investigated. The surface of the HAP rods was modified using OTS and OMS. The surface modified HAP was used to process HAP/PLLA composites. The properties of the composites depend strongly on the nature of the interface. Composites made with OMS or OTS demonstrated a higher elastic modulus. At 1% solids loading the OTS treated sample generated a 40% increase in modulus. Silane treated composites had DMA transitions shifted 10 to 20 degrees higher. "Well-ordered" SAMs improve the dispersion of the inorganic reinforcement in PLLA and promote the formation of mechanical entanglements at the HAP-PLLA interface. As a result load transfer is more complete resulting in higher modulus material.

24 CFR 982.607 - Congregate housing: Lease and HAP contract.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Congregate housing: Lease and HAP... Types Congregate Housing § 982.607 Congregate housing: Lease and HAP contract. For congregate housing, there is a separate lease and HAP contract for each assisted family. ...

HapMap scanning of novel human minor histocompatibility antigens.

PubMed

Kamei, Michi; Nannya, Yasuhito; Torikai, Hiroki; Kawase, Takakazu; Taura, Kenjiro; Inamoto, Yoshihiro; Takahashi, Taro; Yazaki, Makoto; Morishima, Satoko; Tsujimura, Kunio; Miyamura, Koichi; Ito, Tetsuya; Togari, Hajime; Riddell, Stanley R; Kodera, Yoshihisa; Morishima, Yasuo; Takahashi, Toshitada; Kuzushima, Kiyotaka; Ogawa, Seishi; Akatsuka, Yoshiki

2009-05-21

Minor histocompatibility antigens (mHags) are molecular targets of allo-immunity associated with hematopoietic stem cell transplantation (HSCT) and involved in graft-versus-host disease, but they also have beneficial antitumor activity. mHags are typically defined by host SNPs that are not shared by the donor and are immunologically recognized by cytotoxic T cells isolated from post-HSCT patients. However, the number of molecularly identified mHags is still too small to allow prospective studies of their clinical importance in transplantation medicine, mostly due to the lack of an efficient method for isolation. Here we show that when combined with conventional immunologic assays, the large data set from the International HapMap Project can be directly used for genetic mapping of novel mHags. Based on the immunologically determined mHag status in HapMap panels, a target mHag locus can be uniquely mapped through whole genome association scanning taking advantage of the unprecedented resolution and power obtained with more than 3 000 000 markers. The feasibility of our approach could be supported by extensive simulations and further confirmed by actually isolating 2 novel mHags as well as 1 previously identified example. The HapMap data set represents an invaluable resource for investigating human variation, with obvious applications in genetic mapping of clinically relevant human traits.

Using formal specification in the Guidance and Control Software (GCS) experiment. Formal design and verification technology for life critical systems

NASA Technical Reports Server (NTRS)

Weber, Doug; Jamsek, Damir

1994-01-01

The goal of this task was to investigate how formal methods could be incorporated into a software engineering process for flight-control systems under DO-178B and to demonstrate that process by developing a formal specification for NASA's Guidance and Controls Software (GCS) Experiment. GCS is software to control the descent of a spacecraft onto a planet's surface. The GCS example is simplified from a real example spacecraft, but exhibits the characteristics of realistic spacecraft control software. The formal specification is written in Larch.

24 CFR 982.616 - Shared housing: Lease and HAP contract.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Shared housing: Lease and HAP... Types Shared Housing § 982.616 Shared housing: Lease and HAP contract. For assistance in a shared housing unit, there is a separate HAP contract and lease for each assisted family. ...

24 CFR 982.454 - Termination of HAP contract: Insufficient funding.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Termination of HAP contract... Assistance Payments Contract and Owner Responsibility § 982.454 Termination of HAP contract: Insufficient funding. The PHA may terminate the HAP contract if the PHA determines, in accordance with HUD requirements...

In situ remediation and phytotoxicity assessment of lead-contaminated soil by biochar-supported nHAP.

PubMed

Yang, Zhangmei; Fang, Zhanqiang; Tsang, Pokeung Eric; Fang, Jianzhang; Zhao, Dongye

2016-11-01

In this study, a kind of biochar-supported nano-hydroxyapatite (nHAP@BC) material was used in in-situ remediation of lead-contaminated soil. Column experiments were performed to compare the mobility of nHAP@BC and Bare-nHAP. The immobilization, accumulation and toxic effects of Pb in the after-amended soil were assessed by the in vitro toxicity tests and pot experiments. The column experiments showed a significant improvement in the mobility of nHAP@BC. The immobilization rate of Pb in the soil was 74.8% after nHAP@BC remediation. Sequential extraction procedures revealed that the residual fraction of Pb increased by 66.6% after nHAP@BC remediation, which greatly reduced the bioavailability of Pb in the soil. In addition, pot experiments indicated that nHAP@BC could effectively reduce the upward translocation capacity of Pb in a soil-plant system. The concentration of Pb in the aerial part of the cabbage mustard was 0.1 mg/kg, which is lower than the tolerance limit (0.3 mg/kg). nHAP@BC can remediate Pb-contaminated soil effectively, which can restore soil quality for planting. Copyright © 2016 Elsevier Ltd. All rights reserved.

26 CFR 1.964-2 - Treatment of blocked earnings and profits.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 10 2013-04-01 2013-04-01 false Treatment of blocked earnings and profits. 1... blocked earnings and profits. (a) General rule. If, in accordance with paragraph (d) of this section, it... profits of a controlled foreign corporation for the taxable year (determined under § 1.964-1) was subject...

26 CFR 1.964-2 - Treatment of blocked earnings and profits.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 10 2012-04-01 2012-04-01 false Treatment of blocked earnings and profits. 1... blocked earnings and profits. (a) General rule. If, in accordance with paragraph (d) of this section, it... profits of a controlled foreign corporation for the taxable year (determined under § 1.964-1) was subject...

26 CFR 1.964-2 - Treatment of blocked earnings and profits.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 10 2011-04-01 2011-04-01 false Treatment of blocked earnings and profits. 1... blocked earnings and profits. (a) General rule. If, in accordance with paragraph (d) of this section, it... profits of a controlled foreign corporation for the taxable year (determined under § 1.964-1) was subject...

Design of Natural Hydroxyapatite as bio-composite ceramics (HAP): Experimental and Numerical Study

NASA Astrophysics Data System (ADS)

Belghazi, Z.; Katundi, D.; Ayari, F.; Bayraktar, E.

2011-01-01

Hydroxyapatite (HAP—Ca10(PO4)6 (OH)2), which exhibits excellent biocompatibility in the body, is one of the most widely used bioactive ceramics for biomedical applications. Along with the ability to carry the load, one of the most important properties of materials used for bone replacement is biocompatibility. In fact, HAP is a bioactive material and it can incorporate into bone structures, supporting bone in-growth without breaking down or dissolving, and it interacts with the living tissue due to the presence of free calcium and phosphate compounds. Generally, Al2O3 powder is added to HAP powder in order to obtain high fracture toughness. Al2O3 has good mechanical properties as compared with HAP, and exhibits extremely high stability with human tissues [1-6]. In this paper, the effect of microwave sintering temperature on the relative density, hardness, and phase purity of compacted bovine Hydroxyapatite (BHA) powder was reported. This research is a comprehensive attempt to develop Hydroxyapatite bio composite ceramics reinforced with alumina—Al2O3, pure titanium and pure pulverised boron powder. A Finite Element (FEM) analysis is also used for modelling to simulate the macroscopic behaviour of this material, taking into account the relevant microscopic scales.

Computational Design of High-χ Block Oligomers for Accessing 1 nm Domains.

PubMed

Chen, Qile P; Barreda, Leonel; Oquendo, Luis E; Hillmyer, Marc A; Lodge, Timothy P; Siepmann, J Ilja

2018-05-22

Molecular dynamics simulations are used to design a series of high-χ block oligomers (HCBOs) that can self-assemble into a variety of mesophases with domain sizes as small as 1 nm. The exploration of these oligomers with various chain lengths, volume fractions, and chain architectures at multiple temperatures reveals the presence of ordered lamellae, perforated lamellae, and hexagonally packed cylinders. The achieved periods are as small as 3.0 and 2.1 nm for lamellae and cylinders, respectively, which correspond to polar domains of approximately 1 nm. Interestingly, the detailed phase behavior of these oligomers is distinct from that of either solvent-free surfactants or block polymers. The simulations reveal that the behavior of these HCBOs is a product of an interplay between both "surfactant factors" (headgroup interactions, chain flexibility, and interfacial curvature) and "block polymer factors" (χ, chain length N, and volume fraction f). This insight promotes the understanding of molecular features pivotal for mesophase formation at the sub-5 nm length scale, which facilitates the design of HCBOs tailored toward particular desired morphologies.

26 CFR 1.964-2 - Treatment of blocked earnings and profits.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 10 2014-04-01 2013-04-01 true Treatment of blocked earnings and profits. 1.964... blocked earnings and profits. (a) General rule. If, in accordance with paragraph (d) of this section, it... profits of a controlled foreign corporation for the taxable year (determined under § 1.964-1) was subject...

40 CFR 63.5796 - What are the organic HAP emissions factor equations in Table 1 to this subpart, and how are they...

Code of Federal Regulations, 2014 CFR

2014-07-01

... Organic Hap Emissions Factors for Open Molding and Centrifugal Casting § 63.5796 What are the organic HAP... emissions factors. Equations are available for each open molding operation and centrifugal casting operation... incorporated in the facility's air emissions permit and are based on actual facility HAP emissions test data...

40 CFR 63.5796 - What are the organic HAP emissions factor equations in Table 1 to this subpart, and how are they...

Code of Federal Regulations, 2013 CFR

2013-07-01

... Organic Hap Emissions Factors for Open Molding and Centrifugal Casting § 63.5796 What are the organic HAP... emissions factors. Equations are available for each open molding operation and centrifugal casting operation... incorporated in the facility's air emissions permit and are based on actual facility HAP emissions test data...

40 CFR 63.5796 - What are the organic HAP emissions factor equations in Table 1 to this subpart, and how are they...

Code of Federal Regulations, 2012 CFR

2012-07-01

... Organic Hap Emissions Factors for Open Molding and Centrifugal Casting § 63.5796 What are the organic HAP... emissions factors. Equations are available for each open molding operation and centrifugal casting operation... incorporated in the facility's air emissions permit and are based on actual facility HAP emissions test data...

Luteogenic Hormones Act through a Vascular Endothelial Growth Factor-Dependent Mechanism to Up-Regulate α5β1 and αvβ3 Integrins, Promoting the Migration and Survival of Human Luteinized Granulosa Cells

PubMed Central

Rolaki, Alexandra; Coukos, George; Loutradis, Dimitris; DeLisser, Horace M.; Coutifaris, Christos; Makrigiannakis, Antonis

2007-01-01

The formation of the corpus luteum (CL) is critical for the establishment of a successful pregnancy. After ovulation, the CL develops from the remnants of the ovulated ovarian follicle. This process, which involves varying cell-matrix interactions, is poorly characterized. To understand the role and potential regulation of cell-matrix interactions in the formation of the CL, we investigated the expression and activity of the matrix protein fibronectin (FN) and several of its integrin receptors on luteinized granulosa cells (GCs). In situ, FN and several FN-binding integrins were detected around luteinizing GCs during the early luteal phase, although expression declined in the late luteal phase. In vitro, GCs released FN, and stimulation of these cells with human chorionic gonadotropin increased the surface expression of FN, α5β1, and αvβ3. Up-regulation of these proteins on GCs was reproduced by stimulation with vascular endothelial growth factor (VEGF) and was inhibited by anti-VEGF antibody. Lastly, expression of α5β1 and αvβ3 mediated adhesion to FN, facilitated migration, and prevented apoptosis. These data suggest that in vivo luteogenic hormones, in part through a VEGF-dependent mechanism, stimulate selected integrin-matrix adhesive interactions that promote the motility and survival of GCs and thus contribute to the formation and preservation of the CL. PMID:17456762

Mxi1 is a repressor of the c-Myc promoter and reverses activation by USF.

PubMed

Lee, T C; Ziff, E B

1999-01-08

The basic region/helix-loop-helix/leucine zipper (B-HLH-LZ) oncoprotein c-Myc is abundant in proliferating cells and forms heterodimers with Max protein that bind to E-box sites in DNA and stimulate genes required for proliferation. A second B-HLH-LZ protein, Mxi1, is induced during terminal differentiation, and forms heterodimers with Max that also bind E-boxes but tether the mSin3 transcriptional repressor protein along with histone deacetylase thereby antagonizing Myc-dependent activation. We show that Mxi1 also antagonizes Myc by a second pathway, repression of transcription from the major c-myc promoter, P2. Repression was independent of Mxi1 binding to mSin3 but dependent on the Mxi1 LZ and COOH-terminal sequences, including putative casein kinase II phosphorylation sites. Repression targeted elements of the myc P2 promoter core (-35/+10), where it reversed transactivation by the constitutive transcription factor, USF. We show that Zn2+ induction of a stably transfected, metallothionein promoter-regulated mxi1 gene blocked the ability of serum to induce transcription of the endogenous c-myc gene and cell entry into S phase. Thus, induction of Mxi1 in terminally differentiating cells may block Myc function by repressing the c-myc gene P2 promoter, as well as by antagonizing Myc-dependent transactivation through E-boxes.

The origin and distribution of HAPs elements in relation to maceral composition of the A1 lignite bed (Paleocene, Calvert Bluff Formation, Wilcox Group), Calvert mine area, east-central Texas

USGS Publications Warehouse

Crowley, Sharon S.; Warwick, Peter D.; Ruppert, Leslie F.; Pontolillo, James

1997-01-01

The origin and distribution of twelve potentially Hazardous Air Pollutants (HAPs; As, Be, Cd, Cr, Co, Hg, Mn, Ni, Pb, Sb, Se, and U) identified in the 1990 Clean Air Act Amendments were examined in relation to the maceral composition of the A1 bed (Paleocene, Calvert Bluff Formation, Wilcox Group) of the Calvert mine in east-central Texas. The 3.2 m-thick A1 bed was divided into nine incremental channel samples (7 lignite samples and 2 shaley coal samples) on the basis of megascopic characteristics. Results indicate that As, Cd, Cr, Ni, Pb, Sb, and U are strongly correlated with ash yield and are enriched in the shaley coal samples. We infer that these elements are associated with inorganic constituents in the coal bed and may be derived from a penecontemporaneous stream channel located several kilometers southeast of the mining block. Of the HAPs elements studied, Mn and Hg are the most poorly correlated to ash yield. We infer an organic association for Mn; Hg may be associated with pyrite. The rest of the trace elements (Be, Co, and Se) are weakly correlated with ash yield. Further analytical work is necessary to determine the mode of occurrence for these elements. Overall, concentrations of the HAPs elements are generally similar to or less than those reported in previous studies of lignites of the Wilcox Group, east-central region, Texas. Petrographic analysis indicates the following ranges in composition for the seven lignite samples: liptinites (5–8%), huminites (88–95%), and inertinites (trace amounts to 7%). Samples from the middle portion of the A1 bed contain abundant crypto-eugelinite compared to the rest of the samples; this relationship suggests that the degradation of plant material was an important process during the development of the peat mire. With the exception of Hg and Mn, relatively low levels of the HAPs elements studied are found in the samples containing abundant crypto-eugelinite. We infer that the peat-forming environment for this

The Use of the City-Block Metric in Multidimensional Scaling.

ERIC Educational Resources Information Center

Busk, Patricia

A specific Normative Location Theory procedure, called hyperbolic approximation (HAP), is suggested as a possible "new" initial-configuration strategy for multidimensional scaling in the city-block metric. First, the performance of this strategy was investigated using fourteen simulated data sets. Second, the scaling in Euclidean space…

Candida albicans Hap43 Is a Repressor Induced under Low-Iron Conditions and Is Essential for Iron-Responsive Transcriptional Regulation and Virulence ▿

PubMed Central

Hsu, Po-Chen; Yang, Cheng-Yao; Lan, Chung-Yu

2011-01-01

Candida albicans is an opportunistic fungal pathogen that exists as normal flora in healthy human bodies but causes life-threatening infections in immunocompromised patients. In addition to innate and adaptive immunities, hosts also resist microbial infections by developing a mechanism of “natural resistance” that maintains a low level of free iron to restrict the growth of invading pathogens. C. albicans must overcome this iron-deprived environment to cause infections. There are three types of iron-responsive transcriptional regulators in fungi; Aft1/Aft2 activators in yeast, GATA-type repressors in many fungi, and HapX/Php4 in Schizosaccharomyces pombe and Aspergillus species. In this study, we characterized the iron-responsive regulator Hap43, which is the C. albicans homolog of HapX/Php4 and is repressed by the GATA-type repressor Sfu1 under iron-sufficient conditions. We provide evidence that Hap43 is essential for the growth of C. albicans under low-iron conditions and for C. albicans virulence in a mouse model of infection. Hap43 was not required for iron acquisition under low-iron conditions. Instead, it was responsible for repression of genes that encode iron-dependent proteins involved in mitochondrial respiration and iron-sulfur cluster assembly. We also demonstrated that Hap43 executes its function by becoming a transcriptional repressor and accumulating in the nucleus in response to iron deprivation. Finally, we found a connection between Hap43 and the global corepressor Tup1 in low-iron-induced flavinogenesis. Taken together, our data suggest a complex interplay among Hap43, Sfu1, and Tup1 to coordinately regulate iron acquisition, iron utilization, and other iron-responsive metabolic activities. PMID:21131439

Association Mapping and Haplotype Analysis of a 3.1-Mb Genomic Region Involved in Fusarium Head Blight Resistance on Wheat Chromosome 3BS

PubMed Central

Hao, Chenyang; Wang, Yuquan; Hou, Jian; Feuillet, Catherine; Balfourier, Francois; Zhang, Xueyong

2012-01-01

A previous study provided an in-depth understanding of molecular population genetics of European and Asian wheat gene pools using a sequenced 3.1-Mb contig (ctg954) on chromosome 3BS. This region is believed to carry the Fhb1 gene for response to Fusarium head blight. In this study, 266 wheat accessions were evaluated in three environments for Type II FHB response based on the single floret inoculation method. Hierarchical clustering (UPGMA) based on a Manhattan dissimilarity matrix divided the accessions into eight groups according to five FHB-related traits which have a high correlation between them; Group VIII comprised six accessions with FHB response levels similar to variety Sumai 3. Based on the compressed mixed linear model (MLM), association analysis between five FHB-related traits and 42 molecular markers along the 3.1-Mb region revealed 12 significant association signals at a threshold of P<0.05. The highest proportion of phenotypic variation (6.2%) in number of diseased spikelets (NDS) occurred at locus cfb6059, and the physical distance was about 2.9 Kb between umn10 and this marker. Haplotype block (HapB) analysis using a sliding window LD of 5 markers, detected six HapBs in the 3.1-Mb region at r2>0.1 and P<0.001 between random closely linked markers. F-tests among Haps with frequencies >0.05 within each HapB at r2>0.1 and P<0.001 showed significant differences between the Hap carried by FHB resistant resources, such as Sumai 3 and Wangshuibai, and susceptible genotypes in HapB3 and HapB6. These results suggest that Fhb1 is located within HapB6, with the possibility that another gene is located at or near HapB3. SSR markers and Haps detected in this study will be helpful in further understanding the genetic basis of FHB resistance, and provide useful information for marker-assisted selection of Fhb1 in wheat breeding. PMID:23071572

VizieR Online Data Catalog: Equivalent widths and atomic data for GCs (Lamb+, 2015)

NASA Astrophysics Data System (ADS)

Lamb, M. P.; Venn, K. A.; Shetrone, M. D.; Sakari, C. M.; Pritzl, B. J.

2017-11-01

Optical spectra were gathered with the High Resolution Spectrograph (HRS; Tull 1998, Proc. SPIE, 3355, 387) on the HET. The HRS was configured at resolution R=30000 with 2x2 pixel binning using the 2 arcsec fibre. The HRS splits the incoming beam on to two CCD chips, from which the spectral regions 6000-7000 Å (red chip) and 4800-5900 Å (blue chip) were extracted for this work. Two standard stars were also observed, RGB stars with previously published spectral analyses in each of the GCs M3 and M13. (2 data files).

40 CFR 63.5335 - How do I determine the actual HAP loss?

Code of Federal Regulations, 2011 CFR

2011-07-01

... to the leather; (iii) Mass fraction of HAP in each applied finish; (iv) Date of the recorded entry... recorded finish usage by the corresponding mass fraction of HAP in the finish. The result is the HAP loss... the pounds of each recorded finish usage by the corresponding mass fraction of HAP in the finish. The...

Engineered electrospun poly(caprolactone)/polycaprolactone-g-hydroxyapatite nano-fibrous scaffold promotes human fibroblasts adhesion and proliferation.

PubMed

Keivani, F; Shokrollahi, P; Zandi, M; Irani, S; F Shokrolahi; Khorasani, S C

2016-11-01

Polycaprolactone (PCL)/hydroxyapatite nano-composites are among the best candidates for tissue engineering. However, interactions between nHAp and PCL are difficult to control leading to inhomogeneous dispersion of the bio-ceramic particles. Grafting of polymer chains at high density/chain length while promotes the phase compatibility may result in reduced HAp exposed surface area and therefore, bioactivity is compromised. This issue is addressed here by grafting PCL chains onto HAp nano-particles through ring opening polymerization of ε-caprolactone (PCL-g-HAp). FTIR and TGA analysis showed that PCL (6.9wt%), was successfully grafted on the HAp. PCL/PCL-g-HAp nano-fibrous scaffold showed up to 10 and 33% enhancement in tensile strength and modulus, respectively, compared to those of PCL/HAp. The effects of HAp on the in vitro HAp formation were investigated for both the PCL/HAp and PCL/PCL-g-HAp scaffolds. Precipitation of HAp on the nano-composite scaffolds observed after 15days incubation in simulated body fluid (SBF), as confirmed by scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX). Human fibroblasts were seeded on PCL, PCL/HAp and PCL/PCL-g-HAp scaffolds. According to MTT assay, the highest cell proliferation was recorded for PCL/PCL-g-HAp nano-composite, at all time intervals (1-21days, P<0.001). Fluorescent microscopy (of DAPI stained samples) and electron microscopy images showed that all nano-fibrous scaffolds (PCL, PCL/HAp, and PCL/PCL-g-HAp), were non-toxic against cells, while more cell adhesion, and the most uniform cell distribution observed on the PCL/PCL-g-HAp. Overall, grafting of relatively short chains of PCL on the surface of HAp nano-particles stimulates fibroblasts adhesion and proliferation on the PCL/PCL-g-HAp nano-composite. Copyright © 2016 Elsevier B.V. All rights reserved.

A comparison of cataloged variation between International HapMap Consortium and 1000 Genomes Project data.

PubMed

Buchanan, Carrie C; Torstenson, Eric S; Bush, William S; Ritchie, Marylyn D

2012-01-01

Since publication of the human genome in 2003, geneticists have been interested in risk variant associations to resolve the etiology of traits and complex diseases. The International HapMap Consortium undertook an effort to catalog all common variation across the genome (variants with a minor allele frequency (MAF) of at least 5% in one or more ethnic groups). HapMap along with advances in genotyping technology led to genome-wide association studies which have identified common variants associated with many traits and diseases. In 2008 the 1000 Genomes Project aimed to sequence 2500 individuals and identify rare variants and 99% of variants with a MAF of <1%. To determine whether the 1000 Genomes Project includes all the variants in HapMap, we examined the overlap between single nucleotide polymorphisms (SNPs) genotyped in the two resources using merged phase II/III HapMap data and low coverage pilot data from 1000 Genomes. Comparison of the two data sets showed that approximately 72% of HapMap SNPs were also found in 1000 Genomes Project pilot data. After filtering out HapMap variants with a MAF of <5% (separately for each population), 99% of HapMap SNPs were found in 1000 Genomes data. Not all variants cataloged in HapMap are also cataloged in 1000 Genomes. This could affect decisions about which resource to use for SNP queries, rare variant validation, or imputation. Both the HapMap and 1000 Genomes Project databases are useful resources for human genetics, but it is important to understand the assumptions made and filtering strategies employed by these projects.

Activation of the sigma receptor 1 modulates AMPA receptor-mediated light-evoked excitatory postsynaptic currents in rat retinal ganglion cells.

PubMed

Liu, Lei-Lei; Deng, Qin-Qin; Weng, Shi-Jun; Yang, Xiong-Li; Zhong, Yong-Mei

2016-09-22

Sigma receptor (σR), a unique receptor family, is classified into three subtypes: σR1, σR2 and σR3. It was previously shown that σR1 activation induced by 1μM SKF10047 (SKF) suppressed N-methyl-d-aspartate (NMDA) receptor-mediated responses of rat retinal ganglion cells (GCs) and the suppression was mediated by a distinct Ca(2+)-dependent phospholipase C (PLC)-protein kinase C (PKC) pathway. In the present work, using whole-cell patch-clamp techniques in rat retinal slice preparations, we further demonstrate that SKF of higher dosage (50μM) significantly suppressed AMPA receptor (AMPAR)-mediated light-evoked excitatory postsynaptic currents (L-EPSCs) of retinal ON-type GCs (ON GCs), and the effect was reversed by the σR1 antagonist BD1047, suggesting the involvement of σR1. The SKF (50μM) effect was unlikely due to a change in glutamate release from bipolar cells, as suggested by the unaltered paired-pulse ratio (PPR) of AMPAR-mediated EPSCs of ON GCs. SKF (50μM) did not change L-EPSCs of ON GCs when the G protein inhibitor GDP-β-S or the protein kinase G (PKG) inhibitor KT5823 was intracellularly infused. Calcium imaging further revealed that SKF (50μM) did not change intracellular calcium concentration in GCs and persisted to suppress L-EPSCs when intracellular calcium was chelated by BAPTA. The SKF (50μM) effect was intact when protein kinase A (PKA) and phosphatidylinostiol (PI)-PLC signaling pathways were both blocked. We conclude that the SKF (50μM) effect is Ca(2+)-independent, PKG-dependent, but not involving PKA, PI-PLC pathways. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Kinematic Modeling Of The Milky Way Using The RAVE And GCS Stellar Surveys

NASA Astrophysics Data System (ADS)

Sharma, Sanjib; Rave Collaboration

2014-01-01

We investigate the kinematic parameters of the Milky Way disc using the Radial Velocity (RAVE) and Geneva-Copenhagen (GCS) stellar surveys. We do this by fitting a kinematic model to the data. Using two distinct Markov Chain Monte Carlo (MCMC) techniques, we investigate the full posterior distributions of the parameters given the data. For RAVE, we restrict ourselves to angular position and radial velocity for each star since these quantities are determined to high accuracy. For GCS, the data consist of the full 6 dimensional phase space but, in contrast to RAVE, are confined to the Solar neighborhood only. We show results using the traditional Gaussian distribution function and compare to the Shu distribution function that handles non-circular orbits more accurately. We investigate the `age-velocity dispersion' relation (AVR) for the three kinematic components (σ_R,σ_φ, σ_z), the radial dependence of the velocity dispersions, the Solar peculiar motion (U_Sun,V_Sun, W_Sun) and the circular velocity (v_c) at the Sun. We investigate models with and without a thick disc. We find that the kinematic parameters derived from RAVE and GCS are in good agreement. The Shu model fits the RAVE data better than the Gaussian model, but a perfect fit could not be found for either model. Furthermore, the Gaussian model predicts a positive radial gradient for the velocity dispersion, while the Shu model does not. The measured Solar peculiar motion, U_Sun=10.5 ±0.13, V_Sun=10.27±0.11, and W_Sun=7.44± 0.09, is in good agreement with estimates of Schonrich et al (2010) but our values for (U_Sun, V_Sun) are slightly lower. We stress that V_Sun is a highly model-dependent quantity and claims of accuracy must be treated with caution. For RAVE, we find that v_c = 212 ±1.4 km/s ; this is a lower bound on the true value as the vertical dependence of asymmetric drift for an isothermal population has been ignored in our analysis.

