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Sample records for 7a 7b 7c

  1. MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c.

    PubMed

    Gururajan, A; Naughton, M E; Scott, K A; O'Connor, R M; Moloney, G; Clarke, G; Dowling, J; Walsh, A; Ismail, F; Shorten, G; Scott, L; McLoughlin, D M; Cryan, J F; Dinan, T G

    2016-01-01

    There is a growing emphasis in the field of psychiatry on the need to identify candidate biomarkers to aid in diagnosis and clinical management of depression, particularly with respect to predicting response to specific therapeutic strategies. MicroRNAs are small nucleotide sequences with the ability to regulate gene expression at the transcriptomic level and emerging evidence from a range of studies has highlighted their biomarker potential. Here we compared healthy controls (n=20) with patients diagnosed with major depression (n=40) and who were treatment-resistant to identify peripheral microRNA biomarkers, which could be used for diagnosis and to predict response to electroconvulsive therapy (ECT) and ketamine (KET) infusions, treatments that have previously shown to be effective in treatment-resistant depression (TRD). At baseline and after treatment, blood samples were taken and symptom severity scores rated using the Hamilton Depression Rating Scale (HDRS). Samples were analyzed for microRNA expression using microarray and validated using quantitative PCR. As expected, both treatments reduced HDRS scores. Compared with controls, the baseline expression of the microRNA let-7b was less by ~40% in TRD patients compared with controls. The baseline expression of let-7c was also lower by ~50% in TRD patients who received ECT. Bioinformatic analysis revealed that let-7b and let-7c regulates the expression of 27 genes in the PI3k-Akt-mTOR signaling pathway, which has previously been reported to be dysfunctional in depression. The expression of miR-16, miR-182, miR-451 and miR-223 were similar to that in controls. Baseline microRNA expression could not predict treatment response and microRNAs were unaffected by treatment. Taken together, we have identified let-7b and let-7c as candidate biomarkers of major depression. PMID:27483380

  2. Metal-Dependent Regulation of ATP7A and ATP7B in Fibroblast Cultures

    PubMed Central

    Lenartowicz, Malgorzata; Moos, Torben; Ogórek, Mateusz; Jensen, Thomas G.; Møller, Lisbeth B.

    2016-01-01

    Deficiency of one of the copper transporters ATP7A and ATP7B leads to the rare X-linked disorder Menkes Disease (MD) or the rare autosomal disorder Wilson disease (WD), respectively. In order to investigate whether the ATP7A and the ATP7B genes may be transcriptionally regulated, we measured the expression level of the two genes at various concentrations of iron, copper, and insulin. Treating fibroblasts from controls or from individuals with MD or WD for 3 and 10 days with iron chelators revealed that iron deficiency led to increased transcript levels of both ATP7A and ATP7B. Copper deficiency obtained by treatment with the copper chelator led to a downregulation of ATP7A in the control fibroblasts, but surprisingly not in the WD fibroblasts. In contrast, the addition of copper led to an increased expression of ATP7A, but a decreased expression of ATP7B. Thus, whereas similar regulation patterns for the two genes were observed in response to iron deficiency, different responses were observed after changes in the access to copper. Mosaic fibroblast cultures from female carriers of MD treated with copper or copper chelator for 6–8 weeks led to clonal selection. Cells that express the normal ATP7A allele had a selective growth advantage at high copper concentrations, whereas more surprisingly, cells that express the mutant ATP7A allele had a selective growth advantage at low copper concentrations. Thus, although the transcription of ATP7A is regulated by copper, clonal growth selection in mosaic cell cultures is affected by the level of copper. Female carriers of MD are rarely affected probably due to a skewed inactivation of the X-chromosome bearing the ATP7A mutation. PMID:27587995

  3. Metal-Dependent Regulation of ATP7A and ATP7B in Fibroblast Cultures.

    PubMed

    Lenartowicz, Malgorzata; Moos, Torben; Ogórek, Mateusz; Jensen, Thomas G; Møller, Lisbeth B

    2016-01-01

    Deficiency of one of the copper transporters ATP7A and ATP7B leads to the rare X-linked disorder Menkes Disease (MD) or the rare autosomal disorder Wilson disease (WD), respectively. In order to investigate whether the ATP7A and the ATP7B genes may be transcriptionally regulated, we measured the expression level of the two genes at various concentrations of iron, copper, and insulin. Treating fibroblasts from controls or from individuals with MD or WD for 3 and 10 days with iron chelators revealed that iron deficiency led to increased transcript levels of both ATP7A and ATP7B. Copper deficiency obtained by treatment with the copper chelator led to a downregulation of ATP7A in the control fibroblasts, but surprisingly not in the WD fibroblasts. In contrast, the addition of copper led to an increased expression of ATP7A, but a decreased expression of ATP7B. Thus, whereas similar regulation patterns for the two genes were observed in response to iron deficiency, different responses were observed after changes in the access to copper. Mosaic fibroblast cultures from female carriers of MD treated with copper or copper chelator for 6-8 weeks led to clonal selection. Cells that express the normal ATP7A allele had a selective growth advantage at high copper concentrations, whereas more surprisingly, cells that express the mutant ATP7A allele had a selective growth advantage at low copper concentrations. Thus, although the transcription of ATP7A is regulated by copper, clonal growth selection in mosaic cell cultures is affected by the level of copper. Female carriers of MD are rarely affected probably due to a skewed inactivation of the X-chromosome bearing the ATP7A mutation. PMID:27587995

  4. Post irradiation analysis of RERTR-7A, 7B and RERTR-8 tests

    SciTech Connect

    Hofman, G.L.; Kim, Yeon Soo; Shevlyakov, G.V.; Robinson, A.B.

    2008-07-15

    Addition of 2 wt% or more of silicon in the Al matrix for U-Mo/Al dispersion fuel has proved to be effective in reducing interaction layer growth from the RERTR-7A test to a burnup of {approx}100 at% U-235 (LEU equivalent). The recent RERTR-8 test also showed the consistent results. In this paper, we present the post irradiation analysis results of these tests. A considerable number of monolithic fuel plates were irradiated in the RERTR-7A and RERTR-8 tests. The post irradiation results of these plates are also included. The RERTR-7B test was a lower burnup test with similar power to the RERTR-7A. In this test, dispersion fuel plates with U-7Mo-1Ti and U- 7Mo-2Zr in Al-5Si were irradiated. The post irradiation results of these plates are also covered. (author)

  5. TRIPOLI-4 criticality calculations for MOX fuelled SNEAK 7A and 7B fast critical assemblies

    SciTech Connect

    Lee, Y. K.

    2012-07-01

    A prototype Generation IV fast neutron reactor is under design and development in France. The MOX fuel will be introduced into this self-generating core in order to demonstrate low net plutonium production. To support the TRIPOLI-4 Monte Carlo transport code in criticality calculations of fast reactors, the effective delayed neutron fraction {beta}eff estimation and the Probability Tables (PT) option to treat the unresolved resonance region of cross-sections are two essentials. In this study, TRIPOLI-4 calculations have been made using current nuclear data libraries JEFF-3.1.1 and ENDF/B-VII.0 to benchmark the reactor physics parameters of the MOX fuelled SNEAK 7A and 7B fast critical assemblies. TRIPOLI-4 calculated K{sub eff} and {beta}eff of the homogeneous R-Z models and the 3D multi-cell models have been validated against the measured ones. The impact of the PT option on K{sub eff} is 340 {+-} 10 pcm for SNEAK 7A core and 410 {+-} 12 pcm for 7B. Four-group spectra and energy spectral indices, f8/f5, f9/f5, and c8/f5 in the two SNEAK cores have also been calculated with the TRIPOLI-4 mesh tally. Calculated spectrum-hardening index f8/f5 is 0.0418 for SNEAK 7A and 0.0315 for 7B. From this study the SNEAK 3D models have been verified for the next revision of IRPhE (International Handbook of Evaluated Reactor Physics Benchmark Experiments). (authors)

  6. Development and demonstration of techniques for reducing occupational radiation doses during refueling outages. Tasks 7A/7B. Advanced outage management and radiation exposure control

    SciTech Connect

    Not Available

    1985-03-01

    Objectives of Tasks 7A and 7B were to develop and demonstrate computer based systems to assist plant management and staff in utilizing information more effectively to reduce occupational exposures received as a result of refueling outages, and to shorten the duration of the outage. The Advanced Outage Management (AOM) Tool (Task 7A) is an automated outage planning system specifically designed to meet the needs of nuclear plant outage management. The primary objective of the AOM tool is to provide a computerized system that can manipulate the information typically associated with outage planning and scheduling to furnish reports and schedules that more accurately project the future course of the outage. The Radiation Exposure Control (REC) Tool (Task 7B) is a computerized personnel radiation exposure accounting and management system designed to enable nuclear plant management to project and monitor total personnel radiation exposure on a real-time basis. The two systems were designed to operate on the same computer system and interface through a common database that enables information sharing between plant organizations not typically interfaced. This interfacing provides outage planners with a means of incorporating occupational radiation exposure as a factor for making decisions on the course of an outage.

  7. Novel insights into the assembly and function of human nuclear-encoded cytochrome c oxidase subunits 4, 5a, 6a, 7a and 7b.

    PubMed

    Fornuskova, Daniela; Stiburek, Lukas; Wenchich, Laszlo; Vinsova, Kamila; Hansikova, Hana; Zeman, Jiri

    2010-06-15

    Mammalian CcO (cytochrome c oxidase) is a hetero-oligomeric protein complex composed of 13 structural subunits encoded by both the mitochondrial and nuclear genomes. To study the role of nuclear-encoded CcO subunits in the assembly and function of the human complex, we used stable RNA interference of COX4, COX5A and COX6A1, as well as expression of epitope-tagged Cox6a, Cox7a and Cox7b, in HEK (human embryonic kidney)-293 cells. Knockdown of Cox4, Cox5a and Cox6a resulted in reduced CcO activity, diminished affinity of the residual enzyme for oxygen, decreased holoCcO and CcO dimer levels, increased accumulation of CcO subcomplexes and gave rise to an altered pattern of respiratory supercomplexes. An analysis of the patterns of CcO subcomplexes found in both knockdown and overexpressing cells identified a novel CcO assembly intermediate, identified the entry points of three late-assembled subunits and demonstrated directly the essential character as well as the interdependence of the assembly of Cox4 and Cox5a. The ectopic expression of the heart/muscle-specific isoform of the Cox6 subunit (COX6A2) resulted in restoration of both CcO holoenzyme and activity in COX6A1-knockdown cells. This was in sharp contrast with the unaltered levels of COX6A2 mRNA in these cells, suggesting the existence of a fixed expression programme. The normal amount and function of respiratory complex I in all of our CcO-deficient knockdown cell lines suggest that, unlike non-human CcO-deficient models, even relatively small amounts of CcO can maintain the normal biogenesis of this respiratory complex in cultured human cells. PMID:20307258

  8. Iowa Commercial Pesticide Applicator Manual, Category 7A: General and Household Pest Control. CS-19. Category 7B: Termite Control, CS-20. Category 7C: Food Industry Pest Control, CS-21. Category 7D: Community Insect Control, CS-22.

    ERIC Educational Resources Information Center

    Stockdale, Harold J., Ed.; And Others

    This manual provides information needed to meet specific standards for certification as a pesticide applicator. The first section discusses general and household pest control and is concerned with parasitic pests and man, stored product pests, and irritating vertebrates. Section two is devoted to identifying and controlling structural pests such…

  9. The Tumor Suppressor BCL7B Functions in the Wnt Signaling Pathway

    PubMed Central

    Uehara, Tomoko; Kage-Nakadai, Eriko; Yoshina, Sawako; Imae, Rieko; Mitani, Shohei

    2015-01-01

    Human BCL7 gene family consists of BCL7A, BCL7B, and BCL7C. A number of clinical studies have reported that BCL7 family is involved in cancer incidence, progression, and development. Among them, BCL7B, located on chromosome 7q11.23, is one of the deleted genes in patients with Williams-Beuren syndrome. Although several studies have suggested that malignant diseases occurring in patients with Williams-Beuren syndrome are associated with aberrations in BCL7B, little is known regarding the function of this gene at the cellular level. In this study, we focused on bcl-7, which is the only homolog of BCL7 gene family in Caenorhabditis elegans, and analyzed bcl-7 deletion mutants. As a result, we found that bcl-7 is required for the asymmetric differentiation of epithelial seam cells, which have self-renewal properties as stem cells and divide asymmetrically through the WNT pathway. Distal tip cell development, which is regulated by the WNT pathway in Caenorhabditis elegans, was also affected in bcl-7-knockout mutants. Interestingly, bcl-7 mutants exhibited nuclear enlargement, reminiscent of the anaplastic features of malignant cells. Furthermore, in KATOIII human gastric cancer cells, BCL7B knockdown induced nuclear enlargement, promoted the multinuclei phenotype and suppressed cell death. In addition, this study showed that BCL7B negatively regulates the Wnt-signaling pathway and positively regulates the apoptotic pathway. Taken together, our data indicate that BCL7B/BCL-7 has some roles in maintaining the structure of nuclei and is involved in the modulation of multiple pathways, including Wnt and apoptosis. This study may implicate a risk of malignancies with BCL7B-deficiency, such as Williams-Beuren syndrome. PMID:25569233

  10. ATP7B detoxifies silver in ciliated airway epithelial cells

    SciTech Connect

    Ibricevic, Aida; Brody, Steven L.; Youngs, Wiley J.; Cannon, Carolyn L.

    2010-03-15

    Silver is a centuries-old antibiotic agent currently used to treat infected burns. The sensitivity of a wide range of drug-resistant microorganisms to silver killing suggests that it may be useful for treating refractory lung infections. Toward this goal, we previously developed a methylated caffeine silver acetate compound, SCC1, that exhibits broad-spectrum antimicrobial activity against clinical strains of bacteria in vitro and when nebulized to lungs in mouse infection models. Preclinical testing of high concentrations of SCC1 in primary culture mouse tracheal epithelial cells (mTEC) showed selective ciliated cell death. Ciliated cell death was induced by both silver- and copper-containing compounds but not by the methylated caffeine portion of SCC1. We hypothesized that copper transporting P-type ATPases, ATP7A and ATP7B, play a role in silver detoxification in the airway. In mTEC, ATP7A was expressed in non-ciliated cells, whereas ATP7B was expressed only in ciliated cells. The exposure of mTEC to SCC1 induced the trafficking of ATP7B, but not ATP7A, suggesting the presence of a cell-specific silver uptake and detoxification mechanisms. Indeed, the expression of the copper uptake protein CTR1 was also restricted to ciliated cells. A role of ATP7B in silver detoxification was further substantiated when treatment of SCC1 significantly increased cell death in ATP7B shRNA-treated HepG2 cells. In addition, mTEC from ATP7B{sup -/-} mice showed enhanced loss of ciliated cells compared to wild type. These studies are the first to demonstrate a cell type-specific expression of the Ag{sup +}/Cu{sup +} transporters ATP7A, ATP7B, and CTR1 in airway epithelial cells and a role for ATP7B in detoxification of these metals in the lung.

  11. ATP7B expression confers multidrug resistance through drug sequestration

    PubMed Central

    Moinuddin, F M; Shinsato, Yoshinari; Komatsu, Masaharu; Mitsuo, Ryoichi; Minami, Kentaro; Yamamoto, Masatatsu; Kawahara, Kohich; Hirano, Hirofumi; Arita, Kazunori; Furukawa, Tatsuhiko

    2016-01-01

    We previously reported that ATP7B is involved in cisplatin resistance and ATP7A confers multidrug resistance (MDR) in cancer cells. In this study, we show that ATP7B expressing cells also are resistant to doxorubicin, SN-38, etoposide, and paclitaxel as well as cisplatin. In ATP7B expressing cells, doxorubicin relocated from the nuclei to the late-endosome at 4 hours after doxorubicin exposure. EGFP-ATP7B mainly colocalized with doxorubicin. ATP7B has six metal binding sites (MBSs) in the N-terminal cytoplasmic region. To investigate the role of the MBSs of ATP7B in doxorubicin resistance, we used three mutant ATP7B (Cu0, Cu6 and M6C/S) expressing cells. Cu0 has no MBSs, Cu6 has only the sixth MBS and M6C/S carries CXXC to SXXS mutation in the sixth MBS. Cu6 expressing cells were less resistance to the anticancer agents than wild type ATP7B expressing cells, and had doxorubicin sequestration in the late-endosome. Cu0- and M6C/S-expressing cells were sensitive to doxorubicin. In these cells, doxorubicin did not relocalize to the late-endosome. EGFP-M6C/S mainly localized to the trans-Golgi network (TGN) even in the presence of copper. Thus the cysteine residues in the sixth MBS of ATP7B are essential for MDR phenotype. Finally, we found that ammonium chloride and tamoxifen suppressed late endosomal sequestration of doxorubicin, thereby attenuating drug resistance. These results suggest that the sequestration depends on the acidity of the vesicles partly. We here demonstrate that ATP7B confers MDR by facilitating nuclear drug efflux and late endosomal drug sequestration. PMID:26988911

  12. Estimated Environmental Exposures for MISSE-7B

    NASA Technical Reports Server (NTRS)

    Finckenor, Miria M.; Moore, Chip; Norwood, Joseph K.; Henrie, Ben; DeGroh, Kim

    2012-01-01

    This paper details the 18-month environmental exposure for Materials International Space Station Experiment 7B (MISSE-7B) ram and wake sides. This includes atomic oxygen, ultraviolet radiation, particulate radiation, thermal cycling, meteoroid/space debris impacts, and observed contamination. Atomic oxygen fluence was determined by measured mass and thickness loss of polymers of known reactivity. Diodes sensitive to ultraviolet light actively measured solar radiation incident on the experiment. Comparisons to earlier MISSE flights are discussed.

  13. SLUDGE BATCH 7B GLASS VARIABILITY STUDY

    SciTech Connect

    Johnson, F.; Edwards, T.

    2011-10-25

    The Defense Waste Processing Facility (DWPF) is preparing to initiate processing Sludge Batch 7b (SB7b). In support of the upcoming processing, the Savannah River National Laboratory (SRNL) provided a recommendation to utilize Frits 418 with a 6% Na{sub 2}O addition (26 wt% Na{sub 2}O in sludge) and 702 with a 4% Na{sub 2}O addition (24 wt% Na{sub 2}O in sludge) to process SB7b. This recommendation was based on assessments of the compositional projections for SB7b available at the time from the Savannah River Remediation (SRR). To support qualification of SB7b, SRNL executed a variability study to assess the applicability of the current durability models for SB7b. The durability models were assessed over the expected composition range of SB7b, including potential caustic additions, combined with Frits 702 and 418 over a 32-40% waste loading (WL) range. Thirty four glasses were selected based on Frits 418 and 702 coupled with the sludge projections with an additional 4-6% Na{sub 2}O to reflect the potential caustic addition. Six of these glasses, based on average nominal sludge compositions including the appropriate caustic addition, were developed for both Frit 418 and Frit 702 at 32, 36 and 40% WL to provide coverage in the center of the anticipated SB7b glass region. All glasses were fabricated and characterized using chemical composition analysis, X-ray diffraction (XRD) and the Product Consistency Test (PCT). To comply with the DWPF Glass Product Control Program, a total of thirty four glasses were fabricated to assess the applicability of the current DWPF PCCS durability models. Based on the measured PCT response, all of the glasses were acceptable with respect to the Environmental Assessment (EA) benchmark glass regardless of thermal history. The NL[B] values of the SB7b variability study glasses were less than 1.99 g/L as compared to 16.695 g/L for EA. A small number of the D-optimally selected 'outer layer' extreme vertices (EV) glasses were not predictable

  14. Analysis Of The Sludge Batch 7b (Macrobatch 9) DWPF Pour Stream Glass Sample

    SciTech Connect

    Johnson, F. C.; Crawford, C. L.; Pareizs, J. M.

    2013-11-18

    The Defense Waste Processing Facility (DWPF) began processing Sludge Batch 7b (SB7b), also referred to as Macrobatch 9 (MB9), in January 2012. SB7b is a blend of the heel of Tank 40 from Sludge Batch 7a (SB7a) and the SB7b material that was transferred to Tank 40 from Tank 51. SB7b was processed using Frit 418. During processing of each sludge batch, the DWPF is required to take at least one glass sample to meet the objectives of the Glass Product Control Program (GPCP), which is governed by the DWPF Waste Form Compliance Plan, and to complete the necessary Production Records so that the final glass product may be disposed of at a Federal Repository. Two pour stream glass samples were collected while processing SB7b. The samples were transferred to the Savannah River National Laboratory (SRNL) where one was analyzed and the other was archived. The following conclusions were drawn from the analytical results provided in this report: The sum of oxides for the official SB7b pour stream glass is within the Product Composition Control System (PCCS) limits (95-105 wt%); The average calculated Waste Dilution Factor (WDF) for SB7b is 2.3. In general, the measured radionuclide content of the official SB7b pour stream glass is in good agreement with the calculated values from the Tank 40 dried sludge results from the SB7b Waste Acceptance Program Specification (WAPS) sample; As in previous pour stream samples, ruthenium and rhodium inclusions were detected by Scanning Electron Microscopy-Electron Dispersive Spectroscopy (SEM-EDS) in the SB7b pour stream sample; The Product Consistency Test (PCT) results indicate that the official SB7b pour stream glass meets the waste acceptance criteria for durability with a normalized boron release of 0.8 g/L, which is an order of magnitude less than the Environmental Assessment (EA) glass; The measured density of the SB7b pour stream glass was 2.70 g/cm{sup 3}; The Fe{sup 2+}/ΣFe ratio of the SB7b pour stream samples was 0.07.

  15. SLUDGE BATCH 7B QUALIFICATION ACTIVITIES WITH SRS TANK FARM SLUDGE

    SciTech Connect

    Pareizs, J.; Click, D.; Lambert, D.; Reboul, S.

    2011-11-16

    Waste Solidification Engineering (WSE) has requested that characterization and a radioactive demonstration of the next batch of sludge slurry - Sludge Batch 7b (SB7b) - be completed in the Shielded Cells Facility of the Savannah River National Laboratory (SRNL) via a Technical Task Request (TTR). This characterization and demonstration, or sludge batch qualification process, is required prior to transfer of the sludge from Tank 51 to the Defense Waste Processing Facility (DWPF) feed tank (Tank 40). The current WSE practice is to prepare sludge batches in Tank 51 by transferring sludge from other tanks. Discharges of nuclear materials from H Canyon are often added to Tank 51 during sludge batch preparation. The sludge is washed and transferred to Tank 40, the current DWPF feed tank. Prior to transfer of Tank 51 to Tank 40, SRNL typically simulates the Tank Farm and DWPF processes with a Tank 51 sample (referred to as the qualification sample). With the tight schedule constraints for SB7b and the potential need for caustic addition to allow for an acceptable glass processing window, the qualification for SB7b was approached differently than past batches. For SB7b, SRNL prepared a Tank 51 and a Tank 40 sample for qualification. SRNL did not receive the qualification sample from Tank 51 nor did it simulate all of the Tank Farm washing and decanting operations. Instead, SRNL prepared a Tank 51 SB7b sample from samples of Tank 7 and Tank 51, along with a wash solution to adjust the supernatant composition to the final SB7b Tank 51 Tank Farm projections. SRNL then prepared a sample to represent SB7b in Tank 40 by combining portions of the SRNL-prepared Tank 51 SB7b sample and a Tank 40 Sludge Batch 7a (SB7a) sample. The blended sample was 71% Tank 40 (SB7a) and 29% Tank 7/Tank 51 on an insoluble solids basis. This sample is referred to as the SB7b Qualification Sample. The blend represented the highest projected Tank 40 heel (as of May 25, 2011), and thus, the highest

  16. TANK 40 FINAL SB7B CHEMICAL CHARACTERIZATION RESULTS

    SciTech Connect

    Bannochie, C.

    2012-03-15

    /free OH{sup -}/other base, total inorganic carbon/total organic carbon (TIC/TOC) analyses, and Cs-137 gamma scan. Weighted dilutions of slurry were submitted for IC, TIC/TOC, and total base/free OH{sup -}/other base analyses. Activities for U-233, U-235, and Pu-239 were determined from the ICP-MS data for the aqua regia digestions of the Tank 40 WAPS slurry using the specific activity of each isotope. The Pu-241 value was determined from a Pu-238/-241 method developed by SRNL AD and previously described. The following conclusions were drawn from the analytical results reported here: (1) The ratios of the major elements for the SB7b WAPS sample are different from those measured for the SB7a WAPS sample. There is less Al and Mn relative to Fe than the previous sludge batch. (2) The elemental composition of this sample and the analyses conducted here are reasonable and consistent with DWPF batch data measurements in light of DWPF pre-sample concentration and SRAT product heel contributions to the DWPF SRAT receipt analyses. The element ratios for Al/Fe, Ca/Fe, Mn/Fe, and U/Fe agree within 10% between this work and the DWPF Sludge Receipt and Adjustment Tank (SRAT) receipt analyses. (3) Sulfur in the SB7b WAPS sample is 82% soluble, slightly less than results reported for SB3, SB4, and SB6 samples but unlike the 50% insoluble sulfur observed in the SB5 WAPS sample. In addition, 23% of the soluble sulfur is not present as sulfate in SB7b. (4) The average activities of the fissile isotopes of interest in the SB7b WAPS sample are (in {mu}Ci/g of total dried solids): 4.22E-02 U-233, 6.12E-04 U-235, 1.08E+01 Pu-239, and 5.09E+01 Pu-241. The full radionuclide composition will be reported in a future document. (5) The fission product noble metal and Ag concentrations appear to have largely peaked in previous DWPF sludge batches, with the exception of Ru, which still shows a slight increase in SB7b.

  17. SULFATE SOLUBILITY LIMIT VERIFICATION FOR DWPF SLUDGE BATCH 7B

    SciTech Connect

    Fox, K.

    2011-10-03

    the targeted values. The results for the SB7b glasses fabricated with Frit 418 showed an apparent trend of increasing sulfate retention with increasing Na{sub 2}O additions to the 5/25/11 sludge projection. This trend appears contradictory to other recent studies of sulfate retention in Defense Waste Processing Facility (DWPF) type glasses. Additional apparent contradictions to this trend were found in the data collected in the present study. Overall, the results for the SB7b sulfate study glasses with Frit 418 and the 5/25/11 projection with Na{sub 2}O additions showed that subtle changes in this complex glass composition impacted the degree of sulfate retention. These results do however provide confidence that a 0.6 wt % sulfate limit in glass is warranted for Frit 418 with the SB7b compositions evaluated in this study. The results for the SB7b glasses fabricated with Frit 702 are consistent with those of the previous SB7a study in that Frit 702 allowed for higher sulfate retention as compared to Frit 418 for the same sludge compositions. It is recommended that the DWPF implement a sulfate concentration limit of 0.6 wt % in glass for SB7b processing with Frit 418. If a higher than projected sulfate concentration is measured when SB7b processing begins (i.e., if a sulfate concentration higher than 0.6 wt % becomes necessary to achieve targeted waste loadings), DWPF should consider a transition to Frit 702. The sulfate limit could likely be raised to 0.8 wt % by transitioning to this frit. However, if DWPF considers transitioning from Frit 418 to Frit 702, additional glasses should be fabricated to confirm this higher limit due to the issues with incorrect B{sub 2}O{sub 3} concentrations for some of the glasses made with Frit 702 in this study. There are several factors other than sulfate retention that must also be carefully considered prior to changing frit compositions.

  18. CoRoT-7b: SUPER-EARTH OR SUPER-Io?

    SciTech Connect

    Barnes, Rory; Kaib, Nathan A.; Raymond, Sean N.; Greenberg, Richard; Jackson, Brian

    2010-02-01

    CoRoT-7b, a planet about 70% larger than the Earth orbiting a Sun-like star, is the first-discovered rocky exoplanet, and hence has been dubbed a 'super-Earth'. Some initial studies suggested that since the planet is so close to its host star, it receives enough insolation to partially melt its surface. However, these past studies failed to take into consideration the role that tides may play in this system. Even if the planet's eccentricity has always been zero, we show that tidal decay of the semimajor axis could have been large enough that the planet formed on a wider orbit which received less insolation. Moreover, CoRoT-7b could be tidally heated at a rate that dominates its geophysics and drives extreme volcanism. In this case, CoRoT-7b is a 'super-Io' that, like Jupiter's volcanic moon, is dominated by volcanism and rapid resurfacing. Such heating could occur with an eccentricity of just 10{sup -5}. This small value could be driven by CoRoT-7c if its own eccentricity is larger than {approx}10{sup -4}. CoRoT-7b may be the first of a class of planetary super-Ios likely to be revealed by the CoRoT and Kepler spacecraft.

  19. CoRoT-7b: Super-Earth or Super-Io?

    NASA Astrophysics Data System (ADS)

    Barnes, Rory; Raymond, Sean N.; Greenberg, Richard; Jackson, Brian; Kaib, Nathan A.

    2010-02-01

    CoRoT-7b, a planet about 70% larger than the Earth orbiting a Sun-like star, is the first-discovered rocky exoplanet, and hence has been dubbed a "super-Earth." Some initial studies suggested that since the planet is so close to its host star, it receives enough insolation to partially melt its surface. However, these past studies failed to take into consideration the role that tides may play in this system. Even if the planet's eccentricity has always been zero, we show that tidal decay of the semimajor axis could have been large enough that the planet formed on a wider orbit which received less insolation. Moreover, CoRoT-7b could be tidally heated at a rate that dominates its geophysics and drives extreme volcanism. In this case, CoRoT-7b is a "super-Io" that, like Jupiter's volcanic moon, is dominated by volcanism and rapid resurfacing. Such heating could occur with an eccentricity of just 10-5. This small value could be driven by CoRoT-7c if its own eccentricity is larger than ~10-4. CoRoT-7b may be the first of a class of planetary super-Ios likely to be revealed by the CoRoT and Kepler spacecraft.

  20. Synergistic Antifungal Activity of Berberine Derivative B-7b and Fluconazole

    PubMed Central

    Li, Li Ping; Liu, Wei; Liu, Hong; Zhu, Fang; Zhang, Da Zhi; Shen, Hui; Xu, Zheng; Qi, Yun Peng; Zhang, Shi Qun; Chen, Si Min; He, Li Juan; Cao, Xin Ju; Huang, Xin; Zhang, Jun Dong; Yan, Lan; An, Mao Mao; Jiang, Yuan Ying

    2015-01-01

    Our previous study demonstrated berberine (BBR) and fluconazole (FLC) used concomitantly exhibited a synergism against FLC-resistant Candida albicans in vitro. We also suggested BBR played a major antifungal role in the synergism of FLC and BBR, while FLC increased intracellular BBR concentrations. Our following systematic structural modification and reconstruction of BBR core identified the novel scaffold of N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acet-amide derivatives 7a-i, including B-7b and B-7d exhibiting remarkable synergistic antifungal activity and low cytotoxicity. Here, the study mainly investigated the synergistic activity of FLC and B-7b and the underlying mechanism. In vitro interaction of FLC and B-7b was investigated against 30 FLC-resistant clinical isolates of C. albicans and non-C. albicans species, including Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei and Cryptococcus neoformans. The potent synergistic activity of B-7b in combination with FLC against FLC-resistant C. albicans was found through the checkerboard microdilution assay. The findings of agar diffusion tests and time-kill curves confirmed its better synergism with FLC. And as expected, B-7b exhibited much lower cytotoxicity than BBR to human umbilical vein endothelial cells. In contrast to BBR, we found that endogenous ROS augmentation was not involved in the synergism of FLC and B-7b. According to the results from our present comparative proteomic study, it seemed that the disruption of protein folding and processing and the weakening of cells’ self-defensive ability contributed to the synergism of FLC and B-7b. Together, these results suggested novel scaffold BBR derivative B-7b could be a promising synergist in combination with FLC for the treatment of invasive fungal infections. PMID:25992630

  1. Determination Of Reportable Radionuclides For DWPF Sludge Batch 7B (Macrobatch 9)

    SciTech Connect

    Crawford, C. L.; Diprete, D. P.

    2012-12-17

    The DWPF is receiving radioactive sludge slurry from HLW Tank 40. The radioactive sludge slurry in Tank 40 is a blend of the heel from Sludge Batch 7a (SB7a) and Sludge Batch 7b (SB7b) that was transferred to Tank 40 from Tank 51. The blend of sludge in Tank 40 is also referred to as Macrobatch 9 (MB9). This report develops the list of reportable radionuclides and associated activities as a function of time. Twenty-seven radionuclides have been identified as reportable for DWPF SB7b. Each of these radionuclides has a half-life greater than ten years and contributes more than 0.01% of the radioactivity on a Curie basis at some point from production through the 1100 year period between 2015 and 3115. For SB7b, all of the radionuclides in the Design Basis glass are reportable except for three radionuclides: Pd-107, Cs-135, and Th-230. At no time during the 1100- year period between 2015 and 3115 did any of these three radionuclides contribute to more than 0.01% of the radioactivity on a Curie basis. The radionuclide measurements made for SB7b are the most extensive conducted to date. Some method development/refinement occurred during the conduct of these measurements, leading to lower detection limits and more accurate measurement of some isotopes than was previously possible.

  2. DWPF SIMULANT CPC STUDIES FOR SB7B

    SciTech Connect

    Koopman, D.

    2011-11-01

    same acid stoichiometric factor. The slow acid addition in MCU seemed to alter the reactions that consumed the small excess acid present such that hydrogen generation was promoted relative to sludge-only processing. The coupled test reached higher wt.% total solids, and this likely contributed to the SME cycle hydrogen limit being exceeded at 110% KMA. It is clear from the trends in the SME processing GC data, however, that the frit slurry formic acid contributed to driving the hydrogen generation rate above the SME cycle limit. Hydrogen generation rates after the second frit addition generally exceeded those after the first frit addition. SRAT formate loss increased with increasing acid stoichiometry (15% to 35%). A substantial nitrate gain which was observed to have occurred after acid addition (and nitrite destruction) was reversed to a net nitrate loss in runs with higher acid stoichiometry (nitrate in SRAT product less than sum of sludge nitrate and added nitric acid). Increased ammonium ion formation was also indicated in the runs with nitrate loss. Oxalate loss on the order 20% was indicated in three of the four acid stoichiometry runs and in the coupled flowsheet run. The minimum acid stoichiometry run had no indicated loss. The losses were of the same order as the official analytical uncertainty of the oxalate concentration measurement, but were not randomly distributed about zero loss, so some actual loss was likely occurring. Based on the entire set of SB7b test data, it is recommended that DWPF avoid concentrating additional sludge solids in single SRAT batches to limit the concentrations of noble metals to SB7a processing levels (on a grams noble metal per SRAT batch basis). It is also recommended that DWPF drop the formic acid addition that accompanies the process frit 418 additions, since SME cycle data showed considerable catalytic activity for hydrogen generation from this additional acid (about 5% increase in stoichiometry occurred from the frit

  3. PROCEEDINGS: 1990 SO2 CONTROL SYMPOSIUM - VOLUME 4: SESSIONS 7A, 7B, AND POSTERS

    EPA Science Inventory

    The proceedings document 110 papers presented at the Symposium held in New Orleans, LA, May 8-11, 1990. opics included SO2 control economics, furnace sorbent injection, byproduct utilization, spray dryer technology, wet flue gas desulfurization (FGD) and combined SOx/NOx control ...

  4. The Roles of Tidal Evolution and Evaporative Mass Loss in the Origin of CoRoT-7 b

    NASA Technical Reports Server (NTRS)

    Jackson, Brian; Miller, Neil; Barnes, Rory; Raymond, Sean N.; Fortney, Jonathan J.; Greenberg, Richard

    2010-01-01

    CoRoT-7 b is the first confirmed rocky exoplanet, but, with an orbital semimajor axis of 0.0172 au, its origins may be unlike any rocky planet in our Solar System. In this study, we consider the roles of tidal evolution and evaporative mass loss in CoRoT-7 b's history, which together have modified the planet's mass and orbit. If CoRoT-7 b has always been a rocky body, evaporation may have driven off almost half its original mass, but the mass loss may depend sensitively on the extent of tidal decay of its orbit. As tides caused CoRoT-7 b's orbit to decay, they brought the planet closer to its host star, thereby enhancing the mass loss rate. Such a large mass loss also suggests the possibility that CoRoT-7 b began as a gas giant planet and had its original atmosphere completely evaporated. In this case, we find that CoRoT-7 b's original mass probably did not exceed 200 Earth masses (about two-third of a Jupiter mass). Tides raised on the host star by the planet may have significantly reduced the orbital semimajor axis, perhaps causing the planet to migrate through mean-motion resonances with the other planet in the system, CoRoT-7 c. The coupling between tidal evolution and mass loss may be important not only for CoRoT-7 b but also for other close-in exoplanets, and future studies of mass loss and orbital evolution may provide insight into the origin and fate of close-in planets, both rocky and gaseous.

  5. 7. B & O RAILROAD BRIDGE. PHILADELPHIA, PHILADELPHIA CO., PA. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. B & O RAILROAD BRIDGE. PHILADELPHIA, PHILADELPHIA CO., PA. Sec. 1101, MP 3.11. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

  6. Overview of Materials International Space Station Experiment 7B

    NASA Technical Reports Server (NTRS)

    Jaworske, Donald A.; Siamidis, John

    2009-01-01

    Materials International Space Station Experiment 7B (MISSE 7B) is the most recent in a series of experiments flown on the exterior of International Space Station for the purpose of determining the durability of materials and components in the space environment. A collaborative effort among the Department of Defense, the National Aeronautics and Space Administration, industry, and academia, MISSE 7B will be flying a number of NASA experiments designed to gain knowledge in the area of space environmental effects to mitigate risk for exploration missions. Consisting of trays called Passive Experiment Containers, the suitcase sized payload opens on hinges and allows active and passive experiments contained within to be exposed to the ram and wake or zenith and nadir directions in low Earth orbit, in essence, providing a test bed for atomic oxygen exposure, ultraviolet radiation exposure, charged particle radiation exposure, and thermal cycling. New for MISSE 7B is the ability to monitor experiments actively, with data sent back to Earth via International Space Station communications. NASA?s active and passive experiments cover a range of interest for the Agency. Materials relevant to the Constellation Program include: solar array materials, seal materials, and thermal protection system materials. Materials relevant to the Exploration Technology Development Program include: fabrics for spacesuits, materials for lunar dust mitigation, and new thermal control coatings. Sensors and components on MISSE 7B include: atomic oxygen fluence monitors, ultraviolet radiation sensors, and electro-optical components. In addition, fundamental space environmental durability science experiments are being flown to gather atomic oxygen erosion data and thin film polymer mechanical and optical property data relevant to lunar lander insulation and the James Web Space Telescope. This paper will present an overview of the NASA experiments to be flown on MISSE 7B, along with a summary of the

  7. Neuroendocrine secretory protein 7B2: structure, expression and functions.

    PubMed Central

    Mbikay, M; Seidah, N G; Chrétien, M

    2001-01-01

    7B2 is an acidic protein residing in the secretory granules of neuroendocrine cells. Its sequence has been elucidated in many phyla and species. It shows high similarity among mammals. A Pro-Pro-Asn-Pro-Cys-Pro polyproline motif is its most conserved feature, being carried by both vertebrate and invertebrate sequences. It is biosynthesized as a precursor protein that is cleaved into an N-terminal fragment and a C-terminal peptide. In neuroendocrine cells, 7B2 functions as a specific chaperone for the proprotein convertase (PC) 2. Through the sequence around its Pro-Pro-Asn-Pro-Cys-Pro motif, it binds to an inactive proPC2 and facilitates its transport from the endoplasmic reticulum to later compartments of the secretory pathway where the zymogen is proteolytically matured and activated. Its C-terminal peptide can inhibit PC2 in vitro and may contribute to keep the enzyme transiently inactive in vivo. The PC2-7B2 model defines a new neuroendocrine paradigm whereby proteolytic activation of prohormones and proneuropeptides in the secretory pathway is spatially and temporally regulated by the dynamics of interactions between converting enzymes and their binding proteins. Interestingly, unlike PC2-null mice, which are viable, 7B2-null mutants die early in life from Cushing's disease due to corticotropin ('ACTH') hypersecretion by the neurointermediate lobe, suggesting a possible involvement of 7B2 in secretory granule formation and in secretion regulation. The mechanism of this regulation is yet to be elucidated. 7B2 has been shown to be a good marker of several neuroendocrine cell dysfunctions in humans. The possibility that anomalies in its structure and expression could be aetiological causes of some of these dysfunctions warrants investigation. PMID:11439082

  8. Diverse Functional Properties of Wilson Disease ATP7B Variants

    PubMed Central

    Huster, Dominik; Kühne, Angelika; Bhattacharjee, Ashima; Raines, Lily; Jantsch, Vanessa; Noe, Johannes; Schirrmeister, Wiebke; Sommerer, Ines; Sabri, Osama; Berr, Frieder; Mössner, Joachim; Stieger, Bruno; Caca, Karel; Lutsenko, Svetlana

    2012-01-01

    BACKGROUND & AIMS Wilson disease is a severe disorder of copper metabolism caused by mutations in ATP7B, which encodes a copper-transporting adenosine triphosphatase. The disease presents with a variable phenotype that complicates the diagnostic process and treatment. Little is known about the mechanisms that contribute to the different phenotypes of the disease. METHODS We analyzed 28 variants of ATP7B from patients with Wilson disease that affected different functional domains; the gene products were expressed using the baculovirus expression system in Sf9 cells. Protein function was analyzed by measuring catalytic activity and copper (64Cu) transport into vesicles. We studied intracellular localization of variants of ATP7B that had measurable transport activities and were tagged with green fluorescent protein in mammalian cells using confocal laser scanning microscopy. RESULTS Properties of ATP7B variants with pathogenic amino-acid substitution varied greatly even if substitutions were in the same functional domain. Some variants had complete loss of catalytic and transport activity, whereas others lost transport activity but retained phosphor-intermediate formation or had partial losses of activity. In mammalian cells, transport-competent variants differed in stability and subcellular localization. CONCLUSIONS Variants in ATP7B associated with Wilson disease disrupt the protein’s transport activity, result in its mislocalization, and reduce its stability. Single assays are insufficient to accurately predict the effects of ATP7B variants the function of its product and development of Wilson disease. These findings will contribute to our understanding of genotype–phenotype correlation and mechanisms of disease pathogenesis. PMID:22240481

  9. 19 CFR 4.7c - Vessel stow plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Vessel stow plan. 4.7c Section 4.7c Customs Duties... VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.7c Vessel stow plan. Vessel stow... and the container status message requirements pursuant to § 4.7d of this part, for all vessels...

  10. 19 CFR 4.7c - Vessel stow plan.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Vessel stow plan. 4.7c Section 4.7c Customs Duties... VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.7c Vessel stow plan. Vessel stow... and the container status message requirements pursuant to § 4.7d of this part, for all vessels...

  11. 19 CFR 4.7c - Vessel stow plan.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Vessel stow plan. 4.7c Section 4.7c Customs Duties... VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.7c Vessel stow plan. Vessel stow... and the container status message requirements pursuant to § 4.7d of this part, for all vessels...

  12. Wnt7b is an important intrinsic regulator of hair follicle stem cell homeostasis and hair follicle cycling

    PubMed Central

    Kandyba, Eve; Kobielak, Krzysztof

    2014-01-01

    The hair follicle (HF) is an exceptional mini-organ to study the mechanisms which regulate HF morphogenesis, cycling, hair follicle stem cell (hfSCs) homeostasis and progeny differentiation. During morphogenesis, Wnt signaling is well characterized in the initiation of HF patterning but less is known about which particular Wnt ligands are required and whether individual Wnt ligands act in an indispensable or redundant manner during postnatal hfSCs anagen onset and HF cycle progression. Previously, we described the function of the Bone morphogenetic protein (BMP) signaling target gene WNT7a in intrinsic regulation of hfSCs homeostasis in vivo. Here, we investigated the role of Wnt7b, which was also intrinsically up-regulated in hfSCs during physiological and precocious anagen after BMP inhibition in vivo. We demonstrated Wnt7b to be a direct target of canonical BMP signaling in hfSCs and using Wnt7b conditional gene targeting during HF morphogenesis revealed disrupted HF cycling including a shorter anagen, premature catagen onset with overall shorter hair production and diminished HF differentiation marker expression. Additionally, we observed that postnatal ablation of Wnt7b resulted in delayed HF activation, affecting both the HG and bulge hfSCs but still maintaining a two-step sequence of HF stimulation. Interestingly, Wnt7b cKO hfSCs participated in re-formation of the new HF bulge, but with slower self-renewal. These findings demonstrate the importance of intrinsic Wnt7b expression in hfSCs regulation and normal HF cycling and surprisingly reveal a non-redundant role for Wnt7b in the control of HF anagen length and catagen entry which was not compensated by other Wnt ligands. PMID:24222445

  13. Wnt7b is an important intrinsic regulator of hair follicle stem cell homeostasis and hair follicle cycling.

    PubMed

    Kandyba, Eve; Kobielak, Krzysztof

    2014-04-01

    The hair follicle (HF) is an exceptional mini-organ to study the mechanisms which regulate HF morphogenesis, cycling, hair follicle stem cell (hfSCs) homeostasis, and progeny differentiation. During morphogenesis, Wnt signaling is well-characterized in the initiation of HF patterning but less is known about which particular Wnt ligands are required and whether individual Wnt ligands act in an indispensable or redundant manner during postnatal hfSCs anagen onset and HF cycle progression. Previously, we described the function of the bone morphogenetic protein (BMP) signaling target gene WNT7a in intrinsic regulation of hfSCs homeostasis in vivo. Here, we investigated the role of Wnt7b, which was also intrinsically upregulated in hfSCs during physiological and precocious anagen after BMP inhibition in vivo. We demonstrated Wnt7b to be a direct target of canonical BMP signaling in hfSCs and using Wnt7b conditional gene targeting during HF morphogenesis revealed disrupted HF cycling including a shorter anagen, premature catagen onset with overall shorter hair production, and diminished HF differentiation marker expression. Additionally, we observed that postnatal ablation of Wnt7b resulted in delayed HF activation, affecting both the hair germ and bulge hfSCs but still maintaining a two-step sequence of HF stimulation. Interestingly, Wnt7b cKO hfSCs participated in reformation of the new HF bulge, but with slower self-renewal. These findings demonstrate the importance of intrinsic Wnt7b expression in hfSCs regulation and normal HF cycling and surprisingly reveal a nonredundant role for Wnt7b in the control of HF anagen length and catagen entry which was not compensated by other Wnt ligands. PMID:24222445

  14. Decreased Lin7b Expression in Layer 5 Pyramidal Neurons May Contribute to Impaired Corticostriatal Connectivity in Huntington Disease

    PubMed Central

    Zucker, Birgit; Kama, Jibrin A.; Kuhn, Alexandre; Thu, Doris; Orlando, Lianna R.; Dunah, Anthone W.; Gokce, Ozgun; Taylor, David M.; Lambeck, Johann; Friedrich, Bernd; Lindenberg, Katrin S.; Faull, Richard L.M.; Weiller, Cornelius; Young, Anne B.; Luthi-Carter, Ruth

    2010-01-01

    Motor dysfunction, cognitive impairment and regional cortical atrophy indicate cerebral cortical involvement in Huntington disease (HD). To address the hypothesis that abnormal corticostriatal connectivity arises from polyglutamine-related alterations in cortical gene expression, we isolated layer 5 cortical neurons by laser-capture microdissection and analyzed transcriptome-wide mRNA changes in them. Enrichment of transcription factor mRNAs including foxp2, tbr1, and neuroD6, and neurotransmission- and plasticity-related RNAs including sema5A, pclo, ntrk2, cntn1 and lin7b were observed. Layer 5 motor cortex neurons of transgenic R6/2 HD mice also demonstrated numerous transcriptomic changes, including decreased expression of mRNAs encoding the lin7 homolog b, (lin7b, also known as veli-2 and mals2). Decreases in LIN7B and CNTN1 RNAs were also detected in human HD layer 5 motor cortex neurons. lin7b, a scaffold protein implicated in synaptic plasticity, neurite outgrowth and cellular polarity, was decreased at the protein level in layer 5 cortical neurons in R6/2 mice and human HD brains. Decreases in Lin7b and Lin7a mRNAs were detected in R6/2 cortex as early as 6 weeks of age, suggesting that this is an early pathogenetic event. Thus, decreased cortical LIN7 expression may contribute to abnormal corticostriatal connectivity in HD. PMID:20720508

  15. AUF1 promotes let-7b loading on Argonaute 2.

    PubMed

    Yoon, Je-Hyun; Jo, Myung Hyun; White, Elizabeth J F; De, Supriyo; Hafner, Markus; Zucconi, Beth E; Abdelmohsen, Kotb; Martindale, Jennifer L; Yang, Xiaoling; Wood, William H; Shin, Yu Mi; Song, Ji-Joon; Tuschl, Thomas; Becker, Kevin G; Wilson, Gerald M; Hohng, Sungchul; Gorospe, Myriam

    2015-08-01

    Eukaryotic gene expression is tightly regulated post-transcriptionally by RNA-binding proteins (RBPs) and microRNAs. The RBP AU-rich-binding factor 1 (AUF1) isoform p37 was found to have high affinity for the microRNA let-7b in vitro (Kd = ∼ 6 nM) in cells. Ribonucleoprotein immunoprecipitation, in vitro association, and single-molecule-binding analyses revealed that AUF1 promoted let-7b loading onto Argonaute 2 (AGO2), the catalytic component of the RNA-induced silencing complex (RISC). In turn, AGO2-let-7 triggered target mRNA decay. Our findings uncover a novel mechanism by which AUF1 binding and transfer of microRNA let-7 to AGO2 facilitates let-7-elicited gene silencing. PMID:26253535

  16. THE MASS OF CoRoT-7b

    SciTech Connect

    Hatzes, Artie P.; Wuchterl, Guenther; Fridlund, Malcolm; Gandolfi, Davide; Nachmani, Gil; Mazeh, Tsevi; Valencia, Diana; Hebrard, Guillaume; Borde, Pascal; Carone, Ludmila; Paetzold, Martin; Udry, Stephane; Bouchy, Francois; Deleuil, Magali; Moutou, Claire; Barge, Pierre; Deeg, Hans; Tingley, Brandon; Dvorak, Rudolf; Ferraz-Mello, Sylvio E-mail: malcolm.fridlund@esa.int; and others

    2011-12-10

    The mass of CoRoT-7b, the first transiting super-Earth exoplanet, is still a subject of debate. A wide range of masses have been reported in the literature ranging from as high as 8 M{sub Circled-Plus} to as low as 2.3 M{sub Circled-Plus }. This range in mass is largely due to the activity level of the star that contributes a significant amount of radial velocity (RV) 'jitter' and how the various methods correct this jitter. Although most mass determinations give a density consistent with a rocky planet, the lower value permits a bulk composition that can be up to 50% water. We present an analysis of the CoRoT-7b RV measurements that uses very few and simple assumptions in treating the activity signal. By analyzing those RV data for which multiple measurements were made in a given night, we remove the activity related RV contribution without any a priori model. We argue that the contribution of activity to the final RV curve is negligible and that the K-amplitude due to the planet is well constrained. This yields a mass of 7.42 {+-} 1.21 M{sub Circled-Plus} and a mean density of {rho} = 10.4 {+-} 1.8 gm cm{sup -3}. CoRoT-7b is similar in mass and radius to the second rocky planet to be discovered, Kepler-10b, and within the errors they have identical bulk densities-they are virtual twins. These bulk densities lie close to the density-radius relationship for terrestrial planets similar to what is seen for Mercury. CoRoT-7b and Kepler-10b may have an internal structure more like Mercury than the Earth.

  17. The Mass of CoRoT-7b

    NASA Astrophysics Data System (ADS)

    Hatzes, Artie P.; Fridlund, Malcolm; Nachmani, Gil; Mazeh, Tsevi; Valencia, Diana; Hébrard, Guillaume; Carone, Ludmila; Pätzold, Martin; Udry, Stephane; Bouchy, Francois; Deleuil, Magali; Moutou, Claire; Barge, Pierre; Bordé, Pascal; Deeg, Hans; Tingley, Brandon; Dvorak, Rudolf; Gandolfi, Davide; Ferraz-Mello, Sylvio; Wuchterl, Günther; Guenther, Eike; Guillot, Tristan; Rauer, Heike; Erikson, Anders; Cabrera, Juan; Csizmadia, Szilard; Léger, Alain; Lammer, Helmut; Weingrill, Jörg; Queloz, Didier; Alonso, Roi; Rouan, Daniel; Schneider, Jean

    2011-12-01

    The mass of CoRoT-7b, the first transiting super-Earth exoplanet, is still a subject of debate. A wide range of masses have been reported in the literature ranging from as high as 8 M ⊕ to as low as 2.3 M ⊕. This range in mass is largely due to the activity level of the star that contributes a significant amount of radial velocity (RV) "jitter" and how the various methods correct this jitter. Although most mass determinations give a density consistent with a rocky planet, the lower value permits a bulk composition that can be up to 50% water. We present an analysis of the CoRoT-7b RV measurements that uses very few and simple assumptions in treating the activity signal. By analyzing those RV data for which multiple measurements were made in a given night, we remove the activity related RV contribution without any a priori model. We argue that the contribution of activity to the final RV curve is negligible and that the K-amplitude due to the planet is well constrained. This yields a mass of 7.42 ± 1.21 M ⊕ and a mean density of ρ = 10.4 ± 1.8 gm cm-3. CoRoT-7b is similar in mass and radius to the second rocky planet to be discovered, Kepler-10b, and within the errors they have identical bulk densities—they are virtual twins. These bulk densities lie close to the density-radius relationship for terrestrial planets similar to what is seen for Mercury. CoRoT-7b and Kepler-10b may have an internal structure more like Mercury than the Earth.

  18. Tank 40 Final SB7b Chemical Characterization Results

    SciTech Connect

    Bannochie, C. J.

    2012-11-06

    A sample of Sludge Batch 7b (SB7b) was taken from Tank 40 in order to obtain radionuclide inventory analyses necessary for compliance with the Waste Acceptance Product Specifications (WAPS). The SB7b WAPS sample was also analyzed for chemical composition including noble metals and fissile constituents. At the Savannah River National Laboratory (SRNL) the 3-L Tank 40 SB7b sample was transferred from the shipping container into a 4-L high density polyethylene bottle and solids were allowed to settle over the weekend. Supernate was then siphoned off and circulated through the shipping container to complete the transfer of the sample. Following thorough mixing of the 3-L sample, a 558 g sub-sample was removed. This sub-sample was then utilized for all subsequent analytical samples. Eight separate aliquots of the slurry were digested, four with HNO{sub 3}/HCl (aqua regia) in sealed Teflon vessels and four with NaOH/Na{sub 2}O{sub 2} (alkali or peroxide fusion) using Zr crucibles. Two Analytical Reference Glass ? 1 (ARG-1) standards were digested along with a blank for each preparation. Each aqua regia digestion and blank was diluted to 1:100 mL with deionized water and submitted to Analytical Development (AD) for inductively coupled plasma ? atomic emission spectroscopy (ICP-AES) analysis, inductively coupled plasma ? mass spectrometry (ICP-MS) analysis, atomic absorption spectroscopy (AA) for As and Se, and cold vapor atomic absorption spectroscopy (CV-AA) for Hg. Equivalent dilutions of the alkali fusion digestions and blank were submitted to AD for ICP-AES analysis. Tank 40 SB7b supernate was collected from a mixed slurry sample in the SRNL Shielded Cells and submitted to AD for ICP-AES, ion chromatography (IC), total base/free OH{sup -}/other base, total inorganic carbon/total organic carbon (TIC/TOC) analyses, and Cs-137 gamma scan. Weighted dilutions of slurry were submitted for IC, TIC/TOC, and total base/free OH-/other base analyses. Activities for U-233, U-235

  19. KEPLER-7b: A TRANSITING PLANET WITH UNUSUALLY LOW DENSITY

    SciTech Connect

    Latham, David W.; Buchhave, Lars A.; Furesz, Gabor; Geary, John C.; Borucki, William J.; Koch, David G.; Lissauer, Jack J.; Rowe, Jason F.; Brown, Timothy M.; Basri, Gibor; Batalha, Natalie M.; Caldwell, Douglas A.; Jenkins, Jon M.; Cochran, William D.; Dunham, Edward W.; Gautier, Thomas N.; Howell, Steve B.; Marcy, Geoffrey W.; Monet, David G.

    2010-04-20

    We report on the discovery and confirmation of Kepler-7b, a transiting planet with unusually low density. The mass is less than half that of Jupiter, M {sub P} = 0.43 M {sub J}, but the radius is 50% larger, R {sub P} = 1.48 R {sub J}. The resulting density, {rho}{sub P} = 0.17 g cm{sup -3}, is the second lowest reported so far for an extrasolar planet. The orbital period is fairly long, P = 4.886 days, and the host star is not much hotter than the Sun, T {sub eff} = 6000 K. However, it is more massive and considerably larger than the Sun, M {sub *} = 1.35 M {sub sun} and R {sub *} = 1.84 R {sub sun}, and must be near the end of its life on the main sequence.

  20. THE HIGH ALBEDO OF THE HOT JUPITER KEPLER-7 b

    SciTech Connect

    Demory, Brice-Olivier; Seager, Sara; Madhusudhan, Nikku; Kjeldsen, Hans; Christensen-Dalsgaard, Joergen; Gillon, Michael; Rowe, Jason F.; Borucki, William J.; Koch, David G.; Welsh, William F.; Adams, Elisabeth R.; Dupree, Andrea; McCarthy, Don; Kulesa, Craig

    2011-07-01

    Hot Jupiters are expected to be dark from both observations (albedo upper limits) and theory (alkali metals and/or TiO and VO absorption). However, only a handful of hot Jupiters have been observed with high enough photometric precision at visible wavelengths to investigate these expectations. The NASA Kepler mission provides a means to widen the sample and to assess the extent to which hot Jupiter albedos are low. We present a global analysis of Kepler-7 b based on Q0-Q4 data, published radial velocities, and asteroseismology constraints. We measure an occultation depth in the Kepler bandpass of 44 {+-} 5 ppm. If directly related to the albedo, this translates to a Kepler geometric albedo of 0.32 {+-} 0.03, the most precise value measured so far for an exoplanet. We also characterize the planetary orbital phase light curve with an amplitude of 42 {+-} 4 ppm. Using atmospheric models, we find it unlikely that the high albedo is due to a dominant thermal component and propose two solutions to explain the observed planetary flux. First, we interpret the Kepler-7 b albedo as resulting from an excess reflection over what can be explained solely by Rayleigh scattering, along with a nominal thermal component. This excess reflection might indicate the presence of a cloud or haze layer in the atmosphere, motivating new modeling and observational efforts. Alternatively, the albedo can be explained by Rayleigh scattering alone if Na and K are depleted in the atmosphere by a factor of 10-100 below solar abundances.

  1. DETERMINATION OF REPORTABLE RADIONUCLIDES FOR DWPF SLUDGE BATCH 7B (MACROBATCH 9)

    SciTech Connect

    Crawford, C. L.; Diprete, D. P.

    2014-05-01

    The Waste Acceptance Product Specifications (WAPS) 1.2 require that “The Producer shall report the inventory of radionuclides (in Curies) that have half-lives longer than 10 years and that are, or will be, present in concentrations greater than 0.05 percent of the total inventory for each waste type indexed to the years 2015 and 3115”. As part of the strategy to comply with WAPS 1.2, the Defense Waste Processing Facility (DWPF) will report for each waste type, all radionuclides (with half-lives greater than 10 years) that have concentrations greater than 0.01 percent of the total inventory from time of production through the 1100 year period from 2015 through 3115. The initial listing of radionuclides to be included is based on the design-basis glass as identified in the Waste Form Compliance Plan (WCP) and Waste Form Qualification Report (WQR). However, it is required that this list be expanded if other radionuclides with half-lives greater than 10 years are identified that may meet the greater than 0.01% criterion for Curie content. Specification 1.6 of the WAPS, International Atomic Energy Agency (IAEA) Safeguards Reporting for High Level Waste (HLW), requires that the ratio by weights of the following uranium and plutonium isotopes be reported: U-233, U-234, U-235, U-236, U-238, Pu-238, Pu-239, Pu-240, Pu-241, and Pu- 242. Therefore, the complete set of reportable radionuclides must also include this set of U and Pu isotopes. The DWPF is receiving radioactive sludge slurry from HLW Tank 40. The radioactive sludge slurry in Tank 40 is a blend of the heel from Sludge Batch 7a (SB7a) and Sludge Batch 7b (SB7b) that was transferred to Tank 40 from Tank 51. The blend of sludge in Tank 40 is also referred to as Macrobatch 9 (MB9). This report develops the list of reportable radionuclides and associated activities as a function of time. The DWPF will use this list and the activities as one of the inputs for the development of the Production Records that relate to

  2. Determination Of Reportable Radionuclides For DWPF Sludge Batch 7B (Macrobatch 9)

    SciTech Connect

    Crawford, C. L.; DiPrete, D. P.

    2013-08-22

    The Waste Acceptance Product Specifications (WAPS) 1.2 require that “The Producer shall report the inventory of radionuclides (in Curies) that have half-lives longer than 10 years and that are, or will be, present in concentrations greater than 0.05 percent of the total inventory for each waste type indexed to the years 2015 and 3115”. As part of the strategy to comply with WAPS 1.2, the Defense Waste Processing Facility (DWPF) will report for each waste type, all radionuclides (with half-lives greater than 10 years) that have concentrations greater than 0.01 percent of the total inventory from time of production through the 1100 year period from 2015 through 3115. The initial listing of radionuclides to be included is based on the design-basis glass as identified in the Waste Form Compliance Plan (WCP) and Waste Form Qualification Report (WQR). However, it is required that this list be expanded if other radionuclides with half-lives greater than 10 years are identified that may meet the greater than 0.01% criterion for Curie content. Specification 1.6 of the WAPS, International Atomic Energy Agency (IAEA) Safeguards Reporting for High Level Waste (HLW), requires that the ratio by weights of the following uranium and plutonium isotopes be reported: U-233, U-234, U-235, U-236, U-238, Pu-238, Pu-239, Pu-240, Pu-241, and Pu-242. Therefore, the complete set of reportable radionuclides must also include this set of U and Pu isotopes. The DWPF is receiving radioactive sludge slurry from HLW Tank 40. The radioactive sludge slurry in Tank 40 is a blend of the heel from Sludge Batch 7a (SB7a) and Sludge Batch 7b (SB7b) that was transferred to Tank 40 from Tank 51. The blend of sludge in Tank 40 is also referred to as Macrobatch 9 (MB9). This report develops the list of reportable radionuclides and associated activities as a function of time. The DWPF will use this list and the activities as one of the inputs for the development of the Production Records that relate to

  3. Copper directs ATP7B to the apical domain of hepatic cells via basolateral endosomes.

    PubMed

    Nyasae, Lydia K; Schell, Michael J; Hubbard, Ann L

    2014-12-01

    Physiologic Cu levels regulate the intracellular location of the Cu ATPase ATP7B. Here, we determined the routes of Cu-directed trafficking of endogenous ATP7B in the polarized hepatic cell line WIF-B and in the liver in vivo. Copper (10 µm) caused ATP7B to exit the trans-Golgi network (TGN) in vesicles, which trafficked via large basolateral endosomes to the apical domain within 1 h. Although perturbants of luminal acidification had little effect on the TGN localization of ATP7B in low Cu, they blocked delivery to the apical membrane in elevated Cu. If the vesicular proton-pump inhibitor bafilomycin-A1 (Baf) was present with Cu, ATP7B still exited the TGN, but accumulated in large endosomes located near the coverslip, in the basolateral region. Baf washout restored ATP7B trafficking to the apical domain. If ATP7B was staged apically in high Cu, Baf addition promoted the accumulation of ATP7B in subapical endosomes, indicating a blockade of apical recycling, with concomitant loss of ATP7B at the apical membrane. The retrograde pathway to the TGN, induced by Cu removal, was far less affected by Baf than the anterograde (Cu-stimulated) case. Overall, loss of acidification-impaired Cu-regulated trafficking of ATP7B at two main sites: (i) sorting and exit from large basolateral endosomes and (ii) recycling via endosomes near the apical membrane. PMID:25243755

  4. EOS7C-ECBM Version 1.0

    2012-11-14

    EOS7C is an equation of state module for the TOUGH2 program for CO2 or N2 in Methane (CH4) Reservoirs. In the present work, additions have been made to the EOS7C Version 1.0 module to include the Enhanced Coal Bed Methane (ECBM) modifications developed by Webb (2003). In addition, the Dusty Gas Model for gas-phase diffusion (Webb 2001) has been included. The ECBM modification to the EOS7C equation of state incorporate the extended Langmuir isothem formore » sorbing gases, including the change in porosity associated with the sorbed gas mass. Comparison to hand calculations for pure gas and binary mixture shows very good agreement. Application to a CO2 well injection problem by Law et al. (2002). The Dusty Model modification add options to calculate gas diffusion using the Dusty-Gas Model including separate and coupled approaches. Comparison to low-permeability pure gas diffusion data shows excellent agreement. The results from the DGM are compared to the Fick's Law behavior for diffusion across a capillary fringe. The differences between the models are small due to the relatively high permeability (10-11 m2) of the problem.« less

  5. EOS7C-ECBM Version 1.0

    SciTech Connect

    2012-11-14

    EOS7C is an equation of state module for the TOUGH2 program for CO2 or N2 in Methane (CH4) Reservoirs. In the present work, additions have been made to the EOS7C Version 1.0 module to include the Enhanced Coal Bed Methane (ECBM) modifications developed by Webb (2003). In addition, the Dusty Gas Model for gas-phase diffusion (Webb 2001) has been included. The ECBM modification to the EOS7C equation of state incorporate the extended Langmuir isothem for sorbing gases, including the change in porosity associated with the sorbed gas mass. Comparison to hand calculations for pure gas and binary mixture shows very good agreement. Application to a CO2 well injection problem by Law et al. (2002). The Dusty Model modification add options to calculate gas diffusion using the Dusty-Gas Model including separate and coupled approaches. Comparison to low-permeability pure gas diffusion data shows excellent agreement. The results from the DGM are compared to the Fick's Law behavior for diffusion across a capillary fringe. The differences between the models are small due to the relatively high permeability (10-11 m2) of the problem.

  6. The neuroendocrine polypeptide 7B2 is an endogenous inhibitor of prohormone convertase PC2.

    PubMed Central

    Martens, G J; Braks, J A; Eib, D W; Zhou, Y; Lindberg, I

    1994-01-01

    The subtilisin-like prohormone convertase PC2 and the polypeptide 7B2 (an intracellularly cleaved protein of unknown function) are both selectively present in the regulated secretory pathway of neurons and endocrine cells. Here we demonstrate that intact recombinant 7B2 is a potent inhibitor of PC2 and prevents proPC2 cleavage in vitro, whereas the 7B2 cleavage product is virtually inactive. The PC2-related proteinase PC1/PC3 is not inhibited by 7B2. Furthermore, the carboxyl-terminal half of the 7B2 protein sequence is distantly related to the so-called potato inhibitor I family (which includes subtilisin inhibitors). Our findings indicate that 7B2 is a physiological inhibitor of PC2 and may provide alternative avenues for the manipulation of peptide hormone levels. Images PMID:8016065

  7. Novel alternative splice variants of rat phosphodiesterase 7B showing unique tissue-specific expression and phosphorylation.

    PubMed Central

    Sasaki, Takashi; Kotera, Jun; Omori, Kenji

    2002-01-01

    cDNA species coding for novel variants of cyclic-AMP-specific phosphodiesterases (PDEs), namely the PDE7B family, were isolated from rats and characterized. Rat PDE7B1 (RNPDE7B1) was composed of 446 amino acid residues. Rat PDE7B2 (RNPDE7B2) and PDE7B3 (RNPDE7B3), which possessed unique N-terminal sequences, consisted of 359 and 459 residues respectively. Northern hybridization analysis showed that rat PDE7B transcripts were particularly abundant in the striatum and testis. PCR analyses revealed that rat PDE7B2 transcripts were restricted to the testis and that low levels of PDE7B3 transcripts were expressed in the heart, lung and skeletal muscle. In situ hybridization analysis demonstrated that rat PDE7B transcripts were expressed in striatal neurons and spermatocytes. In spermatocytes, rat PDE7B transcripts were expressed in a stage-specific manner during spermatogenesis. The K(m) values of recombinant rat PDE7B1, PDE7B2 and PDE7B3 for cAMP were 0.05, 0.07 and 0.05 microM respectively. Each rat PDE7B variant was the most sensitive to 3-isobutyl-1-methylxanthine (IC(50) 1.5-2.1 microM). Two phosphorylation sites for cAMP-dependent protein kinase (PKA) were found in rat PDE7B1 and PDE7B3, whereas rat PDE7B2 possessed one site. PKA-dependent phosphorylation was observed in C-terminal phosphorylation sites of three rat PDE7B variants, in addition to unique N-terminal regions of rat PDE7B1 and PDE7B3. Unique tissue distribution and PKA-dependent phosphorylation of PDE7B variants suggested that each variant has a specific role for cellular functions via cAMP signalling in various tissues. PMID:11772393

  8. Let-7b Inhibits Human Cancer Phenotype by Targeting Cytochrome P450 Epoxygenase 2J2

    PubMed Central

    Yang, Shenglan; Gong, Wei; Wang, Yan; Cianflone, Katherine; Tang, Jiarong; Wang, Dao Wen

    2012-01-01

    Background MicroRNAs (miRNAs) are small, noncoding RNA molecules of 20 to 22 nucleotides that regulate gene expression by binding to their 3′ untranslated region (3′UTR). Increasing data implicate altered miRNA participation in the progress of cancer. We previously reported that CYP2J2 epoxygenase promotes human cancer phenotypes. But whether and how CYP2J2 is regulated by miRNA is not understood. Methods and Results Using bioinformatics analysis, we found potential target sites for miRNA let-7b in 3′UTR of human CYP2J2. Luciferase and western blot assays revealed that CYP2J2 was regulated by let-7b. In addition, let-7b decreased the enzymatic activity of endogenous CYP2J2. Furthermore, let-7b may diminish cell proliferation and promote cell apoptosis of tumor cells via posttranscriptional repression of CYP2J2. Tumor xenografts were induced in nude mice by subcutaneous injection of MDA-MB-435 cells. The let-7b expression vector, pSilencer-let-7b, was injected through tail vein every 3 weeks. Let-7b significantly inhibited the tumor phenotype by targeting CYP2J2. Moreover, quantitative real-time polymerase chain reaction and western blotting were used to determine the expression levels of let-7b and CYP2J2 protein from 18 matched lung squamous cell cancer and adjacent normal lung tissues; the expression level of CYP2J2 was inversely proportional to that of let-7b. Conclusions Our results demonstrated that the decreased expression of let-7b could lead to the high expression of CYP2J2 protein in cancerous tissues. These findings suggest that miRNA let-7b reduces CYP2J2 expression, which may contribute to inhibiting tumor phenotypes. PMID:22761738

  9. 29 CFR 778.602 - Special overtime provisions under section 7(b).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Special overtime provisions under section 7(b). 778.602... COMPENSATION Miscellaneous § 778.602 Special overtime provisions under section 7(b). (a) Daily and weekly... subsection. Under these provisions, when an employee works in excess of both the daily and weekly...

  10. 29 CFR 778.602 - Special overtime provisions under section 7(b).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Special overtime provisions under section 7(b). 778.602... COMPENSATION Miscellaneous § 778.602 Special overtime provisions under section 7(b). (a) Daily and weekly... subsection. Under these provisions, when an employee works in excess of both the daily and weekly...

  11. 29 CFR 778.602 - Special overtime provisions under section 7(b).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Special overtime provisions under section 7(b). 778.602... COMPENSATION Miscellaneous § 778.602 Special overtime provisions under section 7(b). (a) Daily and weekly... subsection. Under these provisions, when an employee works in excess of both the daily and weekly...

  12. 29 CFR 778.602 - Special overtime provisions under section 7(b).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Special overtime provisions under section 7(b). 778.602... COMPENSATION Miscellaneous § 778.602 Special overtime provisions under section 7(b). (a) Daily and weekly... subsection. Under these provisions, when an employee works in excess of both the daily and weekly...

  13. 29 CFR 778.602 - Special overtime provisions under section 7(b).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Special overtime provisions under section 7(b). 778.602... COMPENSATION Miscellaneous § 778.602 Special overtime provisions under section 7(b). (a) Daily and weekly... subsection. Under these provisions, when an employee works in excess of both the daily and weekly...

  14. CYP7B1 Enzyme Deletion Impairs Reproductive Behaviors in Male Mice

    PubMed Central

    Oyola, Mario G.; Zuloaga, Damian G.; Carbone, David; Malysz, Anna M.; Acevedo-Rodriguez, Alexandra; Handa, Robert J.

    2015-01-01

    In addition to androgenic properties mediated via androgen receptors, dihydrotestosterone (DHT) also regulates estrogenic functions via an alternate pathway. These estrogenic functions of DHT are mediated by its metabolite 5α-androstane-3β, 17β-diol (3β-diol) binding to estrogen receptor β (ERβ). CYP7B1 enzyme converts 3β-diol to inactive 6α- or 7α-triols and plays an important role as a regulator of estrogenic functions mediated by 3β-diol. Using a mutant mouse carrying a null mutation for the CYP7B1 gene (CYP7B1KO), we examined the contribution of CYP7B1 on physiology and behavior. Male, gonadectomized (GDX) CYP7B1KO and their wild type (WT) littermates were assessed for their behavioral phenotype, anxiety-related behavioral measures, and hypothalamic pituitary adrenal axis reactivity. No significant effects of genotype were evident in anxiety-like behaviors in open field (OFA), light-dark (L/D) exploration, and elevated plus maze (EPM). T significantly reduced open arm time on the EPM while not affecting L/D exploratory and OFA behaviors in CYP7B1KO and WT littermates. T also attenuated the corticosterone response to EPM in both genotypes. In GDX animals, T was able to reinstate male-specific reproductive behaviors (latencies and number of mounts, intromission, and ejaculations) in the WT but not in the CYP7B1KO mice. The male reproductive behavior defect in CYP7B1KO seems to be due to their inability to distinguish olfactory cues from a behavioral estrus female. CYP7B1KO mice also showed a reduction in androgen receptor mRNA expression in the olfactory bulb. Our findings suggest a novel role for the CYP7B1 enzyme in the regulation of male reproductive behaviors. PMID:25849728

  15. IRF-7, a new interferon regulatory factor associated with Epstein-Barr virus latency.

    PubMed Central

    Zhang, L; Pagano, J S

    1997-01-01

    The Epstein-Barr virus (EBV) BamHI Q promoter (Qp) is the only promoter used for the transcription of Epstein-Barr virus nuclear antigen 1 (EBNA-1) mRNA in cells in the most restricted (type I) latent infection state. However, Qp is inactive in type III latency. With the use of the yeast one-hybrid system, a new cellular gene has been identified that encodes proteins which bind to sequence in Qp. The deduced amino acid sequence of the gene has significant homology to the interferon regulatory factors (IRFs). This new gene and products including two splicing variants are designated IRF-7A, IRF-7B, and IRF-7C. The expression of IRF-7 is predominantly in spleen, thymus, and peripheral blood leukocytes (PBL). IRF-7 proteins were identified in primary PBL with specific antiserum against IRF-7B protein. IRF-7s can bind to interferon-stimulated response element (ISRE) sequence and repress transcriptional activation by both interferon and IRF-1. Additionally, a functional viral ISRE sequence, 5'-GCGAAAACGAAAGT-3', has been identified in Qp. Finally, the expression of IRF-7 is consistently high in type III latency cells and almost undetectable in type I latency, corresponding to the activity of endogenous Qp in these latency states and the ability of the IRF-7 proteins to repress Qp-reporter constructs. The identification of a functional viral ISRE and association of IRF-7 with type III latency may be relevant to the mechanism of regulation of Qp. PMID:9315633

  16. Wilson Disease Protein ATP7B Utilizes Lysosomal Exocytosis to Maintain Copper Homeostasis

    PubMed Central

    Polishchuk, Elena V.; Concilli, Mafalda; Iacobacci, Simona; Chesi, Giancarlo; Pastore, Nunzia; Piccolo, Pasquale; Paladino, Simona; Baldantoni, Daniela; van IJzendoorn, Sven C.D.; Chan, Jefferson; Chang, Christopher J.; Amoresano, Angela; Pane, Francesca; Pucci, Piero; Tarallo, Antonietta; Parenti, Giancarlo; Brunetti-Pierri, Nicola; Settembre, Carmine; Ballabio, Andrea; Polishchuk, Roman S.