The expression of cytokines and β -defensin 2, - 3, -4 in rabbit bone tissue after hydroxyapatite (HAp), α- Tricalcium phosphate (α-TCP) and polymethylmethacrylate (PMMA) implantation

NASA Astrophysics Data System (ADS)

Vamze, J.; Pilmane, M.; Skagers, A.

2012-08-01

Bone loss induced by inflammation is one of the complications after biomaterial implantation. There is no much data on expression of cytokines and defensins into the bone tissue around the implants in literature. The aim of this work was to investigate the distribution and appearance of interleukin (IL)-1, IL-6, IL-8, IL-10 and (β - defensin (BD)-2, BD-3, BD-4 after the implantation of different biomaterials. Bone developing zones, signs of bone-implant contact and low expression of pro-inflammatory cytokine IL-1, IL-6 and anti-inflammatory cytokine IL-10 in experimental tissue with pure HAp and unburned HAp implants indicate a potential advantage of this material in terms of its biocompatibility over the other materials used in our study.

24 CFR 983.205 - Term of HAP contract.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Term of HAP contract. 983.205 Section 983.205 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT... DEVELOPMENT PROJECT-BASED VOUCHER (PBV) PROGRAM Housing Assistance Payments Contract § 983.205 Term of HAP...

24 CFR 983.205 - Term of HAP contract.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Term of HAP contract. 983.205 Section 983.205 Housing and Urban Development Regulations Relating to Housing and Urban Development... DEVELOPMENT PROJECT-BASED VOUCHER (PBV) PROGRAM Housing Assistance Payments Contract § 983.205 Term of HAP...

MicroRNA-194 promotes osteoblast differentiation via downregulating STAT1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Jun; He, Xijing; Wei, Wenzhi

Osteoblast differentiation is a vital process in maintaining bone homeostasis in which various transcriptional factors, signaling molecules, and microRNAs (miRNAs) are involved. Recently, signal transducer and activator of transcription 1 (STAT1) has been found to play an important role in regulating osteoblast differentiation. Here, we identified that STAT1 expression was regulated by miR-194. Using mouse bone mesenchymal stem cells (BMSCs), we found that miR-194 expression was significantly increased following osteoblast differentiation induction. Overexpression of miR-194 by lentivirus-mediated gene transfer markedly increased osteoblast differentiation, whereas inhibition of miR-194 significantly suppressed osteoblast differentiation of BMSCs. Using a dual-luciferase reporter assay, a directmore » interaction between miR-194 and the 3′-untranslated region (UTR) of STAT1 was confirmed. Additionally, miR-194 regulated mRNA and protein expression of STAT1 in BMSCs. Further analysis showed that miR-194 overexpression promoted the nuclear translocation of runt-related transcription factor 2 (Runx2), which is critical for osteoblast differentiation. In contrast, inhibition of miR-194 blocked the nuclear translocation of Runx2. Moreover, overexpression of STAT1 significantly blocked Runx2 nuclear translocation and osteoblast differentiation mediated by miR-194 overexpression. Taken together, our data suggest that miR-194 regulates osteoblast differentiation through modulating STAT1-mediated Runx2 nuclear translocation. - Highlights: • Overexpression of miR-194 significantly increased osteoblast differentiation. • miR-194 directly targeted the 3′- UTR of STAT1. • miR-194 regulated the expression of STAT1. • Overexpression of miR-194 promoted the nuclear translocation of Runx2.« less

Direct block of native and cloned (Kir2.1) inward rectifier K+ channels by chloroethylclonidine

PubMed Central

Barrett-Jolley, R; Dart, C; Standen, N B

1999-01-01

We have investigated the inhibition of inwardly rectifying potassium channels by the α-adrenergic agonist/antagonist chloroethylclonidine (CEC). We used two preparations; two-electrode voltage-clamp of rat isolated flexor digitorum brevis muscle and whole-cell patch-clamp of cell lines transfected with Kir2.1 (IRK1).In skeletal muscle and at a membrane potential of −50 mV, chloroethylclonidine (CEC), an agonist at α2-adrenergic receptors and an antagonist at α1x-receptors, was found to inhibit the inward rectifier current with a Ki of 30 μM.The inhibition of skeletal muscle inward rectifier current by CEC was not mimicked by clonidine, adrenaline or noradrenaline and was not sensitive to high concentrations of α1-(prazosin) or α2-(rauwolscine) antagonists.The degree of current inhibition by CEC was found to vary with the membrane potential (approximately 70% block at −50 mV c.f. ∼10% block at −190 mV). The kinetics of this voltage dependence were further investigated using recombinant inward rectifier K+ channels (Kir2.1) expressed in the MEL cell line. Using a two pulse protocol, we calculated the time constant for block to be ∼8 s at 0 mV, and the rate of unblock was described by the relationship τ=exp((Vm+149)/22) s.This block was effective when CEC was applied to either the inside or the outside of patch clamped cells, but ineffective when a polyamine binding site (aspartate 172) was mutated to asparagine.The data suggest that the clonidine-like imidazoline compound, CEC, inhibits inward rectifier K+ channels independently of α-receptors by directly blocking the channel pore, possibly at an intracellular polyamine binding site. PMID:10516659

One-pot chemoselective synthesis of novel pyrrole-substituted pyrido [2,3-d]pyrimidines using [γ-Fe2O3@HAp-SO3H] as an efficient nanocatalyst

NASA Astrophysics Data System (ADS)

Jahanshahi, Parivash; Mamaghani, Manouchehr; Haghbin, Fereshteh; Nia, Roghayeh Hossein; Rassa, Mehdi

2018-03-01

Novel (1-methyl-1H-pyrrol-2-yl)-[2,3-d]pyrimidine derivatives were synthesized chemoselectively in good to high yields (81-90%) and short reaction times (7-14 min) by hydroxyapatite-encapsulated-γ-Fe2O3 supported sulfonic acid ([γ-Fe2O3@HAp-SO3H]) catalyzed condensation of 3-(1-methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile, 6-amino-2-(alkylthio)pyrimidin-4(3H)-one and various aromatic aldehydes. The easy work-up of the products, rapidity, high efficiency and recyclability of the catalyst are advantages of this protocol. The antibacterial activity of the newly synthesized products was investigated. Some of the products showed encouraging activity.

Loss of Bin1 Promotes the Propagation of Tau Pathology.

PubMed

Calafate, Sara; Flavin, William; Verstreken, Patrik; Moechars, Diederik

2016-10-18

Tau pathology propagates within synaptically connected neuronal circuits, but the underlying mechanisms are unclear. BIN1-amphiphysin2 is the second most prevalent genetic risk factor for late-onset Alzheimer's disease. In diseased brains, the BIN1-amphiphysin2 neuronal isoform is downregulated. Here, we show that lowering BIN1-amphiphysin2 levels in neurons promotes Tau pathology propagation whereas overexpression of neuronal BIN1-amphiphysin2 inhibits the process in two in vitro models. Increased Tau propagation is caused by increased endocytosis, given our finding that BIN1-amphiphysin2 negatively regulates endocytic flux. Furthermore, blocking endocytosis by inhibiting dynamin also reduces Tau pathology propagation. Using a galectin-3-binding assay, we show that internalized Tau aggregates damage the endosomal membrane, allowing internalized aggregates to leak into the cytoplasm to propagate pathology. Our work indicates that lower BIN1 levels promote the propagation of Tau pathology by efficiently increasing aggregate internalization by endocytosis and endosomal trafficking. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Trehalose-Based Block Copolycations Promote Polyplex Stabilization for Lyophilization and in Vivo pDNA Delivery

PubMed Central

2015-01-01

The development and thorough characterization of nonviral delivery agents for nucleic acid and genome editing therapies are of high interest to the field of nanomedicine. Indeed, this vehicle class offers the ability to tune chemical architecture/biological activity and readily package nucleic acids of various sizes and morphologies for a variety of applications. Herein, we present the synthesis and characterization of a class of trehalose-based block copolycations designed to stabilize polyplex formulations for lyophilization and in vivo administration. A 6-methacrylamido-6-deoxy trehalose (MAT) monomer was synthesized from trehalose and polymerized via reversible addition–fragmentation chain transfer (RAFT) polymerization to yield pMAT43. The pMAT43 macro-chain transfer agent was then chain-extended with aminoethylmethacrylamide (AEMA) to yield three different pMAT-b-AEMA cationic-block copolymers, pMAT-b-AEMA-1 (21 AEMA repeats), -2 (44 AEMA repeats), and -3 (57 AEMA repeats). These polymers along with a series of controls were used to form polyplexes with plasmids encoding firefly luciferase behind a strong ubiquitous promoter. The trehalose-coated polyplexes were characterized in detail and found to be resistant to colloidal aggregation in culture media containing salt and serum. The trehalose-polyplexes also retained colloidal stability and promoted high gene expression following lyophilization and reconstitution. Cytotoxicity, cellular uptake, and transfection ability were assessed in vitro using both human glioblastoma (U87) and human liver carcinoma (HepG2) cell lines wherein pMAT-b-AEMA-2 was found to have the optimal combination of high gene expression and low toxicity. pMAT-b-AEMA-2 polyplexes were evaluated in mice via slow tail vein infusion. The vehicle displayed minimal toxicity and discouraged nonspecific internalization in the liver, kidney, spleen, and lungs as determined by quantitative polymerase chain reaction (qPCR) and fluorescence imaging

A comparison of cataloged variation between International HapMap Consortium and 1000 Genomes Project data

PubMed Central

Buchanan, Carrie C; Torstenson, Eric S; Bush, William S

2012-01-01

Background Since publication of the human genome in 2003, geneticists have been interested in risk variant associations to resolve the etiology of traits and complex diseases. The International HapMap Consortium undertook an effort to catalog all common variation across the genome (variants with a minor allele frequency (MAF) of at least 5% in one or more ethnic groups). HapMap along with advances in genotyping technology led to genome-wide association studies which have identified common variants associated with many traits and diseases. In 2008 the 1000 Genomes Project aimed to sequence 2500 individuals and identify rare variants and 99% of variants with a MAF of <1%. Methods To determine whether the 1000 Genomes Project includes all the variants in HapMap, we examined the overlap between single nucleotide polymorphisms (SNPs) genotyped in the two resources using merged phase II/III HapMap data and low coverage pilot data from 1000 Genomes. Results Comparison of the two data sets showed that approximately 72% of HapMap SNPs were also found in 1000 Genomes Project pilot data. After filtering out HapMap variants with a MAF of <5% (separately for each population), 99% of HapMap SNPs were found in 1000 Genomes data. Conclusions Not all variants cataloged in HapMap are also cataloged in 1000 Genomes. This could affect decisions about which resource to use for SNP queries, rare variant validation, or imputation. Both the HapMap and 1000 Genomes Project databases are useful resources for human genetics, but it is important to understand the assumptions made and filtering strategies employed by these projects. PMID:22319179

Overexpression and Purification of C-terminal Fragment of the Passenger Domain of Hap Protein from Nontypeable Haemophilus influenzae in a Highly Optimized Escherichia coli Expression System

PubMed Central

Tabatabaee, Akram; Siadat, Seyed Davar; Moosavi, Seyed Fazllolah; Aghasadeghi, Mohammad Reza; Memarnejadian, Arash; Pouriayevali, Mohammad Hassan; Yavari, Neda

2013-01-01

Background Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory tract disease and initiates infection by colonization in nasopharynx. The Haemophilus influenzae (H. influenzae) Hap adhesin is an auto transporter protein that promotes initial interaction with human epithelial cells. Hap protein contains a 110 kDa internal passenger domain called “HapS” and a 45 kDa C-terminal translocator domain called “Hapβ”. Hap adhesive activity has been recently reported to be connected to its Cell Binding Domain (CBD) which resides within the 311 C-terminal residues of the internal passenger domain of the protein. Furthermore, immunization with this CBD protein has been shown to prevent bacterial nasopharynx colonization in animal models. Methods To provide enough amounts of pure HapS protein for vaccine studies, we sought to develop a highly optimized system to overexpress and purify the protein in large quantities. To this end, pET24a-cbd plasmid harboring cbd sequence from NTHi ATCC49766 was constructed and its expression was optimized by testing various expression parameters such as growth media, induction temperature, IPTG inducer concentration, induction stage and duration. SDS-PAGE and Western-blotting were used for protein analysis and confirmation and eventually the expressed protein was easily purified via immobilized metal affinity chromatography (IMAC) using Ni-NTA columns. Results The highest expression level of target protein was achieved when CBD expressing E. coli BL21 (DE3) cells were grown at 37°C in 2xTY medium with 1.0 mM IPTG at mid-log phase (OD600 nm equal to 0.6) for 5 hrs. Amino acid sequence alignment of expressed CBD protein with 3 previously published CBD amino acid sequences were more than %97 identical and antigenicity plot analysis further revealed 9 antigenic domains which appeared to be well conserved among different analyzed CBD sequences. Conclusion Due to the presence of high similarity among CBD from NTHi ATCC

Emodin inhibits breast cancer growth by blocking the tumor-promoting feedforward loop between cancer cells and macrophages

PubMed Central

Iwanowycz, Stephen; Wang, Junfeng; Hodge, Johnie; Wang, Yuzhen; Yu, Fang; Fan, Daping

2016-01-01

Macrophage infiltration correlates with severity in many types of cancer. Tumor cells recruit macrophages and educate them to adopt an M2-like phenotype through the secretion of chemokines and growth factors, such as MCP1 and CSF1. Macrophages in turn promote tumor growth through supporting angiogenesis, suppressing anti-tumor immunity, modulating extracellular matrix remodeling, and promoting tumor cell migration. Thus tumor cells and macrophages interact to create a feedforward loop supporting tumor growth and metastasis. In this study, we tested the ability of emodin, a Chinese herb-derived compound, to inhibit breast cancer growth in mice and examined the underlying mechanisms. Emodin was used to treat mice bearing EO771 or 4T1 breast tumors. It was shown that emodin attenuated tumor growth by inhibiting macrophage infiltration and M2-like polarization, accompanied by increased T cell activation and reduced angiogenesis in tumors. The tumor inhibitory effects of emodin were lost in tumor-bearing mice with macrophage depletion. Emodin inhibited IRF4, STAT6, and C/EBPβ signaling and increased inhibitory histone H3 lysine 27 tri-methylation (H3K27m3) on the promoters of M2 related genes in tumor-associated macrophages. In addition, emodin inhibited tumor cell secretion of MCP1and CSF1, as well as expression of surface anchoring molecule Thy-1, thus suppressing macrophage migration towards and adhesion to tumor cells. These results suggest that emodin acts on both breast cancer cells and macrophages and effectively blocks the tumor-promoting feedforward loop between the two cell types, thereby inhibiting breast cancer growth and metastasis. PMID:27196773

40 CFR 63.1569 - What are my requirements for HAP emissions from bypass lines?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true What are my requirements for HAP emissions from bypass lines? 63.1569 Section 63.1569 Protection of Environment ENVIRONMENTAL PROTECTION... HAP emissions from bypass lines? (a) What work practice standards must I meet? (1) You must meet each...

A new series of HAPs as anti-HBV agents targeting at capsid assembly.

PubMed

Yang, Xiu-yan; Xu, Xiao-qian; Guan, Hua; Wang, Li-li; Wu, Qin; Zhao, Guo-ming; Li, Song

2014-09-01

A series of novel Heteroaryldihydropyrimidines (HAPs) derivatives were designed and synthesized as potent inhibitors of HBV capsid assembly. These compounds were prepared from efforts to optimize an earlier series of HAPs, and compounds Mo1, Mo7, Mo8, Mo10, Mo12, and Mo13 demonstrated potent inhibition of HBV DNA replication at submicromolar range. Copyright © 2014. Published by Elsevier Ltd.

Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma.

PubMed

Wang, Q; Lu, Y; Li, R; Jiang, Y; Zheng, Y; Qian, J; Bi, E; Zheng, C; Hou, J; Wang, S; Yi, Q

2018-01-01

Our previous studies showed that macrophages (MФs), especially myeloma-associated MФs (MAMs), induce chemoresistance in human myeloma. Here we explored the potential of targeting MФs, by using colony-stimulating factor 1 receptor (CSF1R)-blocking mAbs, to treat myeloma. Our results showed that CSF1R blockade specifically inhibited the differentiation, proliferation and survival of murine M2 MФs and MAMs, and repolarized MAMs towards M1-like MФs in vitro. CSF1R blockade alone inhibited myeloma growth in vivo, by partially depleting MAMs, polarizing MAMs to the M1 phenotype, and inducing a tumor-specific cytotoxic CD4 + T-cell response. Similarly, genetically depleting MФs in myeloma-bearing MM DTR mice retarded myeloma growth in vivo. Furthermore, the combination of CSF1R blockade and chemotherapy such as bortezomib or melphalan displayed an additive therapeutic efficacy against established myeloma. Finally, a fully human CSF1R blocking mAb, similar to its murine counterpart, was able to inhibit the differentiation, proliferation and survival of human MФs. Thus, this study provides the first direct in vivo evidence that MΦs and MAMs are indeed important for myeloma development and progression. Our results also suggest that targeting MAMs by CSF1R blocking mAbs may be promising methods to (re)sensitize myeloma cells to chemotherapy and promote anti-myeloma immune responses in patients.

Vancomycin incorporated chitosan/gelatin coatings coupled with TiO2-SrHAP surface modified cp-titanium for osteomyelitis treatment.

PubMed

D, Nancy; N, Rajendran

2018-04-15

Commercially pure Titanium (Cp-Ti) was electrophoretically modified using double layer coatings consisting of TiO 2 -SrHAP as the first layer (TH) followed by vancomycin incorporated Chitosan/Gelatin as the second layer (THV). The nano crystalline phase of coated Strontium incorporated hydroxyapatite (Sr-HAP) confirmed through X-ray diffraction studies (XRD). The polyelectrolyte complex formation between chitosan and gelatin, the stability of the drug, the bonding between chitosan and Sr-HAP were confirmed through infra-red spectroscopic studies (IR). The average roughness (R a ) value calculated from atomic force microscopy (AFM) corroborates with the water contact angle data, which clearly confirms the tuning property of the surface in relation to the surface energy and roughness of the coated samples. The total amount of vancomycin encapsulated was calculated to be 11.5 μg. Antibacterial activity was found against both Staphylococcus aureus strains methicillin resistant Staphylococcus aureus (MRSA) and methicillin sensitive Staphylococcus aureus (MRSA) for a drug concentration of 2.74 μg released after 12 h of immersion. The in-vitro cell culture studies showed enhanced cellular activity for THV samples. Thus, THV samples have a dual action at the surface, by resisting the bacterial adhesion and enhancing cellular interaction at the bio-interface, making it a promising candidate to treat osteomyelitis infection. Copyright © 2018. Published by Elsevier B.V.

DA-9801 promotes neurite outgrowth via ERK1/2-CREB pathway in PC12 cells.

PubMed

Won, Jong Hoon; Ahn, Kyong Hoon; Back, Moon Jung; Ha, Hae Chan; Jang, Ji Min; Kim, Ha Hyung; Choi, Sang-Zin; Son, Miwon; Kim, Dae Kyong

2015-01-01

In the present study, we examined the mechanisms underlying the effect of DA-9801 on neurite outgrowth. We found that DA-9801 elicits its effects via the mitogen-activated protein kinase (MEK) extracellular signal-regulated kinase (ERK)1/2-cAMP response element-binding protein (CREB) pathway. DA-9801, an extract from a mixture of Dioscorea japonica and Dioscorea nipponica, was reported to promote neurite outgrowth in PC12 cells. The effects of DA-9801 on cell viability and expression of neuronal markers were evaluated in PC12 cells. To investigate DA-9801 action, specific inhibitors targeting the ERK signaling cascade were used. No cytotoxicity was observed in PC12 cells at DA-9801 concentrations of less than 30 µg/mL. In the presence of nerve growth factor (NGF, 2 ng/mL), DA-9801 promoted neurite outgrowth and increased the relative mRNA levels of neurofilament-L (NF-L), a marker of neuronal differentiation. The Raf-1 inhibitor GW5074 and MEK inhibitor PD98059 significantly attenuated DA-9801-induced neurite outgrowth. Additionally, the MEK1 and MEK2 inhibitor SL327 significantly attenuated the increase in the percentage of neurite-bearing PC12 cells induced by DA-9801 treatment. Conversely, the selective p38 mitogen-activated protein kinase inhibitor SB203580 did not attenuate the DA-9801 treatment-induced increase in the percentage of neurite-bearing PC12 cells. DA-9801 enhanced the phosphorylation of ERK1/2 and CREB in PC12 cells incubated with and without NGF. Pretreatment with PD98059 blocked the DA-9801-induced phosphorylation of ERK1/2 and CREB. In conclusion, DA-9801 induces neurite outgrowth by affecting the ERK1/2-CREB signaling pathway. Insights into the mechanism underlying this effect of DA-9801 may suggest novel potential strategies for the treatment of peripheral neuropathy.

Grape pomace extract exerts antioxidant effects through an increase in GCS levels and GST activity in muscle and endothelial cells

PubMed Central

GOUTZOURELAS, NIKOLAOS; STAGOS, DIMITRIOS; HOUSMEKERIDOU, ANASTASIA; KARAPOULIOU, CHRISTINA; KERASIOTI, EFTHALIA; ALIGIANNIS, NEKTARIOS; SKALTSOUNIS, ALEXIOS L; SPANDIDOS, DEMETRIOS A; TSATSAKIS, ARISTIDIS M; KOURETAS, DEMETRIOS

2015-01-01

In a previous study, we demonstrated that a grape pomace extract (GPE) exerted antioxidant activity in endothelial (EA.hy926) and muscle (C2C12) cells through an increase in glutathione (GSH) levels. In the present study, in order to elucidate the mechanisms responsible for the antioxidant activity of GPE, its effects on the expression of critical antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD)1, heme oxygenase 1 (HO-1) and gamma-glutamylcysteine synthetase (GCS) were assessed in EA.hy926 and C2C12 cells. Moreover, the effects of GPE on CAT, SOD and glutathione S-transferase (GST) enzymatic activity were evaluated. For this purpose, the C2C12 and EA.hy926 cells were treated with GPE at low and non-cytotoxic concentrations (2.5 and 10 µg/ml for the C2C12 cells; 0.068 and 0.250 µg/ml for the EA.hy926 cells) for 3, 6, 12, 18 and 24 h. Following incubation, enzymatic expression and activity were assessed. The results revealed that treatment with GPE significantly increased GCS levels and GST activity in both the C2C12 and EA.hy926 cells. However, GPE significantly decreased CAT levels and activity, but only in the muscle cells, while it had no effect on CAT levels and activity in the endothelial cells. Moreover, treatment with GPE had no effect on HO-1 and SOD expression and activity in both cell lines. Therefore, the present results provide further evidence of the crucial role of GSH systems in the antioxidant effects exerted by GPE. Thus, GPE may prove to be effective for use as a food supplement for the treatment of oxidative stress-induced pathological conditions of the cardiovascular and skeletal muscle systems, particularly those associated with low GSH levels. PMID:26082074

40 CFR Table 8 to Subpart Wwww of... - Initial Compliance With Organic HAP Emissions Limits

Code of Federal Regulations, 2010 CFR

2010-07-01

... SOURCE CATEGORIES National Emissions Standards for Hazardous Air Pollutants: Reinforced Plastic... organic HAP emissions limit . . . You have demonstrated initial complianceif . . . 1. open molding and... contents. 2. open molding centrifugal casting, continuous lamination/casting, SMC and BMC manufacturing...

40 CFR Table 8 to Subpart Wwww of... - Initial Compliance With Organic HAP Emissions Limits

Code of Federal Regulations, 2014 CFR

2014-07-01

.... open molding and centrifugal casting operations a. an organic HAP emissions limit shown in Tables 3 or... method meet the appropriate organic HAP contents. 2. open molding centrifugal casting, continuous... reduction is being claimed, are using direct die injection, and/or wet-area enclosures that meet the...

40 CFR Table 8 to Subpart Wwww of... - Initial Compliance With Organic HAP Emissions Limits

Code of Federal Regulations, 2013 CFR

2013-07-01

.... open molding and centrifugal casting operations a. an organic HAP emissions limit shown in Tables 3 or... method meet the appropriate organic HAP contents. 2. open molding centrifugal casting, continuous... reduction is being claimed, are using direct die injection, and/or wet-area enclosures that meet the...

40 CFR Table 8 to Subpart Wwww of... - Initial Compliance With Organic HAP Emissions Limits

Code of Federal Regulations, 2012 CFR

2012-07-01

.... open molding and centrifugal casting operations a. an organic HAP emissions limit shown in Tables 3 or... method meet the appropriate organic HAP contents. 2. open molding centrifugal casting, continuous... reduction is being claimed, are using direct die injection, and/or wet-area enclosures that meet the...