    2014-01-01

    Summary Copper is an essential yet toxic metal and its overload causes Wilson disease, a disorder due to mutations in copper transporter ATP7B. To remove excess copper into the bile, ATP7B traffics toward canalicular area of hepatocytes. However, the trafficking mechanisms of ATP7B remain elusive. Here, we show that, in response to elevated copper, ATP7B moves from the Golgi to lysosomes and imports metal into their lumen. ATP7B enables lysosomes to undergo exocytosis through the interaction with p62 subunit of dynactin that allows lysosome translocation toward the canalicular pole of hepatocytes. Activation of lysosomal exocytosis stimulates copper clearance from the hepatocytes and rescues the most frequent Wilson-disease-causing ATP7B mutant to the appropriate functional site. Our findings indicate that lysosomes serve as an important intermediate in ATP7B trafficking, whereas lysosomal exocytosis operates as an integral process in copper excretion and hence can be targeted for therapeutic approaches to combat Wilson disease. PMID:24909901

  17. Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis.

    PubMed

    Polishchuk, Elena V; Concilli, Mafalda; Iacobacci, Simona; Chesi, Giancarlo; Pastore, Nunzia; Piccolo, Pasquale; Paladino, Simona; Baldantoni, Daniela; van IJzendoorn, Sven C D; Chan, Jefferson; Chang, Christopher J; Amoresano, Angela; Pane, Francesca; Pucci, Piero; Tarallo, Antonietta; Parenti, Giancarlo; Brunetti-Pierri, Nicola; Settembre, Carmine; Ballabio, Andrea; Polishchuk, Roman S

    2014-06-23

    Copper is an essential yet toxic metal and its overload causes Wilson disease, a disorder due to mutations in copper transporter ATP7B. To remove excess copper into the bile, ATP7B traffics toward canalicular area of hepatocytes. However, the trafficking mechanisms of ATP7B remain elusive. Here, we show that, in response to elevated copper, ATP7B moves from the Golgi to lysosomes and imports metal into their lumen. ATP7B enables lysosomes to undergo exocytosis through the interaction with p62 subunit of dynactin that allows lysosome translocation toward the canalicular pole of hepatocytes. Activation of lysosomal exocytosis stimulates copper clearance from the hepatocytes and rescues the most frequent Wilson-disease-causing ATP7B mutant to the appropriate functional site. Our findings indicate that lysosomes serve as an important intermediate in ATP7B trafficking, whereas lysosomal exocytosis operates as an integral process in copper excretion and hence can be targeted for therapeutic approaches to combat Wilson disease. PMID:24909901

  18. Spontaneous mutation 7B-1 in tomato impairs blue light-induced stomatal opening.

    PubMed

    Hlavinka, Jan; Nauš, Jan; Fellner, Martin

    2013-08-01

    It was reported earlier that 7B-1 mutant in tomato (Solanum lycopersicum L.), an ABA overproducer, is defective in blue light (BL) signaling leading to BL-specific resistance to abiotic and biotic stresses. In this work, we examine responses of stomata to blue, red and white lights, fusicoccin, anion channel blockers (anthracene-9-carboxylic acid; 9-AC and niflumic acid; NIF) and ABA. Our results showed that the aperture of 7B-1 stomata does not increase in BL, suggesting that 7B-1 mutation impairs an element of BL signaling pathway involved in stomatal opening. Similar stomatal responses of 7B-1 and wild type (WT) to fusicoccin or 9-AC points out that activity of H(+)-ATPase and 9-AC-sensitive anion channels per se is not likely affected by the mutation. Since 9-AC restored stomatal opening of 7B-1 in BL, it seems that 9-AC and BL could block similar type of anion channels. The stomata of both genotypes did not respond to NIF neither in darkness nor in any light conditions tested. In light, 9-AC but not NIF restored stomatal opening inhibited by ABA in WT and 7B-1. We suggest that in comparison to WT, the activity of S-type anion channels in 7B-1 is more promoted by increased ABA content, and less reduced by BL, because of the mutant resistance to BL. PMID:23759105

  19. Effects of CYP7B1-mediated catalysis on estrogen receptor activation.

    PubMed

    Pettersson, Hanna; Lundqvist, Johan; Norlin, Maria

    2010-09-01

    Most of the many biological effects of estrogens are mediated via the estrogen receptors ERalpha and beta. The current study examines the role of CYP7B1-mediated catalysis for activation of ER. Several reports suggest that CYP7B1 may be important for hormonal action but previously published studies are contradictory concerning the manner in which CYP7B1 affects ERbeta-mediated response. In the current study, we examined effects of several CYP7B1-related steroids on ER activation, using an estrogen response element (ERE) reporter system. Our studies showed significant stimulation of ER by 5-androstene-3beta,17beta-diol (Aene-diol) and 5alpha-androstane-3beta,17beta-diol (3beta-Adiol). In contrast, the CYP7B1-formed metabolites from these steroids did not activate the receptor, indicating that CYP7B1-mediated metabolism abolishes the ER-stimulating effect of these compounds. The mRNA level of HEM45, a gene known to be stimulated by estrogens, was strongly up-regulated by Aene-diol but not by its CYP7B1-formed metabolite, further supporting this concept. We did not observe stimulation by dehydroepiandrosterone (DHEA) or 7alpha-hydroxy-DHEA, previously suggested to affect ERbeta-mediated response. As part of these studies we examined metabolism of Aene-diol in pig liver which is high in CYP7B1 content. These experiments indicate that CYP7B1-mediated metabolism of Aene-diol is of a similar rate as the metabolism of the well-known CYP7B1 substrates DHEA and 3beta-Adiol. CYP7B1-mediated metabolism of 3beta-Adiol has been proposed to influence ERbeta-mediated growth suppression. Our results indicate that Aene-diol also might be important for ER-related pathways. Our data indicate that low concentrations of Aene-diol can trigger ER-mediated response equally well for both ERalpha and beta and that CYP7B1-mediated conversion of Aene-diol into a 7alpha-hydroxymetabolite will result in loss of action. PMID:20553962

  20. Exploring new physics in the C 7- C 7' plane

    NASA Astrophysics Data System (ADS)

    Descotes-Genon, Sébastien; Ghosh, Diptimoy; Matias, Joaquim; Ramon, Marc

    2011-06-01

    The Wilson coefficient C 7 governing the radiative electromagnetic decays of B meson has been calculated toa very high accuracy in the Standard Model, but experimental bounds on either the magnitude or the sign of C 7 are often model-dependent. In the present paper, we attempt at constraining both the magnitude and sign of C 7 using a systematic approach. We consider already measured observables like the branching ratios of B → X s μ + μ - and B → X s γ, the isospin and CP asymmetries in B → K ∗ γ, as well as A FB and F L in B → K ∗ ℓ + ℓ -. We also discuss the transverse observable A {T/(2)} which, once measured, may help to disentangle some of the scenarios considered. We explore the constraints on C 7, C 9, C 10 as well as their chirality-flipped counterparts. Within our framework, we find that we need to extend the constraints up to 1 .6 σ to allow for the "flipped-sign solution" of C 7. The SM solution for C 7 exhibits a very mild tension if New Physics is allowed in dipole operators only. We provide semi-numerical expressions for all these observables as functions of the relevant Wilson coefficients at the low scale.

  1. Results of International Space Station Vehicle Materials Exposed on MISSE-7B

    NASA Technical Reports Server (NTRS)

    Finckenor, Miria M.; Golden, Johnny L.; O'Rourke, Mary Jane E.; Kravchenko, Michael

    2012-01-01

    Materials samples were exposed to the low Earth orbit (LEO) environment as part of the MISSE-7B flight experiment for 18 months. Optical properties, thickness/mass loss, surface elemental analysis, visual and microscopic analysis for surface change are some of the techniques employed in this investigation. Where possible, the MISSE-7B results are compared to analyses from other LEO experiments. ISS materials currently flying on MISSE-8 are also discussed.

  2. Further Analysis of Materials Exposed on MISSE-6 and-7B

    NASA Technical Reports Server (NTRS)

    Finckenor, Miria; Stewart, Alan F.; Kravchenko, Michael; Deshpande, Mike

    2013-01-01

    Materials samples were exposed to the low Earth orbit (LEO) environment as part of the MISSE- 6 and -7B flight experiments. Optical properties, thickness/mass loss, surface elemental analysis, visual and microscopic analysis for surface change are some of the techniques employed in this investigation. Effects of molecular contamination are discussed. Where possible, the MISSE-6 and -7B results are compared to analyses from other LEO experiments.

  3. Genome Sequence of Leucobacter sp. 4J7B1, a Plant-Osmoprotectant Soil Microorganism

    PubMed Central

    Vílchez, J. I.; García-Fontana, C.; Calvo, C.; González-López, J.

    2015-01-01

    We report the first genome sequence for Leucobacter sp. 4J7B1, a newly described desiccation-tolerant strain. The complete genome sequence of Leucobacter sp. 4J7B1 has been sequenced and is estimated to be around 3.5 Mb in size, with an average GC content of 62.18%. We predict 2,953 protein-coding sequences. PMID:25999566

  4. miR-133a enhances the sensitivity of Hep-2 cells and vincristine-resistant Hep-2v cells to cisplatin by downregulating ATP7B expression.

    PubMed

    Wang, Xurui; Zhu, Wei; Zhao, Xiaodong; Wang, Ping

    2016-06-01

    The expression levels of the copper transporter P-type adenosine triphosphatase (ATP7B) are known correlate with tumor cell sensitivity to cisplatin. However, the mechanisms underlying cisplatin resistance remained poorly understood. Therefore, in the present study, we treated Hep-2 cells and in-house-developed vincristine-resistant Hep-2v cells with 50, 100, or 200 µM cisplatin and assessed cell viability after 24 or 48 h. Hep-2v cells were shown to be resistant to 50-200 µM cisplatin. Furthermore, using immunofluorescence staining and western blot analysis, we noted that ATP7B, but not copper-transporting ATPase 1 (ATP7A), expression was significantly increased in Hep-2v cells, and this increase was maintained at a higher level compared with Hep-2 cells. As ATP7B is a target of microRNA 133a (miR‑133a), the ability of miR‑133a to influence cisplatin sensitivity in Hep-2v cells was then assessed by CCK-8 assay. We noted that miR‑133a expression was lower in both Hep-2 and Hep-2v cells compared with epithelial NP69 cells. Following treatment with 50 µM cisplatin, in Hep-2v cells expressing exogenous miR‑133a we noted reduced ATP7B expression, and these cells had a significantly lower survival rate compared with the control. The present study demonstrates that miR‑133a enhances the sensitivity of multidrug-resistant Hep-2v cells to cisplatin by downregulating ATP7B expression. PMID:27121102

  5. Mutations in COX7B Cause Microphthalmia with Linear Skin Lesions, an Unconventional Mitochondrial Disease

    PubMed Central

    Indrieri, Alessia; van Rahden, Vanessa Alexandra; Tiranti, Valeria; Morleo, Manuela; Iaconis, Daniela; Tammaro, Roberta; D’Amato, Ilaria; Conte, Ivan; Maystadt, Isabelle; Demuth, Stephanie; Zvulunov, Alex; Kutsche, Kerstin; Zeviani, Massimo; Franco, Brunella

    2012-01-01

    Microphthalmia with linear skin lesions (MLS) is an X-linked dominant male-lethal disorder associated with mutations in holocytochrome c-type synthase (HCCS), which encodes a crucial player of the mitochondrial respiratory chain (MRC). Unlike other mitochondrial diseases, MLS is characterized by a well-recognizable neurodevelopmental phenotype. Interestingly, not all clinically diagnosed MLS cases have mutations in HCCS, thus suggesting genetic heterogeneity for this disorder. Among the possible candidates, we analyzed the X-linked COX7B and found deleterious de novo mutations in two simplex cases and a nonsense mutation, which segregates with the disease, in a familial case. COX7B encodes a poorly characterized structural subunit of cytochrome c oxidase (COX), the MRC complex IV. We demonstrated that COX7B is indispensable for COX assembly, COX activity, and mitochondrial respiration. Downregulation of the COX7B ortholog (cox7B) in medaka (Oryzias latipes) resulted in microcephaly and microphthalmia that recapitulated the MLS phenotype and demonstrated an essential function of complex IV activity in vertebrate CNS development. Our results indicate an evolutionary conserved role of the MRC complexes III and IV for the proper development of the CNS in vertebrates and uncover a group of mitochondrial diseases hallmarked by a developmental phenotype. PMID:23122588

  6. sept7b is required for the differentiation of pancreatic endocrine progenitors

    PubMed Central

    Dash, Surjya Narayan; Hakonen, Elina; Ustinov, Jarkko; Otonkoski, Timo; Andersson, Olov; Lehtonen, Sanna

    2016-01-01

    Protection or restoration of pancreatic β-cell mass as a therapeutic treatment for type 1 diabetes requires understanding of the mechanisms that drive the specification and development of pancreatic endocrine cells. Septins are filamentous small GTPases that function in the regulation of cell division, cytoskeletal organization and membrane remodeling, and are involved in various tissue-specific developmental processes. However, their role in pancreatic endocrine cell differentiation remains unknown. Here we show by functional manipulation techniques in transgenic zebrafish lines that suppression of sept7b, the zebrafish ortholog of human SEPT7, profoundly increases the number of endocrine progenitors but limits their differentiation, leading to reduction in β- and α-cell mass. Furthermore, we discovered that shh (sonic hedgehog) expression in the endoderm, essential for the development of pancreatic progenitors of the dorsal pancreatic bud, is absent in larvae depleted of sept7b. We also discovered that sept7b is important for the differentiation of ventral pancreatic bud-derived cells: sept7b-depleted larvae exhibit downregulation of Notch receptors notch1a and notch1b and show precocious differentiation of NeuroD-positive endocrine cells in the intrapancreatic duct and gut epithelium. Collectively, this study provides a novel insight into the development of pancreatic endocrine progenitors, revealing an essential role for sept7b in endocrine progenitor differentiation. PMID:27114183

  7. Early onset of puberty and early ovarian failure in CYP7B1 knockout mice

    PubMed Central

    Omoto, Yoko; Lathe, Richard; Warner, Margaret; Gustafsson, Jan-Åke

    2005-01-01

    CYP7B1 is the enzyme responsible for hydroxylation and termination of the estrogenic actions of the androgen metabolite, 5α-androstane-3β, 17β-diol (3βAdiol). 3βAdiol is estrogenic in ERα or ERβ positive cells only if they do not express CYP7B1. In this study we show that female CYP7B1–/– mice experience early onset of growth of the uterus and mammary glands and commence estrus cycles 2 days earlier than their wild-type littermates. Adult mammary glands and uteri appear to be under continuous estrogenic stimulation. We conclude that, by cell-specific regulation of the estrogenicity of 3βAdiol, CYP7B1 performs two major tasks: (i) it allows 3βAdiol to have growth inhibitory effects through ERβ and (ii) it permits estradiol-specific activation of estrogen receptors by protection of certain cells from the estrogenic effects of 3βAdiol. When CYP7B1 is inactivated, 3βAdiol activates estrogen receptors indiscriminately, and the overall effect is prolonged and inappropriate exposure to estrogen. PMID:15710898

  8. Early onset of puberty and early ovarian failure in CYP7B1 knockout mice.

    PubMed

    Omoto, Yoko; Lathe, Richard; Warner, Margaret; Gustafsson, Jan-Ake

    2005-02-22

    CYP7B1 is the enzyme responsible for hydroxylation and termination of the estrogenic actions of the androgen metabolite, 5alpha-androstane-3beta, 17beta-diol (3betaAdiol). 3betaAdiol is estrogenic in ERalpha or ERbeta positive cells only if they do not express CYP7B1. In this study we show that female CYP7B1(-/-) mice experience early onset of growth of the uterus and mammary glands and commence estrus cycles 2 days earlier than their wild-type littermates. Adult mammary glands and uteri appear to be under continuous estrogenic stimulation. We conclude that, by cell-specific regulation of the estrogenicity of 3betaAdiol, CYP7B1 performs two major tasks: (i) it allows 3betaAdiol to have growth inhibitory effects through ERbeta and (ii) it permits estradiol-specific activation of estrogen receptors by protection of certain cells from the estrogenic effects of 3betaAdiol. When CYP7B1 is inactivated, 3betaAdiol activates estrogen receptors indiscriminately, and the overall effect is prolonged and inappropriate exposure to estrogen. PMID:15710898

  9. Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination.

    PubMed

    Hu, Hongbo; Wang, Hui; Xiao, Yichuan; Jin, Jin; Chang, Jae-Hoon; Zou, Qiang; Xie, Xiaoping; Cheng, Xuhong; Sun, Shao-Cong

    2016-03-01

    Signal transduction from the T cell receptor (TCR) is crucial for T cell-mediated immune responses and, when deregulated, also contributes to the development of autoimmunity. How TCR signaling is regulated is incompletely understood. In this study, we demonstrate a ubiquitin-dependent mechanism in which the deubiquitinase Otud7b has a crucial role in facilitating TCR signaling. Upon TCR ligation, Otud7b is rapidly recruited to the tyrosine kinase Zap70, a central mediator of TCR-proximal signaling. Otud7b deficiency attenuates the activation of Zap70 and its downstream pathways and impairs T cell activation and differentiation, rendering mice refractory to T cell-mediated autoimmune and inflammatory responses. Otud7b facilitated Zap70 activation by deubiquitinating Zap70, thus preventing the association of Zap70 with the negative-regulatory phosphatases Sts1 and Sts2. These findings establish Otud7b as a positive regulator of TCR-proximal signaling and T cell activation, highlighting the importance of deubiquitination in regulating Zap70 function. PMID:26903241

  10. Site-directed mutagenesis, in vivo electroporation and mass spectrometry in search for determinants of the subcellular targeting of Rab7b paralogue in the model eukaryote Paramecium octaurelia.

    PubMed

    Wyroba, E; Kwaśniak, P; Miller, K; Kobyłecki, K; Osińska, M

    2016-01-01

    Protein products of the paralogous genes resulting from the whole genome duplication may acquire new function. The role of post-translational modifications (PTM) in proper targeting of Paramecium Rab7b paralogue - distinct from that of Rab7a directly involved in phagocytosis - was studied using point mutagenesis, proteomic analysis and double immunofluorescence after in vivo electroporation of the mutagenized protein. Here we show that substitution of Thr200 by Ala200 resulted in diminished incorporation of [P32] by 37.4% and of 32 [C14-]UDP-glucose by 24%, respectively, into recombinant Rab7b_200 in comparison to the non-mutagenized control. Double confocal imaging revealed that Rab7b_200 was mistargeted upon electroporation into living cells contrary to non- mutagenized recombinant Rab7b correctly incorporated in the cytostome area. We identified the peptide ion at m/z=677.63+ characteristic for the glycan group attached to Thr200 in Rab7b using nano LC-MS/MS and comparing the peptide map of this protein with that after deglycosylation with the mixture of five enzymes of different specificity. Based on the mass of this peptide ion and quantitative radioactive assays with [P32]and  [C14-]UDP- glucose, the suggested composition of the adduct attached to Thr200 might be (Hex)1(HexNAc)1(Phos)3 or (HexNAc)1 (Deoxyhexose)1 (Phos)1 (HexA)1. These data indicate that PTM of Thr200 located in the hypervariable C-region of Rab7b in Paramecium is crucial for the proper localization/function of this protein. Moreover, these proteins differ also in other PTM: the number of phosphorylated amino acids in Rab7b is much higher than in Rab7a. PMID:27349314

  11. Site-Directed Mutagenesis, in Vivo Electroporation and Mass Spectrometry in Search for Determinants of the Subcellular Targeting of Rab7b Paralogue in the Model Eukaryote Paramecium Octaurelia

    PubMed Central

    Wyroba, E.; Kwaśniak, P.; Miller, K.; Kobyłecki, K.; Osińska, M.

    2016-01-01

    Protein products of paralogous genes resulting from whole genome duplication may acquire new functions. The role of post-translational modifications (PTM) in proper targeting of Paramecium Rab7b paralogue (distinct from that of Rab7a directly involved in phagocytosis) was studied using point mutagenesis, proteomic analysis and double immunofluorescence after in vivo electroporation of the mutagenized protein. Here we show that substitution of Thr200 by Ala diminished the incorporation of [P32] by 37% and of [C14-]UDP-glucose by 24% into recombinant Rab7b_200 in comparison to the non-mutagenized control. Double confocal imaging revealed that Rab7b_200 was mistargeted upon electroporation into living cells in contrast to non-mutagenized recombinant Rab7b correctly incorporated in the cytostome area. Using nano LC-MS/MS to compare the peptide map of Rab7b with that after deglycosylation with a mixture of five enzymes of different specificity we identified a peptide ion at m/z=677.63+ representing a glycan group attached to Thr200. Based on its mass and quantitative assays with [P32] and [C14]UDP-glucose, the suggested composition of the adduct attached to Thr200 is (Hex)1(HexNAc)1(Phos)3 or (HexNAc)1 (Deoxyhexose)1 (Phos)1 (HexA)1. These data indicate that PTM of Thr200 located in the hypervariable C-region of Paramecium octaurelia Rab7b is crucial for the proper localization/function of this protein. Moreover, the two Rab7 paralogues differ also in another PTM: substantially more phosphorylated amino acid residues are in Rab7b than in Rab7a. PMID:27349314

  12. Let-7b-mediated suppression of basigin expression and metastasis in mouse melanoma cells

    SciTech Connect

    Fu, Tzu-Yen; Chang, Chia-Che; Lin, Chun-Ting; Lai, Cong-Hao; Peng, Shao-Yu; Ko, Yi-Ju; Tang, Pin-Chi

    2011-02-15

    Basigin (Bsg), also called extracellular matrix metalloproteinase inducer (EMMPRIN), is highly expressed on the surface of tumor cells and stimulates adjacent fibroblasts or tumor cells to produce matrix metalloproteinases (mmps). It has been shown that Bsg plays an important role in growth, development, cell differentiation, and tumor progression. MicroRNAs (miRNAs) are a class of short endogenous non-protein coding RNAs of 20-25 nucleotides (nt) that function as post-transcriptional regulators of gene expression by base-pairing to their target mRNAs and thereby mediate cleavage of target mRNAs or translational repression. In this study, let-7b, one of the let-7 family members, was investigated for its effect on the growth and invasiveness of the mouse melanoma cell line B16-F10. We have shown that let-7b can suppress the expression of Bsg in B16-F10 cells and also provided evidence that this suppression could result in the indirect suppression of mmp-9. The ability of B16-F10 cells transfected with let-7b to invade or migrate was significantly reduced. In addition, let-7b transfected B16-F10 cells displayed an inhibition of both cellular proliferation and colony formation. Furthermore, it was shown that the overexpression of let-7b in B16-F10 cells could reduce lung metastasis. Taken together, the present study identifies let-7b as a tumor suppressor that represses cancer cell proliferation and migration as well as tumor metastasis in mouse melanoma cells.

  13. Growth characteristics of primary M7C3 carbide in hypereutectic Fe-Cr-C alloy

    PubMed Central

    Liu, Sha; Zhou, Yefei; Xing, Xiaolei; Wang, Jibo; Ren, Xuejun; Yang, Qingxiang

    2016-01-01

    The microstructure of the hypereutectic Fe-Cr-C alloy is observed by optical microscopy (OM). The initial growth morphology, the crystallographic structure, the semi-molten morphology and the stacking faults of the primary M7C3 carbide are observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The in-suit growth process of the primary M7C3 carbide was observed by confocal laser microscope (CLM). It is found that the primary M7C3 carbide in hypereutectic Fe-Cr-C alloy is irregular polygonal shape with several hollows in the center and gaps on the edge. Some primary M7C3 carbides are formed by layers of shell or/and consist of multiple parts. In the initial growth period, the primary M7C3 carbide forms protrusion parallel to {} crystal planes. The extending and revolving protrusion forms the carbide shell. The electron backscattered diffraction (EBSD) maps show that the primary M7C3 carbide consists of multiple parts. The semi-molten M7C3 carbide contains unmelted shell and several small-scale carbides inside, which further proves that the primary M7C3 carbide is not an overall block. It is believed that the coalescence of the primary M7C3 carbides is ascribed to the growing condition of the protrusion and the gap filling process. PMID:27596718

  14. Growth characteristics of primary M7C3 carbide in hypereutectic Fe-Cr-C alloy.

    PubMed

    Liu, Sha; Zhou, Yefei; Xing, Xiaolei; Wang, Jibo; Ren, Xuejun; Yang, Qingxiang

    2016-01-01

    The microstructure of the hypereutectic Fe-Cr-C alloy is observed by optical microscopy (OM). The initial growth morphology, the crystallographic structure, the semi-molten morphology and the stacking faults of the primary M7C3 carbide are observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The in-suit growth process of the primary M7C3 carbide was observed by confocal laser microscope (CLM). It is found that the primary M7C3 carbide in hypereutectic Fe-Cr-C alloy is irregular polygonal shape with several hollows in the center and gaps on the edge. Some primary M7C3 carbides are formed by layers of shell or/and consist of multiple parts. In the initial growth period, the primary M7C3 carbide forms protrusion parallel to {} crystal planes. The extending and revolving protrusion forms the carbide shell. The electron backscattered diffraction (EBSD) maps show that the primary M7C3 carbide consists of multiple parts. The semi-molten M7C3 carbide contains unmelted shell and several small-scale carbides inside, which further proves that the primary M7C3 carbide is not an overall block. It is believed that the coalescence of the primary M7C3 carbides is ascribed to the growing condition of the protrusion and the gap filling process. PMID:27596718

  15. High DRC Levels Are Associated with Let-7b Overexpression in Women with Breast Cancer

    PubMed Central

    Encarnación, Jarline; Ortiz, Carmen; Vergne, Ralphdy; Vargas, Wanda; Coppola, Domenico; Matta, Jaime L.

    2016-01-01

    Nucleotide Excision Repair (NER) is a critical pathway involved in breast cancer (BC). We have previously published that a low DNA repair capacity (DRC) is associated with a higher risk of BC in Puerto Rican women. Let-7b belongs to a miRNA family with tumor suppressor activity that targets oncogenes. We isolated miRNAs from plasma of 153 Puerto Rican women with and without BC. DRC was measured in lymphocytes by means of a host cell reactivation assay. These women were divided into four groups according to their DRC level: High (>3.8%) and low (<3.8%). The four groups consisted of BC patients with high (n = 35) and low (n = 43) DRC and controls with high (n = 39) and low (n = 36) DRC. Epidemiologic data were collected at initial BC diagnosis and almost five years after diagnosis. A significant difference in Let-7b expression was found in BC patients with high DRC versus the remaining groups (p < 0.001). Thus, our data reveal a possible role of Let-7b on DRC during breast carcinogenesis. Our study is innovative because it provides the first evidence that Let-7b may play role in DRC regulation (through the NER repair pathway) in BC. PMID:27271599

  16. Let-7b promotes alpaca hair growth via transcriptional repression of TGFβR I.

    PubMed

    Yan, Shen; Yu, Zhang; Ning, Liu; Hai-Dong, Wang; Jian-Shan, Xie; Shu-Yuan, Gao; Jia-Qi, Cheng; Xiu-Ju, Yu; Ting, Wang; Chang-Sheng, Dong; Xiao-Yan, He

    2016-02-10

    The young male alpaca ear and the back skins were used to investigate the effect of transforming growth factor receptor-β I (TGFβR I) on alpaca hair follicles and hair growth. The expression level and location of TGFβR I in alpaca ear and dorsal skin were detected through real-time quantitative PCR (RT-PCR) and paraffin section immunohistochemical technique (ICC-P). The results shown TGFβR I was lower expression in back skin compared to ear skin and the mean density of the positive reaction in ear skin was significantly higher than back skin. The targeted relationship with let-7b was detected using the dual-luciferase reporter vector of TGFβR I, which showed a significant target relationship between let-7b and TGFβR I. After transfection with let-7b eukaryotic expression vector, the relative mRNA expression of TGFβR I in alpaca skin fibroblasts did not differ, while the relative protein level was significantly decreased. In summary, a higher TGFβR I expression level in the ear skin suggests that TGFβR I may inhibit coat hair elongation. Further studies showed TGFβR I protein was downregulated by let-7b through transcriptional repression. PMID:26611528

  17. High DRC Levels Are Associated with Let-7b Overexpression in Women with Breast Cancer.

    PubMed

    Encarnación, Jarline; Ortiz, Carmen; Vergne, Ralphdy; Vargas, Wanda; Coppola, Domenico; Matta, Jaime L

    2016-01-01

    Nucleotide Excision Repair (NER) is a critical pathway involved in breast cancer (BC). We have previously published that a low DNA repair capacity (DRC) is associated with a higher risk of BC in Puerto Rican women. Let-7b belongs to a miRNA family with tumor suppressor activity that targets oncogenes. We isolated miRNAs from plasma of 153 Puerto Rican women with and without BC. DRC was measured in lymphocytes by means of a host cell reactivation assay. These women were divided into four groups according to their DRC level: High (>3.8%) and low (<3.8%). The four groups consisted of BC patients with high (n = 35) and low (n = 43) DRC and controls with high (n = 39) and low (n = 36) DRC. Epidemiologic data were collected at initial BC diagnosis and almost five years after diagnosis. A significant difference in Let-7b expression was found in BC patients with high DRC versus the remaining groups (p < 0.001). Thus, our data reveal a possible role of Let-7b on DRC during breast carcinogenesis. Our study is innovative because it provides the first evidence that Let-7b may play role in DRC regulation (through the NER repair pathway) in BC. PMID:27271599

  18. Whole-Genome Sequence of Stenotrophomonas maltophilia ZBG7B Reveals Its Biotechnological Potential

    PubMed Central

    Chong, Teik-Min; Adrian, Tan-Guan-Sheng; Kher, Heng Leong; Hong, Kar-Wai; Grandclément, Catherine; Faure, Denis; Yin, Wai-Fong; Dessaux, Yves

    2015-01-01

    Stenotrophomonas maltophilia ZBG7B was isolated from vineyard soil of Zellenberg, France. Here, we present the draft genome sequence of this bacterial strain, which has facilitated the prediction of function for several genes encoding biotechnologically important enzymes, such as xylosidase, xylanase, laccase, and chitinase. PMID:26659682

  19. Whole-Genome Sequence of Stenotrophomonas maltophilia ZBG7B Reveals Its Biotechnological Potential.

    PubMed

    Chan, Kok-Gan; Chong, Teik-Min; Adrian, Tan-Guan-Sheng; Kher, Heng Leong; Hong, Kar-Wai; Grandclément, Catherine; Faure, Denis; Yin, Wai-Fong; Dessaux, Yves

    2015-01-01

    Stenotrophomonas maltophilia ZBG7B was isolated from vineyard soil of Zellenberg, France. Here, we present the draft genome sequence of this bacterial strain, which has facilitated the prediction of function for several genes encoding biotechnologically important enzymes, such as xylosidase, xylanase, laccase, and chitinase. PMID:26659682

  20. Microbial Desulfurization of Gasoline in a Mycobacterium goodii X7B Immobilized-Cell System

    PubMed Central

    Li, Fuli; Xu, Ping; Feng, Jinhui; Meng, Ling; Zheng, Yuan; Luo, Lailong; Ma, Cuiqing

    2005-01-01

    Mycobacterium goodii X7B, which had been primarily isolated as a bacterial strain capable of desulfurizing dibenzothiophene to produce 2-hydroxybiphenyl via the 4S pathway, was also found to desulfurize benzothiophene. The desulfurization product was identified as o-hydroxystyrene by gas chromatography (GC)-mass spectrometry analysis. This strain appeared to have the ability to remove organic sulfur from a broad range of sulfur species in gasoline. When Dushanzi straight-run gasoline (DSRG227) containing various organic sulfur compounds was treated with immobilized cells of strain X7B for 24 h, the total sulfur content significantly decreased, from 227 to 71 ppm at 40°C. GC flame ionization detection and GC atomic emission detection analysis were used to qualitatively evaluate the effects of M. goodii X7B treatment on the contents of gasoline. In addition, when immobilized cells were incubated at 40°C with DSRG275, the sulfur content decreased from 275 to 54 ppm in two consecutive reactions. With this excellent efficiency, strain X7B is considered a good potential candidate for industrial applications for the biodesulfurization of gasoline. PMID:15640198

  1. Role of an adaptor protein Lin-7B in brain development: possible involvement in autism spectrum disorders.

    PubMed

    Mizuno, Makoto; Matsumoto, Ayumi; Hamada, Nanako; Ito, Hidenori; Miyauchi, Akihiko; Jimbo, Eriko F; Momoi, Mariko Y; Tabata, Hidenori; Yamagata, Takanori; Nagata, Koh-Ichi

    2015-01-01

    Using comparative genomic hybridization analysis for an autism spectrum disorder (ASD) patient, a 73-Kb duplication at 19q13.33 (nt. 49 562 755-49 635 956) including LIN7B and 5 other genes was detected. We then identified a novel frameshift mutation in LIN7B in another ASD patient. Since LIN7B encodes a scaffold protein essential for neuronal function, we analyzed the role of Lin-7B in the development of cerebral cortex. Acute knockdown of Lin-7B with in utero electroporation caused a delay in neuronal migration during corticogenesis. When Lin-7B was knocked down in cortical neurons in one hemisphere, their axons failed to extend efficiently into the contralateral hemisphere after leaving the corpus callosum. Meanwhile, enhanced expression of Lin-7B had no effects on both cortical neuron migration and axon growth. Notably, silencing of Lin-7B did not affect the proliferation of neuronal progenitors and stem cells. Taken together, Lin-7B was found to play a pivotal role in corticogenesis through the regulation of excitatory neuron migration and interhemispheric axon growth, while further analyses are required to directly link functional defects of Lin-7B to ASD pathophysiology. Lin-7 plays a pivotal role as a scaffold protein in synaptic development and plasticity. Based on genetic analyses we identified mutations in LIN-7B gene in some ASD (autism-spectrum disorder) patients. Functional defects in Lin-7B caused abnormal neuronal migration and interhemispheric axon growth during mouse brain development. Thus, functional deficiency in Lin-7B could be implicated in clinical phenotypes in some ASD patients through bringing about abnormal cortical architecture. PMID:25196215

  2. Mutational analysis of ATP7B in Chinese Wilson disease patients.

    PubMed

    Hua, Rui; Hua, Fang; Jiao, Yonggeng; Pan, Yu; Yang, Xu; Peng, Shanshan; Niu, Junqi

    2016-01-01

    Wilson Disease (WD) is an inborn error of copper metabolism inherited in an autosomal recessive manner caused by the mutations in the P-type ATPase gene (ATP7B). In this study, we screen and detect the mutations of the ATP7B gene in unrelated Chinese WD patients. A total of 68 individuals from ten provinces of China with WD were recruited. Of them, 43 were males and 25 were females, and their onset ages were from 1 to 48 years with a median onset age of 22.2 years. All the exons and exon/intron boundaries of ATP7B gene of the patients were sequenced and aligned to the referred ATP7B gene sequence. The results suggested that 66 of the 68 patents carried with at least one mutation and 48 different mutations were identified including 34 missense, one synonymous, two nonsense, two splicing, and nine frameshift mutations (five insertion and four deletion). Among these mutations, c.2333G>T, c.2310C>G, c.2975C>T, and c.3443T>C were the most prevalent mutants and c.2310C>G always linked with c.2333G>T. The eighth, 11(th), and 18(th) exons carried more mutations (6/48, 5/48, and 5/48, respectively) than others. After comparing with the mutations reported previously, 22 out of the 48 mutations were identified as novel mutations. A popular algorithm, Polyphen-2, was used to predict the effects of the amino-acid substitution due to the mutations on the structure and function of ATP7B function and the predicted results indicated that all the missense mutations were unfavorable except c.121A>G and c.748G>A. Phenotype/genotype correlation analysis suggested that the patients with c.2975C>T or c.3809A>G often presented WD features before 12 years old while the patients with c.3443T>C almost presented WD after 12 years old. This is the first time to identify the common mutations contributing to early onset age in Chinese WD patients. Our study will broaden our knowledge about ATP7B mutations in WD patients. PMID:27398169

  3. Mutational analysis of ATP7B in Chinese Wilson disease patients

    PubMed Central

    Hua, Rui; Hua, Fang; Jiao, Yonggeng; Pan, Yu; Yang, Xu; Peng, Shanshan; Niu, Junqi

    2016-01-01

    Wilson Disease (WD) is an inborn error of copper metabolism inherited in an autosomal recessive manner caused by the mutations in the P-type ATPase gene (ATP7B). In this study, we screen and detect the mutations of the ATP7B gene in unrelated Chinese WD patients. A total of 68 individuals from ten provinces of China with WD were recruited. Of them, 43 were males and 25 were females, and their onset ages were from 1 to 48 years with a median onset age of 22.2 years. All the exons and exon/intron boundaries of ATP7B gene of the patients were sequenced and aligned to the referred ATP7B gene sequence. The results suggested that 66 of the 68 patents carried with at least one mutation and 48 different mutations were identified including 34 missense, one synonymous, two nonsense, two splicing, and nine frameshift mutations (five insertion and four deletion). Among these mutations, c.2333G>T, c.2310C>G, c.2975C>T, and c.3443T>C were the most prevalent mutants and c.2310C>G always linked with c.2333G>T. The eighth, 11th, and 18th exons carried more mutations (6/48, 5/48, and 5/48, respectively) than others. After comparing with the mutations reported previously, 22 out of the 48 mutations were identified as novel mutations. A popular algorithm, Polyphen-2, was used to predict the effects of the amino-acid substitution due to the mutations on the structure and function of ATP7B function and the predicted results indicated that all the missense mutations were unfavorable except c.121A>G and c.748G>A. Phenotype/genotype correlation analysis suggested that the patients with c.2975C>T or c.3809A>G often presented WD features before 12 years old while the patients with c.3443T>C almost presented WD after 12 years old. This is the first time to identify the common mutations contributing to early onset age in Chinese WD patients. Our study will broaden our knowledge about ATP7B mutations in WD patients. PMID:27398169

  4. MicroRNAs let-7b/i suppress human glioma cell invasion and migration by targeting IKBKE directly

    SciTech Connect

    Tian, Yuan; Hao, Shaobo; Ye, Minhua; Zhang, Anling; Nan, Yang; Wang, Guangxiu; Jia, Zhifan; Yu, Kai; Guo, Lianmei; Pu, Peiyu; Huang, Qiang; Zhong, Yue

    2015-03-06

    We demonstrated that IKBKE is overexpressed in human gliomas and that the downregulation of IKBKE markedly inhibits the proliferative and invasive abilities of glioma cells, which is consistent with the results reported by several different research groups. Therefore, IKBKE represents a promising therapeutic target for the treatment of glioma. In the present study, we verified that the microRNAs let-7b and let-7i target IKBKE through luciferase assays and found that let-7b/i mimics can knock down IKBKE and upregulate E-cadherin through western blot analysis. Moreover, the expression levels of let-7b/i were significantly lower in glioma cell lines than that in normal brain tissues, as determined by quantitative real-time PCR. Furthermore, let-7b/i inhibit the invasion and migration of glioma cells, as determined through wound healing and Transwell assays. The above-mentioned data suggest that let-7b/i inhibit the invasive ability of glioma cells by directly downregulating IKBKE and indirectly upregulating E-cadherin. - Highlights: • Let-7b and let-7i are downregulated in glioma cell lines. • IKBKE is a target gene of let-7b/i. • Let-7b/i inhibit the invasion and migration of glioma cells. • Let-7b/i upregulate E-cadherin by downregulating IKBKE.