Sedimentary reservoir oxidation during geologic CO2 sequestration

NASA Astrophysics Data System (ADS)

Lammers, Laura N.; Brown, Gordon E.; Bird, Dennis K.; Thomas, Randal B.; Johnson, Natalie C.; Rosenbauer, Robert J.; Maher, Katharine

2015-04-01

Injection of carbon dioxide into subsurface geologic reservoirs during geologic carbon sequestration (GCS) introduces an oxidizing supercritical CO2 phase into a subsurface geologic environment that is typically reducing. The resulting redox disequilibrium provides the chemical potential for the reduction of CO2 to lower free energy organic species. However, redox reactions involving carbon typically require the presence of a catalyst. Iron oxide minerals, including magnetite, are known to catalyze oxidation and reduction reactions of C-bearing species. If the redox conditions in the reservoir are modified by redox transformations involving CO2, such changes could also affect mineral stability, leading to dissolution and precipitation reactions and alteration of the long-term fate of CO2 in GCS reservoirs. We present experimental evidence that reservoirs with reducing redox conditions are favorable environments for the relatively rapid abiotic reduction of CO2 to organic molecules. In these experiments, an aqueous suspension of magnetite nanoparticles was reacted with supercritical CO2 under pressure and temperature conditions relevant to GCS in sedimentary reservoirs (95-210 °C and ∼100 bars of CO2). Hydrogen production was observed in several experiments, likely caused by Fe(II) oxidation either at the surface of magnetite or in the aqueous phase. Heating of the Fe(II)-rich system resulted in elevated PH2 and conditions favorable for the reduction of CO2 to acetic acid. Implications of these results for the long-term fate of CO2 in field-scale systems were explored using reaction path modeling of CO2 injection into reservoirs containing Fe(II)-bearing primary silicate minerals, with kinetic parameters for CO2 reduction obtained experimentally. The results of these calculations suggest that the reaction of CO2 with reservoir constituents will occur in two primary stages (1) equilibration of CO2 with organic acids resulting in mineral-fluid disequilibrium, and

A double candidate survivable routing protocol for HAP network

NASA Astrophysics Data System (ADS)

He, Panfeng; Li, Chunyue; Ni, Shuyan

2016-11-01

To improve HAP network invulnerability, and at the same time considering the quasi-dynamic topology in HAP network, a simple and reliable routing protocol is proposed in the paper. The protocol firstly uses a double-candidate strategy for the next-node select to provide better robustness. Then during the maintenance stage, short hello packets instead of long routing packets are used only to check link connectivity in the quasi-dynamic HAP network. The route maintenance scheme based on short hello packets can greatly reduce link spending. Simulation results based on OPNET demonstrate the effectiveness of the proposed routing protocol.

Powered Explicit Guidance Modifications and Enhancements for Space Launch System Block-1 and Block-1B Vehicles

NASA Technical Reports Server (NTRS)

Von der Porten, Paul; Ahmad, Naeem; Hawkins, Matt; Fill, Thomas

2018-01-01

NASA is currently building the Space Launch System (SLS) Block-1 launch vehicle for the Exploration Mission 1 (EM-1) test flight. NASA is also currently designing the next evolution of SLS, the Block-1B. The Block-1 and Block-1B vehicles will use the Powered Explicit Guidance (PEG) algorithm (of Space Shuttle heritage) for closed loop guidance. To accommodate vehicle capabilities and design for future evolutions of SLS, modifications were made to PEG for Block-1 to handle multi-phase burns, provide PEG updated propulsion information, and react to a core stage engine out. In addition, due to the relatively low thrust-to-weight ratio of the Exploration Upper Stage (EUS) and EUS carrying out Lunar Vicinity and Earth Escape missions, certain enhancements to the Block-1 PEG algorithm are needed to perform Block-1B missions to account for long burn arcs and target translunar and hyperbolic orbits. This paper describes the design and implementation of modifications to the Block-1 PEG algorithm as compared to Space Shuttle. Furthermore, this paper illustrates challenges posed by the Block-1B vehicle and the required PEG enhancements. These improvements make PEG capable for use on the SLS Block-1B vehicle as part of the Guidance, Navigation, and Control (GN&C) System.

mPGES-1-derived prostaglandin E2 stimulates Stat3 to promote podocyte apoptosis.

PubMed

Yu, Jing; Wu, Yimei; Wang, Lu; Zhang, Wen; Xu, Man; Song, Jiayu; Fu, Yu; Cui, Yiyun; Gong, Wei; Li, Shuzhen; Xia, Weiwei; Huang, Songming; Zhang, Aihua; Jia, Zhanjun

2017-11-01

We previously reported that microsomal prostaglandin E synthase-1 (mPGES-1) contributed to adriamycin (Adr)-induced podocyte apoptosis. However, the molecular mechanism remains unclear. Here we studied the role of mPGES-1/PGE2 cascade in activating Stat3 signaling and the contribution of Stat3 in PGE2- and Adr-induced podocyte apoptosis. In murine podocytes, PGE2 dose- and time-dependently increased the phosphorylation of Stat3 in line with the enhanced cell apoptosis and reduced podocyte protein podocin. In agreement with the increased Stat3 phosphorylation, Stat3-derived cytokines including IL-6, IL-17, MCP-1, and ICAM-1 were significantly upregulated following PGE2 treatment. By application of a specific Stat3 inhibitor S3I-201, PGE2-induced podocyte apoptosis was largely abolished in parallel with a blockade of podocin reduction. Next, we observed that Adr treatment also enhanced p-Stat3 and activated mPGES-1/PGE2 cascade. Blockade of Stat3 by S3I-201 significantly ameliorated Adr-induced cell apoptosis and podocin reduction. More interestingly, silencing mPGES-1 in podocytes by mPGES-1 siRNA blocked Adr-induced increments of Stat-3 phosphorylation, PGE2 production, and Stat3-derived inflammatory cytokines. Taken together, this study suggested that mPGES-1-derived PGE2 could activate Stat3 signaling to promote podocyte apoptosis. Targeting mPGES-1/PGE2/Stat3 signaling might be a potential strategy for the treatment of podocytopathy.

Rapid formation of complexity in the total synthesis of natural products enabled by oxabicyclo[2.2.1]heptene building blocks.

PubMed

Schindler, Corinna S; Carreira, Erick M

2009-11-01

This critical review showcases examples of rapid formation of complexity in total syntheses starting from 7-oxabicyclo[2.2.1]hept-5-ene derivatives. An overview of methods allowing synthetic access to these building blocks is provided and their application in recently developed synthetic transformations to structurally complex systems is illustrated. In addition, the facile access to a novel oxabicyclo[2.2.1]heptene derived building block is presented which significantly enlarges the possibilities of previously known chemical transformations and is highlighted in the enantioselective route to the core of the banyaside and suomilide natural products (107 references).

Impact of epigallocatechin‑3‑gallate on expression of nuclear factor erythroid 2‑related factor 2 and γ‑glutamyl cysteine synthetase genes in oxidative stress‑induced mouse renal tubular epithelial cells.

PubMed

Du, Xuanyi; Yu, Jinfeng; Sun, Xiaohan; Qu, Shaochuan; Zhang, Haitao; Hu, Mengying; Yang, Shufen; Zhou, Ping

2018-06-01

The aim of the present study was to investigate the antioxidant response mechanism of epigallocatechin‑3‑gallate (EGCG) in H2O2‑induced mouse renal tubular epithelial cells (MRTECs). The cultured MRTECs were divided into normal, H2O2 (control) and EGCG treatment groups. The MTT assay was used to assess cell viability, and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), immunocytochemical and western blot analyses were performed to detect the expression of nuclear factor erythroid 2‑related factor 2 (Nrf2) and γ‑glutamyl cysteine synthetase (γ‑GCS). EGCG was able to mitigate H2O2‑mediated cell damage. The RT‑qPCR results demonstrated that EGCG was able to upregulate the gene expression of Nrf2 and γ‑GCS in MRTECs in a dose‑dependent manner. The immunocytochemistry and western blot analyses demonstrated that EGCG was able to increase the protein expression of Nrf2 and γ‑GCS in MRTECs in a dose‑dependent manner. Oxidative stress may lead to a decrease in the viability of MRTECs, while EGCG was able to promote the expression of Nrf2 and γ‑GCS in MRTECs, thereby improving the antioxidant capacity of the cells and promoting the repair of oxidative stress injury.

miR-204 inhibits angiogenesis and promotes sensitivity to cetuximab in head and neck squamous cell carcinoma cells by blocking JAK2-STAT3 signaling.

PubMed

Wu, Qingwei; Zhao, Yingying; Wang, Peihua

2018-03-01

This study aims to investigate the roles of miR-204 in tumor angiogenesis of head and neck squamous cell carcinoma (HNSCC). Here, we found that miR-204 level was reduced in HNSCC tissues relative to that in normal adjacent tissues. Overexpression of miR-204 promoted tumor angiogenesis in HNSCC cells. Mechanistically, JAK2 was identified as a direct target of miR-204, and miR-204 overexpression blocked JAK2/STAT3 pathway. Moreover, overexpression of JAK2 attenuated the inhibition of miR-204 on tumor angiogenesis of HNSCC. Furthermore, overexpression of miR-204 enhanced sensitivity of cetuximab in HNSCC cells, this effect was attenuated by JAK2 overexpression too. Importantly, JAK2 expression was negatively correlated with miR-204 level in HNSCC tissues. Therefore, miR-204 acts as a tumor suppressor by blocking JAK2/STAT3 pathway in HNSCC cells. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

26 CFR 1.1248-2 - Earnings and profits attributable to a block of stock in simple cases.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Earnings and profits attributable to a block of... Gains and Losses § 1.1248-2 Earnings and profits attributable to a block of stock in simple cases. (a... person sells or exchanges a block of stock (as defined in paragraph (b) of this section) in a foreign...

Environmental testing of block 2 solar cell modules

NASA Technical Reports Server (NTRS)

Griffith, J. S.

1979-01-01

The testing procedures and results of samples of the LSA Project Block 2 procurement of silicon solar cell modules are described. Block 2 was the second large scale procurement of silicon solar cell modules made by the JPL Low-cost Solar Array Project with deliveries in 1977 and early 1978. The results showed that the Block 2 modules were greatly improved over Block 1 modules. In several cases it was shown that design improvements were needed to reduce environmental test degradation. These improvements were incorporated during this production run.

Emodin Inhibits Breast Cancer Growth by Blocking the Tumor-Promoting Feedforward Loop between Cancer Cells and Macrophages.

PubMed

Iwanowycz, Stephen; Wang, Junfeng; Hodge, Johnie; Wang, Yuzhen; Yu, Fang; Fan, Daping

2016-08-01

Macrophage infiltration correlates with severity in many types of cancer. Tumor cells recruit macrophages and educate them to adopt an M2-like phenotype through the secretion of chemokines and growth factors, such as MCP1 and CSF1. Macrophages in turn promote tumor growth through supporting angiogenesis, suppressing antitumor immunity, modulating extracellular matrix remodeling, and promoting tumor cell migration. Thus, tumor cells and macrophages interact to create a feedforward loop supporting tumor growth and metastasis. In this study, we tested the ability of emodin, a Chinese herb-derived compound, to inhibit breast cancer growth in mice and examined the underlying mechanisms. Emodin was used to treat mice bearing EO771 or 4T1 breast tumors. It was shown that emodin attenuated tumor growth by inhibiting macrophage infiltration and M2-like polarization, accompanied by increased T-cell activation and reduced angiogenesis in tumors. The tumor inhibitory effects of emodin were lost in tumor-bearing mice with macrophage depletion. Emodin inhibited IRF4, STAT6, and C/EBPβ signaling and increased inhibitory histone H3 lysine 27 tri-methylation (H3K27m3) on the promoters of M2-related genes in tumor-associated macrophages. In addition, emodin inhibited tumor cell secretion of MCP1 and CSF1, as well as expression of surface anchoring molecule Thy-1, thus suppressing macrophage migration toward and adhesion to tumor cells. These results suggest that emodin acts on both breast cancer cells and macrophages and effectively blocks the tumor-promoting feedforward loop between the two cell types, thereby inhibiting breast cancer growth and metastasis. Mol Cancer Ther; 15(8); 1931-42. ©2016 AACR. ©2016 American Association for Cancer Research.

The β2-adrenoreceptor gene promoter polymorphisms may modulate β2-agonist- and glucocorticoid-induced IgE synthesis.

PubMed

Chalubinski, M; Grzegorczyk, J; Grzelak, A; Jarzebska, M; Kowalski, M L

2014-01-01

β2-adrenoreceptor (β2-AR) agonists and glucocorticoids (GCS) were shown to induce IgE synthesis in human PBMCs. Serum total IgE levels are associated with single nucleotide polymorphisms (SNPs) of the β2-AR gene. We aimed to assess the association of the effect of fenoterol (β2-AR agonist) on IL-4-driven and budesonide-induced IgE synthesis with genetic variants of β2-AR. The study included 25 individuals: 13 with allergic asthma and/or allergic rhinitis and 12 healthy volunteers. PBMCs were cultured with IL-4, fenoterol and/or budesonide, and IgE concentrations in supernatants were assessed. Five SNPs in positions: -47, -20, 46, 79 and 252 of β2-AR were determined by direct DNA sequencing. In -47 T/T and -20 T/T patients, incubation with fenoterol resulted in decreased IgE production, whereas in -47 C/T and -47 C/C as well as in -20 C/T and -20 C/C individuals, it was enhanced. In contrast to fenoterol, budesonide-induced IgE synthesis was significantly increased in -47 T/T and -20 T/T patients as compared to -47 C/T, -47 C/C, -20 C/T and -47 C/C individuals. Polymorphisms in positions 46, 79 and 252 were not associated with fenoterol- or budesonide-modulated IgE synthesis. No differences in the distribution of IgE synthesis was seen between atopic and non-atopic individuals carrying the same alleles. The differential effect of β2-agonists and GCS on IgE synthesis may be associated with genetic variants of promoter region of the β2-AR gene. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

40 CFR Table 8 to Subpart Wwww of... - Initial Compliance With Organic HAP Emissions Limits

Code of Federal Regulations, 2011 CFR

2011-07-01

... organic HAP emissions limit . . . You have demonstrated initial complianceif . . . 1. open molding and... contents. 2. open molding centrifugal casting, continuous lamination/casting, SMC and BMC manufacturing... die injection, and/or wet-area enclosures that meet the criteria of § 63.5830. 6. pultrusion...

Porcine circovirus type 2 activates PI3K/Akt and p38 MAPK pathways to promote interleukin-10 production in macrophages via Cap interaction of gC1qR

PubMed Central

Wang, Tongtong; Zhang, Xiujuan; Chen, Yu; Cui, Beibei; Li, Delong; Zhao, Xiaomin; Zhang, Wenlong; Chang, Lingling; Tong, Dewen

2016-01-01

Porcine circovirus type 2 (PCV2) infection caused PCV2-associated diseases (PCVAD) is one of the major emerging immunosuppression diseases in pig industry. In this study, we investigated how PCV2 inoculation increases interleukin (IL)-10 expression in porcine alveolar macrophages (PAMs). PCV2 inoculation significantly upregulated IL-10 expression compared with PCV1. Upon initial PCV2 inoculation, PI3K/Akt cooperated with NF-κB pathways to promote IL-10 transcription via p50, CREB and Ap1 transcription factors, whereas inhibition of PI3K/Akt activation blocked Ap1 and CREB binding to the il10 promoter, and decreased the binding level of NF-κB1 p50 with il10 promoter, leading to great reduction in early IL-10 transcription. In the later phase of inoculation, PCV2 further activated p38 MAPK and ERK pathways to enhance IL-10 production by promoting Sp1 binding to the il10 promoter. For PCV2-induced IL-10 production in macrophages, PCV2 capsid protein Cap, but not the replicase Rep or ORF3, was the critical component. Cap activated PI3K/Akt, p38 MAPK, and ERK signaling pathways to enhance IL-10 expression. In the whole process, gC1qR mediated PCV2-induced PI3K/Akt and p38 MAPK activation to enhance IL-10 induction by interaction with Cap. Depletion of gC1qR blocked PI3K/Akt and p38 MAPK activation, resulting in significant decrease in IL-10 production in PCV2-inoculated cells. Thus, gC1qR might be a critical functional receptor for PCV2-induced IL-10 production. Taken together, these data demonstrated that Cap protein binding with host gC1qR induction of PI3K/Akt and p38 MAPK signalings activation is a critical process in enhancing PCV2-induced IL-10 production in porcine alveolar macrophages. PMID:26883107

GABRG1 and GABRA2 as Independent Predictors for Alcoholism in Two Populations

PubMed Central

Enoch, Mary-Anne; Hodgkinson, Colin A.; Yuan, Qiaoping; Albaugh, Bernard; Virkkunen, Matti; Goldman, David

2008-01-01

The chromosome 4 cluster of GABAA receptor genes is predominantly expressed in the brain reward circuitry and this chromosomal region has been implicated in linkage scans for alcoholism. Variation in one chromosome 4 gene, GABRA2, has been robustly associated with alcohol use disorders (AUD) although no functional locus has been identified. Since HapMap data reveals moderate long-distance linkage disequilibrium across GABRA2 and the adjacent gene, GABRG1, it is possible that the functional locus is in GABRG1. We genotyped 24 SNPs across GABRG1 and GABRA2 in two population isolates: 547 Finnish Caucasian men (266 alcoholics) and 311 community-derived Plains Indian men and women (181 alcoholics). In both the Plains Indians and the Caucasians: (a) the GABRG1 haplotype block(s) did not extend to GABRA2; (b) GABRG1 haplotypes and SNPs were significantly associated with AUD; (c) there was no association between GABRA2 haplotypes and AUD; (d) there were several common (≥ 0.05) haplotypes that spanned GABRG1 and GABRA2 (341 kb), three of which were present in both populations: one of these ancestral haplotypes was associated with AUD, the other two were more common in non-alcoholics; this association was determined by GABRG1; (e) in the Finns, three less common (< 0.05) extended haplotypes showed an association with AUD that was determined by GABRA2. Our results suggest that there are likely to be independent, complex contributions from both GABRG1 and GABRA2 to alcoholism vulnerability. PMID:18818659

POLLUTION PREVENTION CASE STUDIES: LOW-VOC/HAP WOOD FURNITURE COATINGS

EPA Science Inventory

This article provides a brief profile of the wood furniture industry, discusses pollution prevention activities typically implemented, describes the four low-VOC/HAP coating technologies studied. and summarizes one case study for each of the low-VOC/HAP coating yechnologies inves...

A biocompatible and novelly-defined Al-HAP adsorption membrane for highly effective removal of fluoride from drinking water.

PubMed

He, Junyong; Chen, Kai; Cai, Xingguo; Li, Yulian; Wang, Chengming; Zhang, Kaisheng; Jin, Zhen; Meng, Fanli; Wang, Xuguang; Kong, Lingtao; Liu, Jinhuai

2017-03-15

A biocompatible and novelly-defined adsorption membrane for rapid removal of fluoride was prepared. Both adsorption and membrane techniques were used in this research. Al(OH) 3 nanoparticles modified hydroxyapatite (Al-HAP) nanowires were developed and made into Al-HAP membrane. The adsorption data of Al-HAP adsorbent could be well described by Freundlich isotherm model while the adsorption kinetic followed pseudo-second-order model. The maximum of adsorption capacity was 93.84mg/g when the fluoride concentration was 200mg/L. The adsorption mechanism was anion exchanges and electrostatic interactions. The contribution rates of HAP nanowires and Al(OH) 3 nanoparticles in fluoride removal were 36.70% and 63.30%, respectively. The fixed-bed column test demonstrate that the Al-HAP was biocompatible and in a good stability during the process of water treatment. The fluoride removal abilities of Al-HAP membrane with 0.3mm thickness could reach 1568L/m 2 when fluoride concentrations were 5mg/L. This study indicated that the Al-HAP membrane could be developed into a very viable technology for highly effective removal of fluoride from drinking water. Copyright © 2016 Elsevier Inc. All rights reserved.

Reliable Genetic Labeling of Adult-Born Dentate Granule Cells Using Ascl1 CreERT2 and Glast CreERT2 Murine Lines.

PubMed

Yang, Sung M; Alvarez, Diego D; Schinder, Alejandro F

2015-11-18

Newly generated dentate granule cells (GCs) are relevant for input discrimination in the adult hippocampus. Yet, their precise contribution to information processing remains unclear. To address this question, it is essential to develop approaches to precisely label entire cohorts of adult-born GCs. In this work, we used genetically modified mice to allow conditional expression of tdTomato (Tom) in adult-born GCs and characterized their development and functional integration. Ascl1(CreERT2);CAG(floxStopTom) and Glast(CreERT2);CAG(floxStopTom) mice resulted in indelible expression of Tom in adult neural stem cells and their lineage upon tamoxifen induction. Whole-cell recordings were performed to measure intrinsic excitability, firing behavior, and afferent excitatory connectivity. Developing GCs were also staged by the expression of early and late neuronal markers. The slow development of adult-born GCs characterized here is consistent with previous reports using retroviral approaches that have revealed that a mature phenotype is typically achieved after 6-8 weeks. Our findings demonstrate that Ascl1(CreERT2) and Glast(CreERT2) mouse lines enable simple and reliable labeling of adult-born GC lineages within restricted time windows. Therefore, these mice greatly facilitate tagging new neurons and manipulating their activity, required for understanding adult neurogenesis in the context of network remodeling, learning, and behavior. Our study shows that Ascl1(CreERT2) and Glast(CreERT2) mice lines can be used to label large cohorts of adult-born dentate granule cells with excellent time resolution. Neurons labeled in this manner display developmental and functional profiles that are in full agreement with previous findings using thymidine analogs and retroviral labeling, thus providing an alternative approach to tackle fundamental questions on circuit remodeling. Because of the massive neuronal targeting and the simplicity of this method, genetic labeling will

HBV core promoter mutations promote cellular proliferation through E2F1-mediated upregulation of S-phase kinase-associated protein 2 transcription.

PubMed

Huang, Yuehua; Tai, Andrew W; Tong, Shuping; Lok, Anna S F

2013-06-01

Hepatitis B virus (HBV) core promoter (CP) mutations have been associated with an increased risk of hepatocellular carcinoma (HCC) in clinical studies. We previously reported that a combination of CP mutations seen in HCC patients, expressed in HBx gene, increased SKP2 (S-phase kinase-associated protein 2) expression, thereby promoting cellular proliferation. Here, we investigate the possible mechanisms by which CP mutations upregulate SKP2. We used immunoblotting and ATPlite assay to validate the effect of CP mutations in full-length HBV genome on cell cycle regulator levels and cell proliferation. Activation of SKP2 mRNA was assessed by quantitative real-time PCR in primary human hepatocytes (PHH) and HCC cell lines. Effect of CP mutations on SKP2 promoter activity was determined by luciferase assay. Target regulation of E2F1 on SKP2 was analyzed by siRNAs. CP mutations in full-length HBV genome upregulated SKP2 expression, thereby downregulating cell cycle inhibitors and accelerating cellular proliferation. CP mutations enhanced SKP2 promoter activity but had no effect on SKP2 protein stability. Mapping of the SKP2 promoter identified a region necessary for activation by CP mutations that contains an E2F1 response element. Knocking down E2F1 reduced the effects of CP mutations on SKP2 and cellular proliferation. The effect of CP mutations on E2F1 might be mediated through hyperphosphorylation of RB. HBV CP mutations enhance SKP2 transcription by activating the E2F1 transcription factor and in turn downregulate cell cycle inhibitors, thus providing a potential mechanism for an association between CP mutations and HCC. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The catecholestrogen, 2-hydroxyestradiol-17beta, acts as a G protein-coupled estrogen receptor 1 (GPER/GPR30) antagonist to promote the resumption of meiosis in zebrafish oocytes.

PubMed

Chourasia, Tapan K; Pang, Yefei; Thomas, Peter

2015-03-01

Estradiol-17beta (E2) maintains high cAMP levels and meiotic arrest in zebrafish oocytes through activation of G protein-coupled estrogen receptor (GPER). The catecholestrogen 2-hydroxyestradiol-17beta (2-OHE2) has an opposite effect to that of E2 on oocyte maturation (OM) and cAMP levels in Indian catfish oocytes. We tested the hypothesis that 2-OHE2 is produced in zebrafish ovaries and promotes the resumption of oocyte meiosis through its action as a GPER antagonist. Ovarian 2-OHE2 production by estrogen-2-hydroxylase (EH) was up-regulated by gonadotropin treatment at the onset of OM, consistent with a physiological role for 2-OHE2 in regulating OM. The increases in EH activity and OM were blocked by treatment with CYP1A1 and CYP1B1 inhibitors. Expression of cyp1a, cyp1b1, and cyp1c mRNAs was increased by gonadotropin treatment, further implicating these Cyp1s in 2-OHE2 synthesis prior to OM. Conversely, aromatase activity and cyp19a1 mRNA expression declined during gonadotropin induction of OM. 2-OHE2 treatment significantly increased spontaneous OM in defolliculated zebrafish oocytes and reversed the inhibition of OM by E2 and the GPER agonist G-1. 2-OHE2 was an effective competitor of [(3)H]-E2 binding to recombinant zebrafish GPER expressed in HEK-293 cells. 2-OHE2 also antagonized estrogen actions through GPER on cAMP production in zebrafish oocytes, resulting in a reduction in cAMP levels. Stimulation of OM by 2-OHE2 was blocked by pretreatment of defolliculated oocytes with the GPER antibody. Collectively, the results suggest that 2-OHE2 functions as a GPER antagonist and promotes OM in zebrafish through blocking GPER-dependent E2 inhibition of the resumption of OM. © 2015 by the Society for the Study of Reproduction, Inc.

Development of bioactive porous α-TCP/HAp beads for bone tissue engineering.

PubMed

Asaoka, Teruo; Ohtake, Shoji; Furukawa, Katsuko S; Tamura, Akito; Ushida, Takashi

2013-11-01

Porous beads of bioactive ceramics such as hydroxyapatite (HAp) and tribasic calcium phosphate (TCP) are considered a promising scaffold for cultivating bone cells. To realize this, α-TCP/HAp functionally graded porous beads are fabricated with two main purposes: to maintain the function of the scaffold with sufficient strength up to the growth of new bone, and is absorbed completely after the growth. HAp is a bioactive material that has both high strength and strong tissue-adhesive properties, but is not readily absorbed by the human body. On the contrary, α-TCP is highly bioabsorbable, resulting in a scaffold that is absorbed before it is completely replaced by bone. In this study, we produced porous, bead-shaped carriers as scaffolds for osteoblast culture. To control the solubility in vivo, the fabricated beads contained α-TCP at the center and HAp at the surface. Cell adaptability of these beads for bone tissue engineering was confirmed in vitro. It was found that α-TCP/HAp bead carriers exhibit low toxicity in the initial stages of cell seeding and cell adhesion. The presence of HAp in the composite bead form effectively increased ALP activity. In conclusion, it is suggested that these newly developed α-TCP/HAp beads are a promising tool for bone tissue engineering. Copyright © 2013 Wiley Periodicals, Inc.

A randomized comparison of ropivacaine 0.1% and 0.2% for continuous interscalene block after shoulder surgery.

PubMed

Yang, Chun Woo; Jung, Sung Mee; Kang, Po Soon; Kwon, Hee Uk; Cho, Choon Kyu; Lee, Younsuk; Kim, Chul Woung; Kim, Su Young

2013-03-01

The optimal concentration of ropivacaine for continuous interscalene block after shoulder surgery is currently unknown. Fifty-six patients received a perineural infusion of either ropivacaine 0.1% or 0.2% for 48 hours after shoulder surgery. We assessed pain scores as primary end points and supplemental analgesia, ropivacaine consumption, motor block, side effects, and patient satisfaction as secondary end points. Pain scores were not statistically different during the infusion periods; however, supplemental analgesia consumption was higher in the group receiving ropivacaine 0.1% during the first 24 hours (64% vs 28%, P = 0.022). Other secondary end points were statistically inconclusive. These results suggest that ropivacaine 0.2% provides more effective analgesia than ropivacaine 0.1% during the first 24 hours for continuous interscalene block after shoulder surgery.

40 CFR 63.1297 - Standards for slabstock flexible polyurethane foam production-HAP ABA emissions from the...

Code of Federal Regulations, 2012 CFR

2012-07-01

... polyurethane foam production-HAP ABA emissions from the production line. 63.1297 Section 63.1297 Protection of... Pollutants for Flexible Polyurethane Foam Production § 63.1297 Standards for slabstock flexible polyurethane... § 63.1293(a)(1) shall control HAP ABA emissions from the slabstock polyurethane foam production line in...

40 CFR 63.1297 - Standards for slabstock flexible polyurethane foam production-HAP ABA emissions from the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... polyurethane foam production-HAP ABA emissions from the production line. 63.1297 Section 63.1297 Protection of... Pollutants for Flexible Polyurethane Foam Production § 63.1297 Standards for slabstock flexible polyurethane... § 63.1293(a)(1) shall control HAP ABA emissions from the slabstock polyurethane foam production line in...

40 CFR 63.1297 - Standards for slabstock flexible polyurethane foam production-HAP ABA emissions from the...

Code of Federal Regulations, 2011 CFR

2011-07-01

... polyurethane foam production-HAP ABA emissions from the production line. 63.1297 Section 63.1297 Protection of... Pollutants for Flexible Polyurethane Foam Production § 63.1297 Standards for slabstock flexible polyurethane... § 63.1293(a)(1) shall control HAP ABA emissions from the slabstock polyurethane foam production line in...

Unexpected Relationships and Inbreeding in HapMap Phase III Populations

PubMed Central

Stevens, Eric L.; Baugher, Joseph D.; Shirley, Matthew D.; Frelin, Laurence P.; Pevsner, Jonathan

2012-01-01

Correct annotation of the genetic relationships between samples is essential for population genomic studies, which could be biased by errors or omissions. To this end, we used identity-by-state (IBS) and identity-by-descent (IBD) methods to assess genetic relatedness of individuals within HapMap phase III data. We analyzed data from 1,397 individuals across 11 ethnic populations. Our results support previous studies (Pemberton et al., 2010; Kyriazopoulou-Panagiotopoulou et al., 2011) assessing unknown relatedness present within this population. Additionally, we present evidence for 1,657 novel pairwise relationships across 9 populations. Surprisingly, significant Cotterman's coefficients of relatedness K1 (IBD1) values were detected between pairs of known parents. Furthermore, significant K2 (IBD2) values were detected in 32 previously annotated parent-child relationships. Consistent with a hypothesis of inbreeding, regions of homozygosity (ROH) were identified in the offspring of related parents, of which a subset overlapped those reported in previous studies (Gibson et al. 2010; Johnson et al. 2011). In total, we inferred 28 inbred individuals with ROH that overlapped areas of relatedness between the parents and/or IBD2 sharing at a different genomic locus between a child and a parent. Finally, 8 previously annotated parent-child relationships had unexpected K0 (IBD0) values (resulting from a chromosomal abnormality or genotype error), and 10 previously annotated second-degree relationships along with 38 other novel pairwise relationships had unexpected IBD2 (indicating two separate paths of recent ancestry). These newly described types of relatedness may impact the outcome of previous studies and should inform the design of future studies relying on the HapMap Phase III resource. PMID:23185369

Arsenic induced progesterone production in a caspase-3-dependent manner and changed redox status in preovulatory granulosa cells.

PubMed

Yuan, Xiao-Hua; Lu, Cai-Ling; Yao, Nan; An, Li-Sha; Yang, Bai-Qing; Zhang, Chuan-Ling; Ma, Xu

2012-01-01

Arsenic contamination is a principal environmental health threat throughout the world. However, little is known about the effect of arsenic on steroidogenesis in granulosa cells (GCs). We found that the treatment of preovulatory GCs with arsenite stimulated progesterone production. A significant increase in serum level of progesterone was observed in female Sprague-Dawley rats following arsenite treatment at a dose of 10 mg/L/rat/day for 7 days. Further experiments demonstrated that arsenite treatment did not change the level of intracellular cyclic AMP (cAMP) or phosphorylated ERK1/2 in preovulatory GCs; however, progesterone production was significantly decreased when cAMP-dependent protein kinase (PKA) or ERK1/2 pathway was inhibited. This implied that the effect of arsenite on progesterone production may require cAMP/PKA and ERK1/2 signaling but not depend on them. Furthermore, we found that arsenite decreased intracellular reactive oxygen species (ROS) but increased the antioxidant glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm) in parallel to the changes in progesterone production. Progesterone antagonist blocked the arsenic-stimulated increase of GSH levels. Arsenite treatment induced caspase-3 activation, although no apoptosis was observed. Inhibition of caspase-3 activity significantly decreased progesterone production stimulated by arsenite or follicle-stimulating hormone (FSH). GSH depletion with buthionine sulfoximine led to cell apoptosis in response to arsenite treatment. Collectively, this study demonstrated for the first time that arsenite stimulates progesterone production through cleaved/active caspase-3-dependent pathway, and the increase of GSH level promoted by progesterone production may protect GCs against apoptosis and maintain the steroidogenesis of GCs in response to arsenite treatment. Copyright © 2011 Wiley Periodicals, Inc.

Use of a crossed high alcohol preferring (cHAP) mouse model with the NIAAA-model of chronic-binge ethanol intake to study liver injury.

PubMed

Thompson, Kyle J; Nazari, Shayan S; Jacobs, W Carl; Grahame, Nicholas J; McKillop, Iain H

2017-11-01

This study sought to compare mice bred to preferentially consume high amounts of alcohol (crossed-high alcohol preferring, cHAP) to c57BL/6 (C57) mice using a chronic-binge ethanol ingestion model to induce alcoholic liver disease (ALD). Male C57 and cHAP mice were randomized to a Lieber-DeCarli control (LDC) diet, Lieber-DeCarli 5% (v/v) ethanol (LDE) diet or free-choice between 10% (v/v) ethanol in drinking water (EtOH-DW) and DW. After 4 weeks mice were gavaged with either 9 g/kg maltose-dextrin (LDC+MD) or 5 g/kg EtOH (LDE+Binge, EtOH-DW+Binge). Nine hours later tissue and serum were collected and analyzed. cHAP mice on EtOH-DW consumed significantly more ethanol than cHAP or C57 mice maintained on LDE. However, cHAP and C57 mice on the LDE+Binge regiment had greater hepatosteatosis and overall degree of liver injury compared to EtOH-DW+Binge. Changes in pro-inflammatory gene expression was more pronounced in cHAP mice than C57 mice. Analysis of liver enzymes revealed a robust induction of CYP2E1 in C57 and cHAP mice maintained on EtOH-DW+Binge or LDE+Binge. However, while C57 mice exhibited higher basal hepatic glutathione than cHAP mice, these mice appeared more susceptible to oxidative stress following LDE+Binge than cHAP counterparts. Despite cHAP mice consuming more total ethanol prior to gavage when maintained on EtOH-DW, LDE followed by gavage created a more severe model of ALD in both C57 and cHAP mice. These data suggest factors other than total amount of alcohol consumed affect degree of ALD development in the chronic-binge model in cHAP mice. cHAP mice voluntarily consume high amounts of ethanol and exhibited hepatic injury when subject to chronic-binge ethanol feeding with the Lieber-DeCarli diet. However, hepatic injury was reduced in cHAP mice in a chronic-binge model following voluntary high ethanol consumption in drinking water. © The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Cell type-specific regulatory effects of glucocorticoids on cutaneous TLR2 expression and signalling.

PubMed

Su, Qi; Pfalzgraff, Anja; Weindl, Günther

2017-07-01

Glucocorticoids (GCs) induce Toll-like receptor (TLR) 2 expression and synergistically upregulate TLR2 with pro-inflammatory cytokines or bacteria. These paradoxical effects have drawn attention to the inflammatory initiating or promoting effects of GCs, as GC treatment can provoke inflammatory skin diseases. Here, we aimed to investigate the regulatory effects of GCs in human skin cells of different epidermal and dermal layers. We found that Dex induced TLR2 expression mainly in undifferentiated and less in calcium-induced differentiated keratinocytes but not in HaCaT cells or fibroblasts, however, Dex reduced TLR1/6 expression. Stimulation with Dex under inflammatory conditions further increased TLR2 but not TLR1 or TLR6 levels in keratinocytes. Increased ligand-induced interaction of TLR2 with MyD88 and expression of the adaptor protein TRAF6 indicated enhanced TLR2 signalling, whereas TLR2/1 or TLR2/6 signalling was not increased in Dex-pretreated keratinocytes. GC-increased TLR2 expression was negatively regulated by JNK MAPK signalling when stimulated with Propionibacterium acnes. Our results provide novel insights into the molecular mechanisms of glucocorticoid-mediated expression and function of TLR2 in human skin cells and the understanding of the mechanisms of corticosteroid side effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

24 CFR 983.206 - HAP contract amendments (to add or substitute contract units).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false HAP contract amendments (to add or... Contract § 983.206 HAP contract amendments (to add or substitute contract units). (a) Amendment to substitute contract units. At the discretion of the PHA and subject to all PBV requirements, the HAP contract...

Deletion of HAPS_2096 Increases Sensitivity to Cecropin B in Haemophilus parasuis.

PubMed

Chen, Fanjie; Hu, Han; Li, Zhonghua; Huang, Jiacheng; Cai, Xuwang; Wang, Chunmei; He, Qigai; Cao, Jiyue

2015-01-01

Cecropin B (CB) is a very effective natural antimicrobial peptide that has shown great potential for future antimicrobial drug development. HAPS_2096 is a Haemophilus parasuis gene that encodes the periplasmic substrate-binding protein of an ATP-binding cassette-type amino acid transporter. In this research, we constructed and verified an HAPS_2096 deletion mutant and a complementary HAPS_2096 mutant of H. parasuis JS0135. A bactericidal assay revealed that the HAPS_2096 deletion mutant was significantly more sensitive than the wild-type strain to 0.25-0.5 µg/ml CB. However, the gene complementation alleviated the CB sensitivity of the mutant. Immunoelectron microscopy observation following a 30-min treatment with a sublethal concentration of CB (0.25 μg/ml) revealed more extensive morphological damage in the mutant strain than in the wild-type strain. Hence, our results suggest that the HAPS_2096 gene contributes to H. parasuis resistance to CB. © 2015 S. Karger AG, Basel.

Population differences in the rate of proliferation of international HapMap cell lines.

PubMed

Stark, Amy L; Zhang, Wei; Zhou, Tong; O'Donnell, Peter H; Beiswanger, Christine M; Huang, R Stephanie; Cox, Nancy J; Dolan, M Eileen

2010-12-10

The International HapMap Project is a resource for researchers containing genotype, sequencing, and expression information for EBV-transformed lymphoblastoid cell lines derived from populations across the world. The expansion of the HapMap beyond the four initial populations of Phase 2, referred to as Phase 3, has increased the sample number and ethnic diversity available for investigation. However, differences in the rate of cellular proliferation between the populations can serve as confounders in phenotype-genotype studies using these cell lines. Within the Phase 2 populations, the JPT and CHB cell lines grow faster (p < 0.0001) than the CEU or YRI cell lines. Phase 3 YRI cell lines grow significantly slower than Phase 2 YRI lines (p < 0.0001), with no widespread genetic differences based on common SNPs. In addition, we found significant growth differences between the cell lines in the Phase 2 ASN populations and the Han Chinese from the Denver metropolitan area panel in Phase 3 (p < 0.0001). Therefore, studies that separate HapMap panels into discovery and replication sets must take this into consideration. Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

A Malaria Vaccine Based on the Polymorphic Block 2 Region of MSP-1 that Elicits a Broad Serotype-Spanning Immune Response

PubMed Central

Cowan, Graeme J. M.; Creasey, Alison M.; Dhanasarnsombut, Kelwalin; Thomas, Alan W.; Remarque, Edmond J.; Cavanagh, David R.

2011-01-01

Polymorphic parasite antigens are known targets of protective immunity to malaria, but this antigenic variation poses challenges to vaccine development. A synthetic MSP-1 Block 2 construct, based on all polymorphic variants found in natural Plasmodium falciparum isolates has been designed, combined with the relatively conserved Block 1 sequence of MSP-1 and expressed in E.coli. The MSP-1 Hybrid antigen has been produced with high yield by fed-batch fermentation and purified without the aid of affinity tags resulting in a pure and extremely thermostable antigen preparation. MSP-1 hybrid is immunogenic in experimental animals using adjuvants suitable for human use, eliciting antibodies against epitopes from all three Block 2 serotypes. Human serum antibodies from Africans naturally exposed to malaria reacted to the MSP-1 hybrid as strongly as, or better than the same serum reactivities to individual MSP-1 Block 2 antigens, and these antibody responses showed clear associations with reduced incidence of malaria episodes. The MSP-1 hybrid is designed to induce a protective antibody response to the highly polymorphic Block 2 region of MSP-1, enhancing the repertoire of MSP-1 Block 2 antibody responses found among immune and semi-immune individuals in malaria endemic areas. The target population for such a vaccine is young children and vulnerable adults, to accelerate the acquisition of a full range of malaria protective antibodies against this polymorphic parasite antigen. PMID:22073118

Navigation and Positioning System Using High Altitude Platforms Systems (HAPS)

NASA Astrophysics Data System (ADS)

Tsujii, Toshiaki; Harigae, Masatoshi; Harada, Masashi

Recently, some countries have begun conducting feasibility studies and R&D projects on High Altitude Platform Systems (HAPS). Japan has been investigating the use of an airship system that will function as a stratospheric platform for applications such as environmental monitoring, communications and broadcasting. If pseudolites were mounted on the airships, their GPS-like signals would be stable augmentations that would improve the accuracy, availability, and integrity of GPS-based positioning systems. Also, the sufficient number of HAPS can function as a positioning system independent of GPS. In this paper, a system design of the HAPS-based positioning system and its positioning error analyses are described.

40 CFR 63.5796 - What are the organic HAP emissions factor equations in Table 1 to this subpart, and how are they...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Emissions Factors for Open Molding and Centrifugal Casting § 63.5796 What are the organic HAP emissions... factors. Equations are available for each open molding operation and centrifugal casting operation and... incorporated in the facility's air emissions permit and are based on actual facility HAP emissions test data...

40 CFR 63.5796 - What are the organic HAP emissions factor equations in Table 1 to this subpart, and how are they...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Emissions Factors for Open Molding and Centrifugal Casting § 63.5796 What are the organic HAP emissions... factors. Equations are available for each open molding operation and centrifugal casting operation and... incorporated in the facility's air emissions permit and are based on actual facility HAP emissions test data...

Cells Recognize and Prefer Bone-like Hydroxyapatite: Biochemical Understanding of Ultrathin Mineral Platelets in Bone.

PubMed

Liu, Cuilian; Zhai, Halei; Zhang, Zhisen; Li, Yaling; Xu, Xurong; Tang, Ruikang

2016-11-09

Hydroxyapatite (HAP) nanocrystallites in all types of bones are distinguished by their ultrathin characteristics, which are uniaxially oriented with fibrillar collagen to uniquely expose the (100) faces. We speculate that living organisms prefer the specific crystal morphology and orientation of HAP because of the interactions between cells and crystals at the mineral-cell interface. Here, bone-like platy HAP (p-HAP) and two different rod-like HAPs were synthesized to investigate the ultrathin mineral modulating effect on cell bioactivity and bone generation. Cell viability and osteogenic differentiation of mesenchymal stem cells (MSCs) were significantly promoted by the platy HAP with (100) faces compared to rod-like HAPs with (001) faces as the dominant crystal orientation, which indicated that MSCs can recognize the crystal face and prefer the (100) HAP faces. This face-specific preference is dependent on the selective adsorption of fibronectin (FN), a plasma protein that plays a central role in cell adhesion, on the HAP surface. This selective adsorption is further confirmed by molecule dynamics (MD) simulation. Our results demonstrate that it is an intelligent choice for cells to use ultrathin HAP with a large (100) face as a basic building block in the hierarchical structure of bone, which is crucial to the promotion of MSCs osteoinductions during bone formation.

Effects of tianeptine on onset time of pentylenetetrazole-induced seizures in mice: possible role of adenosine A1 receptors.

PubMed

Uzbay, Tayfun I; Kayir, Hakan; Ceyhan, Mert

2007-02-01

Depression is a common psychiatric problem in epileptic patients. Thus, it is important that an antidepressant agent has anticonvulsant activity. This study was organized to investigate the effects of tianeptine, an atypical antidepressant, on pentylenetetrazole (PTZ)-induced seizure in mice. A possible contribution of adenosine receptors was also evaluated. Adult male Swiss-Webster mice (25-35 g) were subjects. PTZ (80 mg/kg, i.p.) was injected to mice 30 min after tianeptine (2.5-80 mg/kg, i.p.) or saline administration. The onset times of 'first myoclonic jerk' (FMJ) and 'generalized clonic seizures' (GCS) were recorded. Duration of 600 s was taken as a cutoff time in calculation of the onset time of the seizures. To evaluate the contribution of adenosine receptors in the effect of tianeptine, a nonspecific adenosine receptor antagonist caffeine, a specific A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a specific A2A receptor antagonist 8-(3-chlorostyryl) caffeine (CSC) or their vehicles were administered to the mice 15 min before tianeptine (80 mg/kg) or saline treatments. Tianeptine (40 and 80 mg/kg) pretreatment significantly delayed the onset time of FMJ and GCS. Caffeine (10-60 mg/kg, i.p.) dose-dependently blocked the retarding effect of tianeptine (80 mg/kg) on the onset times of FMJ and GCS. DPCPX (20 mg/kg) but not CSC (1-8 mg/kg) blocked the effect of tianeptine (80 mg/kg) on FMJ. Our results suggest that tianeptine delayed the onset time of PTZ-induced seizures via adenosine A1 receptors in mice. Thus, this drug may be a useful choice for epileptic patients with depression.

26 CFR 1.1248-2 - Earnings and profits attributable to a block of stock in simple cases.

Code of Federal Regulations, 2011 CFR

2011-04-01

... earnings and profits of the corporation accumulated for the taxable year (computed without any reduction... 26 Internal Revenue 11 2011-04-01 2011-04-01 false Earnings and profits attributable to a block of... Determining Capital Gains and Losses § 1.1248-2 Earnings and profits attributable to a block of stock in...

Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study.

PubMed

de Vries, Paul S; Sabater-Lleal, Maria; Chasman, Daniel I; Trompet, Stella; Ahluwalia, Tarunveer S; Teumer, Alexander; Kleber, Marcus E; Chen, Ming-Huei; Wang, Jie Jin; Attia, John R; Marioni, Riccardo E; Steri, Maristella; Weng, Lu-Chen; Pool, Rene; Grossmann, Vera; Brody, Jennifer A; Venturini, Cristina; Tanaka, Toshiko; Rose, Lynda M; Oldmeadow, Christopher; Mazur, Johanna; Basu, Saonli; Frånberg, Mattias; Yang, Qiong; Ligthart, Symen; Hottenga, Jouke J; Rumley, Ann; Mulas, Antonella; de Craen, Anton J M; Grotevendt, Anne; Taylor, Kent D; Delgado, Graciela E; Kifley, Annette; Lopez, Lorna M; Berentzen, Tina L; Mangino, Massimo; Bandinelli, Stefania; Morrison, Alanna C; Hamsten, Anders; Tofler, Geoffrey; de Maat, Moniek P M; Draisma, Harmen H M; Lowe, Gordon D; Zoledziewska, Magdalena; Sattar, Naveed; Lackner, Karl J; Völker, Uwe; McKnight, Barbara; Huang, Jie; Holliday, Elizabeth G; McEvoy, Mark A; Starr, John M; Hysi, Pirro G; Hernandez, Dena G; Guan, Weihua; Rivadeneira, Fernando; McArdle, Wendy L; Slagboom, P Eline; Zeller, Tanja; Psaty, Bruce M; Uitterlinden, André G; de Geus, Eco J C; Stott, David J; Binder, Harald; Hofman, Albert; Franco, Oscar H; Rotter, Jerome I; Ferrucci, Luigi; Spector, Tim D; Deary, Ian J; März, Winfried; Greinacher, Andreas; Wild, Philipp S; Cucca, Francesco; Boomsma, Dorret I; Watkins, Hugh; Tang, Weihong; Ridker, Paul M; Jukema, Jan W; Scott, Rodney J; Mitchell, Paul; Hansen, Torben; O'Donnell, Christopher J; Smith, Nicholas L; Strachan, David P; Dehghan, Abbas

2017-01-01

An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5×10-8 is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5×10-8), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development.

Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study

PubMed Central

de Vries, Paul S.; Sabater-Lleal, Maria; Chasman, Daniel I.; Trompet, Stella; Kleber, Marcus E.; Chen, Ming-Huei; Wang, Jie Jin; Attia, John R.; Marioni, Riccardo E.; Weng, Lu-Chen; Grossmann, Vera; Brody, Jennifer A.; Venturini, Cristina; Tanaka, Toshiko; Rose, Lynda M.; Oldmeadow, Christopher; Mazur, Johanna; Basu, Saonli; Yang, Qiong; Ligthart, Symen; Hottenga, Jouke J.; Rumley, Ann; Mulas, Antonella; de Craen, Anton J. M.; Grotevendt, Anne; Taylor, Kent D.; Delgado, Graciela E.; Kifley, Annette; Lopez, Lorna M.; Berentzen, Tina L.; Mangino, Massimo; Bandinelli, Stefania; Morrison, Alanna C.; Hamsten, Anders; Tofler, Geoffrey; de Maat, Moniek P. M.; Draisma, Harmen H. M.; Lowe, Gordon D.; Zoledziewska, Magdalena; Sattar, Naveed; Lackner, Karl J.; Völker, Uwe; McKnight, Barbara; Huang, Jie; Holliday, Elizabeth G.; McEvoy, Mark A.; Starr, John M.; Hysi, Pirro G.; Hernandez, Dena G.; Guan, Weihua; Rivadeneira, Fernando; McArdle, Wendy L.; Slagboom, P. Eline; Zeller, Tanja; Psaty, Bruce M.; Uitterlinden, André G.; de Geus, Eco J. C.; Stott, David J.; Binder, Harald; Hofman, Albert; Franco, Oscar H.; Rotter, Jerome I.; Ferrucci, Luigi; Spector, Tim D.; Deary, Ian J.; März, Winfried; Greinacher, Andreas; Wild, Philipp S.; Cucca, Francesco; Boomsma, Dorret I.; Watkins, Hugh; Tang, Weihong; Ridker, Paul M.; Jukema, Jan W.; Scott, Rodney J.; Mitchell, Paul; Hansen, Torben; O'Donnell, Christopher J.; Smith, Nicholas L.; Strachan, David P.

2017-01-01

An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5×10−8 is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5×10−8), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development. PMID:28107422

Activation of the ζ receptor 1 suppresses NMDA responses in rat retinal ganglion cells.

PubMed

Zhang, X-J; Liu, L-L; Jiang, S-X; Zhong, Y-M; Yang, X-L

2011-03-17

The sigma receptor 1 (σR1) has been shown to modulate the activity of several voltage- and ligand-gated channels. Using patch-clamp techniques in rat retinal slice preparations, we demonstrated that activation of σR1 by SKF10047 (SKF) or PRE-084 suppressed N-methyl-D-aspartate (NMDA) receptor-mediated current responses from both ON and OFF type ganglion cells (GCs), dose-dependently, and the effect could be blocked by the σR1 antagonist BD1047 or the σR antagonist haloperidol. The suppression by SKF of NMDA currents was abolished with pre-incubation of the G protein inhibitor GDP-β-S or the Gi/o activator mastoparan. We further explored the intracellular signaling pathway responsible for the SKF-induced suppression of NMDA responses. Application of either cAMP/the PKA inhibitor Rp-cAMP or cGMP/the PKG inhibitor KT5823 did not change the SKF-induced effect, suggesting the involvement of neither cAMP/PKA nor cGMP/PKG pathway. In contrast, suppression of NMDA responses by SKF was abolished by internal infusion of the phosphatidylinostiol-specific phospholipase C (PLC) inhibitor U73122, but not by the phosphatidylcholine-PLC inhibitor D609. SKF-induced suppression of NMDA responses was dependent on intracellular Ca2+ concentration ([Ca2+]i), as evidenced by the fact that the effect was abolished when [Ca2+]i was buffered with 10 mM BAPTA. The SKF effect was blocked by xestospongin-C/heparin, IP3 receptor antagonists, but unchanged by ryanodine/caffeine, ryanodine receptor modulators. Furthermore, application of protein kinase C inhibitors Bis IV and Gö6976 eliminated the SKF effect. These results suggest that the suppression of NMDA responses of rat retinal GCs caused by the activation of σR1 may be mediated by a distinct [Ca2+]i-dependent PLC-PKC pathway. This effect of SKF could help ameliorate malfunction of GCs caused by excessive stimulation of NMDA receptors under pathological conditions. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights

24 CFR 982.611 - Group home: Lease and HAP contract.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Group home: Lease and HAP contract. 982.611 Section 982.611 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN... Types Group Home § 982.611 Group home: Lease and HAP contract. For assistance in a group home, there is...