  5. Kepler's optical phase curve of the exoplanet HAT-P-7b.

    PubMed

    Borucki, W J; Koch, D; Jenkins, J; Sasselov, D; Gilliland, R; Batalha, N; Latham, D W; Caldwell, D; Basri, G; Brown, T; Christensen-Dalsgaard, J; Cochran, W D; DeVore, E; Dunham, E; Dupree, A K; Gautier, T; Geary, J; Gould, A; Howell, S; Kjeldsen, H; Lissauer, J; Marcy, G; Meibom, S; Morrison, D; Tarter, J

    2009-08-01

    Ten days of photometric data were obtained during the commissioning phase of the Kepler mission, including data for the previously known giant transiting exoplanet HAT-P-7b. The data for HAT-P-7b show a smooth rise and fall of light from the planet as it orbits its star, punctuated by a drop of 130 +/- 11 parts per million in flux when the planet passes behind its star. We interpret this as the phase variation of the dayside thermal emission plus reflected light from the planet as it orbits its star and is occulted. The depth of the occultation is similar in photometric precision to the detection of a transiting Earth-size planet for which the mission was designed. PMID:19661420

  6. A kinetic study of Trichoderma reesei Cel7B catalyzed cellulose hydrolysis.

    PubMed

    Song, Xiangfei; Zhang, Shujun; Wang, Yefei; Li, Jingwen; He, Chunyan; Yao, Lishan

    2016-06-01

    One prominent feature of Trichoderma reesei (Tr) endoglucanases catalyzed cellulose hydrolysis is that the reaction slows down quickly after it starts (within minutes). But the mechanism of the slowdown is not well understood. A structural model of Tr- Cel7B catalytic domain bound to cellulose was built computationally and the potentially important binding residues were identified and tested experimentally. The 13 tested mutants show different binding properties in the adsorption to phosphoric acid swollen cellulose and filter paper. Though the partitioning parameter to filter paper is about 10 times smaller than that to phosphoric acid swollen cellulose, a positive correlation is shown for two substrates. The kinetic studies show that the reactions slow down quickly for both substrates. This slowdown is not correlated to the binding constant but anticorrelated to the enzyme initial activity. The amount of reducing sugars released after 24h by Cel7B in phosphoric acid swollen cellulose, Avicel and filter paper cellulose hydrolysis is correlated with the enzyme activity against a soluble substrate p-nitrophenyl lactoside. Six of the 13 tested mutants, including N47A, N52D, S99A, N323D, S324A, and S346A, yield ∼15-35% more reducing sugars than the wild type (WT) Cel7B in phosphoric acid swollen cellulose and filter paper hydrolysis. This study reveals that the slowdown of the reaction is not due to the binding of the enzyme to cellulose. The activity of Tr- Cel7B against the insoluble substrate cellulose is determined by the enzyme's capability in hydrolyzing the soluble substrate. PMID:27178789

  7. Improving the activity of Trichoderma reesei cel7B through stabilizing the transition state.

    PubMed

    Wang, Yefei; Song, Xiangfei; Zhang, Shujun; Li, Jingwen; Shu, Zhiyu; He, Chunyan; Huang, Qingshan; Yao, Lishan

    2016-06-01

    Trichoderma reesei (Tr.) cellulases, which convert cellulose to reducing sugars, are a promising catalyst used in the lignocellulosic biofuel production. Improving Tr. cellulases activity, though very difficult, is highly desired due to the recalcitrance of lignocellulose. Meanwhile, it is preferable to enhance the cellulase's promiscuity so that substrates other than cellulose can also be hydrolyzed. In this work, an attempt is made to improve the catalytic activity of a major endogluanase Tr. Cel7B against xylan which crosslinks with cellulose in lignocellulose. By using quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations, the transition state of the xylo-oligosaccharide hydrolysis is identified. Then, mutations are introduced and their effect on the transition state stabilization is ranked based on the free energy calculations. Seven top ranked mutants are evaluated experimentally. Three mutants A208Q, A222D, and G230R show a higher activity than the wild-type Tr. Cel7B in the hydrolysis of xylan (by up to 47%) as well as filter paper (by up to 50%). The combination of the single mutants can further improve the enzyme activity. Our work demonstrates that the free energy method is effective in engineering the Tr. Cel7B activity against xylan and cellulose, and thus may also be useful for improving the activity of other Tr. cellulases. Biotechnol. Bioeng. 2016;113: 1171-1177. © 2015 Wiley Periodicals, Inc. PMID:26616246

  8. New novel mutation of the ATP7B gene in a family with Wilson disease.

    PubMed

    Lee, Jun-Young; Kim, Young-Hyun; Kim, Tae-Woo; Oh, Sun-Young; Kim, Dal-Sik; Shin, Byoung-Soo

    2012-02-15

    Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The WD gene codes for a copper transporting P-type ATPase (ATP7B) are located on chromosome 13q14.3. Mutation of this gene disrupts copper homeostasis, resulting in the accumulation of copper in the liver, brain, kidneys and corneas and copper toxication at these sites. Since the detection of the WD gene in 1993, approximately 300 disease-specific muations have been identified. We recently evaluated a Korean family with WD. The proband, a 17-year-old boy, visited our hospital due to abnormal behaviors including generalized slow movement, dysphagia, drooling and ataxia. Laboratory results revealed decreases in serum copper and ceruloplasmin and an increase in urinary excretion of copper. He had liver cirrhosis, brain lesions and Kayser-Fleischer corenal rings. Molecular genetic analysis of the ATP7B gene demonstrated that he was heterozygous for deletion mutation c.2697_2723del27 in exon 11. Further study of family members revealed that his father and younger brother had the same mutation. The c.2697_2723del27 deletion mutation in exon 11 has not yet been reported as a causative muation of WD and is an in-frame deletion not expected to lead to a frame shift. Therefore, we report a novel mutation of the ATP7B gene in a family with WD. PMID:22075048

  9. AP180-mediated trafficking of Vamp7B limits homotypic fusion of Dictyostelium contractile vacuoles.

    PubMed

    Wen, Yujia; Stavrou, Irene; Bersuker, Kirill; Brady, Rebecca J; De Lozanne, Arturo; O'Halloran, Theresa J

    2009-10-01

    Clathrin-coated vesicles play an established role in endocytosis from the plasma membrane, but they are also found on internal organelles. We examined the composition of clathrin-coated vesicles on an internal organelle responsible for osmoregulation, the Dictyostelium discoideum contractile vacuole. Clathrin puncta on contractile vacuoles contained multiple accessory proteins typical of plasma membrane-coated pits, including AP2, AP180, and epsin, but not Hip1r. To examine how these clathrin accessory proteins influenced the contractile vacuole, we generated cell lines that carried single and double gene knockouts in the same genetic background. Single or double mutants that lacked AP180 or AP2 exhibited abnormally large contractile vacuoles. The enlarged contractile vacuoles in AP180-null mutants formed because of excessive homotypic fusion among contractile vacuoles. The SNARE protein Vamp7B was mislocalized and enriched on the contractile vacuoles of AP180-null mutants. In vitro assays revealed that AP180 interacted with the cytoplasmic domain of Vamp7B. We propose that AP180 directs Vamp7B into clathrin-coated vesicles on contractile vacuoles, creating an efficient mechanism for regulating the internal distribution of fusion-competent SNARE proteins and limiting homotypic fusions among contractile vacuoles. Dictyostelium contractile vacuoles offer a valuable system to study clathrin-coated vesicles on internal organelles within eukaryotic cells. PMID:19692567

  10. Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia.

    PubMed

    Schüle, Rebecca; Brandt, Elisabeth; Karle, Kathrin N; Tsaousidou, Maria; Klebe, Stephan; Klimpe, Sven; Auer-Grumbach, Michaela; Crosby, Andrew H; Hübner, Christian A; Schöls, Ludger; Deufel, Thomas; Beetz, Christian

    2009-04-01

    Hereditary spastic paraplegia (HSP) is a neurodegenerative condition defined clinically by lower limb spasticity and weakness. Homozygous mutations in CYP7B1 have been identified in several consanguineous families that represented HSP type 5 (SPG5), one of the many genetic forms of the disease. We used direct sequencing and multiplex ligation-dependent probe amplification to screen for CYP7B1 alterations in apparently sporadic HSP patients (n = 12) as well as index patients from non-consanguineous families with recessive (n = 8) and dominant (n = 8) transmission of HSP. One sporadic patient showing HSP as well as optic atrophy carried a homozygous nonsense mutation. Compound heterozygosity was observed in a recessive family with a clinically pure phenotype. A heterozygous missense change segregated in a small dominant family. We also found a significant association of a known coding polymorphism with cerebellar signs complicating a primary HSP phenotype. Our findings suggest CYP7B1 alterations to represent a rather frequent cause of HSP that should be considered in patients with various clinical presentations. PMID:18855023

  11. Constraints on the exosphere of CoRoT-7b

    NASA Astrophysics Data System (ADS)

    Guenther, E. W.; Cabrera, J.; Erikson, A.; Fridlund, M.; Lammer, H.; Mura, A.; Rauer, H.; Schneider, J.; Tulej, M.; von Paris, Ph.; Wurz, P.

    2011-01-01

    Context. The small radius and high density of CoRoT-7b implies that this transiting planet belongs to a different species than all transiting planets previously found. Current models suggest that this is the first transiting rocky planet found outside the solar system. Given that the planet orbits a solar-like star at a distance of only 4.5 R*, it is expected that material released from its surface may then form an exosphere. Aims: We constrain the properties of the exosphere by observing the planet in- and out-of-transit. Detecting the exosphere of CoRoT-7b would for the first time allow us to study the material originating in the surface of a rocky extrasolar planet. We scan the entire optical spectrum for any lines originating from the planet, focusing particularly on spectral lines such as those detected in Mercury and Io in our solar system. Methods: Since lines originating in the exosphere are expected to be narrow, we observed CoRoT-7b at high resolution with UVES on the VLT. By subtracting the two spectra from each other, we search for emission and absorption lines originating in the exosphere of CoRoT-7b. Results: In the first step, we focus on Ca I, Ca II, and Na, because these lines have been detected in Mercury. Since the signal-to-noise ratio (S/N) of the spectra is as high as 300, we derive firm upper limits for the flux-range between 1.6 × 10-18 and 3.2 × 10-18 W m-2. For CaO, we find an upper limit of 10-17 W m-2. We also search for emission lines originating in the plasma torus fed by volcanic activity and derive upper limits for these lines. In the whole spectrum we finally try to identify other lines originating in the planet. Conclusions: Except for CaO, the upper limits derived correspond to 2-6 × 10-6 L*, demonstrating the capability of UVES to detect very weak lines. Our observations certainly exclude the extreme interpretations of data for CoRoT-7b, such as an exosphere that emits 2000 times as brightly as Mercury. Based on observations

  12. Wnt7b can replace Ihh to induce hypertrophic cartilage vascularization but not osteoblast differentiation during endochondral bone development.

    PubMed

    Joeng, Kyu Sang; Long, Fanxin

    2014-01-01

    Indian hedgehog (Ihh) is an essential signal that regulates endochondral bone development. We have previously shown that Wnt7b promotes osteoblast differentiation during mouse embryogenesis, and that its expression in the perichondrium is dependent on Ihh signaling. To test the hypothesis that Wnt7b may mediate some aspects of Ihh function during endochondral bone development, we activated Wnt7b expression from the R26-Wnt7b allele with Col2-Cre in the Ihh(-/-) mouse. Artificial expression of Wnt7b rescued vascularization of the hypertrophic cartilage in the Ihh(-/-) mouse, but failed to restore orthotopic osteoblast differentiation in the perichondrium. Similarly, Wnt7b did not recover Ihh-dependent perichondral bone formation in the Ihh(-/-); Gli3(-/-) embryo. Interestingly, Wnt7b induced bone formation at the diaphyseal region of long bones in the absence of Ihh, possibly due to increased vascularization in the area. Thus, Ihh-dependent expression of Wnt7b in the perichondrium may contribute to vascularization of the hypertrophic cartilage during endochondral bone development. PMID:26273517

  13. Dehydroepiandrosterone 7-hydroxylase CYP7B: predominant expression in primate hippocampus and reduced expression in Alzheimer's disease.

    PubMed

    Yau, J L W; Rasmuson, S; Andrew, R; Graham, M; Noble, J; Olsson, T; Fuchs, E; Lathe, R; Seckl, J R

    2003-01-01

    Neurosteroids such as dehydroepiandrosterone (DHEA), pregnenolone and 17beta-estradiol are synthesized by cytochrome P450s from endogenous cholesterol. We previously reported a new cytochrome P450 enzyme, CYP7B, highly expressed in rat and mouse brain that metabolizes DHEA and related steroids by hydroxylation at the 7alpha position. Such 7-hydroxylation can enhance DHEA bioactivity in vivo. Here we show that the reaction is conserved across mammalian species: in addition to mouse and rat, DHEA hydroxylation activity was present in brain extracts from sheep, marmoset and human. Northern blotting using a human CYP7B complementary deoxyribonucleic acid (cDNA) probe confirmed the presence of CYP7B mRNA in marmoset and human hippocampus; CYP7B mRNA was present in marmoset cerebellum and brainstem, with lower levels in hypothalamus and cortex. In situ hybridization to human brain revealed higher levels of CYP7B mRNA in the hippocampus than in cerebellum, cortex, or other brain regions. We also measured CYP7B expression in Alzheimer's disease (AD). CYP7B mRNA was significantly decreased (approximately 50% decline; P<0.05) in dentate neurons from AD subjects compared with controls. A decline in CYP7B activity may contribute the loss of effects of DHEA with ageing and perhaps to the pathophysiology of AD. PMID:14521990

  14. 46 CFR 151.50-86 - Alkyl (C7-C9) nitrates.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Alkyl (C7-C9) nitrates. 151.50-86 Section 151.50-86... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-86 Alkyl (C7-C9) nitrates. (a) The carriage temperature of octyl nitrates must be maintained below 100 °C (212 °F) in order...

  15. 46 CFR 151.50-86 - Alkyl (C7-C9) nitrates.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Alkyl (C7-C9) nitrates. 151.50-86 Section 151.50-86... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-86 Alkyl (C7-C9) nitrates. (a) The carriage temperature of octyl nitrates must be maintained below 100 °C (212 °F) in order...

  16. 46 CFR 153.560 - Special requirements for Alkyl (C7-C9) nitrates.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Special requirements for Alkyl (C7-C9) nitrates. 153.560... Equipment Special Requirements § 153.560 Special requirements for Alkyl (C7-C9) nitrates. (a) The carriage temperature of octyl nitrates must be maintained below 100 °C (212 °F) in order to prevent the occurrence of...

  17. 46 CFR 153.560 - Special requirements for Alkyl (C7-C9) nitrates.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Special requirements for Alkyl (C7-C9) nitrates. 153.560... Equipment Special Requirements § 153.560 Special requirements for Alkyl (C7-C9) nitrates. (a) The carriage temperature of octyl nitrates must be maintained below 100 °C (212 °F) in order to prevent the occurrence of...

  18. 46 CFR 151.50-86 - Alkyl (C7-C9) nitrates.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Alkyl (C7-C9) nitrates. 151.50-86 Section 151.50-86... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-86 Alkyl (C7-C9) nitrates. (a) The carriage temperature of octyl nitrates must be maintained below 100 °C (212 °F) in order...

  19. 46 CFR 153.560 - Special requirements for Alkyl (C7-C9) nitrates.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Special requirements for Alkyl (C7-C9) nitrates. 153.560... Equipment Special Requirements § 153.560 Special requirements for Alkyl (C7-C9) nitrates. (a) The carriage temperature of octyl nitrates must be maintained below 100 °C (212 °F) in order to prevent the occurrence of...

  20. 46 CFR 151.50-86 - Alkyl (C7-C9) nitrates.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Alkyl (C7-C9) nitrates. 151.50-86 Section 151.50-86... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-86 Alkyl (C7-C9) nitrates. (a) The carriage temperature of octyl nitrates must be maintained below 100 °C (212 °F) in order...

  1. 46 CFR 153.560 - Special requirements for Alkyl (C7-C9) nitrates.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Special requirements for Alkyl (C7-C9) nitrates. 153.560... Equipment Special Requirements § 153.560 Special requirements for Alkyl (C7-C9) nitrates. (a) The carriage temperature of octyl nitrates must be maintained below 100 °C (212 °F) in order to prevent the occurrence of...

  2. 46 CFR 151.50-86 - Alkyl (C7-C9) nitrates.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Alkyl (C7-C9) nitrates. 151.50-86 Section 151.50-86... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-86 Alkyl (C7-C9) nitrates. (a) The carriage temperature of octyl nitrates must be maintained below 100 °C (212 °F) in order...

  3. 46 CFR 153.560 - Special requirements for Alkyl (C7-C9) nitrates.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Special requirements for Alkyl (C7-C9) nitrates. 153.560... Equipment Special Requirements § 153.560 Special requirements for Alkyl (C7-C9) nitrates. (a) The carriage temperature of octyl nitrates must be maintained below 100 °C (212 °F) in order to prevent the occurrence of...

  4. Let-7c down-regulation in Helicobacter pylori-related gastric carcinogenesis.

    PubMed

    Fassan, Matteo; Saraggi, Deborah; Balsamo, Laura; Cascione, Luciano; Castoro, Carlo; Coati, Irene; De Bernard, Marina; Farinati, Fabio; Guzzardo, Vincenza; Valeri, Nicola; Zambon, Carlo Federico; Rugge, Massimo

    2016-01-26

    Aberrant let-7c microRNA (miRNA) expression has been observed in Helicobacter pylori-related gastric cancer (GC) but fragmentary information is available on the let-7c dysregulation occurring with each phenotypic change involved in gastric carcinogenesis. Let-7c expression was assessed (qRT-PCR) in a series of 175 gastric biopsy samples representative of the whole spectrum of phenotypic changes involved in H. pylori-related gastric oncogenesis including: i) normal gastric mucosa, as obtained from dyspeptic controls (40 biopsy samples); ii) non-atrophic gastritis (40 samples); iii) atrophic-metaplastic gastritis (35 samples); iv) intra-epithelial neoplasia (30 samples); v) GC (30 samples). Let-7c expression was also tested in 20 biopsy samples obtained from 10 patients before and after H. pylori eradication therapy (median follow-up: 10 weeks; range: 7-14). The results obtained were further validated by in situ hybridization on multiple tissue specimens obtained from 5 surgically treated H. pylori-related GCs. The study also included 40 oxyntic biopsy samples obtained from serologically/histologically confirmed autoimmune gastritis (AIG: 20 corpus-restricted, non-atrophic; 20 corpus-restricted, atrophic-metaplastic). Let-7c expression dropped from non-atrophic gastritis to atrophic-metaplastic gastritis, intra-epithelial neoplasia, and invasive GC (p<0.001). It rose again significantly following H. pylori eradication (p=0.009). As in the H. pylori model, AIG also featured a significant let-7c down-regulation (p<0.001). The earliest phases of the two pathways to gastric oncogenesis (H. pylori-environmental and autoimmune host-related) are characterized by similar let-7c dysregulations. In H. pylori infection, let-7c down-regulation regresses after the bacterium's eradication, while it progresses significantly with the increasing severity of the histological lesions. PMID:26701848

  5. Elastic softening in Fe7C3 with implications for Earth's deep carbon reservoirs

    NASA Astrophysics Data System (ADS)

    Liu, Jiachao; Li, Jie; Ikuta, Daijo

    2016-03-01

    Iron carbide Fe7C3 has recently emerged as a potential host of reduced carbon in Earth's mantle and a candidate component of the inner core, but the equation of state of Fe7C3 is still uncertain, partly because the nature of pressure-induced magnetic transitions in Fe7C3 and their elastic effects remain controversial. Here we report the compression curve of hexagonal Fe7C3 in neon medium with dense pressure sampling and in comparison with pure iron in the same loading. The results revealed elastic softening between 7 GPa and 20 GPa, which can be attributed to noncollinear alignment of spin moments in a state between the ferromagnetic and paramagnetic phases, as expected for Invar-type alloys. The volume reduction associated with the softening would enhance the stability of Fe7C3 in the deeper part of the upper mantle and transition zone. As a result of subsequent spin crossover at higher pressures, Fe7C3 at inner core conditions likely occurs as the nonmagnetic phase, which remains a candidate for the major component of the Earth's central sphere.

  6. Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7(b))

    PubMed Central

    Jasper, J R; Kosaka, A; To, Z P; Chang, D J; Eglen, R M

    1997-01-01

    The rat 5-hydroxytryptamine (5-HT)7 receptor displays two splice variations, a long form, and a truncated splice isoform, arising from the introduction of a stop codon near the carboxy-terminus. The human 5-HT7 receptor gene contains at least two introns and encodes a 445 amino acid 5-HT receptor. A truncated splice variation in the human 5-HT7 receptor was isolated from a human placental cDNA library. In accordance with current NC-IUPHAR nomenclature guidelines, it is suggested that this receptor be denoted as the h5-HT7(b) receptor and the long form of the receptor as h5-HT7(a). The h5-HT7(b) receptor was stably expressed in HEK 293 cells and ligand affinities were determined by displacement of [3H]-5-carboxyamidotryptamine (5-CT; Kd=0.28±0.06 nM, Bmax=7.3±1.7 pmol mg−1 protein). The rank order of affinities (pKi) for a series of ligands was: 5-carboxamidotryptamine (5-CT, 9.65)>5-hydroxytryptamine (5-HT, 9.41)>methiothepin (8.87)>mesulergine (7.87)>8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT, 6.85)>ketanserin (6.44). The h5-HT7(b) receptor coupled positively to adenylyl cyclase in HEK 293 cells. This response was elicited by a number of agonists with the following order of potency (pEC50): 5-CT (8.7±0.11)>5-MeOT (5-methoxytryptamine; 8.1±0.20)>5-HT (7.5±0.13)>tryptamine (5.6±0.36)>8-OH-DPAT (5.3±0.28)>5-methoxytryptamine (5.0±0.06). This rank order was comparable to that observed in the radioligand binding studies. In a similar fashion to that described for the 5-HT7(a) receptor, PCR studies suggested that the 5-HT7(b) receptor mRNA is found in great abundance throughout the brain, in the small intestine and aorta. It is concluded that the h5-HT7 receptor, like the rat receptor, exists as splice variants exhibiting similar pharmacology, signal transduction and distribution. It is thus likely that there exists a complex physiological role for alternate splicing products of the 5-HT7 receptor gene. PMID:9298538

  7. CoRoT-7b: Convection in a Tidally Locked Planet

    NASA Astrophysics Data System (ADS)

    Noack, Lena; Stamenkovic, Vlada; Wagner, Frank W.; Sohl, Frank; Breuer, Doris

    2010-05-01

    The number of terrestrial extrasolar planets found in the past few years is increasing rapidly. Some have masses ranging from 2 to 10 Earth masses, and the habitability of these planets is widely discussed in the planetary community. Due to observational limitations we will mostly be able to observe planets that are very close to its host star, resulting in a potentially tidally locked orbit. Our goal is to investigate if such planets can be habitable at all. But to do so, we first have to understand the convection behaviour of such planets. In this work we model the mantle convection of the recently discovered exoplanet CoRoT-7b [1], which is a planet believed to be tidally locked. The extreme intense insolation in the vicinity of its host star heats the day-side of CoRoT-7b, leading to surface temperatures about 2000 Kelvin higher than on the night-side [1]. CoRoT-7b is about 5 times more massive than the Earth and predominantly composed of dry silicate rock similar to Earth's Moon. A central iron core, if present, would be relatively small [2] with a core mass fraction of no more than 15 wt%. The mantle convection is modelled in a spherical shell [3] using a temperature- and pressure-dependent viscosity. We use a radioactive heat source density similar to present Earth. Coriolis forces are neglected and we assume that CoRoT-7b has no atmosphere. The results show that the lower mantle above the core-mantle boundary is in a more sluggish convection regime as a consequence of the viscosity increase with pressure. Depending on the strength of the viscosity increase, even a so-called low-lid [4] can form and conductive heat transport dominates from the core to the upper part of the mantle. The thermal state of such a deeply situated, conductive lower mantle of CoRoT-7b is not much influenced by the strongly laterally varying surface temperature. However, the temperatures of the upper convecting mantle are found to strongly vary from one side of the planet to the

  8. Basolateral sorting and transcytosis define the Cu+-regulated translocation of ATP7B to the bile canaliculus.

    PubMed

    Lalioti, Vasiliki; Peiró, Ramón; Pérez-Berlanga, Manuela; Tsuchiya, Yo; Muñoz, Angeles; Villalba, Teresa; Sanchez, Carlos; Sandoval, Ignacio V

    2016-06-01

    The Cu(+) pump ATP7B plays an irreplaceable role in the elimination of excess Cu(+) by the hepatocyte into the bile. The trafficking and site of action of ATP7B are subjects of controversy. One current proposal is that an increase in intracellular Cu(+) results in the translocation of ATP7B to the lysosomes and excretion of excess Cu(+) through lysosomal-mediated exocytosis at the bile canaliculus. Here, we show that ATP7B is transported from the trans-Golgi network (TGN) to the bile canaliculus by basolateral sorting and endocytosis, and microtubule-mediated transcytosis through the subapical compartment. Trafficking ATP7B is not incorporated into lysosomes, and addition of Cu(+) does not cause relocalization of lysosomes and the appearance of lysosome markers in the bile canaliculus. Our data reveal the pathway of the Cu(+)-mediated transport of ATP7B from the TGN to the bile canaliculus and indicates that the bile canaliculus is the primary site of ATP7B action in the elimination of excess Cu(.) PMID:27034138

  9. Molecular structure of the Menkes disease gene (ATP7A)

    SciTech Connect

    Dierick, H.A.; Glover, T.W.; Ambrosini, L.

    1995-08-10

    We report a detailed molecular analysis of the genomic structure of the Menkes disease gene (MNK; ATP7A). There are 23 exons in ATP7A covering a genomic region of approximately 140 kb. The size of the individual coding exons varies between 77 and 726 bp, and introns vary in size between 196 bp and approximately 60 kb. All of the splice sites obey the consensus GT-AG rule except the splice donor of intron 9, which is GC instead of GT. The exon following this rare splice donor variant is alternatively spliced. A PGAM pseudogene and two highly polymorphic CA repeats map to introns within the gene. The structure is very similar to that of the closely related Wilson disease gene (WND; ATP7B). From exon 5 (exon 3 in ATP7B) to the end, all of the splice sites occur at exactly the same nucleotide positions as in the WND gene, except for the boundary between exons 17 and 18 (exons 15 and 16 in ATP7B) and a single codon difference at the boundary between exons 4 and 5 of the MNK gene (exons 2 and 3 in ATP7B). In contrast to the WND gene, in which the first four of six metal binding domains are contained in 1 exon, metal binding domains 1 to 4 are divided over 3 exons. The striking similarity of the MNK and WND genes at the genomic level is consistent with their relatively recent divergence from a common ancestral gene. 39 refs., 4 figs., 1 tab.

  10. Physical state of the deep interior of the CoRoT-7b exoplanet

    NASA Astrophysics Data System (ADS)

    Wagner, Frank W.; Sohl, Frank; Rückriemen, Tina; Rauer, Heike

    2011-11-01

    The present study takes the CoRoT-7b exoplanet as an analogue for massive terrestrial planets to investigate conditions, under which intrinsic magnetic fields could be sustained in liquid cores. We examine the effect of depth-dependent transport parameters (e.g., activation volume of mantle rock) on a planet's thermal structure and the related heat flux across the core mantle boundary. For terrestrial planets more massive than the Earth, our calculations suggest that a substantial part of the lowermost mantle is in a sluggish convective regime, primarily due to pressure effects on viscosity. Hence, we find substantially higher core temperatures than previously reported from parameterized convection models. We also discuss the effect of melting point depression in the presence of impurities (e.g., sulfur) in iron-rich cores and compare corresponding melting relations to the calculated thermal structure. Since impurity effects become less important at the elevated pressure and temperature conditions prevalent in the deep interior of CoRoT-7b, iron-rich cores are likely solid, implying that a self-sustained magnetic field would be absent.

  11. A Bayesian analysis of HAT-P-7b using the EXONEST algorithm

    SciTech Connect

    Placek, Ben; Knuth, Kevin H.

    2015-01-13

    The study of exoplanets (planets orbiting other stars) is revolutionizing the way we view our universe. High-precision photometric data provided by the Kepler Space Telescope (Kepler) enables not only the detection of such planets, but also their characterization. This presents a unique opportunity to apply Bayesian methods to better characterize the multitude of previously confirmed exoplanets. This paper focuses on applying the EXONEST algorithm to characterize the transiting short-period-hot-Jupiter, HAT-P-7b (also referred to as Kepler-2b). EXONEST evaluates a suite of exoplanet photometric models by applying Bayesian Model Selection, which is implemented with the MultiNest algorithm. These models take into account planetary effects, such as reflected light and thermal emissions, as well as the effect of the planetary motion on the host star, such as Doppler beaming, or boosting, of light from the reflex motion of the host star, and photometric variations due to the planet-induced ellipsoidal shape of the host star. By calculating model evidences, one can determine which model best describes the observed data, thus identifying which effects dominate the planetary system. Presented are parameter estimates and model evidences for HAT-P-7b.

  12. Improving Trichoderma reesei Cel7B thermostability by targeting the weak spots.

    PubMed

    Zhang, Shujun; Wang, Yefei; Song, Xiangfei; Hong, Jingbo; Zhang, Yu; Yao, Lishan

    2014-10-27

    For proteins that denature irreversibly, the denaturation is typically triggered by a partial unfolding, followed by a permanent change (e.g., aggregation). The regions that initiate the partial unfolding are named "weak spots". In this work, a molecular dynamics (MD) simulation and data analysis protocol is developed to identify the weak spots of Trichoderma reesei Cel7B, an important endoglucanase in cellulose hydrolysis, through assigning the local melting temperature (Tmp) to individual residue pairs. To test the predicted weak spots, a total of eight disulfide bonds were designed in these regions and all enhanced the enzyme thermostability. The increased stability, quantified by ΔT50 (which is the T50 difference between the mutant and the wild type enzyme), is negatively correlated with the MD-predicted Tmp, demonstrating the effectiveness of the protocol and highlighting the importance of the weak spots. Strengthening interactions in these regions proves to be a useful strategy in improving the thermostability of Tr. Cel7B. PMID:25286389

  13. Preliminary X-ray analysis of cellobiohydrolase Cel7B from Melanocarpus albomyces

    SciTech Connect

    Parkkinen, Tarja; Koivula, Anu; Vehmaanperä, Jari; Rouvinen, Juha

    2007-09-01

    The crystallization and preliminary X-ray diffraction analysis of cellobiohydrolase from M. albomyces is reported. Cellobiohydrolases are enzymes that cleave off cellobiose units from cellulose chains in a processive manner. Melanocarpus albomyces Cel7B is a thermostable single-module cellobiohydrolase that has relatively low activity on small soluble substrates at room temperature. It belongs to glycoside hydrolase family 7, which includes endo-β-1,4-glucanases and cellobiohydrolases. Cel7B was crystallized using the hanging-drop vapour-diffusion method and streak-seeding. The crystals belonged to space group P2{sub 1}, with unit-cell parameters a = 50.9, b = 94.5, c = 189.8 Å, β = 90.0° and four monomers in the asymmetric unit. Analysis of the intensity statistics showed that the crystals were pseudo-merohedrally twinned, with a twinning fraction of 0.37. X-ray diffraction data were collected at 1.6 Å resolution using synchrotron radiation.

  14. 76 FR 5066 - Airworthiness Directives; Pratt & Whitney JT8D-7, -7A, -7B, -9, -9A, -11, -15, -15A, -17, -17A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-28

    ...-14398 (70 FR 73361, December 12, 2005). That AD applies to the specified products. The NPRM published in the Federal Register on August 18, 2010 (75 FR 50942). That NPRM proposed to modify the TLS of the... ``significant rule'' under DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979), (3) Will...

  15. 75 FR 50942 - Airworthiness Directives; Pratt & Whitney JT8D-7, -7A, -7B, -9, -9A, -11, -15, -15A, -17, -17A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-18

    ..., 2000 (65 FR 19477-78). Examining the AD Docket You may examine the AD docket on the Internet at http... AD 2005-25-05, Amendment 39- 14398 (70 FR 73361, December 12, 2005), to require revisions to the TLS.... registry. We also estimate that it would take about 10 work-hours per engine to perform the...

  16. "Invar"-like behavior in compressed Fe7C3 with implication for deep carbon cycle

    NASA Astrophysics Data System (ADS)

    Liu, J.; Li, J.; Ikuta, D.

    2014-12-01

    Iron carbide Fe7C3 has recently emerged as a leading candidate component of the inner core because it is likely the first phase to solidify from a liquid containing iron and a small amount of carbon, and previous studies suggest that it provides a good match for the density of the inner core under relevant conditions. Pressure-induced magnetic transitions have been observed in Fe7C3 (Chen et al., 2012). The pressure of the ferromagnetic to paramagnetic transition remains controversial and its effect on equation of state (EoS) is unclear, thus introducing uncertainties in estimating the density of Fe7C3 under inner core pressures. Here we report the lattice parameters and unit cell volume of hexagonal Fe7C3 at 300 K and up to 70 GPa, obtained through synchrotron x-ray diffraction measurements using a diamond anvil cell. The experiments used fine powder of Fe7C3 that was synthesized in the multi-anvil apparatus at the University of Michigan. The sample was embedded in neon pressure medium together with Au powder and ruby spheres as additional pressure markers. We observed significant softening at 5~8 GPa, similar to the reported "invar"-like behavior in Fe-Ni alloy (Dubrovinsky et al., 2001). For comparison, the compression curve of iron in the same loading turned out to be smooth as expected, which confirms that the abnormal behavior in Fe7C3 compression curve is due to its own property change and not an artifact. The new data allow us to establish the equation-of-state (EoS) of Fe7C3 and then estimate the density of Fe7C3 at inner core conditions. References: Chen, B., Gao, L.L., Lavina, B., Dera, P., Alp, E.E., Zhao, J.Y., Li, J., 2012. Magneto-elastic coupling in compressed Fe7C3 supports carbon in Earth's inner core. Geophys Res Lett 39. Dubrovinsky, L., Dubrovinskaia, N., Abrikosov, I.A., Vennstrom, M., Westman, F., Carlson, S., van Schilfgaarde, M., Johansson, B., 2001. Pressure-induced invar effect in Fe-Ni alloys. Phys Rev Lett 86, 4851-4854.

  17. Copper transport during lactation in transgenic mice expressing the human ATP7A protein

    PubMed Central

    Llanos, Roxana M.; Michalczyk, Agnes A.; Freestone, David J.; Currie, Scott; Linder, Maria C.; Ackland, M. Leigh; Mercer, Julian F.B.