24 CFR 982.611 - Group home: Lease and HAP contract.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Group home: Lease and HAP contract. 982.611 Section 982.611 Housing and Urban Development Regulations Relating to Housing and Urban... Types Group Home § 982.611 Group home: Lease and HAP contract. For assistance in a group home, there is...

24 CFR 982.611 - Group home: Lease and HAP contract.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 4 2014-04-01 2014-04-01 false Group home: Lease and HAP contract. 982.611 Section 982.611 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN... Types Group Home § 982.611 Group home: Lease and HAP contract. For assistance in a group home, there is...

The Human Immunodeficiency Virus 1 ASP RNA promotes viral latency by recruiting the Polycomb Repressor Complex 2 and promoting nucleosome assembly

PubMed Central

Zapata, Juan C.; Campilongo, Federica; Barclay, Robert A.; DeMarino, Catherine; Iglesias-Ussel, Maria D.; Kashanchi, Fatah; Romerio, Fabio

2017-01-01

Various epigenetic marks at the HIV-1 5′LTR suppress proviral expression and promote latency. Cellular antisense transcripts known as long noncoding RNAs (lncRNAs) recruit the polycomb repressor complex 2 (PRC2) to gene promoters, which catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3), thus promoting nucleosome assembly and suppressing gene expression. We found that an HIV-1 antisense transcript expressed from the 3′LTR and encoding the antisense protein ASP promotes proviral latency. Expression of ASP RNA reduced HIV-1 replication in Jurkat cells. Moreover, ASP RNA expression promoted the establishment and maintenance of HIV-1 latency in Jurkat E4 cells. We show that this transcript interacts with and recruits PRC2 to the HIV-1 5′LTR, increasing accumulation of the suppressive epigenetic mark H3K27me3, while reducing RNA Polymerase II and thus proviral transcription. Altogether, our results suggest that the HIV-1 ASP transcript promotes epigenetic silencing of the HIV-1 5′LTR and proviral latency through the PRC2 pathway. PMID:28340355

BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression

PubMed Central

Xu, Peng; Raetz, Elizabeth A.; Kitagawa, Mayumi; Virshup, David M.; Lee, Sang Hyun

2013-01-01

Summary BUBR1 is a mitotic phosphoprotein essential for the maintenance of chromosome stability by promoting chromosome congression and proper kinetochore–microtubule (K-fiber) attachment, but the underlying mechanism(s) has remained elusive. Here we identify BUBR1 as a binding partner of the B56 family of Protein Phosphatase 2A regulatory subunits. The interaction between BUBR1 and the B56 family is required for chromosome congression, since point mutations in BUBR1 that block B56 binding abolish chromosome congression. The BUBR1:B56-PP2A complex opposes Aurora B kinase activity, since loss of the complex can be reverted by inhibiting Aurora B. Importantly, we show that the failure of BUBR1 to recruit B56-PP2A also contributes to the chromosome congression defects found in cells derived from patients with the Mosaic Variegated Aneuploidy (MVA) syndrome. Together, we propose that B56-PP2A is a key mediator of BUBR1's role in chromosome congression and functions by antagonizing Aurora B activity at the kinetochore for establishing stable kinetochore–microtubule attachment at the metaphase plate. PMID:23789096

Corticotropin-releasing hormone or dexamethasone regulates rat proopiomelanocortin transcription through Tpit/Pitx-responsive element in its promoter.

PubMed

Murakami, Itsuo; Takeuchi, Sakae; Kudo, Toshiyuki; Sutou, Shizuyo; Takahashi, Sumio

2007-05-01

Tpit/Pitx-responsive element (Tpit/PitxRE), which binds transcription factors Tpit and Pitx1, confers cell-type specific expression of proopiomelanocortin (POMC) gene in pituitary corticotrops where the gene expression is mainly regulated by corticotropin-releasing hormone (CRH) and glucocorticoids (Gcs). CRH stimulates POMC gene expression, which is mediated by the accumulation of intracellular cAMP and requires binding of Nur factors to Nur-responsive element (NurRE). Gcs antagonize NurRE-dependent POMC gene expression through direct interaction between glucocorticoid receptors and Nur factors. We examined whether Tpit/PitxRE and NurRE are involved in CRH/cAMP-induced activation and Gc-induced repression of POMC gene expression by reporter assay in AtT-20 corticotropic cells. Deletion and mutation of Tpit/PitxRE markedly reduced basal activity of the promoter, and those of NurRE decreased the levels of the CRH/cAMP-induced activation. Nifedipine, KN-62, and W-7, specific inhibitors of the L-type calcium channel, calmodulin-dependent protein kinase II, and calmodulin respectively, attenuated CRH/cAMP-induced activation of promoters with three copies of either Tpit/PitxRE or NurRE, indicating that both Tpit/PitxRE and NurRE mediate CRH-induced activation of POMC gene expression in a calcium-dependent manner. Deletion and mutation of Tpit/PitxRE abolished dexamethasone (DEX)-induced repression of POMC gene expression, while those of NurRE did not, indicating that Tpit/PitxRE predominantly mediates Gc-induced repression of POMC transcription. However, DEX treatment attenuated activities of promoters with three copies of either Tpit/PitxRE or NurRE, suggesting that Gcs act at NurRE as well as Tpit/PitxRE to repress POMC gene expression. We conclude that Tpit/PitxRE is an important element by which CRH and Gcs regulate the POMC gene expression.

Fisetin, a dietary flavonoid, induces apoptosis of cancer cells by inhibiting HSF1 activity through blocking its binding to the hsp70 promoter.

PubMed

Kim, Joo Ae; Lee, Somyoung; Kim, Da-Eun; Kim, Moonil; Kwon, Byoung-Mog; Han, Dong Cho

2015-06-01

Heat shock factor 1 (HSF1) is a transcription factor for heat shock proteins (HSPs) expression that enhances the survival of cancer cells exposed to various stresses. HSF1 knockout suppresses carcinogen-induced cancer induction in mice. Therefore, HSF1 is a promising therapeutic and chemopreventive target. We performed cell-based screening with a natural compound collection and identified fisetin, a dietary flavonoid, as a HSF1 inhibitor. Fisetin abolished heat shock-induced luciferase activity with an IC50 of 14 μM in HCT-116 cancer cells. The treatment of HCT-116 with fisetin inhibited proliferation with a GI50 of 23 μM. When the cells were exposed to heat shock in the presence of fisetin, the induction of HSF1 target proteins, such as HSP70, HSP27 and BAG3 (Bcl-2-associated athanogene domain 3), were inhibited. HSP70/BAG3 complexes protect cancer cells from apoptosis by stabilizing anti-apoptotic Bcl-2 family proteins. The downregulation of HSP70/BAG3 by fisetin significantly reduced the amounts of Bcl-2, Bcl-xL and Mcl-1 proteins, subsequently inducing apoptotic cell death. Chromatin immunoprecipitation assays showed that fisetin inhibited HSF1 activity by blocking the binding of HSF1 to the hsp70 promoter. Intraperitoneal treatment of nude mice with fisetin at 30mg/kg resulted in a 35.7% (P < 0.001) inhibition of tumor growth. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

40 CFR 63.5758 - How do I determine the organic HAP content of materials?

Code of Federal Regulations, 2011 CFR

2011-07-01

... Method 311 for determining the mass fraction of organic HAP. Use the procedures specified in paragraphs... in the organic HAP total. Express the mass fraction of each organic HAP you measure as a value...). You may use Method 24 to determine the mass fraction of non-aqueous volatile matter of aluminum...

The Human Immunodeficiency Virus 1 ASP RNA promotes viral latency by recruiting the Polycomb Repressor Complex 2 and promoting nucleosome assembly.

PubMed

Zapata, Juan C; Campilongo, Federica; Barclay, Robert A; DeMarino, Catherine; Iglesias-Ussel, Maria D; Kashanchi, Fatah; Romerio, Fabio

2017-06-01

Various epigenetic marks at the HIV-1 5'LTR suppress proviral expression and promote latency. Cellular antisense transcripts known as long noncoding RNAs (lncRNAs) recruit the polycomb repressor complex 2 (PRC2) to gene promoters, which catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3), thus promoting nucleosome assembly and suppressing gene expression. We found that an HIV-1 antisense transcript expressed from the 3'LTR and encoding the antisense protein ASP promotes proviral latency. Expression of ASP RNA reduced HIV-1 replication in Jurkat cells. Moreover, ASP RNA expression promoted the establishment and maintenance of HIV-1 latency in Jurkat E4 cells. We show that this transcript interacts with and recruits PRC2 to the HIV-1 5'LTR, increasing accumulation of the suppressive epigenetic mark H3K27me3, while reducing RNA Polymerase II and thus proviral transcription. Altogether, our results suggest that the HIV-1 ASP transcript promotes epigenetic silencing of the HIV-1 5'LTR and proviral latency through the PRC2 pathway. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Crystal Structures of the Histo-Aspartic Protease (HAP) from Plasmodium falciparum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhaumik, Prasenjit; Xiao, Huogen; Parr, Charity L.

The structures of recombinant histo-aspartic protease (HAP) from malaria-causing parasite Plasmodium falciparum as apoenzyme and in complex with two inhibitors, pepstatin A and KNI-10006, were solved at 2.5-, 3.3-, and 3.05-{angstrom} resolutions, respectively. In the apoenzyme crystals, HAP forms a tight dimer not seen previously in any aspartic protease. The interactions between the monomers affect the conformation of two flexible loops, the functionally important 'flap' (residues 70-83) and its structural equivalent in the C-terminal domain (residues 238-245), as well as the orientation of helix 225-235. The flap is found in an open conformation in the apoenzyme. Unexpectedly, the active sitemore » of the apoenzyme contains a zinc ion tightly bound to His32 and Asp215 from one monomer and to Glu278A from the other monomer, with the coordination of Zn resembling that seen in metalloproteases. The flap is closed in the structure of the pepstatin A complex, whereas it is open in the complex with KNI-10006. Although the binding mode of pepstatin A is significantly different from that in other pepsin-like aspartic proteases, its location in the active site makes unlikely the previously proposed hypothesis that HAP is a serine protease. The binding mode of KNI-10006 is unusual compared with the binding of other inhibitors from the KNI series to aspartic proteases. The novel features of the HAP active site could facilitate design of specific inhibitors used in the development of antimalarial drugs.« less

Pharmacological properties of pempidine (1:2:2:6:6-pentamethylpiperidine), a new ganglion-blocking compound

PubMed Central

Corne, S. J.; Edge, N. D.

1958-01-01

Pempidine (1:2:2:6:6-pentamethylpiperidine) is a long-acting ganglion-blocking compound which is effective by mouth. By intravenous injection it has a similar potency to hexamethonium on the preganglionically stimulated nictitating membrane of the cat. The compound blocks the effects of intravenous nicotine and of peripheral vagal stimulation on the blood pressure; it also causes dilatation of the pupil after removal of the sympathetic innervation. On the guinea-pig ileum, the predominant effect of the compound is to inhibit nicotine contractions. Pempidine is well absorbed from the gastro-intestinal tract as judged by (a) the low ratio (6.9) of oral to intravenous toxicities, (b) the rapid development of mydriasis in mice after oral administration of small doses, and (c) the rapid onset of hypotension when the compound is injected directly into the duodenum of anaesthetized cats. Other actions include neuromuscular paralysis of curare-like type when large doses of the compound are injected intravenously and central effects such as tremors which occur with near toxic doses. In cats with a low blood pressure, large intravenous doses have a slight pressor action. PMID:13584741

40 CFR 63.1426 - Process vent requirements for determining organic HAP concentration, control efficiency, and...

Code of Federal Regulations, 2010 CFR

2010-07-01

... percent reduction may be measured as total epoxide, total organic HAP, or as TOC minus methane and ethane... TOC (minus methane and ethane) concentrations in all process vent streams and primary and secondary... million by volume total epoxide or TOC limit in § 63.1425(b)(1)(ii) or (b)(2)(iii), the sampling site...

40 CFR 63.5758 - How do I determine the organic HAP content of materials?

Code of Federal Regulations, 2012 CFR

2012-07-01

... part 63). You may use Method 311 for determining the mass fraction of organic HAP. Use the procedures... include it in the organic HAP total. Express the mass fraction of each organic HAP you measure as a value...). You may use Method 24 to determine the mass fraction of non-aqueous volatile matter of aluminum...

40 CFR 63.5758 - How do I determine the organic HAP content of materials?

Code of Federal Regulations, 2014 CFR

2014-07-01

... part 63). You may use Method 311 for determining the mass fraction of organic HAP. Use the procedures... include it in the organic HAP total. Express the mass fraction of each organic HAP you measure as a value...). You may use Method 24 to determine the mass fraction of non-aqueous volatile matter of aluminum...

40 CFR 63.5758 - How do I determine the organic HAP content of materials?

Code of Federal Regulations, 2013 CFR

2013-07-01

... part 63). You may use Method 311 for determining the mass fraction of organic HAP. Use the procedures... include it in the organic HAP total. Express the mass fraction of each organic HAP you measure as a value...). You may use Method 24 to determine the mass fraction of non-aqueous volatile matter of aluminum...

Erratic blocks in NW Poland - geological heritage, conservation and geotourism promotion

NASA Astrophysics Data System (ADS)

Górska-Zabielska, Maria

2015-04-01

Big glacial erratic blocks, transported between 20 ka and 14 ka BP from Scandinavia are still present in the fields and forest of the north-western part of Poland. They present mainly magmatic and metamorphic petrographic types. Among them the most important are indicator erratics, which point to a distinct source region in Sweden, Finland or within the Baltic Sea. The largest boulders, sometimes shrouded in legend, have been protected for ages as natural monuments. Others still wait for such an attention. The largest erratic block in Poland ("Trigław") is located in a small town Tychowo (53°55'42″N 16°15'29″E) in the Middle Pomerania. It is a gneiss with no features pointing to a distinct Scandinavian provenance. Its measurements are: height 7,8 m (3,8 m above surface), length 13,7 m, width 9,3 m, volume around 520 m3, weight 1430 tons. The biggest sedimentary boulder, sandstone ("Mszczonowski Głaz"), is located in a Zawada village (51°54`51,1"N 20°27`16,5"E) in the centre of Poland (beyond the scope of the presentation). Its measurements are: height 3 m, length 12 m, width 3 m, volume around 57 m3, weight 160 tons. The presentation shows the biggest and most interesting Scandinavian boulders blocks from north-western part of Poland, their geological heritage and role, that they play in a local geotourism promotion. Apart from their location in situ, the boulders are also available ex situ, i.e. in erratic gardens. These collections of rocks accompany seats of local nature museums or national parks offices. Also other usage of erratics (stony buildings and road/pavements, fences), known for ages, will be presented. Erratic blocks are favorite destinations for tourists who follow geotouristic trails. The most valuable for a geotourism are these geosites, which are equipped in a board informing about the genesis and geologic value of an erratic. The simpler and more intelligible language, the bigger didactic and touristic value of a geosite.

Calcium carbonate hybrid coating promotes the formation of biomimetic hydroxyapatite on titanium surfaces

NASA Astrophysics Data System (ADS)

Cruz, Marcos Antônio E.; Ruiz, Gilia C. M.; Faria, Amanda N.; Zancanela, Daniela C.; Pereira, Lourivaldo S.; Ciancaglini, Pietro; Ramos, Ana P.

2016-05-01

CaCO3 particles dispersed in liquid media have proven to be good inductors of hydroxyapatite (HAp) growth. However, the use of CaCO3 deposited as thin films for this propose is unknown. Here, we report the growth of CaCO3 continuous films on Langmuir-Blodgett (LB) modified titanium surfaces and its use as HAp growth inductor. The Ti surfaces were modified with two, four, and six layers of dihexadecylphosphate (DHP)-LB films containing Ca2+, exposed to CO2 (g) for 12 h. The modified surfaces were immersed in simulated body fluid (SBF) at 37 °C for 36 h and submitted to bioactivity studies. This procedure originates bioactive coatings composed by non-stoichiometric HAp as evidenced by Fourier-Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), and X-ray Photoelectron Spectroscopy (XPS). The presence of the CaCO3 film as pre-coating diminished the time necessary to growth continuous and homogeneous HAp films using a biomimetic approach. The surface properties of the films regarding their roughness, composition, charge, wettability, and surface free energy (γs) were accessed. The presence of HAp increased the wettability and γs of the surfaces. The coatings are not toxic for osteoblasts as observed for cell viability assays obtained after 7 and 14 days of culture. Moreover, the CaCO3 thin films promote the recovery of the osteoblasts viability more than the Ti surfaces themselves.

Bonding techniques for hybrid active pixel sensors (HAPS)

NASA Astrophysics Data System (ADS)

Bigas, M.; Cabruja, E.; Lozano, M.

2007-05-01

A hybrid active pixel sensor (HAPS) consists of an array of sensing elements which is connected to an electronic read-out unit. The most used way to connect these two different devices is bump bonding. This interconnection technique is very suitable for these systems because it allows a very fine pitch and a high number of I/Os. However, there are other interconnection techniques available such as direct bonding. This paper, as a continuation of a review [M. Lozano, E. Cabruja, A. Collado, J. Santander, M. Ullan, Nucl. Instr. and Meth. A 473 (1-2) (2001) 95-101] published in 2001, presents an update of the different advanced bonding techniques available for manufacturing a hybrid active pixel detector.

In vitro and in vivo tests of PLA/d-HAp nanocomposite

NASA Astrophysics Data System (ADS)

Thom Nguyen, Thi; Hoang, Thai; Mao Can, Van; Son Ho, Anh; Hai Nguyen, Song; Thu Trang Nguyen, Thi; Pham, Thi Nam; Phuong Nguyen, Thu; Le Hien Nguyen, Thi; Thanh Dinh Thi, Mai

2017-12-01

The bioactivity of the PLA/d-HAp nanocomposite with 30 wt.% d-HAp was evaluated by in vitro tests and indicated that after 7 immersion days in SBF solution, PLA amorphous part was hydrolyzed and PLA crystal part was remained. The formation of apatite on the surface of the material was observed. The in vivo test results of PLA/d-HAp nanocomposite (70/30 wt/wt) on femur of dogs displayed that 3 months after grafting, the materials did not induce any osteitis, osteomyelitis or structural abnormalities. The histological and x-ray image demonstrated a growth of the bone into the material area, while osteitis and osteomyelitis were not observed.

Diversity Performance Analysis on Multiple HAP Networks.

PubMed

Dong, Feihong; Li, Min; Gong, Xiangwu; Li, Hongjun; Gao, Fengyue

2015-06-30

One of the main design challenges in wireless sensor networks (WSNs) is achieving a high-data-rate transmission for individual sensor devices. The high altitude platform (HAP) is an important communication relay platform for WSNs and next-generation wireless networks. Multiple-input multiple-output (MIMO) techniques provide the diversity and multiplexing gain, which can improve the network performance effectively. In this paper, a virtual MIMO (V-MIMO) model is proposed by networking multiple HAPs with the concept of multiple assets in view (MAV). In a shadowed Rician fading channel, the diversity performance is investigated. The probability density function (PDF) and cumulative distribution function (CDF) of the received signal-to-noise ratio (SNR) are derived. In addition, the average symbol error rate (ASER) with BPSK and QPSK is given for the V-MIMO model. The system capacity is studied for both perfect channel state information (CSI) and unknown CSI individually. The ergodic capacity with various SNR and Rician factors for different network configurations is also analyzed. The simulation results validate the effectiveness of the performance analysis. It is shown that the performance of the HAPs network in WSNs can be significantly improved by utilizing the MAV to achieve overlapping coverage, with the help of the V-MIMO techniques.

Diversity Performance Analysis on Multiple HAP Networks

PubMed Central

Dong, Feihong; Li, Min; Gong, Xiangwu; Li, Hongjun; Gao, Fengyue

2015-01-01

One of the main design challenges in wireless sensor networks (WSNs) is achieving a high-data-rate transmission for individual sensor devices. The high altitude platform (HAP) is an important communication relay platform for WSNs and next-generation wireless networks. Multiple-input multiple-output (MIMO) techniques provide the diversity and multiplexing gain, which can improve the network performance effectively. In this paper, a virtual MIMO (V-MIMO) model is proposed by networking multiple HAPs with the concept of multiple assets in view (MAV). In a shadowed Rician fading channel, the diversity performance is investigated. The probability density function (PDF) and cumulative distribution function (CDF) of the received signal-to-noise ratio (SNR) are derived. In addition, the average symbol error rate (ASER) with BPSK and QPSK is given for the V-MIMO model. The system capacity is studied for both perfect channel state information (CSI) and unknown CSI individually. The ergodic capacity with various SNR and Rician factors for different network configurations is also analyzed. The simulation results validate the effectiveness of the performance analysis. It is shown that the performance of the HAPs network in WSNs can be significantly improved by utilizing the MAV to achieve overlapping coverage, with the help of the V-MIMO techniques. PMID:26134102

A novel µ-conopeptide, CnIIIC, exerts potent and preferential inhibition of NaV1.2/1.4 channels and blocks neuronal nicotinic acetylcholine receptors

PubMed Central

Favreau, Philippe; Benoit, Evelyne; Hocking, Henry G; Carlier, Ludovic; D' hoedt, Dieter; Leipold, Enrico; Markgraf, René; Schlumberger, Sébastien; Córdova, Marco A; Gaertner, Hubert; Paolini-Bertrand, Marianne; Hartley, Oliver; Tytgat, Jan; Heinemann, Stefan H; Bertrand, Daniel; Boelens, Rolf; Stöcklin, Reto; Molgó, Jordi

2012-01-01

BACKGROUND AND PURPOSE The µ-conopeptide family is defined by its ability to block voltage-gated sodium channels (VGSCs), a property that can be used for the development of myorelaxants and analgesics. We characterized the pharmacology of a new µ-conopeptide (µ-CnIIIC) on a range of preparations and molecular targets to assess its potential as a myorelaxant. EXPERIMENTAL APPROACH µ-CnIIIC was sequenced, synthesized and characterized by its direct block of elicited twitch tension in mouse skeletal muscle and action potentials in mouse sciatic and pike olfactory nerves. µ-CnIIIC was also studied on HEK-293 cells expressing various rodent VGSCs and also on voltage-gated potassium channels and nicotinic acetylcholine receptors (nAChRs) to assess cross-interactions. Nuclear magnetic resonance (NMR) experiments were carried out for structural data. KEY RESULTS Synthetic µ-CnIIIC decreased twitch tension in mouse hemidiaphragms (IC50= 150 nM), and displayed a higher blocking effect in mouse extensor digitorum longus muscles (IC = 46 nM), compared with µ-SIIIA, µ-SmIIIA and µ-PIIIA. µ-CnIIIC blocked NaV1.4 (IC50= 1.3 nM) and NaV1.2 channels in a long-lasting manner. Cardiac NaV1.5 and DRG-specific NaV1.8 channels were not blocked at 1 µM. µ-CnIIIC also blocked the α3β2 nAChR subtype (IC50= 450 nM) and, to a lesser extent, on the α7 and α4β2 subtypes. Structure determination of µ-CnIIIC revealed some similarities to α-conotoxins acting on nAChRs. CONCLUSION AND IMPLICATIONS µ-CnIIIC potently blocked VGSCs in skeletal muscle and nerve, and hence is applicable to myorelaxation. Its atypical pharmacological profile suggests some common structural features between VGSCs and nAChR channels. PMID:22229737

Screening hydroxyapatite for cadmium and lead immobilization in aqueous solution and contaminated soil: The role of surface area.

PubMed

Li, Hongying; Guo, Xisheng; Ye, Xinxin

2017-02-01

Hydroxyapatite (HAP) has been widely used to immobilize many cationic metals in water and soils. The specific reason why an increase in the surface area of HAP enhances cadmium (Cd) uptake, but has no effect on lead (Pb) uptake, is not clear. The aim of this study was to determine the factors causing the differences in sorption behavior between Cd and Pb by evaluating HAPs with different surface areas. We synthesized HAPs with two different surface areas, which were characterized by X-ray diffraction, N 2 adsorption, and scanning electron microscopy, and then evaluated them as sorbents for Cd and Pb removal by testing in single and binary systems. The sorption capacity of large surface area HAP (1.85mmol/g) for Cd in the single-metal system was higher than that of small surface area HAP (0.64mmol/g), but there were no differences between single- and binary-metal solutions containing Pb. After the Cd experiments, the HAP retained a stable structure and intact morphology, which promotes the accessibility of reactive sites for Cd. However, a newly formed precipitate covered the surface and blocked the channels in the presence of Pb, which reduced the number of potential adsorption sites on HAP for Cd and Pb. Remediation experiments using Cd- and Pb-contaminated soil produced similar results to the solution tests. These results indicate that alterations of the structure and morphology during the reaction is an important factor influencing metal sorption to HAP. Copyright © 2016. Published by Elsevier B.V.

Hypochlorous acid-induced heme oxygenase-1 gene expression promotes human endothelial cell survival

PubMed Central

Wei, Yong; Liu, Xiao-ming; Peyton, Kelly J.; Wang, Hong; Johnson, Fruzsina K.; Johnson, Robert A.