    2008-01-01

    Both copper transporting ATPases, ATP7A and ATP7B, are expressed in mammary epithelial cells but their role in copper delivery to milk has not been clarified. We investigated the role of ATP7A in delivery of copper to milk using transgenic mice that over-express human ATP7A. In mammary gland of transgenic mice, human ATP7A protein was 10- to 20-fold higher than in control mice, and was localized to the basolateral membrane of mammary epithelial cells in lactating mice. The copper concentration in the mammary gland of transgenic dams and stomach contents of transgenic pups was significantly reduced compared to non-transgenic mice. The mRNA levels of endogenous Atp7a, Atp7b, and Ctr1 copper transporters in the mammary gland were not altered by the expression of the ATP7A transgene, and the protein levels of Atp7b and ceruloplasmin were similar in transgenic and non-transgenic mice. These data suggest that ATP7A plays a role in removing excess copper from the mammary epithelial cells rather than supplying copper to milk. PMID:18515074

  18. Interaction of Drosophila melanogaster prohormone convertase 2 and 7B2. Insect cell-specific processing and secretion.

    PubMed

    Hwang, J R; Siekhaus, D E; Fuller, R S; Taghert, P H; Lindberg, I

    2000-06-01

    The prohormone convertases (PCs) are an evolutionarily ancient group of proteases required for the maturation of neuropeptide and peptide hormone precursors. In Drosophila melanogaster, the homolog of prohormone convertase 2, dPC2 (amontillado), is required for normal hatching behavior, and immunoblotting data indicate that flies express 80- and 75-kDa forms of this protein. Because mouse PC2 (mPC2) requires 7B2, a helper protein for productive maturation, we searched the fly data base for the 7B2 signature motif PPNPCP and identified an expressed sequence tag clone encoding the entire open reading frame for this protein. dPC2 and d7B2 cDNAs were subcloned into expression vectors for transfection into HEK-293 cells; mPC2 and rat 7B2 were used as controls. Although active mPC2 was detected in medium in the presence of either d7B2 or r7B2, dPC2 showed no proteolytic activity upon coexpression of either d7B2 or r7B2. Labeling experiments showed that dPC2 was synthesized but not secreted from HEK-293 cells. However, when dPC2 and either d7B2 or r7B2 were coexpressed in Drosophila S2 cells, abundant immunoreactive dPC2 was secreted into the medium, coincident with the appearance of PC2 activity. Expression and secretion of dPC2 enzyme activity thus appears to require insect cell-specific posttranslational processing events. The significant differences in the cell biology of the insect and mammalian enzymes, with 7B2 absolutely required for secretion of dPC2 and zymogen conversion occurring intracellularly in the case of dPC2 but not mPC2, support the idea that the Drosophila enzyme has specific requirements for maturation and secretion that can be met only in insect cells. PMID:10749852

  19. Functional analysis and drug response to zinc and D-penicillamine in stable ATP7B mutant hepatic cell lines

    PubMed Central

    Chandhok, Gursimran; Horvath, Judit; Aggarwal, Annu; Bhatt, Mohit; Zibert, Andree; Schmidt, Hartmut HJ

    2016-01-01

    AIM: To study the effect of anti-copper treatment for survival of hepatic cells expressing different ATP7B mutations in cell culture. METHODS: The most common Wilson disease (WD) mutations p.H1069Q, p.R778L and p.C271*, found in the ATP7B gene encoding a liver copper transporter, were studied. The mutations represent major genotypes of the United States and Europe, China, and India, respectively. A human hepatoma cell line previously established to carry a knockout of ATP7B was used to stably express WD mutants. mRNA and protein expression of mutant ATP7B, survival of cells, apoptosis, and protein trafficking were determined. RESULTS: Low temperature increased ATP7B protein expression in several mutants. Intracellular ATP7B localization was significantly impaired in the mutants. Mutants were classified as high, moderate, and no survival based on their viability on exposure to toxic copper. Survival of mutant p.H1069Q and to a lesser extent p.C271* improved by D-penicillamine (DPA) treatment, while mutant p.R778L showed a pronounced response to zinc (Zn) treatment. Overall, DPA treatment resulted in higher cell survival as compared to Zn treatment; however, only combined Zn + DPA treatment fully restored cell viability. CONCLUSION: The data indicate that the basic impact of a genotype might be characterized by analysis of mutant hepatic cell lines. PMID:27122662

  20. Age-related change in plasma concentration of 7B2(a novel pituitary polypeptide) in normal humans

    SciTech Connect

    Natori, S.; Iguchi, H.; Nawata, H.; Kato, K.; Ibayashi, H.; Chretian, M.

    1987-08-24

    Using a specific radioimmunoassay, the authors measured concentrations of plasma 7B2(a novel pituitary polypeptide) immunoreactivity(7B2-IR) in normal human subjects, patients with chronic renal failure and those with liver cirrhosis. Mean(+/-SEM) values of plasma 7B2-IR in normal healthy men and women were 55.8 +/- 1.2 pg/ml (n=266) and 56.1 +/- 0.9 pg/ml (n = 408), respectively. The elevation of plasma 7B2-IR showed a relationship with age of the subjects, in both men(r=0.39, t = 6.86, p < 0.001) and women (r=0.35, t=7.44, p < 0.001). Plasma 7B2-IR concentrations were elevated in patients with chronic renal failure (536 +/- 45 pg/ml, Mean +/- SEM, n = 10) as well as those in liver cirrhosis (95 +/- 10 pg/ml, Mean +/- SEM, n = 15) compared to values in normal subjects, suggesting that 7B2 is mainly eliminated through the kidney and is partly metabolized in the liver. 10 references, 4 figures.

  1. HATS-7b: A Hot Super Neptune Transiting a Quiet K Dwarf Star

    NASA Astrophysics Data System (ADS)

    Bakos, G. Á.; Penev, K.; Bayliss, D.; Hartman, J. D.; Zhou, G.; Brahm, R.; Mancini, L.; de Val-Borro, M.; Bhatti, W.; Jordán, A.; Rabus, M.; Espinoza, N.; Csubry, Z.; Howard, A. W.; Fulton, B. J.; Buchhave, L. A.; Ciceri, S.; Henning, T.; Schmidt, B.; Isaacson, H.; Noyes, R. W.; Marcy, G. W.; Suc, V.; Howe, A. R.; Burrows, A. S.; Lázár, J.; Papp, I.; Sári, P.

    2015-11-01

    We report the discovery by the HATSouth network of HATS-7b, a transiting Super-Neptune with a mass of 0.120 ± 0.012 {M}{{J}}, a radius of {0.563}-0.034+0.046 {R}{{J}}, and an orbital period of 3.1853 days. The host star is a moderately bright (V=13.340\\+/- 0.010 mag, {K}S=10.976\\+/- 0.026 mag) K dwarf star with a mass of 0.849 ± 0.027 {M}⊙ , a radius of {0.815}-0.035+0.049 {R}⊙ , and a metallicity of [{Fe}/{{H}}] =+0.250\\+/- 0.080. The star is photometrically quiet to within the precision of the HATSouth measurements, has low RV jitter, and shows no evidence for chromospheric activity in its spectrum. HATS-7b is the second smallest radius planet discovered by a wide-field ground-based transit survey, and one of only a handful of Neptune-size planets with mass and radius determined to 10% precision. Theoretical modeling of HATS-7b yields a hydrogen-helium fraction of 18 ± 4% (rock-iron core and H2-He envelope), or 9 ± 4% (ice core and H2-He envelope), i.e., it has a composition broadly similar to that of Uranus and Neptune, and very different from that of Saturn, which has 75% of its mass in H2-He. Based on a sample of transiting exoplanets with accurately (<20%) determined parameters, we establish approximate power-law relations for the envelopes of the mass-density distribution of exoplanets. HATS-7b, which, together with the recently discovered HATS-8b, is one of the first two transiting super-Neptunes discovered in the Southern sky, is a prime target for additional follow-up observations with Southern hemisphere facilities to characterize the atmospheres of Super-Neptunes (which we define as objects with mass greater than that of Neptune, and smaller than halfway between that of Neptune and Saturn, i.e., 0.054 {M}{{J}}\\lt {M}{{p}}\\lt 0.18 {M}{{J}}). The HATSouth network is operated by a collaboration consisting of Princeton University (PU), the Max Planck Institute für Astronomie (MPIA), the Australian National University (ANU), and the Pontificia

  2. The extreme physical properties of the CoRoT-7b super-Earth

    NASA Astrophysics Data System (ADS)

    Léger, A.; Grasset, O.; Fegley, B.; Codron, F.; Albarede, A. F.; Barge, P.; Barnes, R.; Cance, P.; Carpy, S.; Catalano, F.; Cavarroc, C.; Demangeon, O.; Ferraz-Mello, S.; Gabor, P.; Grießmeier, J.-M.; Leibacher, J.; Libourel, G.; Maurin, A.-S.; Raymond, S. N.; Rouan, D.; Samuel, B.; Schaefer, L.; Schneider, J.; Schuller, P. A.; Selsis, F.; Sotin, C.

    2011-05-01

    The search for rocky exoplanets plays an important role in our quest for extra-terrestrial life. Here, we discuss the extreme physical properties possible for the first characterised rocky super-Earth, CoRoT-7b ( R pl = 1.58 ± 0.10 R Earth, M pl = 6.9 ± 1.2 M Earth). It is extremely close to its star ( a = 0.0171 AU = 4.48 R st), with its spin and orbital rotation likely synchronised. The comparison of its location in the ( M pl, R pl) plane with the predictions of planetary models for different compositions points to an Earth-like composition, even if the error bars of the measured quantities and the partial degeneracy of the models prevent a definitive conclusion. The proximity to its star provides an additional constraint on the model. It implies a high extreme-UV flux and particle wind, and the corresponding efficient erosion of the planetary atmosphere especially for volatile species including water. Consequently, we make the working hypothesis that the planet is rocky with no volatiles in its atmosphere, and derive the physical properties that result. As a consequence, the atmosphere is made of rocky vapours with a very low pressure ( P ⩽ 1.5 Pa), no cloud can be sustained, and no thermalisation of the planet is expected. The dayside is very hot (2474 ± 71 K at the sub-stellar point) while the nightside is very cold (50-75 K). The sub-stellar point is as hot as the tungsten filament of an incandescent bulb, resulting in the melting and distillation of silicate rocks and the formation of a lava ocean. These possible features of CoRoT-7b could be common to many small and hot planets, including the recently discovered Kepler-10b. They define a new class of objects that we propose to name " Lava-ocean planets".

  3. The KDM2B- let-7b -EZH2 axis in myelodysplastic syndromes as a target for combined epigenetic therapy.

    PubMed

    Karoopongse, Ekapun; Yeung, Cecilia; Byon, John; Ramakrishnan, Aravind; Holman, Zaneta J; Jiang, Peter Y Z; Yu, Qiang; Deeg, H Joachim; Marcondes, A Mario

    2014-01-01

    Both DNA and histone methylation are dysregulated in the myelodysplastic syndromes (MDS). Based on preliminary data we hypothesized that dysregulated interactions of KDM2B, let-7b and EZH2 signals lead to an aberrant epigenetic landscape. Gene expression in CD34+ cells from MDS marrows was analyzed by NanoString miR array and validated by real-time polymerase chain reaction (PCR). The functions of KDM2B, let-7b and EZH2 were characterized in myeloid cell lines and in primary MDS cells. Let-7b levels were significantly higher, and KDM2B and EZH2 expression was lower in primary CD34+ MDS marrow cells (n = 44) than in healthy controls (n = 21; p<0.013, and p<0.0001, respectively). Overexpression of let-7b reduced EZH2 and KDM2B protein levels, and decreased cells in S-phase while increasing G0/G1 cells (p = 0.0005), accompanied by decreased H3K27me3 and cyclin D1. Silencing of KDM2B increased let-7b expression. Treatment with the cyclopentanyl analog of 3-deazaadenosine, DZNep, combined with the DNA hypomethylating agent 5-azacitidine, decreased levels of EZH2, suppressed methylation of di- and tri-methylated H3K27, and increased p16 expression, associated with cell proliferation. Thus, KDM2B, via let-7b/EZH2, promotes transcriptional repression. DZNep bypassed the inhibitory KDM2B/let-7b/EZH2 axis by preventing H3K27 methylation and reducing cell proliferation. DZNep might be able to enhance the therapeutic effects of DNA hypomethylating agents such as 5-azacitidine, currently considered standard therapy for patients with MDS. PMID:25225797

  4. DNA Methylation and Transcriptomic Changes in Response to Different Lights and Stresses in 7B-1 Male-Sterile Tomato

    PubMed Central

    Omidvar, Vahid; Fellner, Martin

    2015-01-01

    We reported earlier that 7B-1 mutant in tomato (Solanum lycopersicum L., cv. Rutgers), an ABA overproducer, is defective in blue light (B) signaling leading to B-specific resistance to abiotic and biotic stresses. Using a methylation-sensitive amplified polymorphism (MSAP) assay, a number of genes were identified, which were differentially methylated between 7B-1 and its wild type (WT) seedlings in white (W), blue (B), red (R) lights and dark (D) or in response to exogenous ABA and mannitol-induced stresses. The genomic methylation level was almost similar in different lights between 7B-1 and WT seedlings, while significant differences were observed in response to stresses in D, but not B. Using a cDNA-AFLP assay, several transcripts were identified, which were differentially regulated between 7B-1 and WT by B or D or in response to stresses. Blue light receptors cryptochrome 1 and 2 (CRY1 and CRY2) and phototropin 1 and 2 (PHOT1 and PHOT2) were not affected by the 7B-1 mutation at the transcriptional level, instead the mutation had likely affected downstream components of the light signaling pathway. 5-azacytidine (5-azaC) induced DNA hypomethylation, inhibited stem elongation and differentially regulated the expression of a number of genes in 7B-1. In addition, it was shown that mir167 and mir390 were tightly linked to auxin signaling pathway in 5-azaC-treated 7B-1 seedlings via the regulation of auxin-response factor (ARF) transcripts. Our data showed that DNA methylation remodeling is an active epigenetic response to different lights and stresses in 7B-1 and WT, and highlighted the differences in epigenetic and transcriptional regulation of light and stress responses between 7B-1 and WT. Furthermore, it shed lights on the crosstalk between DNA hypomethylation and miRNA regulation of ARFs expression. This information could also be used as a benchmark for future studies of male-sterility in other crops. PMID:25849771

  5. Magnetoimpedance studies on ion irradiated Co33Fe33Ni7Si7B20 ribbons

    NASA Astrophysics Data System (ADS)

    Kotagiri, Ganesh; Markandeyulu, G.; Thulasiram, K. V.; Fernandes, W. A.; Misra, D.; Tribedi, L. C.

    2016-04-01

    Magnetoimpedance (MI) effect was studied on amorphous Co33Fe33Ni7Si7B20 ribbons that were irradiated with N+1, Ar+2 and Xe+5 ions, at energy of 75 keV. The (MI)m [maximum MI in each case] values are 9.4% and 11%, 9.9% and 6.5%, the largest, for the as-quenched and N+1, Ar+2 and Xe+5 ion irradiated ribbons respectively, at 2 MHz. The (MI)m value of the N+1 ion irradiated ribbon was observed to be the highest, due to an induced in-plane transverse magnetic anisotropy. The saturation magnetizations of the ion-irradiated ribbons are not seen to change with respect to that of the as-quenched ribbon; a small increase in the Ms was observed only upon irradiation with Xe5+ ions. The interaction between the large number of domains, with large uniaxial anisotropy led to large (MI)m values, at frequencies above 8 MHz in the Ar+2 ion irradiated ribbon.

  6. Evaluating endoglucanase Cel7B-lignin interaction mechanisms and kinetics using quartz crystal microgravimetry.

    PubMed

    Pfeiffer, Katherine A; Sorek, Hagit; Roche, Christine M; Strobel, Kathryn L; Blanch, Harvey W; Clark, Douglas S

    2015-11-01

    The kinetics and mechanisms of protein interactions with solid surfaces are important to fields as diverse as industrial biocatalysis, biomedical engineering, food science, and cell biology. The nonproductive adsorption of cellulase enzymes to lignin, a plant cell wall polymer, reduces their effectiveness in saccharifying biomass. Cellulase has been shown to interact with lignin, but the heterogeneity of lignin surfaces, challenges in measuring irreversible components of these interactions, and fast adsorption rates make quantifying the reaction kinetics difficult. This work employs quartz crystal microgravimetry with dissipation monitoring (QCM-D) for real-time measurement of adsorbed mass on a flat lignin surface. We have developed a method for casting homogeneous lignin films that are chemically similar to lignin found in pretreated biomass, and used QCM-D to compare three models of reversible-irreversible binding behavior: a single-site transition model, a transition model with changing adsorbate footprint, and a two-site transition model. Of the three models tested, the two-site transition model provides the only kinetic mechanism able to describe the behavior of Cel7B binding to lignin. While the direct implications of lignin-cellulase interactions may be limited to biomass deconstruction for renewable energy and green chemistry, the analytical and experimental methods demonstrated in this work are relevant to any system in which the kinetics and reaction mechanism of reversible and irreversible protein adsorption at a solid-liquid interface are important. PMID:25994114

  7. The Terpolymer Produced by Azotobacter Chroococcum 7B: Effect of Surface Properties on Cell Attachment

    PubMed Central

    Bonartsev, Anton; Yakovlev, Sergey; Boskhomdzhiev, Arasha; Zharkova, Irina; Bagrov, Dmitrii; Myshkina, Vera; Mahina, Tatiana; Kharitonova, Elena; Samsonova, Olga; Zernov, Anton; Zhuikov, Vsevolod; Efremov, Yurii; Voinova, Vera; Bonartseva, Garina; Shaitan, Konstantin

    2013-01-01

    The copolymerization of poly(3-hydroxybutyrate) (PHB) is a promising trend in bioengineering to improve biomedical properties, e.g. biocompatibility, of this biodegradable polymer. We used strain Azotobacter chroococcum 7B, an effective producer of PHB, for biosynthesis of not only homopolymer and its main copolymer, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV), but also novel terpolymer, poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-poly(ethylene glycol) (PHB-HV-PEG), using sucrose as the primary carbon source and valeric acid and poly(ethylene glycol) 300 (PEG 300) as additional carbon sources. The chemical structure of PHB-HV-PEG was confirmed by 1H nuclear-magnetic resonance analysis. The physico-chemical properties (molecular weight, crystallinity, hydrophilicity, surface energy) of produced biopolymer, the protein adsorption to the terpolymer, and cell growth on biopolymer films were studied. Despite of low EG-monomers content in bacterial-origin PHB-HV-PEG polymer, the terpolymer demonstrated significant improvement in biocompatibility in vitro in contrast to PHB and PHB-HV polymers, which may be coupled with increased protein adsorption, hydrophilicity and surface roughness of PEG-containing copolymer. PMID:23468935

  8. Characterization of the Dielectric Constant in the Trichoderma reesei Cel7B Active Site.

    PubMed

    Song, Xiangfei; Wang, Yefei; Zhang, Shujun; Yan, Shihai; Li, Tong; Yao, Lishan

    2015-07-27

    An attempt is made to evaluate the dielectric constant of the Trichoderma reesei Cel7B active site. Through kinetic measurements, the pKa value of the catalytic acid E201 is determined. Mutations (away from E201) with net charge changes are introduced to perturb the E201 pKa. It is shown that the mutation with a +1 charge change (including G225R, G230R, and A335R) decreases the pKa of E201, whereas the mutation with a -1 charge change (including Q149E, A222D, G225D, and G230D) increases the pKa. This effect is consistent with the electrostatic interaction between the changed charge and the E201 side chain. The fitting of the experimental data yields an apparent dielectric constant of 25-80. Molecular dynamics simulations with explicit water molecules indicate that the high solvent accessibility of the active site contributes largely to the high dielectric constant. ONIOM calculations show that high dielectric constant benefits the catalysis through decreasing the energy of the transition state relative to that of the enzyme substrate complex. PMID:26114648

  9. A mechanistic study of Trichoderma reesei Cel7B catalyzed glycosidic bond cleavage.

    PubMed

    Zhang, Yu; Yan, Shihai; Yao, Lishan

    2013-07-25

    An ONIOM study is performed to illustrate the mechanism of Trichoderma reesei Cel7B catalyzed p-nitrophenyl lactoside hydrolysis. In both the glycosylation and deglycosylation steps, the reaction proceeds in a concerted way, meaning the nucleophilic attack and the glycosidic bond cleavage occur simultaneously. The glycosylation step is rate limiting with a barrier of 18.9 kcal/mol, comparable to the experimental value derived from the kcat measured in this work. The function of four residues R108, Y146, Y170, and D172, which form a hydrogen-bond network involving the substrate, is studied by conservative mutations. The mutants, including R108K, Y146F, Y170F, and D172N, decrease the enzyme activity by about 150-8000-fold. Molecular dynamics simulations show that the mutations disrupt the hydrogen-bond network, cause the substrate to deviate from active binding and hinder either the proton transfer from E201 to O4(+1) or the nucleophilic attack from E196 to C1(-1). PMID:23822607

  10. Revisiting the transits of CoRoT-7b at a lower activity level

    NASA Astrophysics Data System (ADS)

    Barros, S. C. C.; Almenara, J. M.; Deleuil, M.; Diaz, R. F.; Csizmadia, Sz.; Cabrera, J.; Chaintreuil, S.; Collier Cameron, A.; Hatzes, A.; Haywood, R.; Lanza, A. F.; Aigrain, S.; Alonso, R.; Bordé, P.; Bouchy, F.; Deeg, H. J.; Erikson, A.; Fridlund, M.; Grziwa, S.; Gandolfi, D.; Guillot, T.; Guenther, E.; Leger, A.; Moutou, C.; Ollivier, M.; Pasternacki, T.; Pätzold, M.; Rauer, H.; Rouan, D.; Santerne, A.; Schneider, J.; Wuchterl, G.

    2014-09-01

    The first super-Earth with measured radius discovered was CoRoT-7b and it has opened the new field of rocky exoplanet characterisation. To better understand this interesting system, new observations were taken with the CoRoT satellite. During this run 90 new transits were obtained in the imagette mode. These were analysed together with the previous 151 transits obtained in the discovery run and HARPS radial velocity observations to derive accurate system parameters. A difference is found in the posterior probability distribution of the transit parameters between the previous CoRoT run (LRa01) and the new run (LRa06). We propose that this is due to an extra noise component in the previous CoRoT run suspected of being transit spot occultation events. These lead to the mean transit shape becoming V-shaped. We show that the extra noise component is dominant at low stellar flux levels and reject these transits in the final analysis. We obtained a planetary radius, Rp = 1.585 ± 0.064 R⊕ , in agreement with previous estimates. Combining the planetary radius with the new mass estimates results in a planetary density of 1.19 ± 0.27 ρ⊕ which is consistent with a rocky composition. The CoRoT-7 system remains an excellent test bed for the effects of activity in the derivation of planetary parameters in the shallow transit regime.

  11. Mutations in the 3c and 7b genes of feline coronavirus in spontaneously affected FIP cats.

    PubMed

    Borschensky, C M; Reinacher, M

    2014-10-01

    Feline infectious peritonitis (FIP) is the most frequent lethal infectious disease in cats. However, understanding of FIP pathogenesis is still incomplete. Mutations in the ORF 3c/ORF 7b genes are proposed to play a role in the occurrence of the fatal FIPV biotype. Here, we investigated 282 tissue specimens from 28 cats that succumbed to FIP. Within one cat, viral sequences from different organs were similar or identical, whereas greater discrepancies were found comparing sequences from various cats. Eleven of the cats exhibited deletions in the 3c gene, resulting in truncated amino acid sequences. The 7b gene was affected by deletions only in one cat. In three of the FIP cats, coronavirus isolates with both intact 3c genes as well as 7b genes of full length could also be detected. Thus, deletions or stop codons in the 3c sequence seem to be a frequent but not compelling feature of FIPVs. PMID:25128417

  12. Two novel CYP7B1 mutations in Italian families with SPG5: a clinical and genetic study.

    PubMed

    Criscuolo, Chiara; Filla, Alessandro; Coppola, Giovanni; Rinaldi, Carlo; Carbone, Rosa; Pinto, Stefano; Wang, Qing; de Leva, Maria Fulvia; Salvatore, Elena; Banfi, Sandro; Brunetti, Arturo; Quarantelli, Mario; Geschwind, Daniel H; Pappatà, Sabina; De Michele, Giuseppe

    2009-08-01

    Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders characterized by progressive weakness and spasticity in the lower limbs. Spasticity may occur in isolation (''pure'' HSP) or may be accompanied by other features. Although autosomal recessive HSPs usually have clinically complex phenotypes, mutations within a few genes underlie pure forms. Recently the gene (CYP7B1) responsible for SPG5, a pure recessive HSP, has been identified. The six CYP7B1 coding exons were analysed in four Italian families. Complete clinical assessment was performed in all patients. Blood CYP7B1 mRNA levels were assessed in three patients and six controls. Brain MRI and (18)F-fluoro-deoxy-glucose positron emission tomography (PET) scan were conducted in three patients. Two novel homozygous mutations were identified. Both result in a frameshift and the introduction of a premature stop codon at the C-terminal of the protein. Patients have reduced blood CYP7B1 mRNA levels, suggesting nonsense mediated RNA decay. Although clinical assessment showed a pure form of spastic paraplegia, MRI demonstrated white matter abnormalities in three patients and PET scan revealed cerebellar hypometabolism in one. Based on the results, we report the first Italian families with SPG5 molecular characterization and describe two novel truncating mutations in CYP7B1. The recessive character, the truncating nature of the mutations, and the reduced peripheral blood CYP7B1 mRNA levels suggest that the development of the disease is associated with a loss of function. SPG5 is considered a pure form of HSP, but MRI and PET findings in our patients suggest that SPG5 phenotype may be broader than the pure presentation. PMID:19363635

  13. Let-7c overexpression inhibits dengue virus replication in human hepatoma Huh-7 cells.

    PubMed

    Escalera-Cueto, Manuel; Medina-Martínez, Ingrid; del Angel, Rosa M; Berumen-Campos, Jaime; Gutiérrez-Escolano, Ana Lorena; Yocupicio-Monroy, Martha

    2015-01-22

    MicroRNAs (miRNAs) constitute an important class of non-coding RNA implicated in gene expression regulation. More than 1900 miRNA molecules have been identified in humans and their modulation during viral infection and it is recognized to play a role in latency regulation or in establishing an antiviral state. The liver cells are targets during DENV infection, and alteration of liver functions contributes to severe disease. In this work the miRNAs expression profile of the human hepatoma cell line, Huh-7, infected with DENV-2 was determined using microarray and real-time PCR. Let-7c is one of the miRNAs up-regulated during DENV infection in the hepatic Huh-7 as well as in the macrophage-monocytic cell line U937-DC-SIGN. Let-7c overexpression down-regulates both DENV-2 and DENV-4 infection. Additionally, we found that the transcription factor BACH1, a let-7c target, is also down-regulated during DENV infection. In accordance with this finding, HO-1, the main responsive factor of BACH1 was found up-regulated. The up-regulation of HO-1 may contribute to the stress oxidative response in infected cells. PMID:25445350

  14. Mechanical properties and chemical bonding characteristics of Cr7C3 type multicomponent carbides

    NASA Astrophysics Data System (ADS)

    Xiao, B.; Feng, J.; Zhou, C. T.; Jiang, Y. H.; Zhou, R.

    2011-01-01

    The first principles calculations based on density functional theory are performed to investigate the mechanical properties and chemical bonding features of several Cr7C3 type multicomponent carbides (Fe16Cr12C12, Fe12Cr12W4C12, Fe12Cr12Mo4C12, Fe12Cr12W4C8B4, and Fe12Cr12Mo4C8B4). The full set elastic constants are calculated using stress-strain method. The Voigt-Reuss-Hill approximation is used to evaluate the mechanical moduli. The mechanical anisotropy is characterized by calculating several different anisotropic indexes and factors, such as universal anisotropic index (AU), shear anisotropic factors (A1, A2, and A3), and percent anisotropy (AB and AG). The surface constructions of bulk and Young's moduli are illustrated to indicate the mechanical anisotropy. The obtained results indicate that the presence of B could deteriorate the mechanical moduli of (Fe,Cr)7C3 phase in Cr cast iron slightly. On the other hand, the chemical stability of (Fe,Cr)7C3 carbides is improved due to chemical bonding modifications through doping with B. These conclusions are in agreement with experimental results.

  15. The intersublattice exchange interactions in the R 2Co 7B 3 compounds (R = heavy rare earth)

    NASA Astrophysics Data System (ADS)

    Kowalczyk, A.

    1997-07-01

    The experimental values of Curie temperatures of hexagonal R 2Co 7B 3 (R = heavy rare earth) compounds are used to calculate the effective intersublattice exchange interactions, JRCo, between R and Co sublattices. A mean field approximation is used. The compounds belong to the R n+1Co 3 n+5B 2 n family. The R 2Co 7B 3 is a combination of CaCu 5 and CeCo 3B 2-type structures. The JRCo has a tendency to decrease with increasing atomic number of the rare earth partner. A similar tendency has been found for other Fe and Co-based compounds.

  16. Effect of Carbide Ceramic Zone on Wear Resistance of the (Fe,Cr)7C3/Fe Surface Gradient Composite

    NASA Astrophysics Data System (ADS)

    Ye, Fangxia; Xu, Yunhua; Hojamberdiev, Mirabbos; Lai, Yujun; Wang, Chong; Wang, Xin

    2015-08-01

    In this work, we report on the influence of microstructure and mechanical properties of the (Fe,Cr)7C3 ceramic zone on wear resistance of the (Fe,Cr)7C3/Fe surface gradient composite fabricated by in situ synthesis method followed by a post-heat treatment at 1100 °C for 20 h in argon atmosphere. The phase composition, microstructure, nanoindentation hardness, elastic modulus, fracture toughness, and relative wear resistance of the (Fe,Cr)7C3/Fe surface gradient composite were investigated by means of x-ray diffraction, scanning electron microscopy, nanoindentation tester, and wear resistance testing instrument, respectively. The XRD results showed that (Fe,Cr)7C3 is the predominant crystalline phases in the fabricated composite. The volume fraction of the (Fe,Cr)7C3 particulates formed has a gradient distribution from the surface to the iron matrix, and the microstructure also changes significantly. The (Fe,Cr)7C3 bulk ceramic zone with the volume fraction of about 100% and the (Fe,Cr)7C3 dense ceramic zone with the volume fraction of about 90% were synthesized on the upper surface of the (Fe,Cr)7C3/Fe surface gradient composite, respectively. The average nanoindentation hardness and elastic modulus of the (Fe,Cr)7C3 bulk ceramic zone of the composite were determined to be 12.711 and 256.054 GPa, respectively. The fracture toughness of the (Fe,Cr)7C3 bulk ceramic zone is in the range of 2.06-4.19 MPa m1/2, and its relative wear resistance is about 56 times higher than that of the iron matrix. The (Fe,Cr)7C3 dense ceramic zone with rod-like, secondary (Fe,Cr)7C3 particulates was formed at the bottom of the (Fe,Cr)7C3 bulk ceramic zone. Rod-like, secondary (Fe,Cr)7C3 particulates are dense and grew in the direction of the iron substrate, providing higher wear resistance to the composite. The wear mechanisms of the (Fe,Cr)7C3 bulk and dense ceramic zones are considered to be microcutting, microcracking, and spalling pit.

  17. Light curve analysis for eclipsing systems with exoplanets. The systems Kepler-5b, Kepler-6b, and Kepler-7b

    NASA Astrophysics Data System (ADS)

    Gostev, N. Yu.

    2011-07-01

    High-accuracy light curves for the binaries with exoplanets Kepler-5b, Kepler-6b, and Kepler-7b have been analyzed. The radii of the stars and the planets and the orbital inclinations of the binaries are derived. Reliable estimates of the linear and quadratic limb-darkening coefficients and their confidence intervals (uncertainties) are presented.

  18. Targeted delivery of let-7b to reprogramme tumor-associated macrophages and tumor infiltrating dendritic cells for tumor rejection.

    PubMed

    Huang, Zhen; Gan, Jingjing; Long, Ziyan; Guo, Guangxing; Shi, Xiafei; Wang, Chunming; Zang, Yuhui; Ding, Zhi; Chen, Jiangning; Zhang, Junfeng; Dong, Lei

    2016-06-01

    Both tumor associated macrophages (TAMs) and tumor infiltrating dendritic cells (TIDCs) are important components in the tumor microenvironment that mediate tumor immunosuppression and promote cancer progression. Targeting these cells and altering their phenotypes may become a new strategy to recover their anti-tumor activities and thereby restore the local immune surveillance against tumor. In this study, we constructed a nucleic acid delivery system for the delivery of let-7b, a synthetic microRNA mimic. Our carrier has an affinity for the mannose receptors on TAMs/TIDCs and is responsive to the low-pH tumor microenvironment. The delivery of let-7b could reactivate TAMs/TIDCs by acting as a TLR-7 agonist and suppressing IL-10 production in vitro. In a breast cancer mouse model, let-7b delivered by this system efficiently reprogrammed the functions of TAMs/TIDCs, reversed the suppressive tumor microenvironment, and inhibited tumor growth. Taken together, this strategy, designed based upon TAMs/TIDCs-targeting delivery and the dual biological functions of let-7b (TLR-7 ligand and IL-10 inhibitor), may provide a new approach for cancer immunotherapy. PMID:26994345

  19. 29 CFR 516.21 - Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b)(3) of the Act. 516.21 Section 516.21 Labor Regulations Relating to Labor....21 Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section...

  20. 29 CFR 516.21 - Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b)(3) of the Act. 516.21 Section 516.21 Labor Regulations Relating to Labor....21 Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section...

  1. 29 CFR 516.21 - Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b)(3) of the Act. 516.21 Section 516.21 Labor Regulations Relating to Labor....21 Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section...

  2. 29 CFR 516.21 - Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b)(3) of the Act. 516.21 Section 516.21 Labor Regulations Relating to Labor....21 Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section...

  3. 29 CFR 516.21 - Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section 7(b)(3) of the Act. 516.21 Section 516.21 Labor Regulations Relating to Labor....21 Bulk petroleum employees partially exempt from overtime pay requirements pursuant to section...

  4. PDE7B Is a Novel, Prognostically Significant Mediator of Glioblastoma Growth Whose Expression Is Regulated by Endothelial Cells

    PubMed Central

    Brooks, Michael D.; Jackson, Erin; Warrington, Nicole M.; Luo, Jingqin; Forys, Jason T.; Taylor, Sara; Mao, Diane D.; Leonard, Jeffrey R.; Kim, Albert H.; Piwnica-Worms, David

    2014-01-01

    Cell-cell interactions between tumor cells and constituents of their microenvironment are critical determinants of tumor tissue biology and therapeutic responses. Interactions between glioblastoma (GBM) cells and endothelial cells (ECs) establish a purported cancer stem cell niche. We hypothesized that genes regulated by these interactions would be important, particularly as therapeutic targets. Using a computational approach, we deconvoluted expression data from a mixed physical co-culture of GBM cells and ECs and identified a previously undescribed upregulation of the cAMP specific phosphodiesterase PDE7B in GBM cells in response to direct contact with ECs. We further found that elevated PDE7B expression occurs in most GBM cases and has a negative effect on survival. PDE7B overexpression resulted in the expansion of a stem-like cell subpopulation in vitro and increased tumor growth and aggressiveness in an in vivo intracranial GBM model. Collectively these studies illustrate a novel approach for studying cell-cell interactions and identifying new therapeutic targets like PDE7B in GBM. PMID:25203500

  5. Multi-allele genotyping platform for the simultaneous detection of mutations in the Wilson disease related ATP7B gene.

    PubMed

    Amvrosiadou, Maria; Petropoulou, Margarita; Poulou, Myrto; Tzetis, Maria; Kanavakis, Emmanuel; Christopoulos, Theodore K; Ioannou, Penelope C

    2015-12-01

    Wilson's disease is an inherited disorder of copper transport in the hepatocytes with a wide range of genotype and phenotype characteristics. Mutations in the ATP7B gene are responsible for the disease. Approximately, over 500 mutations in the ATP7B gene have been described to date. We report a method for the simultaneous detection of the ten most common ATP7B gene mutations in Greek patients. The method comprises 3 simple steps: (i) multiplex PCR amplification of fragments in the ATP7B gene flanking the mutations (ii) multiplex primer extension reaction of the unpurified amplification products using allele-specific primers and (iii) visual detection of the primer extension reaction products within minutes by means of dry-reagent multi-allele dipstick assay using anti-biotin conjugated gold nanoparticles. Optimization studies on the efficiency and specificity of the PEXT reaction were performed. The method was evaluated by genotyping 46 DNA samples of known genotype and 34 blind samples. The results were fully concordant with those obtained by reference methods. The method is simple, rapid, cost-effective and it does not require specialized instrumentation or highly qualified personnel. PMID:26580967

  6. Interactions between Metal-binding Domains Modulate Intracellular Targeting of Cu(I)-ATPase ATP7B, as Revealed by Nanobody Binding*

    PubMed Central

    Huang, Yiping; Nokhrin, Sergiy; Hassanzadeh-Ghassabeh, Gholamreza; Yu, Corey H.; Yang, Haojun; Barry, Amanda N.; Tonelli, Marco; Markley, John L.; Muyldermans, Serge; Dmitriev, Oleg Y.; Lutsenko, Svetlana

    2014-01-01

    The biologically and clinically important membrane transporters are challenging proteins to study because of their low level of expression, multidomain structure, and complex molecular dynamics that underlies their activity. ATP7B is a copper transporter that traffics between the intracellular compartments in response to copper elevation. The N-terminal domain of ATP7B (N-ATP7B) is involved in binding copper, but the role of this domain in trafficking is controversial. To clarify the role of N-ATP7B, we generated nanobodies that interact with ATP7B in vitro and in cells. In solution NMR studies, nanobodies revealed the spatial organization of N-ATP7B by detecting transient functionally relevant interactions between metal-binding domains 1–3. Modulation of these interactions by nanobodies in cells enhanced relocalization of the endogenous ATP7B toward the plasma membrane linking molecular and cellular dynamics of the transporter. Stimulation of ATP7B trafficking by nanobodies in the absence of elevated copper provides direct evidence for the important role of N-ATP7B structural dynamics in regulation of ATP7B localization in a cell. PMID:25253690

  7. 75 FR 54692 - Notice of Debarment Pursuant to Section 127.7(c) of the International Traffic in Arms Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-08

    ... of Debarment Pursuant to Section 127.7(c) of the International Traffic in Arms Regulations Title... International Traffic in Arms Regulations. ACTION: Notice. SUMMARY: Notice is hereby given that the Department of State has imposed statutory debarment pursuant to Sec. 127.7(c) of the International Traffic...