2009-01-01

Hypochlorous acid (HOCl) is a unique oxidant generated by the enzyme myeloperoxidase that contributes to endothelial cell dysfunction and death in atherosclerosis. Since myeloperoxidase localizes with heme oxygenase-1 (HO-1) in and around endothelial cells of atherosclerotic lesions, the present study investigated whether there was an interaction between these two enzymes in vascular endothelium. Treatment of human endothelial cells with the myeloperoxidase product HOCl stimulated a concentration- and time-dependent increase in HO-1 protein that resulted in a significant rise in carbon monoxide (CO) production. The induction of HO-1 protein was preceded by a prominent increase in HO-1 mRNA and total and nuclear factor-erythroid 2-related factor 2 (Nrf2). In addition, HOCl induced a significant rise in HO-1 promoter activity that was blocked by mutating the antioxidant response element (ARE) in the promoter or by overexpressing a dominant-negative mutant of Nrf2. The HOCl-mediated induction of Nrf2 or HO-1 was blocked by the glutathione donor N-acetyl-l-cysteine but was unaffected by ascorbic or uric acid. Finally, treatment of endothelial cells with HOCl stimulated mitochondrial dysfunction, caspase-3 activation, and cell death that was potentiated by the HO inhibitor, tin protoporphyrin-IX, or by the knockdown of HO-1, and reversed by the exogenous administration of biliverdin, bilirubin, or CO. These results demonstrate that HOCl induces HO-1 gene transcription via the activation of the Nrf2/ARE pathway to counteract HOCl-mediated mitochondrial dysfunction and cell death. The ability of HOCl to activate HO-1 gene expression may represent a critical adaptive response to maintain endothelial cell viability at sites of vascular inflammation and atherosclerosis. PMID:19625608

PKC-dependent stimulation of the human MCT1 promoter involves transcription factor AP2.

PubMed

Saksena, Seema; Dwivedi, Alka; Gill, Ravinder K; Singla, Amika; Alrefai, Waddah A; Malakooti, Jaleh; Ramaswamy, Krishnamurthy; Dudeja, Pradeep K

2009-02-01

Monocarboxylate transporter (MCT1) plays an important role in the absorption of short-chain fatty acids (SCFA) such as butyrate in the human colon. Previous studies from our laboratory have demonstrated that phorbol ester, PMA (1 microM, 24 h), upregulates butyrate transport and MCT1 protein expression in human intestinal Caco-2 cells. However, the molecular mechanisms involved in the transcriptional regulation of MCT1 gene expression by PMA in the intestine are not known. In the present study, we showed that PMA (0.1 microM, 24 h) increased the MCT1 promoter activity (-871/+91) by approximately fourfold. A corresponding increase in MCT1 mRNA abundance in response to PMA was also observed. PMA-induced stimulation of MCT1 promoter activity was observed as early as 1 h and persisted until 24 h, suggesting that the effects of PMA are attributable to initial PKC activation. Kinase inhibitor and phosphorylation studies indicated that these effects may be mediated through activation of the atypical PKC-zeta isoform. 5'-deletion studies demonstrated that the MCT1 core promoter region (-229/+91) is the PMA-responsive region. Site-directed mutagenesis studies showed the predominant involvement of potential activator protein 2 (AP2) binding site in the activation of MCT1 promoter activity by PMA. In addition, overexpression of AP2 in Caco-2 cells significantly increased MCT1 promoter activity in a dose-dependent manner. These findings showing the regulation of MCT1 promoter by PKC and AP2 are of significant importance for an understanding of the molecular regulation of SCFA absorption in the human intestine.

Homeowners Assistance Program (HAP)

DTIC Science & Technology

1992-06-26

Assistance Program (HAP) References: (a) DoD Instruction 4165.50, "Administration and Operation of the Homeowners Assistance Program ," February 11, 1972...hereby canceled) (b) DoD Directive 5100.54, "Homeowners Assistance Program ," December 29, 1967 (hereby canceled) (c) Section 1013 of Public Law 89-754...Defense Program and annual budgets for the Homeowners Assistance Fund, Defense. m. Publish regulations and forms, subject to review by . the Assistant

Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells

PubMed Central

Hasni Ebou, Moina; Singh-Estivalet, Amrit; Launay, Jean-Marie; Callebert, Jacques; Tronche, François; Ferré, Pascal; Gautier, Jean-François; Guillemain, Ghislaine; Bréant, Bernadette

2016-01-01

Diabetes is a major complication of chronic Glucocorticoids (GCs) treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synthesis was evaluated in vitro after treatment with GCs of either islets from CD1 mice or MIN6 cells, a beta-cell line. We also explored the effect of GCs on the stimulation of serotonin synthesis by several hormones such as prolactin and GLP 1. We finally studied this regulation in islet in two in vivo models: mice treated with GCs and with liraglutide, a GLP1 analog, and mice deleted for the glucocorticoid receptor in the pancreas. We showed in isolated islets and MIN6 cells that GCs decreased expression and activity of the two key enzymes of serotonin synthesis, Tryptophan Hydroxylase 1 (Tph1) and 2 (Tph2), leading to reduced serotonin contents. GCs also blocked the induction of serotonin synthesis by prolactin or by a previously unknown serotonin activator, the GLP-1 analog exendin-4. In vivo, activation of the Glucagon-like-Peptide-1 receptor with liraglutide during 4 weeks increased islet serotonin contents and GCs treatment prevented this increase. Finally, islets from mice deleted for the GR in the pancreas displayed an increased expression of Tph1 and Tph2 and a strong increased serotonin content per islet. In conclusion, our results demonstrate an original inhibition of serotonin synthesis by GCs, both in basal condition and after stimulation by prolactin or activators of the GLP-1 receptor. This regulation may contribute to the deleterious effects of GCs on beta cells. PMID:26901633

SAMHD1 Inhibits LINE-1 Retrotransposition by Promoting Stress Granule Formation

PubMed Central

Xu, Fengwen; Mei, Shan; Le Duff, Yann; Yin, Lijuan; Pang, Xiaojing; Cen, Shan; Jin, Qi; Liang, Chen; Guo, Fei

2015-01-01

The SAM domain and HD domain containing protein 1 (SAMHD1) inhibits retroviruses, DNA viruses and long interspersed element 1 (LINE-1). Given that in dividing cells, SAMHD1 loses its antiviral function yet still potently restricts LINE-1, we propose that, instead of blocking viral DNA synthesis by virtue of its dNTP triphosphohydrolase activity, SAMHD1 may exploit a different mechanism to control LINE-1. Here, we report a new activity of SAMHD1 in promoting cellular stress granule assembly, which correlates with increased phosphorylation of eIF2α and diminished eIF4A/eIF4G interaction. This function of SAMHD1 enhances sequestration of LINE-1 RNP in stress granules and consequent blockade to LINE-1 retrotransposition. In support of this new mechanism of action, depletion of stress granule marker proteins G3BP1 or TIA1 abrogates stress granule formation and overcomes SAMHD1 inhibition of LINE-1. Together, these data reveal a new mechanism for SAMHD1 to control LINE-1 by activating cellular stress granule pathway. PMID:26134849

40 CFR 63.5335 - How do I determine the actual HAP loss?

Code of Federal Regulations, 2010 CFR

2010-07-01

... operation type. (2) Chemical Inventory Mass Balance. Determine the actual monthly HAP loss from your... operation. (2) For facilities using add-on emission control devices, the finish inventory log and the... National Emission Standards for Hazardous Air Pollutants for Leather Finishing Operations Compliance...

Caffeine Blocks HIV-1 Tat-Induced Amyloid Beta Production and Tau Phosphorylation.

PubMed

Soliman, Mahmoud L; Geiger, Jonathan D; Chen, Xuesong

2017-03-01

The increased life expectancy of people living with HIV-1 who are taking effective anti-retroviral therapeutics is now accompanied by increased Alzheimer's disease (AD)-like neurocognitive problems and neuropathological features such as increased levels of amyloid beta (Aβ) and phosphorylated tau proteins. Others and we have shown that HIV-1 Tat promotes the development of AD-like pathology. Indeed, HIV-1 Tat once endocytosed into neurons can alter morphological features and functions of endolysosomes as well as increase Aβ generation. Caffeine has been shown to have protective actions against AD and based on our recent findings that caffeine can inhibit endocytosis in neurons and can prevent neuronal Aβ generation, we tested the hypothesis that caffeine blocks HIV-1 Tat-induced Aβ generation and tau phosphorylation. In SH-SY5Y cells over-expressing wild-type amyloid beta precursor protein (AβPP), we demonstrated that HIV-1 Tat significantly increased secreted levels and intracellular levels of Aβ as well as cellular protein levels of phosphorylated tau. Caffeine significantly decreased levels of secreted and cellular levels of Aβ, and significantly blocked HIV-1 Tat-induced increases in secreted and cellular levels of Aβ. Caffeine also blocked HIV-1 Tat-induced increases in cellular levels of phosphorylated tau. Furthermore, caffeine blocked HIV-1 Tat-induced endolysosome dysfunction as indicated by decreased protein levels of vacuolar-ATPase and increased protein levels of cathepsin D. These results further implicate endolysosome dysfunction in the pathogenesis of AD and HAND, and by virtue of its ability to prevent and/or block neuropathological features associated with AD and HAND caffeine might find use as an effective adjunctive therapeutic agent.

Inhibition of FOXO1/3 promotes vascular calcification.

PubMed

Deng, Liang; Huang, Lu; Sun, Yong; Heath, Jack M; Wu, Hui; Chen, Yabing

2015-01-01

Vascular calcification is a characteristic feature of atherosclerosis, diabetes mellitus, and end-stage renal disease. We have demonstrated that activation of protein kinase B (AKT) upregulates runt-related transcription factor 2 (Runx2), a key osteogenic transcription factor that is crucial for calcification of vascular smooth muscle cells (VSMC). Using mice with SMC-specific deletion of phosphatase and tensin homolog (PTEN), a major negative regulator of AKT, the present studies uncovered a novel molecular mechanism underlying PTEN/AKT/FOXO (forkhead box O)-mediated Runx2 upregulation and VSMC calcification. SMC-specific PTEN deletion mice were generated by crossing PTEN floxed mice with SM22α-Cre transgenic mice. The PTEN deletion resulted in sustained activation of AKT that upregulated Runx2 and promoted VSMC calcification in vitro and arterial calcification ex vivo. Runx2 knockdown did not affect proliferation but blocked calcification of the PTEN-deficient VSMC, suggesting that PTEN deletion promotes Runx2-depedent VSMC calcification that is independent of proliferation. At the molecular level, PTEN deficiency increased the amount of Runx2 post-transcriptionally by inhibiting Runx2 ubiquitination. AKT activation increased phosphorylation of FOXO1/3 that led to nuclear exclusion of FOXO1/3. FOXO1/3 knockdown in VSMC phenocopied the PTEN deficiency, demonstrating a novel function of FOXO1/3, as a downstream signaling of PTEN/AKT, in regulating Runx2 ubiquitination and VSMC calcification. Using heterozygous SMC-specific PTEN-deficient mice and atherogenic ApoE(-/-) mice, we further demonstrated AKT activation, FOXO phosphorylation, and Runx2 ubiquitination in vascular calcification in vivo. Our studies have determined a new causative effect of SMC-specific PTEN deficiency on vascular calcification and demonstrated that FOXO1/3 plays a crucial role in PTEN/AKT-modulated Runx2 ubiquitination and VSMC calcification. © 2014 American Heart Association, Inc.

Modification of the structure and composition of Ca10(PO4)6(OH)2 ceramic coatings by changing the deposition conditions in O2 and Ar

NASA Astrophysics Data System (ADS)

Donkov, N.; Zykova, A.; Safonov, V.; Kolesnikov, D.; Goncharov, I.; Yakovin, S.; Georgieva, V.

2014-05-01

Hydroxyapatite Ca10(PO4)6(OH)2 (HAp) is a material considered to be used to form structural matrices in the mineral phase of bone, dentin and enamel. HAp ceramic materials and coatings are widely applied in medicine and dentistry because of their ability to increase the tissue response to the implant surface and promote bone ingrowth and osseoconduction processes. The deposition conditions affect considerably the structure and bio-functionality of the HAp coatings. We focused our research on developing deposition methods allowing a precise control of the structure and stoichiometric composition of HAp thin films. We found that the use of O2 as a reactive gas improves the quality of the sputtered hydroxyapatite coatings by resulting in the formation of films of better stoichiometry with a fine crystalline structure.

Studies on a Novel Serine Protease of a ΔhapAΔprtV Vibrio cholerae O1 Strain and Its Role in Hemorrhagic Response in the Rabbit Ileal Loop Model

PubMed Central

Syngkon, Aurelia; Elluri, Sridhar; Koley, Hemanta; Rompikuntal, Pramod K.; Saha, Dhira Rani; Chakrabarti, Manoj K.; Bhadra, Rupak K.; Wai, Sun Nyunt; Pal, Amit

2010-01-01

Background Two well-characterized proteases secreted by Vibrio cholerae O1 strains are hemagglutinin protease (HAP) and V. cholerae protease (PrtV). The hapA and prtV knock out mutant, V. cholerae O1 strain CHA6.8ΔprtV, still retains residual protease activity. We initiated this study to characterize the protease present in CHA6.8ΔprtV strain and study its role in pathogenesis in rabbit ileal loop model (RIL). Methodology/Principal Findings We partially purified the residual protease secreted by strain CHA6.8ΔprtV from culture supernatant by anion-exchange chromatography. The major protein band in native PAGE was identified by MS peptide mapping and sequence analysis showed homology with a 59-kDa trypsin-like serine protease encoded by VC1649. The protease activity was partially inhibited by 25 mM PMSF and 10 mM EDTA and completely inhibited by EDTA and PMSF together. RIL assay with culture supernatants of strains C6709 (FA ratio 1.1+/−0.3 n = 3), CHA6.8 (FA ratio 1.08+/−0.2 n = 3), CHA6.8ΔprtV (FA ratio 1.02+/−0.2 n = 3) and partially purified serine protease from CHA6.8ΔprtV (FA ratio 1.2+/−0.3 n = 3) induced fluid accumulation and histopathological studies on rabbit ileum showed destruction of the villus structure with hemorrhage in all layers of the mucosa. RIL assay with culture supernatant of CHA6.8ΔprtVΔVC1649 strain (FA ratio 0.11+/−0.005 n = 3) and with protease incubated with PMSF and EDTA (FA ratio 0.3+/−0.05 n = 3) induced a significantly reduced FA ratio with almost complete normal villus structure. Conclusion Our results show the presence of a novel 59-kDa serine protease in a ΔhapAΔprtV V. cholerae O1 strain and its role in hemorrhagic response in RIL model. PMID:20927349

Identification of a site involved in the block by extracellular Mg2+ and Ba2+ as well as permeation of K+ in the Kir2.1 K+ channel

PubMed Central

Murata, Yoshimichi; Fujiwara, Yuichiro; Kubo, Yoshihiro

2002-01-01

The inward rectifier potassium channel Kir2.1 is more sensitive to the weakly voltage-dependent block by extracellular Mg2+ (Mg02+) than Kir2.2 and Kir2.3. We identified Glu125 in an extracellular loop before the pore region of Kir2.1 as a site responsible for this sensitivity to M02+ block, based on the observations that the Glu125Gln (E125Q) mutation strongly decreased the sensitivity, while a mutation to Glu at the corresponding sites of Kir2.2 and 2.3 led to an increase. The negative charge proved to be crucial since the Glu125Asp (E125D) mutant showed similar properties to the wild type (WT). A similar weakly voltage-dependent block was also caused by extracellular Ca2+ and La3+ in Kir2.1 WT but not in the E125Q mutant. The sensitivity to block by extracellular Ba2+ (Ba02+) was also decreased in the E125Q mutant, although the voltage dependency of half-inhibition concentration was not changed, as reported previously. We additionally observed that the speed of Ba02+ block and recovery was decelerated by the presence of Mg02+ in WT, but not in the E125Q mutant. The sensitivity to the block by Mg02+ was increased by lowering extracellular K+ (K0+), suggesting a competitive interaction of Mg02+ and K0+. The single-channel conductance of the WT in 140 mm K+ was 39.6 pS (0 mm Mg02+) and 11.5 pS (10 mm), while that of the E125Q mutant was 26.0 pS (0 mm) and 19.6 pS (10 mm). These results demonstrate that Mg2+ competes with K+ permeation in the WT and that E125 is required for efficient K+ permeation in the absence of Mg02+. We conclude that E125 in an extracellular loop of Kir2.1 is a site which facilitates K+ permeation and entry of Ba2+ toward a deeper plugging site, and that Mg02+ competes with K0+ and Ba02+ at this site. PMID:12411513

Ae2Sb2X4F2 (Ae = Sr, Ba): new members of the homologous series Ae2M(1+n)X(3+n)F2 designed from rock salt and fluorite 2D building blocks.

PubMed

Kabbour, Houria; Cario, Laurent

2006-03-20

We have designed new compounds within the homologous series Ae2F2M(1+n)X(3+n) (Ae = Sr, Ba; M = main group metal; n = integer) built up from the stacking of 2D building blocks of rock salt and fluorite types. By incrementally increasing the size of the rock salt 2D building blocks, we have obtained two new n = 1 members of this homologous series, namely, Sr2F2Sb2Se4 and Ba2F2Sb2Se4. We then succeeded in synthesizing these compounds using a high-temperature ceramic method. The structure refinements from the powder or single-crystal X-ray diffraction data confirmed presence of the expected alternating stacking of fluorite [Ae2F2] (Ae = Sr, Ba) and rock salt [Sb2Se4] 2D building blocks. However the Ba derivative shows a strong distortion of the [Sb2Se4] block and a concomitant change of the Sb atom coordination likely related to the lone-pair activity.

Genetic variants in SIRT3 transcriptional regulatory region affect promoter activity and fat deposition in three cattle breeds.

PubMed

Gui, Linsheng; Hong, Jieyun; Raza, Sayed Haidar Abbas; Zan, Linsen

2017-04-01

Sirtuin 3 (SIRT3) is a mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase. It has crucial roles in regulating the respiratory chain, in adenosine triphosphate (ATP) production, and in both the citric acid and urea cycles. The aim of this study was to investigate whether SIRT3 could be used as a candidate gene in the breeding of cattle. Expression analysis by quantitative real-time polymerase chain reactions (qPCR) indicated that expression levels of SIRT3 were highest in the kidney, rumen, liver, omasum and muscle. Using sequencing technology on a total of 913 cattle representing three indigenous Chinese beef cattle breeds, three single nucleotide polymorphisms (SNPs) were identified in the promoter region of SIRT3, and five haplotypes representing five potential transcription factor compositions of polymorphic potential cis-acting elements. Association analysis indicated that the Hap3/8 diplotype performed better than other combinations in intramuscular fat content. In addition, the promoter activity with Hap1 haplotype was higher than the Hap8 haplotype, consistent with the association analysis. The results indicate that the polymorphisms in transcription factor binding sites of SIRT3 promoter may affect the transcriptional activity of SIRT3, and thus alter intramuscular fat content in beef cattle. Copyright © 2016 Elsevier Ltd. All rights reserved.

SimHap GUI: An intuitive graphical user interface for genetic association analysis

PubMed Central

Carter, Kim W; McCaskie, Pamela A; Palmer, Lyle J

2008-01-01

Background Researchers wishing to conduct genetic association analysis involving single nucleotide polymorphisms (SNPs) or haplotypes are often confronted with the lack of user-friendly graphical analysis tools, requiring sophisticated statistical and informatics expertise to perform relatively straightforward tasks. Tools, such as the SimHap package for the R statistics language, provide the necessary statistical operations to conduct sophisticated genetic analysis, but lacks a graphical user interface that allows anyone but a professional statistician to effectively utilise the tool. Results We have developed SimHap GUI, a cross-platform integrated graphical analysis tool for conducting epidemiological, single SNP and haplotype-based association analysis. SimHap GUI features a novel workflow interface that guides the user through each logical step of the analysis process, making it accessible to both novice and advanced users. This tool provides a seamless interface to the SimHap R package, while providing enhanced functionality such as sophisticated data checking, automated data conversion, and real-time estimations of haplotype simulation progress. Conclusion SimHap GUI provides a novel, easy-to-use, cross-platform solution for conducting a range of genetic and non-genetic association analyses. This provides a free alternative to commercial statistics packages that is specifically designed for genetic association analysis. PMID:19109877

SimHap GUI: an intuitive graphical user interface for genetic association analysis.

PubMed

Carter, Kim W; McCaskie, Pamela A; Palmer, Lyle J

2008-12-25

Researchers wishing to conduct genetic association analysis involving single nucleotide polymorphisms (SNPs) or haplotypes are often confronted with the lack of user-friendly graphical analysis tools, requiring sophisticated statistical and informatics expertise to perform relatively straightforward tasks. Tools, such as the SimHap package for the R statistics language, provide the necessary statistical operations to conduct sophisticated genetic analysis, but lacks a graphical user interface that allows anyone but a professional statistician to effectively utilise the tool. We have developed SimHap GUI, a cross-platform integrated graphical analysis tool for conducting epidemiological, single SNP and haplotype-based association analysis. SimHap GUI features a novel workflow interface that guides the user through each logical step of the analysis process, making it accessible to both novice and advanced users. This tool provides a seamless interface to the SimHap R package, while providing enhanced functionality such as sophisticated data checking, automated data conversion, and real-time estimations of haplotype simulation progress. SimHap GUI provides a novel, easy-to-use, cross-platform solution for conducting a range of genetic and non-genetic association analyses. This provides a free alternative to commercial statistics packages that is specifically designed for genetic association analysis.

Prx1 and 3.2 kb Col1a1 promoters target distinct bone cell populations in transgenic mice

PubMed Central

Ouyang, Zhufeng; Chen, Zhijun; Ishikawa, Masakazu; Yue, Xiuzhen; Kawanami, Aya; Leahy, Patrick; Greenfield, Edward M.; Murakami, Shunichi

2014-01-01

Bones consist of a number of cell types including osteoblasts and their precursor cells at various stages of differentiation. To analyze cellular organization within the bone, we generated Col1a1CreER-DsRed transgenic mice that express, in osteoblasts, CreER and DsRed under the control of a mouse 3.2 kb Col1a1 promoter. We further crossed Col1a1CreER-DsRed mice with Prx1CreER-GFP mice that express CreER and GFP in osteochondro progenitor cells under the control of a 2.4 kb Prx1 promoter. Since the 3.2 kb Col1a1 promoter becomes active in osteoblasts at early stages of differentiation, and Prx1CreER-GFP-expressing periosteal cells show endogenous Col1a1 expression, we expected to find a cell population in which both the 2.4 kb Prx1 promoter and the 3.2 kb Col1a1 promoter are active. However, our histological and flow cytometric analyses demonstrated that these transgenes are expressed in distinct cell populations. In the periosteum of long bones, Col1a1CreER-DsRed is expressed in the innermost layer directly lining the bone surface, while Prx1CreER-GFP-expressing cells are localized immediately outside of the Col1a1CreER-DsRed-expressing osteoblasts. In the calvaria, Prx1CreER-GFP-expressing cells are also localized in the cranial suture mesenchyme. Our experiments further showed that Col1a1CreER-DsRed-expressing cells lack chondrogenic potential, while the Prx1CreER-GFP-expressing cells show both chondrogenic and osteogenic potential. Our results indicate that Col1a1CreER-DsRed-expressing cells are committed osteoblasts, while Prx1CreER-GFP-expressing cells are osteochondro progenitor cells. The Prx1CreER-GFP and Col1a1CreER-DsRed transgenes will offer novel approaches for analyzing lineage commitment and early stages of osteoblast differentiation under physiologic and pathologic conditions. PMID:24513582

SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK

PubMed Central

Osinski, Adam; Tomchick, Diana R; Brautigam, Chad A

2017-01-01

The Hippo pathway controls tissue growth and homeostasis through a central MST-LATS kinase cascade. The scaffold protein SAV1 promotes the activation of this kinase cascade, but the molecular mechanisms remain unknown. Here, we discover SAV1-mediated inhibition of the PP2A complex STRIPAKSLMAP as a key mechanism of MST1/2 activation. SLMAP binding to autophosphorylated MST2 linker recruits STRIPAK and promotes PP2A-mediated dephosphorylation of MST2 at the activation loop. Our structural and biochemical studies reveal that SAV1 and MST2 heterodimerize through their SARAH domains. Two SAV1–MST2 heterodimers further dimerize through SAV1 WW domains to form a heterotetramer, in which MST2 undergoes trans-autophosphorylation. SAV1 directly binds to STRIPAK and inhibits its phosphatase activity, protecting MST2 activation-loop phosphorylation. Genetic ablation of SLMAP in human cells leads to spontaneous activation of the Hippo pathway and alleviates the need for SAV1 in Hippo signaling. Thus, SAV1 promotes Hippo activation through counteracting the STRIPAKSLMAP PP2A phosphatase complex. PMID:29063833

Manipulation of partially oriented hydroxyapatite building blocks to form flowerlike bundles without acid-base regulation.

PubMed

Wen, Zhenliang; Wang, Zihao; Chen, Jingdi; Zhong, Shengnan; Hu, Yimin; Wang, Jianhua; Zhang, Qiqing

2016-06-01

The application of hydroxyapatite (HAP) in different fields depends greatly on its morphology, composition and structure. Besides, the main inorganic building blocks of human bones and teeth are also HAP. Therefore, accurate shape and aggregation control and of hydroxyapatite particles will be of great interest. Herein, oriented bundles of flowerlike HAP nanorods were successfully prepared through hydrothermal treatment without acid-base regulation, with the mono-alkyl phosphate (MAP) and sodium citrate as surfactant and chelating agent, respectively. The prepared samples were characterized by the X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM) and zeta potential, the pH value and conductivity value of suspension were characterized by pH meter and conductivity measurement. The results showed that the MAP and citrate play an important role in assembly of HAP nanorods without acid-base regulation. Citrate calcium complex could decompose slowly and release citrate ions at hydrothermal conditions. Besides, the further decomposition of citrate ions could release aconitic acid as the reaction time prolongs. Moreover, the possible scheme for the formation process was discussed in detail. Copyright © 2016 Elsevier B.V. All rights reserved.

Luminescence variations in hydroxyapatites doped with Eu2+ and Eu3+ ions.

PubMed

Graeve, Olivia A; Kanakala, Raghunath; Madadi, Abhiram; Williams, Brandon C; Glass, Katelyn C

2010-05-01

We present a detailed analysis of the luminescence behavior of europium-doped hydroxyapatite (HAp) and calcium-deficient hydroxyapatite (Ca-D HAp) nanopowders. The results show that, while both powders are similar in crystallite size, particle size, and morphology, the luminescence behavior differs significantly. For the HAp:Eu powders, the emission is clearly from Eu(3+) ions and corresponds to typical (5)D(0) --> (7)F(J) emissions, whereas for the Ca-D HAp:Eu powders, we also see a broad emission with two peaks at 420 and 445 nm, corresponding to the 4f(6)5d(1) --> 4f(7) ((8)S(7/2)) transition of Eu(2+). The powders are weakly luminescent in the as-synthesized state, as expected for combustion-synthesized materials and have higher emission intensities as the heat treatment temperature is increased. Luminescence spectra obtained using an excitation wavelength of 254 nm are weak for all samples. Excitation wavelengths of 305, 337, and 359 nm, are better at promoting the Eu(3+) and Eu(2+) emissions in hydroxyapatites. We propose that fluorescence measurements are an excellent way of qualitatively determining the phase composition of europium-doped hydroxyapatite powders, since powders that exhibit a blue emission contain substantial amounts of Ca-D HAp, allowing the determination of the presence of this phase in mixed-phase hydroxyapatites. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

[Study on the anti-NTHi infection of Hap recombinant protein in vivo].