  8. Sound velocities of iron carbides (Fe3C and Fe7C3) under core conditions

    NASA Astrophysics Data System (ADS)

    Chen, B.; Li, Z.; Zhang, D.; Liu, J.; Bi, W.; Zhao, J.; Alp, E. E.; Hu, M. Y.; Li, J.

    2014-12-01

    For a carbon-rich core, iron carbides might be the major phase crystallizing to form the Earth's solid inner core. On basis of high-pressure experiments and theoretical calculations, Fe3C, Fe7C3 and more recently Fe2C have been considered as the most stable carbide phase under the inner core conditions. The identity of the stable carbide phase in a carbon-containing inner core is still a topic under active debate. It is crucial to determine the elastic and acoustic properties of the relevant carbide phases to core conditions, in order to test the carbon-rich core composition model. In this study, we have performed nuclear resonant inelastic X-ray scattering (NRIXS) measurements of both Fe7C3 and Fe3C up to core pressures at 300 K and determined their shear-wave (VS) and compressional-wave (VP) velocities for comparison with seismic observations of the inner core. The high-pressure magnetic properties of both phases have also been investigated by X-ray Emission Spectroscopy (XES) and Synchrotron Mössbauer Spectroscopy (SMS). Our results show that the magnetic transitions from ferromagnetic to paramagnetic and then to nonmagnetic in Fe7C3 and Fe3C significantly affects their VS and VP at high pressures. Extrapolating the sound velocities of the nonmagnetic phases to the inner core conditions, we found that sound velocities, particularly VS, of the iron carbides are markedly low comparing with iron and other iron-rich alloys, making them compelling candidates to explain the seismic observations of the inner core. Our hypothesis of a carbon-rich core may also be consistent with geochemical and petrological evidence on deep carbon inventory in Earth's interior.

  9. Hidden carbon in Earth's inner core revealed by shear softening in dense Fe7C3.

    PubMed

    Chen, Bin; Li, Zeyu; Zhang, Dongzhou; Liu, Jiachao; Hu, Michael Y; Zhao, Jiyong; Bi, Wenli; Alp, E Ercan; Xiao, Yuming; Chow, Paul; Li, Jie

    2014-12-16

    Earth's inner core is known to consist of crystalline iron alloyed with a small amount of nickel and lighter elements, but the shear wave (S wave) travels through the inner core at about half the speed expected for most iron-rich alloys under relevant pressures. The anomalously low S-wave velocity (vS) has been attributed to the presence of liquid, hence questioning the solidity of the inner core. Here we report new experimental data up to core pressures on iron carbide Fe7C3, a candidate component of the inner core, showing that its sound velocities dropped significantly near the end of a pressure-induced spin-pairing transition, which took place gradually between 10 GPa and 53 GPa. Following the transition, the sound velocities increased with density at an exceptionally low rate. Extrapolating the data to the inner core pressure and accounting for the temperature effect, we found that low-spin Fe7C3 can reproduce the observed vS of the inner core, thus eliminating the need to invoke partial melting or a postulated large temperature effect. The model of a carbon-rich inner core may be consistent with existing constraints on the Earth's carbon budget and would imply that as much as two thirds of the planet's carbon is hidden in its center sphere. PMID:25453077

  10. Mesenchymal Stem Cells Deliver Exogenous MicroRNA-let7c via Exosomes to Attenuate Renal Fibrosis.

    PubMed

    Wang, Bo; Yao, Kevin; Huuskes, Brooke M; Shen, Hsin-Hui; Zhuang, Junli; Godson, Catherine; Brennan, Eoin P; Wilkinson-Berka, Jennifer L; Wise, Andrea F; Ricardo, Sharon D

    2016-08-01

    The advancement of microRNA (miRNA) therapies has been hampered by difficulties in delivering miRNA to the injured kidney in a robust and sustainable manner. Using bioluminescence imaging in mice with unilateral ureteral obstruction (UUO), we report that mesenchymal stem cells (MSCs), engineered to overexpress miRNA-let7c (miR-let7c-MSCs), selectively homed to damaged kidneys and upregulated miR-let7c gene expression, compared with nontargeting control (NTC)-MSCs. miR-let7c-MSC therapy attenuated kidney injury and significantly downregulated collagen IVα1, metalloproteinase-9, transforming growth factor (TGF)-β1, and TGF-β type 1 receptor (TGF-βR1) in UUO kidneys, compared with controls. In vitro analysis confirmed that the transfer of miR-let7c from miR-let7c-MSCs occurred via secreted exosomal uptake, visualized in NRK52E cells using cyc3-labeled pre-miRNA-transfected MSCs with/without the exosomal inhibitor, GW4869. The upregulated expression of fibrotic genes in NRK52E cells induced by TGF-β1 was repressed following the addition of isolated exosomes or indirect coculture of miR-let7c-MSCs, compared with NTC-MSCs. Furthermore, the cotransfection of NRK52E cells using the 3'UTR of TGF-βR1 confirmed that miR-let7c attenuates TGF-β1-driven TGF-βR1 gene expression. Taken together, the effective antifibrotic function of engineered MSCs is able to selectively transfer miR-let7c to damaged kidney cells and will pave the way for the use of MSCs for therapeutic delivery of miRNA targeted at kidney disease. PMID:27203438

  11. Magnetoimpedance studies on urine treated Co66Ni7Si7B20 ribbons

    NASA Astrophysics Data System (ADS)

    Kotagiri, Ganesh; Markandeyulu, G.; Doble, Mukesh; Nandakumar, V.

    2015-11-01

    Magnetoimpedance (MI) response of Co66Ni7Si7B20 ribbons treated with artificial urine with protein bovine serum albumin (BSA), artificial urine without protein BSA and healthy male urine was studied as a function of time of incubation. The maximum MI [(MI)m] values of the ribbons treated with artificial urine without protein (RTAU) after 3 h, 6 h, 12 h and 24 h of incubation are 30% (at 4 MHz), 15% (at 5 MHz), 14% (at 10 MHz) and 8% (at 13 MHz) respectively. On the other hand, the respective (MI)m values of the ribbons treated with artificial urine with protein (RTAUP) are 33% (at 4 MHz), 25% (at 5 MHz), 20% (at 8 MHz) and 15% (12 MHz). However (MI)m values of the ribbons treated with healthy male urine (RTHMU) after 4 h, 5 h, 10 h and 15 h of incubation are 71% (at 3 MHz), 57% (at 3 MHz), 25% (at 6 MHz) and 25% (at 5 MHz), respectively. The saturation magnetization (Ms) values of RTAU after 3 h, 6 h, 12 h and 24 h of incubation are 71 emu/g, 65 emu/g, 63 emu/g and 60 emu/g respectively whereas, the respective Ms values of RTAUP are 73 emu/g, 69 emu/g, 67 emu/g and 64 emu/g. The Ms values of RTHMU after 4 h, 5 h, 10 h and 15 h of incubation are 96 emu/g, 90 emu/g, 75 emu/g and 75 emu/g respectively. The decrease in Ms and (MI)m values in RTAU and RTAUP compared to as-quenched ribbon is related to the amounts of various elements etched out from the ribbons and increased surface roughness. The Ms and (MI)m values of RTHMU are seen to have increased after 4 h and 5 h of incubation, due to strain relaxation through removal of strain developed during rapid quenching of the ribbons. On the other hand, the Ms and (MI)m values of RTHMU after 10 h and 15 h have decreased due to deterioration of the surface of the ribbons and thus, increase in magnetic (surface) anisotropy. The decrease in (MI)m and MS of RTAU with the time of incubation are more rapid compared to that of RTAUP, probably due to the larger surface anisotropy due to rapid deterioration of the surface of the

  12. The Radio luminosity Function of Radio-Loud Quasars from the 7C Redshift Survey

    NASA Technical Reports Server (NTRS)

    Willott, Chris J.; Rawlings, Steve; Blundell, Katherine M.; Lacy, Mark

    1998-01-01

    We present a complete sample of 24 radio-loud quasars (RLQs) from the new 7C Redshift Survey. Every quasar with a low-frequency (151 MHz) radio flux-density S(sub 151) > 0.5 Jy in two regions of the sky covering 0.013 sr is included; 23 of these have sufficient extended flux to meet the selection criteria, 18 of these have steep radio spectra (hereafter denoted as SSQs). The key advantage of this sample over most samples of RLQs is the lack of an optical magnitude limit. By combining the 7C and 3CRR samples, we have investigated the properties of RLQs as a function of redshift z and radio luminosity L(sub 151). We derive the radio luminosity function (RLF) of RLQs and find that the data are well fitted by a single power-law with slope alpha(sub 1) = 1.9 +/- 0.1 (for H(sub 0) = 50 km/s.Mpc, OMEGA(sub M) = 1, OMEGA(sub DELTA) = 0). We find that there must be a break in the RLQ RLF at log(sub 10)(L(sub 151)/W Hz.sr) approximately < or = 27, in order for the models to be consistent with the 7C and 6C source counts. The z-dependence of the RLF follows a one-tailed gaussian which peaks at z = 1.7 +/- 0.2. We find no evidence for a decline in the co-moving space density of RLQs at higher redshifts. A positive correlation between the radio and optical luminosities of SSQs is observed, confirming a result of Serjeant. We are able to rule out this correlation being due to selection effects or biases in our combined sample. The radio-optical correlation and best-fit model RLF enable us to estimate the distribution of optical magnitudes of quasars in samples selected at low radio frequencies, We con- clude that for samples with S(sub 151) approximately < or = 1 Jy one must use optical data significantly deeper than the POSS-I limit (R approximately equal 20), in order to avoid severe incompleteness.

  13. Recombinant Trichoderma harzianum endoglucanase I (Cel7B) is a highly acidic and promiscuous carbohydrate-active enzyme.

    PubMed

    Pellegrini, Vanessa O A; Serpa, Viviane Isabel; Godoy, Andre S; Camilo, Cesar M; Bernardes, Amanda; Rezende, Camila A; Junior, Nei Pereira; Franco Cairo, João Paulo L; Squina, Fabio M; Polikarpov, Igor

    2015-11-01

    Trichoderma filamentous fungi have been investigated due to their ability to secrete cellulases which find various biotechnological applications such as biomass hydrolysis and cellulosic ethanol production. Previous studies demonstrated that Trichoderma harzianum IOC-3844 has a high degree of cellulolytic activity and potential for biomass hydrolysis. However, enzymatic, biochemical, and structural studies of cellulases from T. harzianum are scarce. This work reports biochemical characterization of the recombinant endoglucanase I from T. harzianum, ThCel7B, and its catalytic core domain. The constructs display optimum activity at 55 °C and a surprisingly acidic pH optimum of 3.0. The full-length enzyme is able to hydrolyze a variety of substrates, with high specific activity: 75 U/mg for β-glucan, 46 U/mg toward xyloglucan, 39 U/mg for lichenan, 26 U/mg for carboxymethyl cellulose, 18 U/mg for 4-nitrophenyl β-D-cellobioside, 16 U/mg for rye arabinoxylan, and 12 U/mg toward xylan. The enzyme also hydrolyzed filter paper, phosphoric acid swollen cellulose, Sigmacell 20, Avicel PH-101, and cellulose, albeit with lower efficiency. The ThCel7B catalytic domain displays similar substrate diversity. Fluorescence-based thermal shift assays showed that thermal stability is highest at pH 5.0. We determined kinetic parameters and analyzed a pattern of oligosaccharide substrates hydrolysis, revealing cellobiose as a final product of C6 degradation. Finally, we visualized effects of ThCel7B on oat spelt using scanning electron microscopy, demonstrating the morphological changes of the substrate during the hydrolysis. The acidic behavior of ThCel7B and its considerable thermostability hold a promise of its industrial applications and other biotechnological uses under extremely acidic conditions. PMID:26156238

  14. cyp7b1 catalyses the 7alpha-hydroxylation of dehydroepiandrosterone and 25-hydroxycholesterol in rat prostate.

    PubMed Central

    Martin, C; Bean, R; Rose, K; Habib, F; Seckl, J

    2001-01-01

    Dehydroepiandrosterone (DHEA) is the most prominent circulating steroid in humans, and it is a precursor for sex-steroid synthesis in peripheral tissues, including the prostate. Recently, enzyme-mediated pre-receptor metabolism has been recognized as a key step in determining steroid action in vivo. Hydroxylation of 3beta-steroids at the 7alpha-position has been reported in rat and human prostate to be a major inhibitory pathway to sex-steroid synthesis/action. However, the molecular identity of the enzyme responsible is so far unknown. We recently described a novel cytochrome P450 enzyme, cyp7b1, strongly expressed in the hippocampus of rodent brain, which catalyses the metabolism of DHEA, pregnenolone and 25-hydroxycholesterol to 7alpha-hydroxy products. In the light of this new enzyme, we have examined its possible role in 7alpha-hydroxylation conversion in rat prostate. NADPH-dependent 7alpha-hydroxylation was confirmed for 3beta-hydroxysteroids including DHEA and androstenediol, as well as 25-hydroxycholesterol. Kinetic analysis yielded an apparent K(m) of 14+/-1 microM for 7alpha-hydroxylation of DHEA in the prostate gland, a value similar to that recorded for recombinant cyp7b1 enzyme [13.6 microM; Rose, Stapleton, Dott, Kieny, Best, Schwarz, Russell, Bjoorkheim, Seckl and Lathe (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 4925-4930]. The V(max) value of the prostate was 46+/-2 pmol/min per mg, and this activity was inhibited by clotrimazole, a P450-enzyme blocker. Moreover, RNA analysis (reverse-transcription PCR, Northern blotting and in situ hybridization) revealed a high expression of cyp7b1 mRNA in the rat prostate, restricted to the epithelium, suggesting that cyp7b1 catalyses oxysterol 7alpha-hydroxylation in the prostate gland. PMID:11284740

  15. Distinct phenotype of a Wilson disease mutation reveals a novel trafficking determinant in the copper transporter ATP7B

    PubMed Central

    Braiterman, Lelita T.; Murthy, Amrutha; Jayakanthan, Samuel; Nyasae, Lydia; Tzeng, Eric; Gromadzka, Grazyna; Woolf, Thomas B.; Lutsenko, Svetlana; Hubbard, Ann L.

    2014-01-01

    Wilson disease (WD) is a monogenic autosomal-recessive disorder of copper accumulation that leads to liver failure and/or neurological deficits. WD is caused by mutations in ATP7B, a transporter that loads Cu(I) onto newly synthesized cupro-enzymes in the trans-Golgi network (TGN) and exports excess copper out of cells by trafficking from the TGN to the plasma membrane. To date, most WD mutations have been shown to disrupt ATP7B activity and/or stability. Using a multidisciplinary approach, including clinical analysis of patients, cell-based assays, and computational studies, we characterized a patient mutation, ATP7BS653Y, which is stable, does not disrupt Cu(I) transport, yet renders the protein unable to exit the TGN. Bulky or charged substitutions at position 653 mimic the phenotype of the patient mutation. Molecular modeling and dynamic simulation suggest that the S653Y mutation induces local distortions within the transmembrane (TM) domain 1 and alter TM1 interaction with TM2. S653Y abolishes the trafficking-stimulating effects of a secondary mutation in the N-terminal apical targeting domain. This result indicates a role for TM1/TM2 in regulating conformations of cytosolic domains involved in ATP7B trafficking. Taken together, our experiments revealed an unexpected role for TM1/TM2 in copper-regulated trafficking of ATP7B and defined a unique class of WD mutants that are transport-competent but trafficking-defective. Understanding the precise consequences of WD-causing mutations will facilitate the development of advanced mutation-specific therapies. PMID:24706876

  16. Spin-orbit alignment for KELT-7b and HAT-P-56b via Doppler tomography with TRES

    NASA Astrophysics Data System (ADS)

    Zhou, George; Latham, David W.; Bieryla, Allyson; Beatty, Thomas G.; Buchhave, Lars A.; Esquerdo, Gilbert A.; Berlind, Perry; Calkins, Michael L.

    2016-08-01

    We present Doppler tomographic analyses for the spectroscopic transits of KELT-7b and HAT-P-56b, two hot-Jupiters orbiting rapidly rotating F-dwarf host stars. These include analyses of archival Tillinghast Reflector Echelle Spectrograph (TRES) observations for KELT-7b, and a new TRES transit observation of HAT-P-56b. We report spin-orbit aligned geometries for KELT-7b (2.7° ± 0.6°) and HAT-P-56b (8° ± 2°). The host stars KELT-7 and HAT-P-56 are among some of the most rapidly rotating planet-hosting stars known. We examine the tidal re-alignment model for the evolution of the spin-orbit angle in the context of the spin rates of these stars. We find no evidence that the rotation rates of KELT-7 and HAT-P-56 have been modified by star-planet tidal interactions, suggesting that the spin-orbit angle of systems around these hot stars may represent their primordial configuration. In fact, KELT-7 and HAT-P-56 are two of three systems in supersynchronous, spin-orbit aligned states, where the rotation periods of the host stars are faster than the orbital periods of the planets.

  17. Degradation of sulphonated azo dye Red HE7B by Bacillus sp. and elucidation of degradative pathways.

    PubMed

    Thakur, Jyoti Kumar; Paul, Sangeeta; Dureja, Prem; Annapurna, K; Padaria, Jasdeep C; Gopal, Madhuban

    2014-08-01

    Bacteria capable of degrading the sulfonated azo dye Red HE7B were isolated from textile mill effluent contaminated soil. The most efficient isolate was identified as Bacillus sp. Azo1 and the isolate could successfully decolorize up to 89% of the dye. The decolorized cultural extract analyzed by HPLC confirmed degradation. Enzymatic analysis showed twofold and fourfold increase in the activity of azoreductase and laccase enzymes, respectively, indicating involvement of both reductive and oxidative enzymes in biodegradation of Red HE7B. Degraded products which were identified by GC/MS analysis included various metabolites like 8-nitroso 1-naphthol, 2-diazonium naphthalene. Mono azo dye intermediate was initially generated from the parent molecule. This mono azo dye was further degraded by the organism, into additional products, depending on the site of cleavage of R-N=N-R molecule. Based on the degradation products identified, three different pathways have been proposed. The mechanism of degradation in two of these pathways is different from that of the previously reported pathway for azo dye degradation. This is the first report of a microbial isolate following multiple pathways for azo dye degradation. Azo dye Red HE7B was observed to be phytotoxic, leading to decrease in root development, shoot length and seedling fresh weight. However, after biotreatment the resulting degradation products were non-phytotoxic. PMID:24682261

  18. Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia.

    PubMed

    Miyake, Masahiro; Yamashiro, Kenji; Tabara, Yasuharu; Suda, Kenji; Morooka, Satoshi; Nakanishi, Hideo; Khor, Chiea-Chuen; Chen, Peng; Qiao, Fan; Nakata, Isao; Akagi-Kurashige, Yumiko; Gotoh, Norimoto; Tsujikawa, Akitaka; Meguro, Akira; Kusuhara, Sentaro; Polasek, Ozen; Hayward, Caroline; Wright, Alan F; Campbell, Harry; Richardson, Andrea J; Schache, Maria; Takeuchi, Masaki; Mackey, David A; Hewitt, Alex W; Cuellar, Gabriel; Shi, Yi; Huang, Luling; Yang, Zhenglin; Leung, Kim Hung; Kao, Patrick Y P; Yap, Maurice K H; Yip, Shea Ping; Moriyama, Muka; Ohno-Matsui, Kyoko; Mizuki, Nobuhisa; MacGregor, Stuart; Vitart, Veronique; Aung, Tin; Saw, Seang-Mei; Tai, E-Shyong; Wong, Tien Yin; Cheng, Ching-Yu; Baird, Paul N; Yamada, Ryo; Matsuda, Fumihiko; Yoshimura, Nagahisa

    2015-01-01

    Myopia can cause severe visual impairment. Here, we report a two-stage genome-wide association study for three myopia-related traits in 9,804 Japanese individuals, which was extended with trans-ethnic replication in 2,674 Chinese and 2,690 Caucasian individuals. We identify WNT7B as a novel susceptibility gene for axial length (rs10453441, Pmeta=3.9 × 10(-13)) and corneal curvature (Pmeta=2.9 × 10(-40)) and confirm the previously reported association between GJD2 and myopia. WNT7B significantly associates with extreme myopia in a case-control study with 1,478 Asian patients and 4,689 controls (odds ratio (OR)meta=1.13, Pmeta=0.011). We also find in a mouse model of myopia downregulation of WNT7B expression in the cornea and upregulation in the retina, suggesting its possible role in the development of myopia. PMID:25823570

  19. Spin-orbit alignment for KELT-7b and HAT-P-56b via Doppler tomography with TRES

    NASA Astrophysics Data System (ADS)

    Zhou, George; Latham, David W.; Bieryla, Allyson; Beatty, Thomas G.; Buchhave, Lars A.; Esquerdo, Gilbert A.; Berlind, Perry; Calkins, Michael L.

    2016-08-01

    We present Doppler tomographic analyses for the spectroscopic transits of KELT-7b and HAT-P-56b, two hot-Jupiters orbiting rapidly rotating F-dwarf host stars. These include analyses of archival TRES observations for KELT-7b, and a new TRES transit observation of HAT-P-56b. We report spin-orbit aligned geometries for KELT-7b (2.7 +/- 0.6 deg) and HAT-P-56b (8 +/- 2 deg). The host stars KELT-7 and HAT-P-56 are among some of the most rapidly rotating planet-hosting stars known. We examine the tidal re-alignment model for the evolution of the spin-orbit angle in the context of the spin rates of these stars. We find no evidence that the rotation rates of KELT-7 and HAT-P-56 have been modified by star-planet tidal interactions, suggesting that the spin-orbit angle of systems around these hot stars may represent their primordial configuration. In fact, KELT-7 and HAT-P-56 are two of three systems in super-synchronous, spin-orbit aligned states, where the rotation periods of the host stars are faster than the orbital periods of the planets.

  20. P7C3 Neuroprotective Chemicals Function by Activating the Rate-limiting Enzyme in NAD Salvage

    PubMed Central

    Wang, Gelin; Han, Ting; Nijhawan, Deepak; Theodoropoulos, Pano; Naidoo, Jacinth; Yadavalli, Sivaramakrishnan; Mirzaei, Hamid; Pieper, Andrew A.; Ready, Joseph M.; McKnight, Steven L.

    2014-01-01

    SUMMARY The P7C3 class of aminopropyl carbazole chemicals fosters the survival of neurons in a variety of rodent models of neurodegeneration or nerve cell injury. To uncover its mechanism of action, an active derivative of P7C3 was modified to contain both a benzophenone for photo-crosslinking and an alkyne for CLICK chemistry. This derivative was found to bind nicotinamide phosphoribosyltransferase (NAMPT), the rate limiting enzyme involved in the conversion of nicotinamide into nicotinamide adenine dinucleotide (NAD). Administration of active P7C3 chemicals to cells treated with doxorubicin, which induces NAD depletion, led to a rebound in intracellular levels of NAD and concomitant protection from doxorubicin-mediated toxicity. Active P7C3 variants likewise enhanced the activity of the purified NAMPT enzyme, providing further evidence that they act by increasing NAD levels through its NAMPT-mediated salvage. PMID:25215490

  1. Protective efficacy of P7C3-S243 in the 6-hydroxydopamine model of Parkinson’s disease

    PubMed Central

    De Jesús-Cortés, Héctor; Miller, Adam D; Britt, Jeremiah K; DeMarco, Anthony J; De Jesús-Cortés, Mayralis; Stuebing, Emily; Naidoo, Jacinth; Vázquez-Rosa, Edwin; Morlock, Lorraine; Williams, Noelle S; Ready, Joseph M; Narayanan, Nandakumar S; Pieper, Andrew A

    2016-01-01

    BACKGROUND There are currently no therapeutic options for patients with Parkinson’s disease that prevent or slow the death of dopaminergic neurons. We have recently identified the novel P7C3 class of neuroprotective molecules that blocks neuron cell death. AIMS The aim of this study was to determine whether treatment with highly active members of the P7C3 series blocks dopaminergic neuron cell death and associated behavioral and neurochemical deficits in the rat 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease. METHODS After unilateral injection of 6-OHDA into the median forebrain bundle, rats were assessed for behavioral function in the open field, cylinder test, and amphetamine-induced circling test. Thereafter, their brains were subjected to neurochemical and immunohistochemical analysis of dopaminergic neuron survival. Analysis was conducted as a function of treatment with P7C3 compounds, with administration initiated either before or after 6-OHDA exposure. RESULTS Animals administered P7C3-A20 or P7C3-S243, two of the most advanced agents in the P7C3 series of neuroprotective compounds, both before and after 6-OHDA exposure showed evidence of protective efficacy in all measures. When P7C3-S243 administration was initiated after 6-OHDA exposure, rats also showed protective efficacy in all measures, which included blocking dopaminergic neuron cell death in ipsilateral substantia nigra pars compacta, preservation of dopamine and its metabolites in ipsilateral striatum, and preservation of normal motor behavior. CONCLUSIONS The P7C3 series of compounds may form the basis for developing new therapeutic agents for slowing or preventing progression of Parkinson’s disease. PMID:27158662

  2. 20 CFR 652.204 - Must funds authorized under section 7(b) of the Act (the Governor's reserve) flow through the One...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the Act (the Governor's reserve) flow through the One-Stop delivery system? 652.204 Section 652.204... § 652.204 Must funds authorized under section 7(b) of the Act (the Governor's reserve) flow through the... categories of activities specified in section 7(b) of the Act. However, these funds may flow through the...

  3. Solvothermal synthesis of Fe7C3 and Fe3C nanostructures with phase and morphology control

    NASA Astrophysics Data System (ADS)

    Williams, Brent; Clifford, Dustin; El-Gendy, Ahmed A.; Carpenter, Everett E.

    2016-07-01

    A phase transition, from orthorhombic Fe3C to hexagonal Fe7C3, was observed using a wet synthesis mediated by hexadecyltrimethylammonium chloride (CTAC). In this study, CTAC has been shown to control carbide phase, morphology, and size of the iron carbide nanostructures. Fe7C3 hexagonal prisms were formed with an average diameter of 960 nm, the thickness of 150 nm, and Fe3C nanostructures with an approximate size of 50 nm. Magnetic studies show ferromagnetic behavior with Ms of 126 emu/g, and Hc of 170 Oe with respect to Fe7C3 and 95 emu/g and 590 Oe with respect to Fe3C. The thermal studies using high temperature x-ray diffraction show stability of Fe7C3 up to 500 °C. Upon slow cooling, the Fe7C3 phase is recovered with an intermediate oxide phase occurring around 300 °C. This study has demonstrated a simple route in synthesizing iron carbides for an in depth magnetic study and crystal phase transition study of Fe7C3 at elevated temperatures.

  4. Effect of Ti additive on (Cr, Fe)7C3 carbide in arc surfacing layer and its refined mechanism

    NASA Astrophysics Data System (ADS)

    Zhou, Yefei; Yang, Yulin; Yang, Jian; Hao, Feifei; Li, Da; Ren, Xuejun; Yang, Qingxiang

    2012-06-01

    Arc surfacing layer of hypoeutectic high chromium cast iron (HCCI) expects refiner carbides in the microstructure to improve its mechanical properties. In this paper, Ti additive as a strong carbide forming element was added in the hypoeutectic HCCI arc surfacing layer. Microstructure of titaniferous hypoeutectic HCCI was studied by optical microscopy, X-ray diffraction and field emission scanning electronic microscopy with energy dispersive spectrometer. Furthermore, the M(M = Cr, Fe)7C3 carbide refinement mechanism was explained by the phase diagram calculation and lattice misfit theory. The results show that, the M7C3 carbide in arc surfacing microstructure of hypoeutectic HCCI has been refined with 2 wt.% Ti additive, and TiC carbide can be observed in/around the M7C3 carbide. With Ti addictive increasing, the micro-hardness along the depth in profile section of layer becomes more uniform, and the wear resistance has been improved. According to the phase diagram calculation, MC carbide precipitates prior to M7C3 carbide in Fe-Cr-C-Ti alloy. In addition, the lattice misfit between (1 1 0)TiC and (0C is 9.257%, which indicates that the TiC as heterogeneous nuclei of the M7C3 is medium effective. Therefore, the M7C3 carbide can be refined.

  5. Chronic P7C3 treatment restores hippocampal neurogenesis in the Ts65Dn mouse model of Down Syndrome [Corrected].

    PubMed

    Latchney, Sarah E; Jaramillo, Thomas C; Rivera, Phillip D; Eisch, Amelia J; Powell, Craig M

    2015-03-30

    Down syndrome (DS) is the most common genetic cause of intellectual disability and developmental delay. In addition to cognitive dysfunction, DS patients are marked by diminished neurogenesis, a neuropathological feature also found in the Ts65Dn mouse model of DS. Interestingly, manipulations that enhance neurogenesis - like environmental enrichment or pharmacological agents - improve cognition in Ts65Dn mice. P7C3 is a proneurogenic compound that enhances hippocampal neurogenesis, cell survival, and promotes cognition in aged animals. However, this compound has not been tested in the Ts65Dn mouse model of DS. We hypothesized that P7C3 treatment would reverse or ameliorate the neurogenic deficits in Ts65Dn mice. To test this, adult Ts65Dn and age-matched wild-type (WT) mice were administered vehicle or P7C3 twice daily for 3 months. After 3 months, brains were examined for indices of neurogenesis, including quantification of Ki67, DCX, activated caspase-3 (AC3), and surviving BrdU-immunoreactive(+) cells in the granule cell layer (GCL) of the hippocampal dentate gyrus. P7C3 had no effect on total Ki67+, DCX+, AC3+, or surviving BrdU+ cells in WT mice relative to vehicle. GCL volume was also not changed. In keeping with our hypothesis, however, P7C3-treated Ts65Dn mice had a significant increase in total Ki67+, DCX+, and surviving BrdU+ cells relative to vehicle. P7C3 treatment also decreased AC3+ cell number but had no effect on total GCL volume in Ts65Dn mice. Our findings show 3 months of P7C3 is sufficient to restore the neurogenic deficits observed in the Ts65Dn mouse model of DS. PMID:25668489

  6. Rocky super-Earth interiors. Structure and internal dynamics of CoRoT-7b and Kepler-10b

    NASA Astrophysics Data System (ADS)

    Wagner, F. W.; Tosi, N.; Sohl, F.; Rauer, H.; Spohn, T.

    2012-05-01

    Aims: We present interior structure models of the recently discovered exoplanets CoRoT-7b and Kepler-10b addressing their bulk compositions, present thermal states, and internal dynamics. We investigate how mantle convection patterns are influenced by the depth-dependence of thermodynamic parameters (e.g., thermal expansivity and conductivity) caused by the extended pressure and temperature ranges within rocky super-Earths. Methods: To model the interior of rocky exoplanets, we construct a four-layer structural model solving the mass and energy balance equations in conjunction with a generalized Rydberg equation of state providing the radial density distribution within each layer. The present thermal state is calculated according to a modified mixing-length approach for highly viscous fluids. Furthermore, the obtained internal structure is used to carry out two-dimensional convection simulations to visualize the mantle convection pattern within massive exoplanets such as CoRoT-7b and Kepler-10b. Results: Both CoRoT-7b and Kepler-10b most likely have large iron cores and a bulk composition similar to that of Mercury. For a planetary radius of Rp = (1.58 ± 0.10) R⊕, a revised total mass of Mp = (7.42 ± 1.21) M⊕, and the existence of a third planet in the CoRoT-7 planetary system, calculations suggest that an iron core of 64 wt-% and a silicate mantle of 36 wt-% is produced owing to the relatively high average compressed density of ρavg = (10.4 ± 1.8) g cm-3. Kepler-10b's planetary radius and total mass yield an iron core of 59.5 wt-%, which complements the silicate mantle of 40.5 wt-%. An enhanced radiogenic heating rate owing to CoRoT-7b's young age (1.2-2.3 Gyr) raises the radial distribution of temperature by only a few hundred Kelvin, but reduces the viscosity by an order of magnitude. The planform of mantle convection is found to be strongly modified for depth-dependent material properties, with hot plumes rising across the whole mantle and cold slabs

  7. Could CoRoT-7b and Kepler-10b be remnants of evaporated gas or ice giants?

    PubMed Central

    Leitzinger, M.; Odert, P.; Kulikov, Yu.N.; Lammer, H.; Wuchterl, G.; Penz, T.; Guarcello, M.G.; Micela, G.; Khodachenko, M.L.; Weingrill, J.; Hanslmeier, A.; Biernat, H.K.; Schneider, J.

    2011-01-01

    We present thermal mass loss calculations over evolutionary time scales for the investigation if the smallest transiting rocky exoplanets CoRoT-7b (∼1.68REarth) and Kepler-10b (∼1.416REarth) could be remnants of an initially more massive hydrogen-rich gas giant or a hot Neptune-class exoplanet. We apply a thermal mass loss formula which yields results that are comparable to hydrodynamic loss models. Our approach considers the effect of the Roche lobe, realistic heating efficiencies and a radius scaling law derived from observations of hot Jupiters. We study the influence of the mean planetary density on the thermal mass loss by placing hypothetical exoplanets with the characteristics of Jupiter, Saturn, Neptune, and Uranus to the orbital location of CoRoT-7b at 0.017 AU and Kepler-10b at 0.01684 AU and assuming that these planets orbit a K- or G-type host star. Our findings indicate that hydrogen-rich gas giants within the mass domain of Saturn or Jupiter cannot thermally lose such an amount of mass that CoRoT-7b and Kepler-10b would result in a rocky residue. Moreover, our calculations show that the present time mass of both rocky exoplanets can be neither a result of evaporation of a hydrogen envelope of a “Hot Neptune” nor a “Hot Uranus”-class object. Depending on the initial density and mass, these planets most likely were always rocky planets which could lose a thin hydrogen envelope, but not cores of thermally evaporated initially much more massive and larger objects. PMID:21969736

  8. Could CoRoT-7b and Kepler-10b be remnants of evaporated gas or ice giants?

    PubMed

    Leitzinger, M; Odert, P; Kulikov, Yu N; Lammer, H; Wuchterl, G; Penz, T; Guarcello, M G; Micela, G; Khodachenko, M L; Weingrill, J; Hanslmeier, A; Biernat, H K; Schneider, J

    2011-10-01

    We present thermal mass loss calculations over evolutionary time scales for the investigation if the smallest transiting rocky exoplanets CoRoT-7b (∼1.68REarth) and Kepler-10b (∼1.416REarth) could be remnants of an initially more massive hydrogen-rich gas giant or a hot Neptune-class exoplanet. We apply a thermal mass loss formula which yields results that are comparable to hydrodynamic loss models. Our approach considers the effect of the Roche lobe, realistic heating efficiencies and a radius scaling law derived from observations of hot Jupiters. We study the influence of the mean planetary density on the thermal mass loss by placing hypothetical exoplanets with the characteristics of Jupiter, Saturn, Neptune, and Uranus to the orbital location of CoRoT-7b at 0.017 AU and Kepler-10b at 0.01684 AU and assuming that these planets orbit a K- or G-type host star. Our findings indicate that hydrogen-rich gas giants within the mass domain of Saturn or Jupiter cannot thermally lose such an amount of mass that CoRoT-7b and Kepler-10b would result in a rocky residue. Moreover, our calculations show that the present time mass of both rocky exoplanets can be neither a result of evaporation of a hydrogen envelope of a "Hot Neptune" nor a "Hot Uranus"-class object. Depending on the initial density and mass, these planets most likely were always rocky planets which could lose a thin hydrogen envelope, but not cores of thermally evaporated initially much more massive and larger objects. PMID:21969736

  9. STUDYING THE ATMOSPHERE OF THE EXOPLANET HAT-P-7b VIA SECONDARY ECLIPSE MEASUREMENTS WITH EPOXI, SPITZER, AND KEPLER

    SciTech Connect

    Christiansen, Jessie L.; Ballard, Sarah; Charbonneau, David; Holman, Matthew J.; Madhusudhan, Nikku; Seager, Sara; Wellnitz, Dennis D.; Deming, Drake; A'Hearn, Michael F.

    2010-02-10

    The highly irradiated transiting exoplanet, HAT-P-7b, currently provides one of the best opportunities for studying planetary emission in the optical and infrared wavelengths. We observe six near-consecutive secondary eclipses of HAT-P-7b at optical wavelengths with the EPOXI spacecraft. We place an upper limit on the relative eclipse depth of 0.055% (95% confidence). We also analyze Spitzer observations of the same target in the infrared, obtaining secondary eclipse depths of 0.098% +- 0.017%, 0.159% +- 0.022%, 0.245% +- 0.031%, and 0.225% +- 0.052% in the 3.6, 4.5, 5.8, and 8.0 {mu}m IRAC bands, respectively. We combine these measurements with the recently published Kepler secondary eclipse measurement and generate atmospheric models for the dayside of the planet that are consistent with both the optical and infrared measurements. The data are best fit by models with a temperature inversion, as expected from the high incident flux. The models predict a low optical albedo of {approx}<0.13, with subsolar abundances of Na, K, TiO, and VO. We also find that the best-fitting models predict that 10% of the absorbed stellar flux is redistributed to the nightside of the planet, which is qualitatively consistent with the inefficient day-night redistribution apparent in the Kepler phase curve. Models without thermal inversions fit the data only at the 1.25sigma level, and also require an overabundance of methane, which is not expected in the very hot atmosphere of HAT-P-7b. We also analyze the eight transits of HAT-P-7b present in the EPOXI data set and improve the constraints on the system parameters, finding a period of P = 2.2047308 +- 0.0000025 days, a stellar radius of R{sub *} = 1.824 +- 0.089 R{sub sun}, a planetary radius of R{sub p} = 1.342 +- 0.068 R{sub Jup}, and an inclination of i = 85.7{sup +3.5}{sub -2.2} deg.