PubMed

Li, Wan-yi; Wang, Bao-ning; Zuo, Feng-qiong; Zeng, Wei; Feng, Feng; Kuang, Yu; Jiang, Zhong-hua; Li, Ming-yuan

2010-07-01

To observe the immune effect of Hap recombinant protein on murine model of bronchopneumonia infected with NTHi, and explore the mechanism about the anti-NTHi infection. The C57BL/6 mice intranasally immunized with purified Hap recombinant protein and CT-B were challenged by NTHi encased in agar beads. The immunifaction of anti-infection was observed through encocyte counting of BALF, bacteria detection of lung and the pathologyical change of lung tissue. In the challenge with NTHi experiment, the inflammatory exudation of the infected murine and pathological change of lung tissue was relieved by combined immunization of Hap recombinant protein and CT-B, and quantity of NTHi in lung of the infected murine was reduced obviously. The Hap recombinant protein also had good ability of anti-NTHi infection in the murine model of NTHi bronchopneumonia. This study could offer the oretical and experimental basis for development of new vaccine against NTHi.

Block-Parallel Data Analysis with DIY2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morozov, Dmitriy; Peterka, Tom

DIY2 is a programming model and runtime for block-parallel analytics on distributed-memory machines. Its main abstraction is block-structured data parallelism: data are decomposed into blocks; blocks are assigned to processing elements (processes or threads); computation is described as iterations over these blocks, and communication between blocks is defined by reusable patterns. By expressing computation in this general form, the DIY2 runtime is free to optimize the movement of blocks between slow and fast memories (disk and flash vs. DRAM) and to concurrently execute blocks residing in memory with multiple threads. This enables the same program to execute in-core, out-of-core, serial,more » parallel, single-threaded, multithreaded, or combinations thereof. This paper describes the implementation of the main features of the DIY2 programming model and optimizations to improve performance. DIY2 is evaluated on benchmark test cases to establish baseline performance for several common patterns and on larger complete analysis codes running on large-scale HPC machines.« less

A role for the gene regulatory module microRNA172/TARGET OF EARLY ACTIVATION TAGGED 1/FLOWERING LOCUS T (miRNA172/TOE1/FT) in the feeding sites induced by Meloidogyne javanica in Arabidopsis thaliana.

PubMed

Díaz-Manzano, Fernando E; Cabrera, Javier; Ripoll, Juan-José; Del Olmo, Iván; Andrés, Mari Fe; Silva, Ana Cláudia; Barcala, Marta; Sánchez, María; Ruíz-Ferrer, Virginia; de Almeida-Engler, Janice; Yanofsky, Martin F; Piñeiro, Manuel; Jarillo, Jose Antonio; Fenoll, Carmen; Escobar, Carolina

2018-01-01

Root knot nematodes (RKNs) penetrate into the root vascular cylinder, triggering morphogenetic changes to induce galls, de novo formed 'pseudo-organs' containing several giant cells (GCs). Distinctive gene repression events observed in early gall/GCs development are thought to be mediated by post-transcriptional silencing via microRNAs (miRNAs), a process that is far from being fully characterized. Arabidopsis thaliana backgrounds with altered activities based on target 35S::MIMICRY172 (MIM172), 35S::TARGET OF EARLY ACTIVATION TAGGED 1 (TOE1)-miR172-resistant (35S::TOE1 R ) and mutant (flowering locus T-10 (ft-10)) lines were used for functional analysis of nematode infective and reproductive parameters. The GUS-reporter lines, MIR172A-E::GUS, treated with auxin (IAA) and an auxin-inhibitor (a-(phenyl ethyl-2-one)-indole-3-acetic acid (PEO-IAA)), together with the MIR172C AuxRE::GUS line with two mutated auxin responsive elements (AuxREs), were assayed for nematode-dependent gene expression. Arabidopsis thaliana backgrounds with altered expression of miRNA172, TOE1 or FT showed lower susceptibility to the RKNs and smaller galls and GCs. MIR172C-D::GUS showed restricted promoter activity in galls/GCs that was regulated by auxins through auxin-responsive factors. IAA induced their activity in galls while PEO-IAA treatment and mutations in AuxRe motifs abolished it. The results showed that the regulatory module miRNA172/TOE1/FT plays an important role in correct GCs and gall development, where miRNA172 is modulated by auxins. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

[Influences of R2O-Al2O3-B2O3-SiO2 system glass and superfine alpha-Al2O3 on the sintering and phase transition of hydroxyapatite ceramics].

PubMed

Wang, Zhiqiang; Chen, Xiaoxu; Cai, Yingji; Lü, Bingling

2003-06-01

The effects of R2O-Al2O3-B2O3-SiO2 system glass and superfine alpha-Al2O3 on the sintering and phase transition of hydroxyapatite (HAP) ceramics were assessed. The results showed that alpha-Al2O3 impeded the sintering of HAP and raised the sintering temperature. When glass and alpha-Al2O3 were used together to reinforce HAP ceramics, better results could be obtained; the bending strength of multiphase HAP ceramics approached 106 MPa when 10% (wt) alpha-Al2O3 and 20%(wt) glass were used and sintered at 1200 for 1 h.

VizieR Online Data Catalog: H-band spectroscopic analysis of 25 bright M31 GCs (Sakari+, 2016)

NASA Astrophysics Data System (ADS)

Sakari, C. M.; Shetrone, M. D.; Schiavon, R. P.; Bizyaev, D.; Prieto, C. A.; Beers, T. C.; Caldwell, N.; Garcia-Hernandez, D. A.; Lucatello, S.; Majewski, S.; O'Connell, R. W.; Pan, K.; Strader, J.

2016-11-01

H-band spectra (1.51-1.69um) of the target clusters were obtained with the moderately high resolution (R=22500) APOGEE spectrograph on the 2.5m Telescope at Apache Point Observatory in 2011 and 2013. The details of the observations can be found in Majewski+ (2015arXiv150905420M) and Zasowski+ (2013AJ....146...81Z), including descriptions of the plates and fibers that were utilized for the observations. The high-resolution optical abundances from Colucci et al. (2009, J/ApJ/704/385 and 2014ApJ...797..116C) are supplemented with new results for five globular clusters (GCs). The new optical spectra were obtained in 2009 and 2010 with the High Resolution Spectrograph on the Hobby-Eberly Telescope at McDonald Observatory in Fort Davis, TX (R=30000; spectral coverage over ~5320-6290 and ~6360-7340Å in the blue and the red, respectively). (5 data files).

B cell IFN-γ receptor signaling promotes autoimmune germinal centers via cell-intrinsic induction of BCL-6

PubMed Central

Jackson, Shaun W.; Jacobs, Holly M.; Arkatkar, Tanvi; Dam, Elizabeth M.; Scharping, Nicole E.; Kolhatkar, Nikita S.; Hou, Baidong; Buckner, Jane H.

2016-01-01

Dysregulated germinal center (GC) responses are implicated in the pathogenesis of human autoimmune diseases, including systemic lupus erythematosus (SLE). Although both type 1 and type 2 interferons (IFNs) are involved in lupus pathogenesis, their respective impacts on the establishment of autoimmune GCs has not been addressed. In this study, using a chimeric model of B cell-driven autoimmunity, we demonstrate that B cell type 1 IFN receptor signals accelerate, but are not required for, lupus development. In contrast, B cells functioning as antigen-presenting cells initiate CD4+ T cell activation and IFN-γ production, and strikingly, B cell–intrinsic deletion of the IFN-γ receptor (IFN-γR) abrogates autoimmune GCs, class-switched autoantibodies (auto-Abs), and systemic autoimmunity. Mechanistically, although IFN-γR signals increase B cell T-bet expression, B cell–intrinsic deletion of T-bet exerts an isolated impact on class-switch recombination to pathogenic auto-Ab subclasses without impacting GC development. Rather, in both mouse and human B cells, IFN-γ synergized with B cell receptor, toll-like receptor, and/or CD40 activation signals to promote cell-intrinsic expression of the GC master transcription factor, B cell lymphoma 6 protein. Our combined findings identify a novel B cell–intrinsic mechanism whereby IFN signals promote lupus pathogenesis, implicating this pathway as a potential therapeutic target in SLE. PMID:27069113

Diosgenin promotes oligodendrocyte progenitor cell differentiation through estrogen receptor-mediated ERK1/2 activation to accelerate remyelination.

PubMed

Xiao, Lin; Guo, Dazhi; Hu, Chun; Shen, Weiran; Shan, Lei; Li, Cui; Liu, Xiuyun; Yang, Wenjing; Zhang, Weidong; He, Cheng

2012-07-01

Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes is a prerequisite for remyelination after demyelination, and impairment of this process is suggested to be a major reason for remyelination failure. Diosgenin, a plant-derived steroid, has been implicated for therapeutic use in many diseases, but little is known about its effect on the central nervous system. In this study, using a purified rat OPC culture model, we show that diosgenin significantly and specifically promotes OPC differentiation without affecting the viability, proliferation, or migration of OPC. Interestingly, the effect of diosgenin can be blocked by estrogen receptor (ER) antagonist ICI 182780 but not by glucocorticoid and progesterone receptor antagonist RU38486, nor by mineralocorticoid receptor antagonist spirolactone. Moreover, it is revealed that both ER-alpha and ER-beta are expressed in OPC, and diosgenin can activate the extracellular signal-regulated kinase 1/2 (ERK1/2) in OPC via ER. The pro-differentiation effect of diosgenin can also be obstructed by the ERK inhibitor PD98059. Furthermore, in the cuprizone-induced demyelination model, it is demonstrated that diosgenin administration significantly accelerates/enhances remyelination as detected by Luxol fast blue stain, MBP immunohistochemistry and real time RT-PCR. Diosgenin also increases the number of mature oligodendrocytes in the corpus callosum while it does not affect the number of OPCs. Taking together, our results suggest that diosgenin promotes the differentiation of OPC into mature oligodendrocyte through an ER-mediated ERK1/2 activation pathway to accelerate remyelination, which implicates a novel therapeutic usage of this steroidal natural product in demyelinating diseases such as multiple sclerosis (MS). Copyright © 2012 Wiley Periodicals, Inc.

SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bae, Sung Jun; Ni, Lisheng; Osinski, Adam

The Hippo pathway controls tissue growth and homeostasis through a central MST-LATS kinase cascade. The scaffold protein SAV1 promotes the activation of this kinase cascade, but the molecular mechanisms remain unknown. Here, we discover SAV1-mediated inhibition of the PP2A complex STRIPAKSLMAP as a key mechanism of MST1/2 activation. SLMAP binding to autophosphorylated MST2 linker recruits STRIPAK and promotes PP2A-mediated dephosphorylation of MST2 at the activation loop. Our structural and biochemical studies reveal that SAV1 and MST2 heterodimerize through their SARAH domains. Two SAV1–MST2 heterodimers further dimerize through SAV1 WW domains to form a heterotetramer, in which MST2 undergoes trans-autophosphorylation. SAV1more » directly binds to STRIPAK and inhibits its phosphatase activity, protecting MST2 activation-loop phosphorylation. Genetic ablation of SLMAP in human cells leads to spontaneous activation of the Hippo pathway and alleviates the need for SAV1 in Hippo signaling. Thus, SAV1 promotes Hippo activation through counteracting the STRIPAKSLMAP PP2A phosphatase complex.« less

HEAO Block 2 study executive summary

NASA Technical Reports Server (NTRS)

1976-01-01

An executive summary is presented of a preliminary study done on several potential High Energy Astronomy Observatory (HEAO) missions which are follow-on missions to the currently defined HEAO program. The purpose was to examine several typical missions and determine the relative complexities associated with them. The four payloads investigated were (1) a 1.2 m Diameter X-ray Telescope observatory, (2) a Large Area Moderate Angular Resolution (LAMAR) observatory, (3) a cosmic ray observatory, and (4) a gamma ray observatory. Each of the four observatories was considered a national facility. Low cost approaches were stressed throughout, with considerable use of HEAO Block I experience and designs effected to provide a high degree of confidence that such approaches were achievable. The use of the Multi-Mission Spacecraft (MMS) and the HEAO Block I spacecraft was considered as a result of this low cost emphasis. Also, NASA standard components were considered, where applicable.

Signalling mechanism for somatostatin receptor 5-mediated suppression of AMPA responses in rat retinal ganglion cells.

PubMed

Deng, Qin-Qin; Sheng, Wen-Long; Zhang, Gong; Weng, Shi-Jun; Yang, Xiong-Li; Zhong, Yong-Mei

2016-08-01

Somatostatin (SRIF) is involved in a variety of physiological functions via the activation of five subtypes of specific receptors (sst1-5). Here, we investigated the effects of SRIF on AMPA receptor (AMPAR)-mediated currents (AMPA currents) in isolated rat retinal ganglion cells (GCs) using patch-clamp techniques. Immunofluorescence double labelling demonstrated the expression of sst5 in rat GCs. Consistent to this, whole cell AMPA currents of GCs were dose-dependently suppressed by SRIF, and the effect was reversed by the sst5 antagonist BIM-23056. Intracellular dialysis of GDP-β-S or pre-incubation with the Gi/o inhibitor pertussis toxin (PTX) abolished the SRIF effect. The SRIF effect was mimicked by the administration of either 8-Br-cAMP or forskolin, but was eliminated by the protein kinase A (PKA) antagonists H-89/KT5720/Rp-cAMP. Moreover, SRIF increased intracellular Ca(2+) levels and did not suppress the AMPA currents when GCs were infused with an intracellular Ca(2+)-free solution or in the presence of ryanodine receptor modulators caffeine/ryanodine. Furthermore, the SRIF effect was eliminated when the activity of calmodulin (CaM), calcineurin and protein phosphatase 1 (PP1) was blocked with W-7, FK-506 and okadaic acid, respectively. SRIF persisted to suppress the AMPA currents when cGMP-protein kinase G (PKG) and phosphatidylinositol (PI)-/phosphatidylcholine (PC)-phospholipase C (PLC) signalling pathways were blocked. In rat flat-mount retinas, SRIF suppressed AMPAR-mediated light-evoked excitatory postsynaptic currents (L-EPSCs) in GCs. We conclude that a distinct Gi/o/cAMP-PKA/ryanodine/Ca(2+)/CaM/calcineurin/PP1 signalling pathway comes into play due to the activation of sst5 to mediate the SRIF effect on GCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanical evaluation of nHAp scaffold coated with poly-3-hydroxybutyrate for bone tissue engineering.

PubMed

Foroughi, Mohammad Reza; Karbasi, Saeed; Ebrahimi-Kahrizsangi, Reza

2013-02-01

Regeneration of bone, cartilage and osteochondral tissues by tissue engineering has attracted intense attention due to its potential advantages over the traditional replacement of tissues with synthetic implants. Nevertheless, there is still a dearth of ideal or suitable scaffolds based on porous biomaterials, and the present study was undertaken to develop and evaluate a useful porous composite scaffold system. In this study, nano hydroxyapatite (nHAp) powder made (about 35-45 nm) by heating at temperature of 900 degrees C and porous hydroxyapatite (40, 50 and 60 wt% solution) for making scaffold, by using Polyurethane sponge replication method. In order to increase the scaffolds mechanical properties, they coated with 2, 4 and 6 wt% Poly-3-hydroxybutyrate (P3HB) for 30 sec and 60 sec, respectively; after the scaffold coated by Polymer and survey results, this scaffold is nHAp/P3HB composite. Based on these results, this scaffold is an optimized one among three tested above mentioned composition and can be utilized in bone tissue engineering. In the result, the best of scaffold is with 50 wt% HAp and 6 wt% P3HB and porosity of present is between 80-90% with compressive strength and modulus 1.51 MPa and 22.73 MPa, respectively, that it can be application in bone tissue engineering.

Hydrogen peroxide inhibits transforming growth factor-β1-induced cell cycle arrest by promoting Smad3 linker phosphorylation through activation of Akt-ERK1/2-linked signaling pathway.

PubMed

Choi, Jiyeon; Park, Seong Ji; Jo, Eun Ji; Lee, Hui-Young; Hong, Suntaek; Kim, Seong-Jin; Kim, Byung-Chul

2013-06-14

Hydrogen peroxide (H2O2) functions as a second messenger in growth factor receptor-mediated intracellular signaling cascade and is tumorigenic by virtue of its ability to promote cell proliferation; however, the mechanisms underlying the growth stimulatory action of H2O2 are less understood. Here we report an important mechanism for antagonistic effects of H2O2 on growth inhibitory response to transforming growth factor-β1 (TGF-β1). In Mv1Lu and HepG2 cells, pretreatment of H2O2 (0.05-0.2 mM) completely blocked TGF-β1-mediated induction of p15(INK4B) expression and increase of its promoter activity. Interestingly, H2O2 selectively suppressed the transcriptional activation potential of Smad3, not Smad2, in the absence of effects on TGF-β1-induced phosphorylation of the COOH-tail SSXS motif of Smad3 and its nuclear translocation. Mechanism studies showed that H2O2 increases the phosphorylation of Smad3 at the middle linker region in a concentration- and time-dependent manner and this effect is mediated by activation of extracellular signal-activated kinase 1/2 through Akt. Furthermore, expression of a mutant Smad3 in which linker phosphorylation sites were ablated significantly abrogated the inhibitory effects of H2O2 on TGF-β1-induced increase of p15(INK4B)-Luc reporter activity and blockade of cell cycle progression from G1 to S phase. These findings for the first time define H2O2 as a signaling molecule that modulate Smad3 linker phosphorylation and its transcriptional activity, thus providing a potential mechanism whereby H2O2 antagonizes the cytostatic function of TGF-β1. Copyright © 2013 Elsevier Inc. All rights reserved.

Process-based control of HAPs emissions from drying wood flakes.

PubMed

Banerjee, Sujit; Pendyala, Krishna; Buchanan, Mike; Yang, Rallming; Abu-Daabes, Malyuba; Otwell, Lawrence P E

2006-04-01

Industrial wood flake drying generates methanol, formaldehyde, and other hazardous air pollutants (HAPs). A simple theoretical model shows that particles smaller than 400 microm will begin to thermally degrade and release disproportionately large quantities of HAPs. This is confirmed in full-scale practice where particles smaller than 500 microm show visible signs of charring. Laboratory measurement of the activation energy for the breakdown of wood tissue into methanol and formaldehyde led to a value of about 17 kcal/mol. The apparent activation energy measured in the field was higher. This result was obtained under nonisothermal conditions and is biased high by the fines fraction of the furnish, which is exposed to elevated temperatures. It is proposed that a combination of screening out the fines fraction smaller than 500 microm and reducing the dryer inlet temperature will substantially reduce emissions, possibly to the point where control devices can be downsized or eliminated. Our findings allow these HAPs reductions to be semiquantitatively estimated.

40 CFR 63.2465 - What requirements must I meet for process vents that emit hydrogen halide and halogen HAP or HAP...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Pollutants: Miscellaneous Organic Chemical Manufacturing Emission Limits, Work Practice Standards, and... the mass emission rate of HAP metals based on process knowledge, engineering assessment, or test data...

Redirection of the Respiro-Fermentative Flux Distribution in Saccharomyces cerevisiae by Overexpression of the Transcription Factor Hap4p

PubMed Central

Blom, Jolanda; De Mattos, M. Joost Teixeira; Grivell, Leslie A.

2000-01-01

Reduction of aerobic fermentation on sugars by altering the fermentative/oxidative balance is of significant interest for optimization of industrial production of Saccharomyces cerevisiae. Glucose control of oxidative metabolism in baker's yeast is partly mediated through transcriptional regulation of the Hap4p subunit of the Hap2/3/4/5p transcriptional activator complex. To alleviate glucose repression of oxidative metabolism, we constructed a yeast strain with constitutively elevated levels of Hap4p. Genetic analysis of expression levels of glucose-repressed genes and analysis of respiratory capacity showed that Hap4p overexpression (partly) relieves glucose repression of respiration. Analysis of the physiological properties of the Hap4p overproducer in batch cultures in fermentors (aerobic, glucose excess) has shown that the metabolism of this strain is more oxidative than in the wild-type strain, resulting in a significant reduced ethanol production and improvement of growth rate and a 40% gain in biomass yield. Our results show that modification of one or more transcriptional regulators can be a powerful and a widely applicable tool for redirection of metabolic fluxes in microorganisms. PMID:10788368

Electrospun PVA/HAp nanocomposite nanofibers: biomimetics of mineralized hard tissues at a lower level of complexity.

PubMed

Kim, Gyeong-Man; Asran, Ashraf Sh; Michler, Georg H; Simon, Paul; Kim, Jeong-Sook

2008-12-01

Based on the biomimetic approaches the present work describes a straightforward technique to mimic not only the architecture (the morphology) but also the chemistry (the composition) of the lowest level of the hierarchical organization of bone. This technique uses an electrospinning (ES) process with polyvinyl alcohol (PVA) and hydroxyapatite (HAp) nanoparticles. To determine morphology, crystalline structures and thermal properties of the resulting electrospun fibers with the pure PVA and PVA/HAp nanocomposite (NC) before electrospinning various techniques were employed, including transmission electron microscopy (TEM), high-resolution TEM (HR-TEM), scanning electron microscopy (SEM), x-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). In addition, FT-IR spectroscopy was carried out to analyze the complex structural changes upon undergoing electrospinning as well as interactions between HAp and PVA. The morphological and crystallographic investigations revealed that the rod-like HAp nanoparticles exhibit a nanoporous morphology and are embedded within the electrospun fibers. A large number of HAp nanorods are preferentially oriented parallel to the longitudinal direction of the electrospun PVA fibers, which closely resemble the naturally mineralized hard tissues of bones. Due to abundant OH groups present in PVA and HAp nanorods, they strongly interact via hydrogen bonding within the electrospun PVA/HAp NC fibers, which results in improved thermal properties. The unique physiochemical features of the electrospun PVA/HAp NC nanofibers prepared by the ES process will open up a wide variety of future applications related to hard tissue replacement and regeneration (bone and dentin), not limited to coating implants.

γ-Glutamylcysteine synthetase (γ-GCS) as a target for overcoming chemo- and radio-resistance of human hepatocellular carcinoma cells.

PubMed

Lin, Li-Ching; Chen, Chi-Fen; Ho, Chun-Te; Liu, Jun-Jen; Liu, Tsan-Zon; Chern, Chi-Liang

2018-04-01

This study uncovered that the genetically endowed intracellular glutathione contents (iGSH) regulated by the catalytic subunit of γ‑glutamylcysteine synthetase heavy chain (γ‑GCSh) as a prime target for overcoming both the inherited and stimuli-activated chemo- and radio-resistance of hepatocellular carcinoma (HCC) cells. Reactive oxygen species (ROS) production and mitochondrial membrane potential (Δψm) were determined by the probe-based flow cytometry. The TUNEL assay was used as an index of radio-sensitivity and the MTT assay was used as an index of chemo-sensitivity against various anti-cancer agents. iGSH and γ‑GCSh activity were measured by HPLC methods. γ‑GCSh-overexpressing GCS30 cell line was established by tetracycline-controlled Tet-OFF gene expression system in SK-Hep-1 cells. The relative radio-sensitivities of a panel of five HCC cells were found to be correlated negatively with both the contents of iGSH and their corresponding γ‑GCSh activities with an order of abundance being Hep G2 > Hep 3B > J5 > Mahlavu > SK-Hep-1, respectively. Similarly, the cytotoxicity response patterns of these HCC cells against arsenic trioxide (ATO), a ROS-producing anti-cancer drug, were exactly identical to the order of ranking instigated by the radiotherapy (RT) treatment. Next, γ‑GCSh-overexpressing GCS30 cells were found to possess excellent ability to profoundly mitigate both the drop of Δψm and apoptotic TUNEL-positive cell population engendered by ATO, cisplatin, doxorubicin, and RT treatments. Our data unequivocally demonstrate that γ‑GCSh may represent a prime target for overcoming anti-cancer drugs and RT resistance for HCC cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Role of Caenorhabditis elegans AKT-1/2 and SGK-1 in Manganese Toxicity.

PubMed

Peres, Tanara V; Arantes, Leticia P; Miah, Mahfuzur R; Bornhorst, Julia; Schwerdtle, Tanja; Bowman, Aaron B; Leal, Rodrigo B; Aschner, Michael

2018-06-07

Excessive levels of the essential metal manganese (Mn) may cause a syndrome similar to Parkinson's disease. The model organism Caenorhabditis elegans mimics some of Mn effects in mammals, including dopaminergic neurodegeneration, oxidative stress, and increased levels of AKT. The evolutionarily conserved insulin/insulin-like growth factor-1 signaling pathway (IIS) modulates worm longevity, metabolism, and antioxidant responses by antagonizing the transcription factors DAF-16/FOXO and SKN-1/Nrf-2. AKT-1, AKT-2, and SGK-1 act upstream of these transcription factors. To study the role of these proteins in C. elegans response to Mn intoxication, wild-type N2 and loss-of-function mutants were exposed to Mn (2.5 to 100 mM) for 1 h at the L1 larval stage. Strains with loss-of-function in akt-1, akt-2, and sgk-1 had higher resistance to Mn compared to N2 in the survival test. All strains tested accumulated Mn similarly, as shown by ICP-MS. DAF-16 nuclear translocation was observed by fluorescence microscopy in WT and loss-of-function strains exposed to Mn. qRT-PCR data indicate increased expression of γ-glutamyl cysteine synthetase (GCS-1) antioxidant enzyme in akt-1 mutants. The expression of sod-3 (superoxide dismutase homologue) was increased in the akt-1 mutant worms, independent of Mn treatment. However, dopaminergic neurons degenerated even in the more resistant strains. Dopaminergic function was evaluated with the basal slowing response behavioral test and dopaminergic neuron integrity was evaluated using worms expressing green fluorescent protein (GFP) under the dopamine transporter (DAT-1) promoter. These results suggest that AKT-1/2 and SGK-1 play a role in C. elegans response to Mn intoxication. However, tissue-specific responses may occur in dopaminergic neurons, contributing to degeneration.

The Pch2 AAA+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects

PubMed Central

Herruzo, Esther; Ontoso, David; González-Arranz, Sara; Cavero, Santiago; Lechuga, Ana; San-Segundo, Pedro A.

2016-01-01

Meiotic cells possess surveillance mechanisms that monitor critical events such as recombination and chromosome synapsis. Meiotic defects resulting from the absence of the synaptonemal complex component Zip1 activate a meiosis-specific checkpoint network resulting in delayed or arrested meiotic progression. Pch2 is an evolutionarily conserved AAA+ ATPase required for the checkpoint-induced meiotic block in the zip1 mutant, where Pch2 is only detectable at the ribosomal DNA array (nucleolus). We describe here that high levels of the Hop1 protein, a checkpoint adaptor that localizes to chromosome axes, suppress the checkpoint defect of a zip1 pch2 mutant restoring Mek1 activity and meiotic cell cycle delay. We demonstrate that the critical role of Pch2 in this synapsis checkpoint is to sustain Mec1-dependent phosphorylation of Hop1 at threonine 318. We also show that the ATPase activity of Pch2 is essential for its checkpoint function and that ATP binding to Pch2 is required for its localization. Previous work has shown that Pch2 negatively regulates Hop1 chromosome abundance during unchallenged meiosis. Based on our results, we propose that, under checkpoint-inducing conditions, Pch2 also possesses a positive action on Hop1 promoting its phosphorylation and its proper distribution on unsynapsed chromosome axes. PMID:27257060

The Pch2 AAA+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects.

PubMed

Herruzo, Esther; Ontoso, David; González-Arranz, Sara; Cavero, Santiago; Lechuga, Ana; San-Segundo, Pedro A

2016-09-19

Meiotic cells possess surveillance mechanisms that monitor critical events such as recombination and chromosome synapsis. Meiotic defects resulting from the absence of the synaptonemal complex component Zip1 activate a meiosis-specific checkpoint network resulting in delayed or arrested meiotic progression. Pch2 is an evolutionarily conserved AAA+ ATPase required for the checkpoint-induced meiotic block in the zip1 mutant, where Pch2 is only detectable at the ribosomal DNA array (nucleolus). We describe here that high levels of the Hop1 protein, a checkpoint adaptor that localizes to chromosome axes, suppress the checkpoint defect of a zip1 pch2 mutant restoring Mek1 activity and meiotic cell cycle delay. We demonstrate that the critical role of Pch2 in this synapsis checkpoint is to sustain Mec1-dependent phosphorylation of Hop1 at threonine 318. We also show that the ATPase activity of Pch2 is essential for its checkpoint function and that ATP binding to Pch2 is required for its localization. Previous work has shown that Pch2 negatively regulates Hop1 chromosome abundance during unchallenged meiosis. Based on our results, we propose that, under checkpoint-inducing conditions, Pch2 also possesses a positive action on Hop1 promoting its phosphorylation and its proper distribution on unsynapsed chromosome axes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Allelic combinations of promoter and exon 2 in DQB1 in dogs and wolves.

PubMed

Berggren, Karin T; Seddon, Jennifer M

2008-07-01

Polymorphism of PBRs of the major histocompatibility complex (MHC) genes is well recognized, but the polymorphism also extends to proximal promoter regions. Examining DQB1 variability in dogs and wolves, we identified 7 promoter variants and 13 exon 2 alleles among 89 dogs, including a previously unknown DQB1 exon 2 allele, and 8 promoter variants and 9 exon 2 alleles among 85 wolves. As expected from previous studies and from a close chromosomal location, strong linkage disequilibrium was demonstrated in both wolves and dogs by having significantly fewer promoter/exon 2 combinations than expected from simulations of randomized data sets. Interestingly, we noticed weaker haplotypic associations in dogs than in wolves. Dogs had twice as many promoter/exon 2 combinations as wolves and an almost 2-fold difference in the number of exon 2 alleles per promoter variant. This difference was not caused by an admixture of breeds in our group of dogs because the high ratio of observed to expected number of haplotypes persisted within a single dog breed, the German Shepherd. Ewens-Watterson tests indicated that both the promoter and exon 2 are under the balancing selection, and both regions appear to be more recently derived in the dog than in the wolf. Hence, although reasons for the differences are unknown, they may relate to altered selection pressure on patterns of expression. Deviations from normal MHC expression patterns have been associated with autoimmune diseases, which occur frequently in several dog breeds. Further knowledge about these deviations may help us understand the source of such diseases.

Predictive value of the APACHE II, SAPS II, SOFA and GCS scoring systems in patients with severe purulent bacterial meningitis.

PubMed

Pietraszek-Grzywaczewska, Iwona; Bernas, Szymon; Łojko, Piotr; Piechota, Anna; Piechota, Mariusz

2016-01-01

Scoring systems in critical care patients are essential for predicting of the patient outcome and evaluating the therapy. In this study, we determined the value of the Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Scale (GCS) scoring systems in the prediction of mortality in adult patients admitted to the intensive care unit (ICU) with severe purulent bacterial meningitis. We retrospectively analysed data from 98 adult patients with severe purulent bacterial meningitis who were admitted to the single ICU between March 2006 and September 2015. Univariate logistic regression identified the following risk factors of death in patients with severe purulent bacterial meningitis: APACHE II, SAPS II, SOFA, and GCS scores, and the lengths of ICU stay and hospital stay. The independent risk factors of patient death in multivariate analysis were the SAPS II score, the length of ICU stay and the length of hospital stay. In the prediction of mortality according to the area under the curve, the SAPS II score had the highest accuracy followed by the APACHE II, GCS and SOFA scores. For the prediction of mortality in a patient with severe purulent bacterial meningitis, SAPS II had the highest accuracy.

Present and future emissions of HAPs from crematories in China

NASA Astrophysics Data System (ADS)

Xue, Yifeng; Tian, Hezhong; Yan, Jing; Xiong, Chengcheng; Pan, Tao; Nie, Lei; Wu, Xiaoqing; Li, Jing; Wang, Wei; Gao, Jiajia; Zhu, Chuanyong; Wang, Kun

2016-01-01

China is the most populous country in the world. The amount of death population has reached 9.65 million and 49.5% of human corpses are cremated by about 1700 crematories spread throughout the country in 2012, leading to considerable discharge of various hazardous air pollutants (HAPs) into the atmosphere and great concerns on regional air quality and health risks for surrounding residents. By using the practicable or best available emission factors, for the first time, a multiple-year emission inventory of typical hazardous air pollutants discharged from crematories in the Chinese mainland, has been established for the historical period of 1990-2012, and the future trends of HAPs emissions until 2030 are forecasted based on three scenarios analysis. Our results show that the total emissions have gradually increased to 906 t of NOX, 443 t of SO2, 2713 t of CO, 477.7 t of PM, 377 t of HCl, 36 t of H2S, 25 t of NH3, 62 t of NMVOCs, 592 kg of Hg, 48 kg of Pb, 14 kg of Cd, 53 kg of As, 40 kg of Cr, 37 kg of Cu, 51 kg of Ni, and 96 g of PCDD/Fs as TEQ (toxic equivalent quantity) by the year 2012. Under the business-as-usual (BAU) scenario, various HAPs emitted from cremators would continuously increase with an average growth rate of 3% till to 2030; whereas the emissions will peak at around 2015 and then decline gradually with varied speed under the two improved control scenarios. To mitigate the associated air pollution and health risks caused by crematories, it is of great necessary for implementing more strict emission standards, applying combustion optimization and requiring installation of best available flue gas purification system, as well as powerful supervision for sound operation of crematories.

Picture of All Solutions of Successive 2-Block Maxbet Problems

ERIC Educational Resources Information Center

Choulakian, Vartan

2011-01-01

The Maxbet method is a generalized principal components analysis of a data set, where the group structure of the variables is taken into account. Similarly, 3-block[12,13] partial Maxdiff method is a generalization of covariance analysis, where only the covariances between blocks (1, 2) and (1, 3) are taken into account. The aim of this paper is…

26 CFR 1.964-2 - Treatment of blocked earnings and profits.

Code of Federal Regulations, 2010 CFR

2010-04-01

... property of a type normally owned by such corporation in the operation of its business or other money which... 26 Internal Revenue 10 2010-04-01 2010-04-01 false Treatment of blocked earnings and profits. 1... earnings and profits. (a) General rule. If, in accordance with paragraph (d) of this section, it is...

E2F mediates induction of the Sp1-controlled promoter of the human DNA polymerase ɛ B-subunit gene POLE2

PubMed Central

Huang, Deqi; Jokela, Maarit; Tuusa, Jussi; Skog, Sven; Poikonen, Kari; Syväoja, Juhani E.

2001-01-01

The B-subunits of replicative DNA polymerases from Archaea to humans belong to the same protein family, suggesting that they share a common fundamental function. We report here the gene structure for the B-subunit of human DNA polymerase ɛ (POLE2), whose expression and transcriptional regulation is typical for replication proteins with some unique features. The 75 bp core promoter region, located within exon 1, contains an Sp1 element that is a critical determinant of promoter activity as shown by the luciferase reporter, electrophoretic mobility shift and DNase I footprinting assays. Two overlapping E2F elements adjacent to the Sp1 element are essential for full promoter activity and serum response. Binding sites for E2F1 and NF-1 reside immediately downstream from the core promoter region. Our results suggest that human POLE2 is regulated by two E2F–pocket protein complexes, one associated with Sp1 and the other with NF-1. So far, only one replicative DNA polymerase B-subunit gene promoter, POLA2 encoding the B-subunit of DNA polymerase α, has been characterized. Mitogenic activation of the POLE2 promoter by an E2F-mediated mechanism resembles that of POLA2, but the regulation of basal promoter activity is different between these two genes. PMID:11433027

40 CFR Table 4 to Subpart Vvvvvv... - Emission Limits and Compliance Requirements for Metal HAP Process Vents

Code of Federal Regulations, 2010 CFR

2010-07-01

... Requirements for Metal HAP Process Vents 4 Table 4 to Subpart VVVVVV of Part 63 Protection of Environment... of Part 63—Emission Limits and Compliance Requirements for Metal HAP Process Vents As required in § 63.11496(f), you must comply with the requirements for metal HAP process vents as shown in the...

A polyvalent hybrid protein elicits antibodies against the diverse allelic types of block 2 in Plasmodium falciparum merozoite surface protein 1.

PubMed

Tetteh, Kevin K A; Conway, David J

2011-10-13

Merozoite surface protein 1 (MSP1) of Plasmodium falciparum has been implicated as an important target of acquired immunity, and candidate components for a vaccine include polymorphic epitopes in the N-terminal polymorphic block 2 region. We designed a polyvalent hybrid recombinant protein incorporating sequences of the three major allelic types of block 2 together with a composite repeat sequence of one of the types and N-terminal flanking T cell epitopes, and compared this with a series of recombinant proteins containing modular sub-components and similarly expressed in Escherichia coli. Immunogenicity of the full polyvalent hybrid protein was tested in both mice and rabbits, and comparative immunogenicity studies of the sub-component modules were performed in mice. The full hybrid protein induced high titre antibodies against each of the major block 2 allelic types expressed as separate recombinant proteins and against a wide range of allelic types naturally expressed by a panel of diverse P. falciparum isolates, while the sub-component modules had partial antigenic coverage as expected. This encourages further development and evaluation of the full MSP1 block 2 polyvalent hybrid protein as a candidate blood-stage component of a malaria vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

40 CFR Table 4 to Subpart Rrrr of... - Default Organic HAP Mass Fraction for Petroleum Solvent Groups 1

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 13 2014-07-01 2014-07-01 false Default Organic HAP Mass Fraction for... PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants...

40 CFR Table 4 to Subpart Rrrr of... - Default Organic HAP Mass Fraction for Petroleum Solvent Groups 1

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 13 2013-07-01 2012-07-01 true Default Organic HAP Mass Fraction for... PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants...

40 CFR Table 4 to Subpart Rrrr of... - Default Organic HAP Mass Fraction for Petroleum Solvent Groups 1

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 13 2012-07-01 2012-07-01 false Default Organic HAP Mass Fraction for... PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants...

Activation of type 2 cannabinoid receptors (CB2R) promotes fatty acid oxidation through the SIRT1/PGC-1α pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Xuqin; Sun, Tao; Wang, Xiaodong, E-mail: xdwang666@hotmail.com

2013-07-05

Highlights: •TC, a CB2R specific agonist, stimulates SIRT1 activity by PKA/CREB pathway. •TC promotes PGC-1α transcriptional activity by increasing its deacetylation. •TC increases the expression of genes linked to FAO and promotes the rate of FAO. •The effects of TC in FAO are dependent on CB2R. •Suggesting CB2R as a target to treat diseases with lipid dysregulation. -- Abstract: Abnormal fatty acid oxidation has been associated with obesity and type 2 diabetes. At the transcriptional level, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) has been reported to strongly increase the ability of hormone nuclear receptors PPARα and ERRα to drive transcriptionmore » of fatty acid oxidation enzymes. In this study, we report that a specific agonist of the type 2 cannabinoid receptor (CB2R) can lead to fatty acid oxidation through the PGC-1α pathway. We have found that CB2R is expressed in differentiated C2C12 myotubes, and that use of the specific agonist trans-caryophyllene (TC) stimulates sirtuin 1 (SIRT1) deacetylase activity by increasing the phosphorylation of cAMP response element-binding protein (CREB), thus leading to increased levels of PGC-1α deacetylation. This use of TC treatment increases the expression of genes linked to the fatty acid oxidation pathway in a SIRT1/PGC-1α-dependent mechanism and also drastically accelerates the rate of complete fatty acid oxidation in C2C12 myotubes, neither of which occur when CB2R mRNA is knocked down using siRNA. These results reveal that activation of CB2R by a selective agonist promotes lipid oxidation through a signaling/transcriptional pathway. Our findings imply that pharmacological manipulation of CB2R may provide therapeutic possibilities to treat metabolic diseases associated with lipid dysregulation.« less

GBP3 promotes glioma cell proliferation via SQSTM1/p62-ERK1/2 axis.

PubMed

Xu, Hui; Sun, Lili; Zheng, Yanwen; Yu, Shuye; Ou-Yang, Jia; Han, Hui; Dai, Xingliang; Yu, Xiaoting; Li, Ming; Lan, Qing

2018-01-01

Guanylate binding proteins (GBPs) are interferon-inducible large GTPases and play a crucial role in cell-autonomous immunity. However, the biology function of GBPs in cancer remains elusive. GBP3 is specifically expressed in adult brain. Here we show that GBP3 is highly elevated in human glioma tumors and glioma cell lines. Overexpression of GBP3 dramatically increased glioma cell proliferation whereas silencing GBP3 by RNA interference produced opposite effects. We further showed that GBP3 expression was able to induce sequestosome-1(SQSTM1, also named p62) expression and activate extracellular signal-regulated kinase (ERK1/2). The SQSTM1-ERK1/2 signaling cascade was essential for GBP3-promoted cell growth because depletion of SQSTM1 markedly reduced the phosphorylated ERK1/2 levels and GBP3-mediated cell growth, and inhibition of mitogen-activated protein kinase/ERK kinase abolished GBP3-induced glioma cell proliferation. Consistently, GBP3 overexpression significantly promoted glioma tumor growth in vivo and its expression was inversely correlated with the survival rate of glioma patients. Taken together, these results for the first time suggest that GBP3 contributes to the proliferation of glioma cells via regulating SQSTM1-ERK1/2 pathway, and GBP3 might represent as a new potential therapeutic target against glioma. Copyright © 2017 Elsevier Inc. All rights reserved.

EBV+ and MSI Gastric Cancers Harbor High PD-L1/PD-1 Expression and High CD8+ Intratumoral Lymphocytes

PubMed Central

De Rosa, Simona; Tibiletti, Maria Grazia; Magnoli, Francesca; Vanoli, Alessandro; Sessa, Fausto; Chiaravalli, Anna Maria

2018-01-01

Both EBV+ and MSI gastric cancers (GCs) have high lymphoid infiltration which is rare in MSS/EBV− cancers. PD-L1/PD-1 interaction leads to a down-regulated immune response and it is one of the most promising targets for gastric cancer immunotherapy. PD-L1/PD-1 and CD8 expression were immunohistochemically investigated in a series of 169 FFPE GCs, including 33 EBV+, 59 MSI and 77 MSS/EBV− cases. PD-L1 membrane immunoreactivity in more than 5% of tumor cells was present in 31/169 GCs and was associated with high levels of CD8 intraepithelial lymphocytes (TILs; p < 0.001). PD-L1+ cases were mainly poorly differentiated (71%), intestinal type (85%) and high lymphoid response (HLR; 90%) tumors. PD-L1 expression was only present in EBV⁺ (46%), MSI (24%) and rare MSS/EBV− (3%) GCs with high CD8+ TILs (p < 0.001). Despite being associated with a better prognosis both in the whole series (p < 0.05) and in the MSI subset, PD-L1 is not an independent prognostic factor. PD-L1 gene amplification was detected in 3/17 cases, including 2/7 EBV+ and 1/8 MSI GC. PD-1⁺ TILs were significantly higher in EBV⁺ than MSI and MSS/EBV− cases. PD-L1/PD-1 pathway is selectively activated in HLR GCs and could be considered an emerging therapeutic target, particularly for EBV and MSI GCs. PMID:29614789

Effects of the adenovirus 2 late promoter on simian virus 40 transcription and replication.

PubMed Central

Grass, D S; Manley, J L

1986-01-01

A 100-base-pair fragment of adenovirus 2 (Ad2) DNA encompassing the major late transcriptional promoter was inserted into the simian virus 40 (SV40) late promoter region at SV40 nucleotide 294 to study the effects of a strong TATA box-containing promoter on SV40 late transcription. pSVAdE contains the insert in an orientation such that it would promote transcription towards the origin and early region of SV40, while the insert is in the opposite orientation in pSVAdL. Nuclease S1 analysis with 5'-end-labeled probes showed that in cells transfected with pSVAdE, the late mRNA initiation sites are essentially the same as in wild type, demonstrating that an insert of 100 base pairs can have no effect on utilization of the SV40 late start sites. In pSVAdL-transfected cells, however, the major late viral initiation site is now in the insert at +1 with respect to the Ad2 major late cap site. However, all of the SV40 initiation sites are still utilized and with the same efficiency relative to each other as in wild type. Thus, it appears that the Ad2 late promoter and the SV40 late promoter can function independently on the same DNA molecule, even when one promoter is embedded within the other. By using cytosine arabinoside to block DNA replication and thereby inhibit the onset of late expression, it has been shown that both the Ad2 late promoter and the SV40 late promoter have similar requirement for DNA replication in this context. In addition, pSVAdL showed dramatically diminished virus viability and VPI expression compared with both wildtype and pSVAdE. Possible explanations for this unexpected finding are discussed. Images PMID:3001338

SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin.

PubMed

Duan, Chaojun; Li, Minghua; Rui, Liangyou

2004-10-15

Leptin regulates energy homeostasis primarily by binding and activating its long form receptor (LRb). Deficiency of either leptin or LRb causes morbid obesity. Leptin stimulates LRb-associated JAK2, thus initiating multiple pathways including the Stat3 and phosphatidylinositol (PI) 3-kinase pathways that mediate leptin biological actions. Here we report that SH2-B, a JAK2-interacting protein, promotes activation of the PI 3-kinase pathway by recruiting insulin receptor substrate 1 (IRS1) and IRS2 in response to leptin. SH2-B directly bound, via its PH and SH2 domain, to both IRS1 and IRS2 both in vitro and in intact cells and mediated formation of a JAK2/SH2-B/IRS1 or IRS2 tertiary complex. Consequently, SH2-B dramatically enhanced leptin-stimulated tyrosine phosphorylation of IRS1 and IRS2 in HEK293 cells stably expressing LRb, thus promoting association of IRS1 and IRS2 with the p85 regulatory subunit of PI 3-kinase and phosphorylation and activation of Akt. SH2-B mutants with lower affinity for IRS1 and IRS2 exhibited reduced ability to promote association of JAK2 with IRS1, tyrosine phosphorylation of IRS1, and association of IRS1 with p85 in response to leptin. Moreover, deletion of the SH2-B gene impaired leptin-stimulated tyrosine phosphorylation of endogenous IRS1 in mouse embryonic fibroblasts (MEF), which was reversed by reintroduction of SH2-B. Similarly, SH2-B promoted growth hormone-stimulated tyrosine phosphorylation of IRS1 in both HEK293 and MEF cells. Our data suggest that SH2-B is a novel mediator of the PI 3-kinase pathway in response to leptin or other hormones and cytokines that activate JAK2.

40 CFR Table 25 to Subpart Uuu of... - Requirements for Performance Tests for Inorganic HAP Emissions From Catalytic Reforming Units

Code of Federal Regulations, 2010 CFR

2010-07-01

... for Inorganic HAP Emissions From Catalytic Reforming Units As stated in § 63.1567(b)(2) and (3), you shall meet each requirement in the following table that applies to you. For each new and existing catalytic reforming unit using . . . You shall . . . Using . . . According to these requirements . . . 1...

40 CFR Table 4 to Subpart Rrrr of... - Default Organic HAP Mass Fraction for Petroleum Solvent Groups 1

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 12 2011-07-01 2009-07-01 true Default Organic HAP Mass Fraction for... PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES National Emission Standards for Hazardous Air Pollutants: Surface Coating of...

40 CFR Table 4 to Subpart Rrrr of... - Default Organic HAP Mass Fraction for Petroleum Solvent Groups 1

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Default Organic HAP Mass Fraction for... PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES National Emission Standards for Hazardous Air Pollutants: Surface Coating of...

The pig CYP2E1 promoter is activated by COUP-TF1 and HNF-1 and is inhibited by androstenone.

PubMed

Tambyrajah, Winston S; Doran, Elena; Wood, Jeffrey D; McGivan, John D

2004-11-15

Functional analysis of the pig cytochrome P4502E1 (CYP2E1) promoter identified two major activating elements. One corresponded to the hepatic nuclear factor 1 (HNF-1) consensus binding sequence at nucleotides -128/-98 and the other was located in the region -292/-266. The binding of proteins in pig liver nuclear extracts to a synthetic double-stranded oligonucleotide corresponding to this more distal activating sequence was studied by electrophoretic mobility shift assay. The minimum protein binding sequence was identified as TGTTCTGACCTCTGGG. Gel super-shift assays identified the protein binding to this site as chick ovalbumin upstream promoter transcription factor 1 (COUP-TF1). Androstenone inhibited promoter activity in transfection experiments only with constructs which included the COUP-TF1 binding site. Androstenone inhibited COUP-TF1 binding to synthetic oligonucleotides but did not affect HNF-1 binding. The results offer an explanation for the inhibition of CYP2E1 protein expression by androstenone in isolated pig hepatocytes and may be relevant to the low expression of hepatic CYP2E1 in those pigs which accumulate high levels of androstenone in vivo.

PKM2 methylation by CARM1 activates aerobic glycolysis to promote tumorigenesis.

PubMed

Liu, Fabao; Ma, Fengfei; Wang, Yuyuan; Hao, Ling; Zeng, Hao; Jia, Chenxi; Wang, Yidan; Liu, Peng; Ong, Irene M; Li, Baobin; Chen, Guojun; Jiang, Jiaoyang; Gong, Shaoqin; Li, Lingjun; Xu, Wei

2017-11-01

Metabolic reprogramming is a hallmark of cancer. Herein we discover that the key glycolytic enzyme pyruvate kinase M2 isoform (PKM2), but not the related isoform PKM1, is methylated by co-activator-associated arginine methyltransferase 1 (CARM1). PKM2 methylation reversibly shifts the balance of metabolism from oxidative phosphorylation to aerobic glycolysis in breast cancer cells. Oxidative phosphorylation depends on mitochondrial calcium concentration, which becomes critical for cancer cell survival when PKM2 methylation is blocked. By interacting with and suppressing the expression of inositol-1,4,5-trisphosphate receptors (InsP 3 Rs), methylated PKM2 inhibits the influx of calcium from the endoplasmic reticulum to mitochondria. Inhibiting PKM2 methylation with a competitive peptide delivered by nanoparticles perturbs the metabolic energy balance in cancer cells, leading to a decrease in cell proliferation, migration and metastasis. Collectively, the CARM1-PKM2 axis serves as a metabolic reprogramming mechanism in tumorigenesis, and inhibiting PKM2 methylation generates metabolic vulnerability to InsP 3 R-dependent mitochondrial functions.

PKM2 methylation by CARM1 activates aerobic glycolysis to promote tumorigenesis

PubMed Central

Liu, Fabao; Ma, Fengfei; Wang, Yuyuan; Hao, Ling; Zeng, Hao; Jia, Chenxi; Wang, Yidan; Liu, Peng; Ong, Irene M; Li, Baobin; Chen, Guojun; Jiang, Jiaoyang; Gong, Shaoqin; Li, Lingjun; Xu, Wei

2017-01-01

Metabolic reprogramming is a hallmark of cancer. Herein we discovered that the key glycolytic enzyme pyruvate kinase M2 isoform (PKM2), but not the related isoform PKM1, is methylated by co-activator associated arginine methyltransferase 1 (CARM1). PKM2 methylation reversibly shifts the balance of metabolism from oxidative phosphorylation to aerobic glycolysis in breast cancer cells. Oxidative phosphorylation depends on mitochondria calcium concentration, which becomes critical for cancer cell survival when PKM2 methylation is blocked. By interacting with and suppressing the expression of inositol 1, 4, 5-trisphosphate receptors (IP3Rs), methylated PKM2 inhibits the influx of calcium from endoplasmic reticulum (ER) to mitochondria. Inhibiting PKM2 methylation with a competitive peptide delivered by nanoparticle perturbs metabolic energy balance in cancer cells, leading to decrease of cell proliferation, migration, and metastasis. Collectively, the CARM1-PKM2 axis serves as a metabolic reprogramming mechanism in tumorigenesis, and inhibiting PKM2 methylation generates metabolic vulnerability to IP3R-dependent mitochondrial functions. PMID:29058718

Bisphenol A promotes cholesterol absorption in Caco-2 cells by up-regulation of NPC1L1 expression.

PubMed

Feng, Dan; Zou, Jun; Zhang, Shanshan; Li, Xuechun; Li, Peiyang; Lu, Minqi

2017-01-06