  10. Emission behavior of sudan red 7B on dogbone-shaped gold nanorods: Aspect ratio dependence of the metallic nanostructures

    NASA Astrophysics Data System (ADS)

    Rahman, Dewan S.; Sharma, Debdulal; Ghosh, Sujit Kumar

    2014-01-01

    Cetyltrimethylammonium bromide-stabilized 'dogbone-shaped' gold nanorods of aspect ratio varying from 1 to 6 have been synthesized by seed-mediated growth method in aqueous medium. Then, sudan red 7B, an alien molecular probe has been used as local probe to elucidate aspect ratio dependence of the nanorods on the photophysical properties of the dye molecules. It is seen that the relative intensity decreases exponentially with increasing aspect ratio and has been attributed to decrease in overall surface area for a particular concentration of the nanorods. The mechanism of fluorescence quenching has been ascribed to the electron and energy transfer processes in the gold-fluorophore hybrid nanostructures.

  11. The transmembrane domain of the severe acute respiratory syndrome coronavirus ORF7b protein is necessary and sufficient for its retention in the Golgi complex.

    PubMed

    Schaecher, Scott R; Diamond, Michael S; Pekosz, Andrew

    2008-10-01

    The severe acute respiratory syndrome coronavirus (SARS-CoV) ORF7b (also called 7b) protein is an integral membrane protein that is translated from a bicistronic open reading frame encoded within subgenomic RNA 7. When expressed independently or during virus infection, ORF7b accumulates in the Golgi compartment, colocalizing with both cis- and trans-Golgi markers. To identify the domains of this protein that are responsible for Golgi localization, we have generated a set of mutant proteins and analyzed their subcellular localizations by indirect immunofluorescence confocal microscopy. The N- and C-terminal sequences are dispensable, but the ORF7b transmembrane domain (TMD) is essential for Golgi compartment localization. When the TMD of human CD4 was replaced with the ORF7b TMD, the resulting chimeric protein localized to the Golgi complex. Scanning alanine mutagenesis identified two regions in the carboxy-terminal portion of the TMD that eliminated the Golgi complex localization of the chimeric CD4 proteins or ORF7b protein. Collectively, these data demonstrate that the Golgi complex retention signal of the ORF7b protein resides solely within the TMD. PMID:18632859

  12. First-principles calculations of properties of orthorhombic iron carbide Fe7C3 at the Earth's core conditions

    NASA Astrophysics Data System (ADS)

    Raza, Zamaan; Shulumba, Nina; Caffrey, Nuala M.; Dubrovinsky, Leonid; Abrikosov, Igor A.

    2015-06-01

    A recently discovered phase of orthorhombic iron carbide o-Fe7C3 [Prescher et al., Nat. Geosci. 8, 220 (2015), 10.1038/ngeo2370] is assessed as a potentially important phase for interpretation of the properties of the Earth's core. In this paper, we carry out first-principles calculations on o-Fe7C3 , finding properties to be in broad agreement with recent experiments, including a high Poisson's ratio (0.38). Our enthalpy calculations suggest that o-Fe7C3 is more stable than Eckstrom-Adcock hexagonal iron carbide (h-Fe7C3 ) below approximately 100 GPa. However, at 150 GPa, the two phases are essentially degenerate in terms of Gibbs free energy, and further increasing the pressure towards Earth's core conditions stabilizes h-Fe7C3 with respect to the orthorhombic phase. Increasing the temperature tends to stabilize the hexagonal phase at 360 GPa, but this trend may change beyond the limit of the quasiharmonic approximation.

  13. Apical targeting and Golgi retention signals reside within a 9-amino acid sequence in the copper-ATPase, ATP7B.

    PubMed

    Braiterman, Lelita; Nyasae, Lydia; Guo, Yan; Bustos, Rodrigo; Lutsenko, Svetlana; Hubbard, Ann

    2009-02-01

    ATP7B is a copper-transporting P-type ATPase present predominantly in liver. In basal copper, hepatic ATP7B is in a post-trans-Golgi network (TGN) compartment where it loads cytoplasmic Cu(I) onto newly synthesized ceruloplasmin. When copper levels rise, the protein redistributes via unique vesicles to the apical periphery where it exports intracellular Cu(I) into bile. We want to understand the mechanisms regulating the copper-sensitive trafficking of ATP7B. Earlier, our laboratory reported the presence of apical targeting/TGN retention information within residues 1-63 of human ATP7B; deletion of these residues resulted in a mutant protein that was not efficiently retained in the post-TGN in low copper and constitutively trafficked to the basolateral membrane of polarized, hepatic WIF-B cells with and without copper (13). In this study, we used mutagenesis and adenovirus infection of WIF-B cells followed by confocal immunofluorescence microscopy analysis to identify the precise retention/targeting sequences in the context of full-length ATP7B. We also analyzed the expression of selected mutants in livers of copper-deficient and -loaded mice. Our combined results clearly demonstrate that nine amino acids, F(37)AFDNVGYE(45), comprise an essential apical targeting determinant for ATP7B in elevated copper and participate in the TGN retention of the protein under low-copper conditions. The signal is novel, does not require phosphorylation, and is highly conserved in approximately 24 species of ATP7B. Furthermore, N41S, which is part of the signal we identified, is the first and only Wilson disease-causing missense mutation in residues 1-63 of ATP7B. Expression of N41S-ATP7B in WIF-B cells severely disabled the targeting and retention of the protein. We present a working model of how this physiologically relevant signal might work. PMID:19033537

  14. INVESTIGATION OF SYSTEMATIC EFFECTS IN KEPLER DATA: SEASONAL VARIATIONS IN THE LIGHT CURVE OF HAT-P-7b

    SciTech Connect

    Van Eylen, V.; Lindholm Nielsen, M.; Hinrup, B.; Tingley, B.; Kjeldsen, H.

    2013-09-10

    With years of Kepler data currently available, the measurement of variations in planetary transit depths over time can now be attempted. To do so, it is of primary importance to understand which systematic effects may affect the measurement of transits. We aim to measure the stability of Kepler measurements over years of observations. We present a study of the depth of about 500 transit events of the Hot Jupiter HAT-P-7b, using 14 quarters (Q0-Q13) of data from the Kepler satellite. We find a systematic variation in the depth of the primary transit, related to quarters of data and recurring yearly. These seasonal variations are about 1%. Within seasons, we find no evidence for trends. We speculate that the cause of the seasonal variations could be unknown field crowding or instrumental artifacts. Our results show that care must be taken when combining transits throughout different quarters of Kepler data. Measuring the relative planetary radius of HAT-P-7b without taking these systematic effects into account leads to unrealistically low error estimates. This effect could be present in all Kepler targets. If so, relative radius measurements of all Hot Jupiters to a precision much better than 1% are unrealistic.

  15. ATMOSPHERE AND SPECTRAL MODELS OF THE KEPLER-FIELD PLANETS HAT-P-7b AND TrES-2

    SciTech Connect

    Spiegel, David S.; Burrows, Adam E-mail: burrows@astro.princeton.ed

    2010-10-10

    We develop atmosphere models of two of the three Kepler-field planets that were known prior to the start of the Kepler mission (HAT-P-7b and TrES-2). We find that published Kepler and Spitzer data for HAT-P-7b appear to require an extremely hot upper atmosphere on the dayside, with a strong thermal inversion and little day-night redistribution. The Spitzer data for TrES-2 suggest a mild thermal inversion with moderate day-night redistribution. We examine the effect of nonequilibrium chemistry on TrES-2 model atmospheres and find that methane levels must be adjusted by extreme amounts in order to cause even mild changes in atmospheric structure and emergent spectra. Our best-fit models to the Spitzer data for TrES-2 lead us to predict a low secondary eclipse planet-star flux ratio ({approx}<2 x 10{sup -5}) in the Kepler bandpass, which is consistent with what very recent observations have found. Finally, we consider how the Kepler-band optical flux from a hot exoplanet depends on the strength of a possible extra optical absorber in the upper atmosphere. We find that the optical flux is not monotonic in optical opacity, and the non-monotonicity is greater for brighter, hotter stars.

  16. EOS7C Version 1.0 TOUGH2 Module for Carbon Dioxide or Nitrogen in Natural Gas

    2008-01-11

    EOS7C is a TOUGH2 module for multicomponent gas mixtures in the systems methane-carbon dioxide (CH{sub 4}-CO{sub 2}) or methane-nitrogen (CH{sub 4}-N{sub 2}) with or without an aqueous phase and H{sub 2}O vapor. EOS7C uses a cubic equation of state and an accurate solubility formulation along with a multiphase Darcy's Law to model flow and transport of gas and aqueous phase mixtures over a wide range of pressures and temperatures appropriate to subsurface geologic carbon sequestrationmore » sites and natural gas reservoirs. EOS7C models supercritical CO{sub 2{ and subcritical CO{sub 2} as a non-condensible gas, hence EOS7C does not model the transitions to liquid or solid CO{sub 2} conditions. The components modeled in EOS7C are water, brine, non-condensible gas, gas tracer, methane, and optional heat. The non-condensible gas (NCG) can be selected by the user to be CO{sub 2} or N{sub 2}. The real gas properties module has options for Peng-Robinson, Redlich-Kwong, or Soave-Redlich-Kwong equations of state to calculate gas mixture density, enthalpy departure, and viscosity. Partitioning of the NCG and CH{sub 4} between the aqueous and gas phases is calculated using a very accurate chemical equilibrium approach. Transport of the gaseous and dissolved components is by advection and Fickian molecular diffusion. EOS7C is written in FORTAN77.« less

  17. Decreased plasma let-7c and miR-152 as noninvasive biomarker for non-small-cell lung cancer

    PubMed Central

    Dou, Hengli; Wang, Yan; Su, Gang; Zhao, Song

    2015-01-01

    Background: Non-small-cell lung cancer (NSCLC) is one of the leading causes of death. The aim of the present study was to compare the expression of let-7c and miR-152 in surgically resected NSCLC cases and healthy cases to evaluate their diagnostic impact. Methods: This hospital-based case-control study included 120 NSCLC patients and 360 healthy controls. The miRNA levels were measured via quantitative reverse transcription-polymerase chain reaction and their association with NSCLC was assessed by statistical data analysis and receiver operating characteristic curves. Results: The expression of let-7c and miR-152 in plasma were found to be downregulated in the patients with NSCLC. Advanced studies showed that the plasma let-7c and miR-152 were correlated with the clinicopathological features such as histological classifications, differentiation status, lymph node metastasis and stage classifications. The ROC curves for the miRNAs revealed a strong diagnostic performance. ROC curve analyses revealed that both plasma let-7c and miR-152 could serve as valuable biomarkers for NSCLC cases from healthy controls with an AUC of 0.714 and 0.845. Conclusion: It was found that let-7c and miR-152 are significantly reduced in plasma samples of NSCLC patients. These findings suggest that detection of circulating let-7c and miR-152 can be developed into a noninvasive and rapid diagnostic tool for the individuals with NSCLC. PMID:26309587

  18. Synthesis and microwave-absorbing properties of Co3Fe7@C core-shell nanostructure

    NASA Astrophysics Data System (ADS)

    Guo, Xiao Dang; Qiao, Xiao Jing; Ren, Qing Guo; Wan, Xiang; Li, Wang Chang; Sun, Zhi Gang

    2015-07-01

    Co3Fe7@C core-shell nanoparticles with high performance of microwave-absorbing properties were prepared by hydrothermal method and heat treatment. The transformation of structural, morphological and magnetic properties among the carbon-encapsulated composites, which were annealed at three different temperatures, were investigated by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). XRD analysis indicated the phase composition of Co3Fe7/CoFe2O4, Fe3C/Co3Fe7 and pure Co3Fe7 at different annealing temperatures. TEM confirmed the Co3Fe7@graphite core-shell nanostructure with an average particle size of 180 nm. The saturation magnetization ( M s) increased monotonically with the increase in temperature, which was attributed to the crystal growth and purity of metallic core. Co3Fe7@graphite nanoparticles exhibited the hysteretic loops of soft ferromagnetic behavior with high M s of 222.85 emu g-1, weak remanent magnetization ( M r) and coercivity ( H c). For Co3Fe7@graphite nanomaterial, a reflection loss exceeding -20 dB was obtained between 2.8 and 10.2 GHz, which almost covering from S-band to X-band. The maximum reflection loss is -26.8 dB at 9 GHz with 1.8 mm thickness. The excellent microwave absorption properties result from the proper electromagnetic match in core-shell nanostructure and the strong natural ferromagnetic resonance.

  19. Computational Investigations of Trichoderma Reesei Cel7A Suggest New Routes for Enzyme Activity Improvements

    SciTech Connect

    Beckham, G. T.; Payne, C. M.; Bu, L.; Taylor, C. B.; McCabe, C.; Chu, J. W.; Himmel, M. E.; Crowley, M. F.

    2012-01-01

    The Trichoderma reesei Family 7 cellulase (Cel7A) is a key industrial enzyme in the production of biofuels from lignocellulosic biomass. It is a multi-modular enzyme with a Family 1 carbohydrate-binding module, a flexible O-glycosylated linker, and a large catalytic domain. We have used simulation to elucidate new functions for the 3 sub-domains, which suggests new routes to increase the activity of this central enzyme. These findings include new roles for glycosylation, which we have shown can be used to tune the binding affinity. We have also examined the structures of the catalytically-active complex of Cel7A and its non-processive counterpart, Cel7B, engaged on cellulose, which suggests allosteric mechanisms involved in chain binding when these cellulases are complexed on cellulose. Our computational results also suggest that product inhibition varies significantly between Cel7A and Cel7B, and we offer a molecular-level explanation for this observation. Finally, we discuss simulations of the absolute and relative binding free energy of cellulose ligands and various mutations along the CD tunnel, which will affect processivity and the ability of Cel7A (and related enzymes) to digest cellulose. These results highlight new considerations in protein engineering for processive and non-processive cellulases for production of lignocellulosic biofuels.

  20. miRNA let-7b modulates macrophage polarization and enhances tumor-associated macrophages to promote angiogenesis and mobility in prostate cancer

    PubMed Central

    Wang, Zhigang; Xu, Lu; Hu, Yinying; Huang, Yanqin; Zhang, Yujuan; Zheng, Xiufen; Wang, Shanshan; Wang, Yifan; Yu, Yanrong; Zhang, Meng; Yuan, Keng; Min, Weiping

    2016-01-01

    Macrophage polarization is a highly plastic physiological process that responds to a variety of environmental factors by changing macrophage phenotype and function. Tumor-associated macrophages (TAMs) are generally recognized as promoting tumor progression. As universal regulators, microRNAs (miRNAs) are functionally involved in numerous critical cellular processes including macrophage polarization. Let-7b, a miRNA, has differential expression patterns in inflamed tissues compared with healthy controls. However, whether and how miRNA let-7b regulates macrophage phenotype and function is unclear. In this report, we find that up-regulation of let-7b is characteristic of prostatic TAMs, and down-regulation of let-7b in TAMs leads to changes in expression profiles of inflammatory cytokines, such as IL-12, IL-23, IL-10 and TNF-α. As a result, TAMs treated with let-7b inhibitors reduce angiogenesis and prostate carcinoma (PCa) cell mobility. Let-7b may play a vital role in regulating macrophage polarization, thus modulating the prognosis of prostate cancer. PMID:27157642

  1. miRNA let-7b modulates macrophage polarization and enhances tumor-associated macrophages to promote angiogenesis and mobility in prostate cancer.

    PubMed

    Wang, Zhigang; Xu, Lu; Hu, Yinying; Huang, Yanqin; Zhang, Yujuan; Zheng, Xiufen; Wang, Shanshan; Wang, Yifan; Yu, Yanrong; Zhang, Meng; Yuan, Keng; Min, Weiping

    2016-01-01

    Macrophage polarization is a highly plastic physiological process that responds to a variety of environmental factors by changing macrophage phenotype and function. Tumor-associated macrophages (TAMs) are generally recognized as promoting tumor progression. As universal regulators, microRNAs (miRNAs) are functionally involved in numerous critical cellular processes including macrophage polarization. Let-7b, a miRNA, has differential expression patterns in inflamed tissues compared with healthy controls. However, whether and how miRNA let-7b regulates macrophage phenotype and function is unclear. In this report, we find that up-regulation of let-7b is characteristic of prostatic TAMs, and down-regulation of let-7b in TAMs leads to changes in expression profiles of inflammatory cytokines, such as IL-12, IL-23, IL-10 and TNF-α. As a result, TAMs treated with let-7b inhibitors reduce angiogenesis and prostate carcinoma (PCa) cell mobility. Let-7b may play a vital role in regulating macrophage polarization, thus modulating the prognosis of prostate cancer. PMID:27157642

  2. Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury.

    PubMed

    Kemp, S W P; Szynkaruk, M; Stanoulis, K N; Wood, M D; Liu, E H; Willand, M P; Morlock, L; Naidoo, J; Williams, N S; Ready, J M; Mangano, T J; Beggs, S; Salter, M W; Gordon, T; Pieper, A A; Borschel, G H

    2015-01-22

    Nerve injuries cause pain, paralysis and numbness that can lead to major disability, and newborns often sustain nerve injuries during delivery that result in lifelong impairment. Without a pharmacologic agent to enhance functional recovery from these injuries, clinicians rely solely on surgery and rehabilitation to treat patients. Unfortunately, patient outcomes remain poor despite application of the most advanced microsurgical and rehabilitative techniques. We hypothesized that the detrimental effects of traumatic neonatal nerve injury could be mitigated with pharmacologic neuroprotection, and tested whether the novel neuroprotective agent P7C3 would block peripheral neuron cell death and enhance functional recovery in a rat neonatal nerve injury model. Administration of P7C3 after sciatic nerve crush injury doubled motor and sensory neuron survival, and also promoted axon regeneration in a dose-dependent manner. Treatment with P7C3 also enhanced behavioral and muscle functional recovery, and reversed pathological mobilization of spinal microglia after injury. Our findings suggest that the P7C3 family of neuroprotective compounds may provide a basis for the development of a new neuroprotective drug to enhance recovery following peripheral nerve injury. PMID:25313000

  3. SPITZER INFRARED OBSERVATIONS AND INDEPENDENT VALIDATION OF THE TRANSITING SUPER-EARTH CoRoT-7 b

    SciTech Connect

    Fressin, Francois; Torres, Guillermo; Charbonneau, David; Pont, Frederic; Knutson, Heather A.; Mazeh, Tsevi; Aigrain, Suzanne; Fridlund, Malcolm; Guillot, Tristan; Rauer, Heike

    2012-01-20

    The detection and characterization of the first transiting super-Earth, CoRoT-7 b, has required an unprecedented effort in terms of telescope time and analysis. Although the star does display a radial-velocity signal at the period of the planet, this has been difficult to disentangle from the intrinsic stellar variability and pinning down the velocity amplitude has been very challenging. As a result, the precise value of the mass of the planet-and even the extent to which it can be considered to be confirmed-has been debated in the recent literature, with six mass measurements published so far based on the same spectroscopic observations, ranging from about 2 to 8 Earth masses. Here we report on an independent validation of the planet discovery using one of the fundamental properties of a transit signal: its achromaticity. We observed four transits of CoRoT-7 b at 4.5 {mu}m and 8.0 {mu}m with the Infrared Array Camera (IRAC) on board the Spitzer Space Telescope in order to determine whether the depth of the transit signal in the near-infrared is consistent with that observed in the CoRoT bandpass, as expected for a planet. We detected the transit and found an average depth of 0.426 {+-} 0.115 mmag at 4.5 {mu}m, which is in good agreement with the depth of 0.350 {+-} 0.011 mmag (ignoring limb darkening) found by CoRoT. The observations at 8.0 {mu}m did not yield a significant detection. The 4.5 {mu}m observations place important constraints on the kinds of astrophysical false positives that could mimic the signal. Combining this with additional constraints reported earlier, we performed an exhaustive exploration of possible blend scenarios for CoRoT-7 b using the BLENDER technique. We are able to rule out the vast majority of false positives, and the remaining ones are found to be much less likely than a true transiting planet. We thus validate CoRoT-7 b as a bona fide planet with a very high degree of confidence, independently of any radial-velocity information

  4. KELT-7b: A Hot Jupiter Transiting a Bright V = 8.54 Rapidly Rotating F-star

    NASA Astrophysics Data System (ADS)

    Bieryla, Allyson; Collins, Karen; Beatty, Thomas G.; Eastman, Jason; Siverd, Robert J.; Pepper, Joshua; Gaudi, B. Scott; Stassun, Keivan G.; Cañas, Caleb; Latham, David W.; Buchhave, Lars A.; Sanchis-Ojeda, Roberto; Winn, Joshua N.; Jensen, Eric L. N.; Kielkopf, John F.; McLeod, Kim K.; Gregorio, Joao; Colón, Knicole D.; Street, Rachel; Ross, Rachel; Penny, Matthew; Mellon, Samuel N.; Oberst, Thomas E.; Fulton, Benjamin J.; Wang, Ji; Berlind, Perry; Calkins, Michael L.; Esquerdo, Gilbert A.; DePoy, Darren L.; Gould, Andrew; Marshall, Jennifer; Pogge, Richard; Trueblood, Mark; Trueblood, Patricia

    2015-07-01

    We report the discovery of KELT-7b, a transiting hot Jupiter with a mass of 1.28+/- 0.18 MJ, radius of {1.533}-0.047+0.046 RJ, and an orbital period of 2.7347749+/- 0.0000039 days. The bright host star (HD 33643; KELT-7) is an F-star with V = 8.54, Teff = 6789{}-49+50 K, [Fe/H] = {0.139}-0.081+0.075, and {log}\\{\\text{}}g\\=4.149+/- 0.019. It has a mass of {1.535}-0.054+0.066 M⊙, a radius of {1.732}-0.045+0.043 R⊙, and is the fifth most massive, fifth hottest, and the ninth brightest star known to host a transiting planet. It is also the brightest star around which Kilodegree Extremely Little Telescope (KELT) has discovered a transiting planet. Thus, KELT-7b is an ideal target for detailed characterization given its relatively low surface gravity, high equilibrium temperature, and bright host star. The rapid rotation of the star (73+/- 0.5 km s-1) results in a Rossiter-McLaughlin effect with an unusually large amplitude of several hundred m s-1. We find that the orbit normal of the planet is likely to be well-aligned with the stellar spin axis, with a projected spin-orbit alignment of λ = 9.°7 ± 5.°2. This is currently the second most rapidly rotating star to have a reflex signal (and thus mass determination) due to a planetary companion measured.

  5. Molecular characterization and bioinformatics analysis of Ncoa7B, a novel ovulation-associated and reproduction system-specific Ncoa7 isoform.

    PubMed

    Shkolnik, Ketty; Ben-Dor, Shifra; Galiani, Dalia; Hourvitz, Ariel; Dekel, Nava

    2008-03-01

    In the present work, we employed bioinformatics search tools to select ovulation-associated cDNA clones with a preference for those representing putative novel genes. Detailed characterization of one of these transcripts, 6C3, by real-time PCR and RACE analyses led to identification of a novel ovulation-associated gene, designated Ncoa7B. This gene was found to exhibit a significant homology to the Ncoa7 gene that encodes a conserved tissue-specific nuclear receptor coactivator. Unlike Ncoa7, Ncoa7B possesses a unique and highly conserved exon at the 5' end and encodes a protein with a unique N-terminal sequence. Extensive bioinformatics analysis has revealed that Ncoa7B has one identifiable domain, TLDc, which has recently been suggested to be involved in protection from oxidative DNA damage. An alignment of TLDc domain containing proteins was performed, and the closest relative identified was OXR1, which also has a corresponding, highly related short isoform, with just a TLDc domain. Moreover, Ncoa7B expression, as seen to date, seems to be restricted to mammals, while other TLDc family members have no such restriction. Multiple tissue analysis revealed that unlike Ncoa7, which was abundant in a variety of tissues with the highest expression in the brain, Ncoa7B mRNA expression is restricted to the reproductive system organs, particularly the uterus and the ovary. The ovarian expression of Ncoa7B was stimulated by human chorionic gonadotropin. Additionally, using real-time PCR, we demonstrated the involvement of multiple signaling pathways for Ncoa7B expression on preovulatory follicles. PMID:18299425

  6. Copper-Induced Translocation of the Wilson Disease Protein ATP7B Independent of Murr1/COMMD1 and Rab7

    PubMed Central

    Weiss, Karl Heinz; Lozoya, Javier Carbajo; Tuma, Sabine; Gotthardt, Daniel; Reichert, Jürgen; Ehehalt, Robert; Stremmel, Wolfgang; Füllekrug, Joachim

    2008-01-01

    Wilson disease is a genetic disorder of copper metabolism. Impaired biliary excretion results in a gradual accumulation of copper, which leads to severe disease. The specific gene defect lies in the Wilson disease protein, ATP7B, a copper-transporting ATPase that is highly active in hepatocytes. The two major functions of ATP7B in the liver are the copper loading of ceruloplasmin in the Golgi apparatus, and the excretion of excess copper into the bile. In response to elevated copper levels, ATP7B shows a unique intracellular trafficking pattern that is required for copper excretion from the Golgi apparatus into dispersed vesicles. We analyzed the translocation of ATP7B by both confocal microscopy and RNA interference, testing current models that suggest the involvement of Murr1/COMMD1 and Rab7 in this pathway. We found that although the ATP7B translocation is conserved among nonhepatic cell lines, there is no co-localization with Murr1/COMMD1 or the Rab marker proteins of the endolysosomal system. Consistent with this finding, the translocation of ATP7B was not impaired by the depletion of either Murr1/COMMD1 or Rab7, or by a dominant-negative Rab7 mutant. In conclusion, our data suggest that the translocation of ATP7B takes place independently of Rab7-regulated endosomal traffic events. Murr1/COMMD1 plays a role in a later step of the copper excretion pathway but is not involved in the translocation of the Wilson disease protein. PMID:18974300

  7. cAMP/PKA/CREB/GLT1 signaling involved in the antidepressant-like effects of phosphodiesterase 4D inhibitor (GEBR-7b) in rats

    PubMed Central

    Liu, Xu; Guo, Haibiao; Sayed, Mohammad Daud SOM; Lu, Yang; Yang, Ting; Zhou, Dongsheng; Chen, Zhongming; Wang, Haitao; Wang, Chuang; Xu, Jiangping

    2016-01-01

    Objectives GEBR-7b, a potential phosphodiesterase 4D inhibitor, has been shown to have memory-enhancing effects in rodents. However, it is still unknown whether GEBR-7b also has the antidepressant-like effects in rats. Herein, we examined the potential of GEBR-7b to attenuate depression-like behaviors in the rat model of depression induced by chronic unpredictable stress (CUS). Next, we also investigated the alterations of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) catalytic subunit (PKAca), cAMP response element-binding (CREB), and glutamate transporter 1 (GLT1) levels produced by GEBR-7b in the rats model of depression. Methods Effects of GEBR-7b on CUS (35 days)-induced depression-like behaviors were examined by measuring immobility time in the forced swimming test (FST). Hippocampal cAMP levels were examined by enzyme-linked immunosorbent assay, whereas PKAca, phosphorylation of CREB (pCREB), CREB, and GLT1 in the hippocampus of rats were subjected to Western blot analysis. Results CUS exposure caused a depression-like behavior evidenced by the increased immobility time in FST. Depression-like behavior induced by CUS was accompanied by a significant increased GLT, decreased cAMP, PKAca, pCREB activities in hippocampus. However, repeated GEBR-7b administration significantly reversed CUS-induced depression-like behavior and changes of cAMP/PKA/CREB/GLT1 signaling. No alteration was observed in locomotor activity in open field test. Conclusion These findings indicate that GEBR-7b reversed the depression-like behaviors induced by CUS in rats, which is at least in part mediated by modulating cAMP, PKAca, pCREB, and GLT1 levels in the hippocampus of rats, supporting its neuroprotective potential against behavioral and biochemical dysfunctions induced by CUS. PMID:26855578

  8. Downregulation of let‑7b promotes COL1A1 and COL1A2 expression in dermis and skin fibroblasts during heat wound repair.

    PubMed

    Liu, Jinyan; Luo, Chengqun; Yin, Zhaoqi; Li, Ping; Wang, Shaohua; Chen, Jia; He, Quanyong; Zhou, Jianda

    2016-03-01

    MicroRNAs (miRs), a class of non‑coding RNAs 18‑25 nucleotides in length, generally serve suppressive role in the regulation of gene expression via directly binding to the 3'‑untranslated region (UTR) of their target mRNA. Previous studies have identified several miRs to be involved in thermal injury repair. However, the role of miR let‑7b during the recovery of thermal injury, in addition to the underlying mechanisms, has not previously been studied. In the present study, the expression of let‑7b was observed to be significantly increased in skin tissue shortly following thermal injury, however, gradually reduced during the recovery of thermal injury. Notably, similar findings were observed in heat‑denatured skin fibroblasts. Furthermore, collagen, type I, alpha 1 (COL1A1) and collagen, type I, alpha 2 (COL1A2), which are associated with the synthesis of type I collagen, were identified as two targets of let‑7b in skin fibroblasts. The overexpression of let‑7b was observed to upregulate the protein expression levels of COL1A1 and COL1A2, while knockdown of let‑7b reduced the levels of COL1A1 and COL1A2 in skin fibroblasts. Furthermore, COL1A1 and COL1A2 were significantly downregulated shortly following thermal injury, while gradually upregulated during healing, in heat‑damaged skin tissue and skin fibroblasts, with the expression profiles opposite to that of let‑7b. Taken together, this suggests that the downregulation of let‑7b in heat‑damaged dermis promotes the synthesis of type I collagen and thus aids in burn wound repair. PMID:26861712

  9. Hexa-D-Arginine treatment increases 7B2•PC2 activity in hyp-mouse osteoblasts and rescues the HYP phenotype

    PubMed Central

    Yuan, Baozhi; Feng, Jian Q.; Bowman, Stephen; Liu, Ying; Blank, Robert D.; Lindberg, Iris; Drezner, Marc K.

    2012-01-01

    Inactivating mutations of PHEX/Phex underlie disease in patients with X-linked hypophosphatemia (XLH) and the hyp-mouse, a murine homologue of the human disorder. Although increased serum FGF-23 underlies the HYP phenotype, the mechanism(s) by which PHEX mutations inhibit FGF-23 degradation and/or enhance production remains unknown. Here we show that treatment of wild type mice with the proprotein convertase (PC) inhibitor, Decanoyl-Arg-Val-Lys-Arg-chloromethyl ketone, increases serum FGF-23 and produces the HYP phenotype. Since PC2 is uniquely co-localized with PHEX in osteoblasts/bone, we examined if PC2 regulates PHEX-dependent FGF-23 cleavage and production. Transfection of murine osteoblasts with PC2 and its chaperone protein 7B2 cleaved FGF-23, while Signe1 (7B2) RNAi transfection, which limited 7B2 protein production, decreased FGF-23 degradation and increased Fgf-23 mRNA and protein. The mechanism by which decreased 7B2•PC2 activity influences Fgf-23 mRNA was linked to reduced conversion of proBMP1 to active BMP1, which resulted in limited cleavage of DMP1, and consequent increased Fgf-23 mRNA. The significance of decreased 7B2•PC2 activity in XLH was confirmed by studies of hyp-mouse bone, which revealed significantly decreased Sgne1 (7B2) mRNA and 7B2 protein, and limited cleavage of proPC2 to active PC2. The expected downstream effects of these changes included decreased FGF-23 cleavage and increased FGF-23 synthesis, secondary to decreased BMP1-mediated degradation of DMP1. Subsequent Hexa-D-Arginine treatment of hyp-mice enhanced bone 7B2•PC2 activity, normalized FGF-23 degradation and production, and rescued the HYP phenotype. These data suggest decreased PHEX-dependent 7B2•PC2 activity is central to the pathogenesis of XLH. PMID:22886699

  10. Alpaca fiber growth is mediated by microRNA let-7b via down-regulation of target gene FGF5.

    PubMed

    Wang, T; Zhang, Y; Wang, H D; Shen, Y; Liu, N; Cao, J; Yu, X J; Dong, C S; He, X Y

    2015-01-01

    MicroRNAs are very small endogenous RNA molecules that play a crucial role in an array of biological processes, including regulation of skin morphogenesis. The microRNA let-7b is thought to modulate animal hair growth, by binding target genes that encode growth factors. Fibroblast growth factor 5 (FGF5) has been previously reported to be involved in the initiation of the catagen phase of hair growth. In this study, we combined previous reports with bioinformatic analysis techniques to identify and validate FGF5 and, using lucerifase assay, confirmed targeted binding of let-7b to FGF5. To investigate the interaction between let-7b and FGF5, alpaca skin fibroblasts were transfected with let-7b over-expression vectors, and then mRNA and protein expression levels of FGF5 and the gene encoding its receptor, FGFR1, were evaluated. Levels of FGF5 mRNA and protein were remarkably lower in transfected groups, as compared to controls. In summary, this study confirmed that let-7b acts as a regulator of skin morphogenesis, by directly targeting FGF5 and down-regulating its expression. It provides the evidence of hair growth regulated by miRNAs in animals and may have important applications in wool production. PMID:26535691

  11. Zbtb7b (Th-POK) regulates the development of IL-17 producing CD1d-restricted mouse NKT-cells

    PubMed Central

    Enders, Anselm; Stankovic, Sanda; Teh, Charis; Uldrich, Adam P.; Yabas, Mehmet; Juelich, Torsten; Altin, John A.; Frankenreiter, Sandra; Bergmann, Hannes; Roots, Carla M.; Kyparissoudis, Konstantinos; Goodnow, Chris C.; Godfrey, Dale I.

    2012-01-01

    CD1d-dependent NKT-cells represent a heterogeneous family of effector T-cells including CD4+CD8− and CD4−CD8− subsets, that respond to glycolipid antigens with rapid and potent cytokine production. NKT-cell development is regulated by a unique combination of factors, however very little is known about factors that control the development of NKT subsets. Here, we analyze a novel mouse strain (helpless) with a mis-sense mutation in the BTB-POZ domain of Zbtb7b and demonstrate that this mutation has dramatic, intrinsic effects on development of NKT-cell subsets. Although NKT-cell numbers are similar in Zbtb7b mutant mice, these cells are hyperproliferative and most lack CD4 and instead express CD8. Moreover, the majority of Zbtb7b mutant NKT-cells in the thymus are RORγt+ and a high frequency produce IL-17 while very few produce IFN-γ or other cytokines, sharply contrasting the profile of normal NKT-cells. Mice heterozygous for the helpless mutation also have reduced numbers of CD4+ NKT-cells and increased production of IL-17 without an increase in CD8+ cells, suggesting that Zbtb7b acts at multiple stages of NKT-cell development. These results reveal Zbtb7b as a critical factor genetically pre-determining the balance of effector subsets within the NKT-cell population. PMID:23105140

  12. First principles study on the electronic structures and stability of Cr 7C 3 type multi-component carbides

    NASA Astrophysics Data System (ADS)

    Xiao, B.; Feng, J.; Zhou, C. T.; Xing, J. D.; Xie, X. J.; Chen, Y. H.

    2008-06-01

    First principles calculations were conducted to investigate the stabilities of six multi-component carbides of Cr 7C 3 by calculating the cohesive energy and formation enthalpy of them. The theoretical predictions were compared with the experimental results and they were in agreement with each other. The electronic structures of the six carbides were also calculated in order to provide more information about the relationship between the stability and crystal compositions at atomic scale.

  13. IUPAC-NIST Solubility Data Series. 96. Amines with Water Part 2. C7-C24 Aliphatic Amines

    NASA Astrophysics Data System (ADS)

    Góral, Marian; Shaw, David G.; Måczyński, Andrzej; Wiśniewska-Gocłowska, Barbara; Oracz, Paweł

    2012-12-01

    The mutual solubilities and related liquid-liquid equilibria of 41 binary systems of C7-C24 aliphatic amines with water are exhaustively and critically reviewed. Reports of experimental determination of solubility that appeared in the primary literature prior to the end of 2010 are compiled. For seven systems, sufficient data are available to allow critical evaluation. All data are expressed as mass percent and mole fraction as well as the originally reported units.

  14. KEPLER'S OPTICAL SECONDARY ECLIPSE OF HAT-P-7b AND PROBABLE DETECTION OF PLANET-INDUCED STELLAR GRAVITY DARKENING

    SciTech Connect

    Morris, Brett M.; Deming, Drake; Mandell, Avi M.

    2013-02-20

    We present observations spanning 355 orbital phases of HAT-P-7 observed by Kepler from 2009 May to 2011 March (Q1-9). We find a shallower secondary eclipse depth than initially announced, consistent with a low optical albedo and detection of nearly exclusively thermal emission, without a reflected light component. We find an approximately 10 ppm perturbation to the average transit light curve near phase -0.02 that we attribute to a temperature decrease on the surface of the star, phased to the orbit of the planet. This cooler spot is consistent with planet-induced gravity darkening, slightly lagging the sub-planet position due to the finite response time of the stellar atmosphere. The brightness temperature of HAT-P-7b in the Kepler bandpass is T{sub B} = 2733 {+-} 21 K and the amplitude of the deviation in stellar surface temperature due to gravity darkening is approximately -0.18 K. The detection of the spot is not statistically unequivocal due its small amplitude, though additional Kepler observations should be able to verify the astrophysical nature of the anomaly.

  15. Optimization of Giant Magnetoimpedance in amorphous (Co1-xFex)89Zr7B4 ribbons

    NASA Astrophysics Data System (ADS)

    Chaturvedi, A.; Phan, M. H.; Srikanth, H.; Leary, A.; McHenry, M. E.

    2010-03-01

    The giant magnetoimpedance (GMI) effect is observed upon the application of a static magnetic field on a soft ferromagnetic material carrying an ac current. GMI is a tool that can be used in a number of applications and especially important for magnetic sensors. There is currently a need for optimizing the effect in new materials and fine tune the material parameters for enhanced GMI and sensitivity. We report systematic studies of the GMI effect and its field sensitivity in (Co1-xFex)89Zr7B4 amorphous ribbons with x=0.00, 0.025, 0.05, 0.075 and 0.10. Magnetoimpedance measurements were carried out along the ribbon axis in applied dc magnetic fields up to 120 Oe over a frequency range of 0.1 ˜ 13 MHz. We find that while the highest value of GMI is achieved for the x = 0 sample, the highest field sensitivity of GMI is achieved for the x=0.025 sample. The Fe doping causes a significant modification of a transverse domain structure thus reducing the GMI effect. We have also studied systematically the influence of Fe doping on field hysteresis and symmetry in GMI profiles, as well as relative contributions of resistance and reactance to magnetoimpedance for all the samples.

  16. Platination of the copper transporter ATP7A involved in anticancer drug resistance.

    PubMed

    Calandrini, Vania; Arnesano, Fabio; Galliani, Angela; Nguyen, Trung Hai; Ippoliti, Emiliano; Carloni, Paolo; Natile, Giovanni

    2014-08-21

    The clinical efficacy of the widely used anticancer drug cisplatin is severely limited by the emergence of resistance. This is related to the drug binding to proteins such as the copper influx transporter Ctr1, the copper chaperone Atox1, and the copper pumps ATP7A and ATP7B. While the binding modes of cisplatin to the first two proteins are known, the structural determinants of platinated ATP7A/ATP7B are lacking. Here we investigate the interaction of cisplatin with the first soluble domain of ATP7A. First, we establish by ESI-MS and (1)H, (13)C, and (15)N NMR that, in solution, the adduct is a monomer in which the sulfur atoms of residues Cys19 and Cys22 are cis-coordinated to the [Pt(NH3)2](2+) moiety. Then, we carry out hybrid Car-Parrinello QM/MM simulations and computational spectroscopy calculations on a model adduct based on the NMR structure of the apo protein and featuring the experimentally determined binding mode of the metal ion. These calculations show quantitative agreement with CD spectra and (1)H, (13)C, and (15)N NMR chemical shifts, thus providing a quantitative molecular view of the 3D binding mode of cisplatin to ATP7A. Importantly, the same comparison rules out a variety of alternative models with different coordination modes, that we explored to test the robustness of the computational approach. Using this combined in silico-in vitro approach we provide here for the first time a quantitative 3D atomic view of the platinum binding to the first soluble domain of ATP7A. PMID:24983998

  17. Cell attachment on poly(3-hydroxybutyrate)-poly(ethylene glycol) copolymer produced by Azotobacter chroococcum 7B

    PubMed Central

    2013-01-01

    Background The improvement of biomedical properties, e.g. biocompatibility, of poly(3-hydroxyalkanoates) (PHAs) by copolymerization is a promising trend in bioengineering. We used strain Azotobacter chroococcum 7B, an effective producer of PHAs, for biosynthesis of not only poly(3-hydroxybutyrate) (PHB) and its main copolymer, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV), but also alternative copolymer, poly(3-hydroxybutyrate)-poly(ethylene glycol) (PHB-PEG). Results In biosynthesis we used sucrose as the primary carbon source and valeric acid or poly(ethylene glycol) 300 (PEG 300) as additional carbon sources. The chemical structure of PHB-PEG and PHB-HV was confirmed by 1H nuclear-magnetic resonance (1H NMR) analysis. The physico-chemical properties (molecular weight, crystallinity, hydrophilicity, surface energy) and surface morphology of films from PHB copolymers were studied. To study copolymers biocompatibility in vitro the protein adsorption and COS-1 fibroblasts growth on biopolymer films by XTT assay were analyzed. Both copolymers had changed physico-chemical properties compared to PHB homopolymer: PHB-HV and PHB-PEG had less crystallinity than PHB; PHB-HV was more hydrophobic than PHB in contrast to PHB-PEG appeared to have greater hydrophilicity than PHB; whereas the morphology of polymer films did not differ significantly. The protein adsorption to PHB-PEG was greater and more uniform than to PHB and PHB-PEG copolymer promoted better growth of COS-1 fibroblasts compared with PHB homopolymer. Conclusions Thus, despite low EG-monomers content in bacterial origin PHB-PEG copolymer, this polymer demonstrated significant improvement in biocompatibility in contrast to PHB and PHB-HV copolymers, which may be coupled with increased protein adsorption and hydrophilicity of PEG-containing copolymer. PMID:23692611

  18. 75 FR 13045 - Airworthiness Directives; CFM International, S.A. CFM56-5, -5B, and -7B Series Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-18

    ... Statement in the Federal Register published on April 11, 2000 (65 FR 19477-78). Examining the AD Docket You... Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Would not have a significant... Directives; CFM International, S.A. CFM56-5, -5B, and -7B Series Turbofan Engines AGENCY: Federal...

  19. 75 FR 34924 - Airworthiness Directives; CFM International, S.A. CFM56-5, -5B, and -7B Series Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-21

    ..., 2010 (75 FR 13045). That action proposed to require removing from service, nine stage 3 LPT disks... 12866; (2) Is not a ``significant rule'' under DOT Regulatory Policies and Procedures (44 FR 11034... International, S.A. CFM56-5, -5B, and -7B series turbofan engines. This AD requires removing from service,...

  20. Structural and dynamic basis of human cytochrome P450 7B1: a survey of substrate selectivity and major active site access channels.

    PubMed

    Cui, Ying-Lu; Zhang, Ji-Long; Zheng, Qing-Chuan; Niu, Rui-Juan; Xu, Yu; Zhang, Hong-Xing; Sun, Chia-Chung

    2013-01-01

    Cytochrome P450 (CYP) 7B1 is a steroid cytochrome P450 7α-hydroxylase that has been linked directly with bile salt synthesis and hereditary spastic paraplegia type 5 (SPG5). The enzyme provides the primary metabolic route for neurosteroids dehydroepiandrosterone (DHEA), cholesterol derivatives 25-hydroxycholesterol (25-HOChol), and other steroids such as 5α-androstane-3β,17β-diol (anediol), and 5α-androstene-3β,17β-diol (enediol). A series of investigations including homology modeling, molecular dynamics (MD), and automatic docking, combined with the results of previous experimental site-directed mutagenesis studies and access channels analysis, have identified the structural features relevant to the substrate selectivity of CYP7B1. The results clearly identify the dominant access channels and critical residues responsible for ligand binding. Both binding free energy analysis and total interaction energy analysis are consistent with the experimental conclusion that 25-HOChol is the best substrate. According to 20 ns MD simulations, the Phe cluster residues that lie above the active site, particularly Phe489, are proposed to merge the active site with the adjacent channel to the surface and accommodate substrate binding in a reasonable orientation. The investigation of CYP7B1-substrate binding modes provides detailed insights into the poorly understood structural features of human CYP7B1 at the atomic level, and will be valuable information for drug development and protein engineering. PMID:23180418

  1. Theoretical vibrations of carbon chains C3, C4, C5, C6, C7, C8, and C9

    NASA Technical Reports Server (NTRS)

    Kurtz, Joe; Adamowicz, Ludwik

    1991-01-01

    The MBPT (2) procedure with the 6-31g (asterisk) basis set was used to study nearly linear carbon chains. The theoretical vibrational frequencies of the molecules C3 through C9 are presented and, for C3 through C6, compared to experimental stretching frequencies and their (C-13)/(C-12) isotopomers. Predictions for C7, C8, and C9 stretching frequencies are calculated by directly scaling the theoretical frequencies with factors derived from experimental-to-theoretical ratios known for the smaller molecules.

  2. PROCEEDINGS: 1991 INTERNATIONAL CONFERENCE ON MUNICIPAL WASTE COMBUSTION - VOLUME 2. SESSIONS 1B, 2B, 3B, 4B, 7A, 7B, 8A, 8B, AND 9B

    EPA Science Inventory

    The three-volumes document 82 presentations by authors from 15 countries at the Second International Conference on Municipal Waste Combustion (MWC) in Tampa, Florida, April 16-19, 1991. The Conference fostered the exchange of current information on research concerning MWC, ash di...

  3. Spectrum and Classification of ATP7B Variants in a Large Cohort of Chinese Patients with Wilson's Disease Guides Genetic Diagnosis

    PubMed Central

    Dong, Yi; Ni, Wang; Chen, Wan-Jin; Wan, Bo; Zhao, Gui-Xian; Shi, Zhu-Qing; Zhang, Yue; Wang, Ning; Yu, Long; Xu, Jian-Feng; Wu, Zhi-Ying

    2016-01-01

    Background: Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by ATP7B pathogenic mutations. The symptoms of WD can be effectively prevented if the affected individuals are identified and intervened early. However, clinical utility of this molecular analysis is challenging due to hundreds of variants with various clinical effects in the gene. Here, we aim to describe the spectrum of ATP7B variants and assess their clinical effects in the Han Chinese population. Methods: The ATP7B gene was directly sequenced in 632 unrelated WD patients and 503 unrelated healthy individuals. The effects of identified variants were classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Different frequency of variants observed in both cases and controls were tested using Chi-square or Fisher's exact tests. Results: We detected 161 non-synonymous variants in these 632 WD patients, 58 of which were novel. Among these variants, 78, 64, 8, 4, and 7 were classified as 'pathogenic variants', 'likely pathogenic variants', 'variants with uncertain significance', 'likely benign variants', and 'benign variants', respectively. Ninety percent (569/632) of these WD patients can be genetically diagnosed with two or more 'pathogenic' or 'likely pathogenic' variants. The 14 most common disease-causing variants were found at least once in 94% (537/569) of genetically diagnosed patients. Conclusions: These data expand the spectrum of ATP7B variants and facilitate effective screening for ATP7B variants for early diagnosis of WD and development of individualized treatment regimens. PMID:27022412

  4. Spectrum of mutations in the ATP binding domain of ATP7B gene of Wilson Disease in a regional Indian cohort.

    PubMed

    Guggilla, Sreenivasa Rao; Senagari, Jalandhar Reddy; Rao, P N; Madireddi, Sujatha

    2015-09-10

    Wilson disease is an autosomal recessive disorder of abnormal copper accumulation in the liver, brain, kidney and cornea, resulting in hepatic and neurological abnormalities, which results from impaired ATP7B protein function due to mutations in candidate ATP7B gene, till date more than 500 disease causing mutations were found. In India most disease causing mutations were identified in ATP-BD. DNA samples of the 101 WD cases and 100 control population were analyzed for mutations. 11 mutations were identified in 57 chromosomes. Three novel mutations, c.3310T>A (p.Cys1104Ser), c.3337C>A (p.Leu1113Met) on exon 15 and c.3877G>A (p.Glu1293Lys) on exon 18 were identified for the first time in the ATP7B gene. Two mutations, c.3121C>T (p.Arg1041Trp) and c.3128T>C (p.Leu1043Pro) on exon 14 were discovered for the first time in Indian Wilson disease patients. Four previously reported mutations c.3008C>T, c.3029A>G on exon 13, c.3182G>A on exon 14 and c.3809A>G on exon 18 from South India were also found in this study. Our research has enriched the spectrum of mutations of the ATP7B gene in the south Indian population. The detection of new mutations in the ATP7B gene can aid in genetic counseling and clinical or/prenatal diagnosis. PMID:25982861

  5. Downregulation of HMGA2 by the pan-deacetylase inhibitor panobinostat is dependent on hsa-let-7b expression in liver cancer cell lines

    SciTech Connect

    Di Fazio, Pietro; Montalbano, Roberta; Neureiter, Daniel; Alinger, Beate; Schmidt, Ansgar; Merkel, Anna Lena; Quint, Karl; Ocker, Matthias

    2012-09-10

    Inhibitors of protein deacetylases represent a novel therapeutic option for cancer diseases due to their effects on transcriptional regulation by interfering with histones acetylation and on several other cellular pathways. Recently, their ability to modulate several transcription factors and, interestingly, also co-factors, which actively participate in formation and modulation of transcription complexes was shown. We here investigate whether HMGA2 (High Mobility Group AT-2 hook), a nuclear non-histone transcriptional co-factor with known oncogenic properties, can be influenced by the novel pan-deacetylase inhibitor panobinostat (LBH589) in human hepatocellular carcinoma models. Panobinostat strongly downregulated HMGA2 in HepG2 and Hep3B cells; this effect was mediated by transcriptional upregulation and promotion of the maturation of the tumorsuppressor miRNA hsa-let-7b, which could inhibit HMGA2 expression via RNA interference pathways. siRNA knockdown of HMGA2 or transfection of hsa-let-7b mimicking oligonucleotides confirmed the role of HMGA2 in regulating cell proliferation and apoptosis in liver cancer cell lines. Co-incubation with panobinostat showed an additive effect on inhibition of cell proliferation using an impedance-based real-time cell analyzer. Treatment of HepG2 xenografts with panobinostat also led to a downregulation of HMGA2 in vivo. These findings show that pan-deacetylase inhibitors also modulate other signaling pathways and networks than histone modifications to influence cell fate. -- Highlights: Black-Right-Pointing-Pointer Panobinostat for the treatment of liver cancer. Black-Right-Pointing-Pointer Panobinostat meddles with miRNAs-dependent transcriptional and translational control. Black-Right-Pointing-Pointer Tumorsuppressor miRNA hsa-let-7b upregulation. Black-Right-Pointing-Pointer HMGA2 is downregulated via RNA interference pathways mediated by hsa-let-7b. Black-Right-Pointing-Pointer Panobinostat determines inhibition of

  6. Hidden carbon in Earth’s inner core revealed by shear softening in dense Fe7C3

    PubMed Central

    Li, Zeyu; Zhang, Dongzhou; Liu, Jiachao; Hu, Michael Y.; Zhao, Jiyong; Bi, Wenli; Alp, E. Ercan; Xiao, Yuming; Chow, Paul; Li, Jie

    2014-01-01

    Earth’s inner core is known to consist of crystalline iron alloyed with a small amount of nickel and lighter elements, but the shear wave (S wave) travels through the inner core at about half the speed expected for most iron-rich alloys under relevant pressures. The anomalously low S-wave velocity (vS) has been attributed to the presence of liquid, hence questioning the solidity of the inner core. Here we report new experimental data up to core pressures on iron carbide Fe7C3, a candidate component of the inner core, showing that its sound velocities dropped significantly near the end of a pressure-induced spin-pairing transition, which took place gradually between 10 GPa and 53 GPa. Following the transition, the sound velocities increased with density at an exceptionally low rate. Extrapolating the data to the inner core pressure and accounting for the temperature effect, we found that low-spin Fe7C3 can reproduce the observed vS of the inner core, thus eliminating the need to invoke partial melting or a postulated large temperature effect. The model of a carbon-rich inner core may be consistent with existing constraints on the Earth's carbon budget and would imply that as much as two thirds of the planet's carbon is hidden in its center sphere. PMID:25453077

  7. Is there any relationship between Toll-like receptor 3 c.1377C/T and -7C/A polymorphisms and susceptibility to Crimean Congo hemorrhagic fever?

    PubMed

    Engin, Aynur; Arslan, Serdal; Özbilüm, Nil; Bakir, Mehmet

    2016-10-01

    Crimean-Congo hemorrhagic fever (CCHF) is an infectious disease that is caused by CCHF virus. A family of transmembrane receptors called as Toll-like receptors (TLRs) selectively acts in recognizing a wide range of microbial components and endogenous molecules released by damaged tissue and have been preserved throughout evolution. TLRs initiate some signaling cascades which activate the innate immune system. Mainly four TLRs act in protection against viral infections; TLR3 is one of them. TLR3 identifies dsRNA. By producing inflammatory cytokines and type I interferons, it generates an antiviral immune response. Proper response to TLR ligands may be impaired by single nucleotide polymorphisms (SNPs) within TLR genes in some indviduals, and this can cause varied susceptibility to infections. In the present work, polymerase chain reaction-based restriction fragment length polymorphism is used to analyze the frequencies of TLR3 (c.1377C/T and -7C/A) polymorphisms in 149 CCHF patients and 171 healthy adults as controls, in Cumhuriyet University, Sivas/Turkey. We also investigated the relation between these polymorphisms and severity or mortality of CCHF disease. This is the first study investigating the TLR3 SNPs in patients with CCHF. In the present study, the frequency of the TLR3 (c.1377C/T and -7A/C) genotypes in fatal and non-fatal cases were comparable, however, the homozygous mutant (TT) genotype frequency of TLR3 c.1377C/T in CCHF patients was significantly higher than that of the healthy controls. In conclusion, presence of TLR3 c.1377 TT genotype may have a role in the susceptibility to CCHF. J. Med. Virol. 88:1690-1696, 2016. © 2016 Wiley Periodicals, Inc. PMID:26959380

  8. MicroRNA let-7b induces lens epithelial cell apoptosis by targeting leucine-rich repeat containing G protein-coupled receptor 4 (Lgr4) in age-related cataract.

    PubMed

    Dong, Yuchen; Zheng, Yajuan; Xiao, Jun; Zhu, Chao; Zhao, Meisheng

    2016-06-01

    Owing to a rapidly aging population, vision impairment caused by age-related cataract has become very common. Age-related cataract has also become one of the principal causes of blindness, and apoptosis of lens epithelial cells contributes to non-congenital cataract development. Previous studies have reported that microRNA let-7b (let-7b) is upregulated in cataractous lens epithelial cells, and the expression level of let-7b is positively associated with N, C and P cataract scores. However, the role of let-7b in the development of age-related cataract remains unclear. Here, we observed that the expression level of let-7b in the anterior lens capsules of age-related cataract was significantly higher than that in the normal anterior lens capsules. We performed ultraviolet (UV) irradiation to induce lens epithelial cell apoptosis. The results showed that the expression level of let-7b in lens epithelial cells which were treated by UV irradiation was significantly higher than that in the control, and let-7b promoted UV irradiation-induced apoptosis. Furthermore, we showed that leucine-rich repeat containing G protein-coupled receptor 4 (Lgr4) was a direct target of let-7b, and let-7b modulated lens epithelial cell apoptosis by directly targeting Lgr4. These findings will offer new insights into our understanding of the molecular mechanisms underlying the pathogenesis of cataract. PMID:27179410

  9. The high stability of boron-doped lithium clusters Li 5B, Li 6B +/- and Li 7B: A case of the phenomenological shell model

    NASA Astrophysics Data System (ADS)

    Tai, Truong Ba; Nguyen, Minh Tho

    2010-04-01

    A quantum chemical investigation of the clusters Li 5B, Li 6B +, Li 6B - and Li 7B was performed using the DFT, MP2 and CCSD(T) methods. The high symmetry structures ( C4v, 1A 1), ( Oh, 1A 1g) and ( D5h, 1A1') turnout to be the global minima for Li 5B, Li 6B + and Li 7B, respectively. These clusters are predicted to be highly stable species with large vertical ionization energies, and large HOMO-LUMO gaps. Chemical bonding of clusters was probed using an electron localizability indicator (ELI) which indicates a large aromatic character. The high stability of these clusters can be accounted for by the phenomenological shell model.

  10. Quantitative Measurement of the Proportions of High-Order Harmonics for the 4B7B Soft-X-Ray Source at Beijing Synchrotron Radiation Facility

    NASA Astrophysics Data System (ADS)

    Zhu, Tuo; Shang, Wanli; Zhang, Wenhai; Yang, Jiamin; Xiong, Gang; Zhao, Yang; Kuang, Longyu; Zhao, Yidong; Zheng, Lei; Cui, Mingqi; Tang, Kun; Ma, Chenyan

    2013-12-01

    A transmission grating coupled with an X-ray charge coupled device (CCD) is used to quantitatively measure the proportion of high-order harmonics of the soft-X-ray source of beam line 4B7B. The results show that the monochromatic X-ray has third-order and second-order harmonics. The proportion of second-order harmonic of 4B7B is less than 9.0% and the third-order harmonic is below 0.7% when no suppressing method is applied. When suppression methods are used, the proportion of second-order harmonic is less than 1.7% and the third-order harmonic is ignorable.

  11. MicroRNA 138, let-7b, and 125a inhibitors differentially alter sleep and EEG delta-wave activity in rats

    PubMed Central

    Clinton, James M.; Krueger, James M.

    2012-01-01

    Sleep deprivation was previously reported to alter microRNA (miRNA) levels in the brain; however, the direct effects of any miRNA on sleep have only been described recently. We determined miRNA 138 (miR-138), miRNA let-7b (let-7b), and miRNA 125a-5p (miR-125a) levels in different brain areas at the transitions between light and dark. In addition, we examined the extent to which inhibiting these miRNAs affects sleep and EEG measures. We report that the levels of multiple miRNAs differ at the end of the sleep-dominant light period vs. the end of the wake-dominant dark period in cortical areas, hippocampus, and hypothalamus. For instance, in multiple regions of the cortex, miR-138, let-7b, and miR-125a expression was higher at the end of the dark period compared with the end of the light period. Intracerebroventricular injection of a specific inhibitor (antiMIR) to miR-138 suppressed sleep and nonrapid eye movement sleep (NREMS) EEG delta power. The antiMIR to let-7b did not affect time in state but decreased NREMS EEG delta power, whereas the antiMIR to miR-125a failed to affect sleep until after 3 days and did not affect EEG delta power on any day. We conclude that miRNAs are uniquely expressed at different times and in different structures in the brain and have discrete effects and varied timings on several sleep phenotypes and therefore, likely play a role in the regulation of sleep. PMID:23104698

  12. Regulation of 11β-hydroxysteroid dehydrogenase type 1 and 7α-hydroxylase CYP7B1 during social stress.

    PubMed

    Vodička, Martin; Ergang, Peter; Mikulecká, Anna; Řeháková, Lenka; Klusoňová, Petra; Makal, Jakub; Soták, Matúš; Musílková, Jana; Zach, Petr; Pácha, Jiří

    2014-01-01

    11β-hydroxysteroid dehydrogenase type 1 (11HSD1) is an enzyme that amplifies intracellular glucocorticoid concentration by the conversion of inert glucocorticoids to active forms and is involved in the interconversion of 7-oxo- and 7-hydroxy-steroids, which can interfere with the activation of glucocorticoids. The presence of 11HSD1 in the structures of the hypothalamic-pituitary-adrenal (HPA) axis suggests that this enzyme might play a role in the regulation of HPA output. Here we show that the exposure of Fisher 344 rats to mild social stress based on the resident-intruder paradigm increased the expression of 11HSD1 and CYP7B1, an enzyme that catalyzes 7-hydroxylation of steroids. We found that social behavioral profile of intruders was significantly decreased whereas their plasma levels of corticosterone were increased more than in residents. The stress did not modulate 11HSD1 in the HPA axis (paraventricular nucleus, pituitary, adrenal cortex) but selectively upregulated 11HSD1 in some regions of the hippocampus, amygdala and prelimbic cortex. In contrast, CYP7B1 was upregulated not only in the hippocampus and amygdala but also in paraventricular nucleus and pituitary. Furthermore, the stress downregulated 11HSD1 in the thymus and upregulated it in the spleen and mesenteric lymphatic nodes whereas CYP7B1 was upregulated in all of these lymphoid organs. The response of 11HSD1 to stress was more obvious in intruders than in residents and the response of CYP7B1 to stress predominated in residents. We conclude that social stress induces changes in enzymes of local metabolism of glucocorticoids in lymphoid organs and in brain structures associated with the regulation of the HPA axis. In addition, the presented data clearly suggest a role of 11HSD1 in modulation of glucocorticoid feedback of the HPA axis during stress. PMID:24586766

  13. Expression of WNT5A in Idiopathic Pulmonary Fibrosis and Its Control by TGF-β and WNT7B in Human Lung Fibroblasts.

    PubMed

    Newman, Donna R; Sills, W Shane; Hanrahan, Katherine; Ziegler, Amanda; Tidd, Kathleen McGinnis; Cook, Elizabeth; Sannes, Philip L

    2016-02-01

    The wingless (Wnt) family of signaling ligands contributes significantly to lung development and is highly expressed in patients with usual interstitial pneumonia (UIP). We sought to define the cellular distribution of Wnt5A in the lung tissue of patients with idiopathic pulmonary fibrosis (IPF) and the signaling ligands that control its expression in human lung fibroblasts and IPF myofibroblasts. Tissue sections from 40 patients diagnosed with IPF or UIP were probed for the immunolocalization of Wnt5A. Further, isolated lung fibroblasts from normal or IPF human lungs, adenovirally transduced for the overexpression or silencing of Wnt7B or treated with TGF-β1 or its inhibitor, were analyzed for Wnt5A protein expression. Wnt5A was expressed in IPF lungs by airway and alveolar epithelium, smooth muscle cells, endothelium, and myofibroblasts of fibroblastic foci and throughout the interstitium. Forced overexpression of Wnt7B with or without TGF-β1 treatment significantly increased Wnt5A protein expression in normal human smooth muscle cells and fibroblasts but not in IPF myofibroblasts where Wnt5A was already highly expressed. The results demonstrate a wide distribution of Wnt5A expression in cells of the IPF lung and reveal that it is significantly increased by Wnt7B and TGF-β1, which, in combination, could represent key signaling pathways that modulate the pathogenesis of IPF. PMID:26538547

  14. Combustion synthesis and luminescent properties of a blue-green emitting phosphor: (Ba1.95, Eu0.05)ZnSi2O7:B3+

    NASA Astrophysics Data System (ADS)

    Yao, Shan-Shan; Li, Yuan-Yuan; Xue, Li-Hong; You, Yan; Yan, You-Wei

    2009-12-01

    A blue-green emitting phosphor (Ba1.95, Eu0.05)ZnSi2O7: B{/x 3+} was prepared by combustion synthesis and an efficient blue-green emission under near-ultraviolet was observed. The luminescence, crystallinity and particle sizes were investigated by using luminescence spectrometry, X-ray diffractometry (XRD) and scanning electron microscopy (SEM). The emission spectrum shows a single band centered at 503 nm, which corresponds to the 4 f 65 d 1 →4 f 7 transition of Eu2+. The excitation spectrum is a broad band extending from 260 to 465 nm, which matches the emission of ultraviolet light-emitting diodes. The optical absorption spectra of the (Ba1.95, Eu0.05)ZnSi2O7: B{/0.06 3+} exhibited band-gap energies of 3.9 eV. The results showed that boric acid was effective in improving the luminescence intensity of (Ba1.95, Eu0.05)ZnSi2O7, and the optimum molar ratio of boric acid to zinc nitrate was about 0.06. The phosphor (Ba1.95, Eu0.05)ZnSi2O7: B{0.06/3+} synthesized by combustion method showed 1.5 times improved emission intensity compared with that of the Ba1.95ZnSi2O7: Eu{0.05/2+} phosphor under λ ex = 353 nm.

  15. Abnormal epigenetic regulation of the gene expression levels of Wnt2b and Wnt7b: Implications for neural tube defects

    PubMed Central

    BAI, BAOLING; CHEN, SHUYUAN; ZHANG, QIN; JIANG, QIAN; LI, HUILI

    2016-01-01

    The association between Wnt genes and neural tube defects (NTDs) is recognized, however, it remains to be fully elucidated. Our previous study demonstrated that epigenetic mechanisms are affected in human NTDs. Therefore, the present study aimed to evaluate whether Wnt2b and Wnt7b are susceptible to abnormal epigenetic modification in NTDs, using chromatin immunoprecipitation assays to evaluate histone enrichments and the MassARRAY platform to detect the methylation levels of target regions within Wnt genes. The results demonstrated that the transcriptional activities of Wnt2b and Wnt7b were abnormally upregulated in mouse fetuses with NTDs and, in the GC-rich promoters of these genes, histone 3 lysine 4 (H3K4) acetylation was enriched, whereas H3K27 trimethylation was reduced. Furthermore, several CpG sites in the altered histone modification of target regions were significantly hypomethylated. The present study also detected abnormal epigenetic modifications of these Wnt genes in human NTDs. In conclusion, the present study detected abnormal upregulation in the levels of Wnt2b and Wnt7b, and hypothesized that the alterations may be due to the ectopic opening of chromatin structure. These results improve understanding of the dysregulation of epigenetic modification of Wnt genes in NTDs. PMID:26548512

  16. A comparative study of Cr7C3, Fe3C and Fe2B in cast iron both from ab initio calculations and experiments

    NASA Astrophysics Data System (ADS)

    Xiao, B.; Xing, J. D.; Feng, J.; Zhou, C. T.; Li, Y. F.; Su, W.; Xie, X. J.; Cheng, Y. H.

    2009-06-01

    The ground state properties of three compounds, Cr7C3, Fe3C and Fe2B, are investigated using ab initio calculations based on density functional theory. Formation enthalpy values indicate that Cr7C3 is the most stable crystal among the three compounds. Fe3C is metastable which has a positive heat of formation value. The calculated bulk modulus, shear modulus and Young's modulus value of Cr7C3 are 311 GPa, 143.8 GPa and 374 GPa, respectively. The bulk modulus values of Fe2B and Fe3C are 194 GPa and 258 GPa. We also find that both the hardness and the stiffness of the Cr7C3 type carbides can be improved by doping with B, W, Mo, etc. The bulk modulus of transition metal doped Fe2B is considerably higher than pure Fe2B. The electronic structures of Fe2B and Fe3C are ferromagnetic and the evaluated average magnetic moment of Fe is 2.09μB/atom for Fe3C and 2.02μB/atom for Fe2B, respectively. Micro-indentation test results indicate that Cr7C3 is the hardest phase among the three phases and shows excellent wear resistance performance under three-body abrasive experiments. The experimental results are in agreement with the theoretical prediction that Cr7C3 is the best both in stability and mechanical performance.

  17. Microstructure and Dry Sliding Wear Behavior of Fe-Based (Cr, Fe)7C3 Composite Coating Fabricated by PTA Welding Process

    NASA Astrophysics Data System (ADS)

    Yuan, Y. L.; Li, Z. G.

    2013-11-01

    Using Cr3C2 and Fe-CrNiBSi powder blends as raw materials, an α-Fe matrix composite coating reinforced by in situ (Cr, Fe)7C3 rods, with a thickness of about 3.6 mm, was fabricated on the surface of AISI A36 low carbon steel by means of plasma-transferred arc welding. The results of microstructural analysis show that in the coating, a large number of carbides, (Cr, Fe)7C3, in rod shape grow, and radiate around some half-dissolved Cr3C2 particles. The results of dry sliding wear tests at loads 100, 200, and 300 N show that the wear resistances of (Cr, Fe)7C3-reinforced coating, respectively, are about 6.9, 14.9, and 17 times higher than that of nonreinforced pure Fe-CrNiBSi alloy coating; the average value and fluctuation range of friction coefficient (FC) of (Cr, Fe)7C3-reinforced coating are less than those of pure Fe-CrNiBSi alloy coating; the main wear mechanisms of pure Fe-CrNiBSi alloy coating are ploughing, deformation, and adhesive wear, whereas those of (Cr, Fe)7C3-reinforced coating are microcutting, abrasive, and oxidation wear; the cracks on surfaces of (Cr, Fe)7C3 rods increased with the increasing loads; and the matrix α-Fe can prevent them from extending further in the composite coating.

  18. LiVP2O7/C: A New Insertion Anode Material for High-Rate Lithium-Ion Battery Applications.

    PubMed

    Mani, Vellaisamy; Kalaiselvi, Nallathamby

    2016-04-18

    LiVP2O7/C, popularly known so far as an environmentally compatible and economically viable lithium battery cathode material, was exploited for the first time as an anode through the current study. LiVP2O7/C was synthesized by adopting oxalyl dihydrazide assisted solution combustion method and explored as an anode material in rechargeable lithium cell assembly. Notably, an initial capacity of 600 mAh g(-1) was exhibited by LiVP2O7/C anode, at the rate of 0.5 C along with an excellent Coulombic efficiency of 99% up to 150 cycles. The title anode demonstrates its suitability for high capacity and high rate applications by way of exhibiting appreciable capacity values of 200, 150, 120, and 110 mAh g(-1), under the influence of 2, 4, 6, and 8 C rates, respectively. Further, LiVP2O7/C anode, when subjected to a high current 10 C rate, exhibits an acceptable capacity of 107 mAh g(-1) up to 500 cycles, which is closer to its theoretical capacity value of 117 mAh g(-1). The study demonstrates the possibility of exploiting LiVP2O7/C as yet another potential anode and thereby opens a newer avenue to explore wide variety of LiMP2O7/C composites for their probable anode behavior in rechargeable lithium batteries. PMID:27065103

  19. 3.6 and 4.5 μm Spitzer Phase Curves of the Highly Irradiated Hot Jupiters WASP-19b and HAT-P-7b

    NASA Astrophysics Data System (ADS)

    Wong, Ian; Knutson, Heather A.; Kataria, Tiffany; Lewis, Nikole K.; Burrows, Adam; Fortney, Jonathan J.; Schwartz, Joel; Shporer, Avi; Agol, Eric; Cowan, Nicolas B.; Deming, Drake; Désert, Jean-Michel; Fulton, Benjamin J.; Howard, Andrew W.; Langton, Jonathan; Laughlin, Gregory; Showman, Adam P.; Todorov, Kamen

    2016-06-01

    We analyze full-orbit phase curve observations of the transiting hot Jupiters WASP-19b and HAT-P-7b at 3.6 and 4.5 μm, obtained using the Spitzer Space Telescope. For WASP-19b, we measure secondary eclipse depths of 0.485%+/- 0.024% and 0.584%+/- 0.029% at 3.6 and 4.5 μm, which are consistent with a single blackbody with effective temperature 2372 ± 60 K. The measured 3.6 and 4.5 μm secondary eclipse depths for HAT-P-7b are 0.156%+/- 0.009% and 0.190%+/- 0.006%, which are well described by a single blackbody with effective temperature 2667 ± 57 K. Comparing the phase curves to the predictions of one-dimensional and three-dimensional atmospheric models, we find that WASP-19b’s dayside emission is consistent with a model atmosphere with no dayside thermal inversion and moderately efficient day–night circulation. We also detect an eastward-shifted hotspot, which suggests the presence of a superrotating equatorial jet. In contrast, HAT-P-7b’s dayside emission suggests a dayside thermal inversion and relatively inefficient day–night circulation; no hotspot shift is detected. For both planets, these same models do not agree with the measured nightside emission. The discrepancies in the model-data comparisons for WASP-19b might be explained by high-altitude silicate clouds on the nightside and/or high atmospheric metallicity, while the very low 3.6 μm nightside planetary brightness for HAT-P-7b may be indicative of an enhanced global C/O ratio. We compute Bond albedos of 0.38 ± 0.06 and 0 (\\lt 0.08 at 1σ ) for WASP-19b and HAT-P-7b, respectively. In the context of other planets with thermal phase curve measurements, we show that WASP-19b and HAT-P-7b fit the general trend of decreasing day–night heat recirculation with increasing irradiation.

  20. A Mature Galaxy Cluster at z=1.58 around the Radio Galaxy 7C1753+6311

    NASA Astrophysics Data System (ADS)

    Cooke, E. A.; Hatch, N. A.; Stern, D.; Rettura, A.; Brodwin, M.; Galametz, A.; Wylezalek, D.; Bridge, C.; Conselice, C. J.; De Breuck, C.; Gonzalez, A. H.; Jarvis, M.

    2016-01-01

    We report on the discovery of a z = 1.58 mature cluster around the high-redshift radio galaxy 7C 1753+6311, first identified in the Clusters Around Radio-loud active galactic nuclei survey. Two-thirds of the excess galaxies within the central 1 Mpc lie on a red sequence with a color that is consistent with an average formation redshift of zf ∼ 3. We show that 80 ± 6% of the red sequence galaxies in the cluster core are quiescent, while the remaining 20% are red due to dusty star formation. We demonstrate that the cluster has an enhanced quiescent galaxy fraction that is three times that of the control field. We also show that this enhancement is mass dependent: 91 ± 9% of the {M}*\\gt {10}10.5M⊙ cluster galaxies are quiescent, compared to only 36 ± 2% of field galaxies, whereas the fraction of quiescent galaxies with lower masses is the same in the cluster and field environments. The presence of a dense core and a well-formed, quiescent red sequence suggest that this is a mature cluster. This means that distant radio galaxies do not solely reside in young, uncollapsed protoclusters, rather they can be found in clusters in a wide range of evolutionary states.

  1. Structural characterization of M7C3-type carbide precipitated in the aging treated 100Mn13 steel

    NASA Astrophysics Data System (ADS)

    Dong, Linnan; Ding, Zhimin; Liang, Bo; Xu, Zhenfeng

    2015-11-01

    The distribution and the microstructure of carbides and pearlite, orientation relationships of pearlitic component phase in 100Mn13 steel by solution treatment at 1050 °C and aging treatment at 525 °C were investigated by optical microscope and transmission electron microscope. The results show that there is a large number of carbides and pearlite forming within the austenite grain and at the grain boundaries. The carbides in the pearlite of 100Mn13 steel have two kinds of morphologies, namely flaky and short rod. The type of carbides is M7C3. The carbides with different morphologies in the pearlite have different crystallographic orientation relationships with the ferrite. The orientation relationships between the flaky carbides and the ferrite are ?, ?, while the orientation relationships between the short-rod carbides and the ferrite are ?, ?. The short-rod carbides distribute directionally and orderly on the ferrite, which is similar to the morphology of the interphase precipitate. Therefore, the class-interphase precipitate mechanism is proposed in this study.

  2. Decreased expression of let-7c is associated with non-response of muscle-invasive bladder cancer patients to neoadjuvant chemotherapy

    PubMed Central

    Vinall, Ruth L.; Tepper, Clifford G.; Ripoll, Alexandra A. Z.; Gandour-Edwards, Regina F.; Durbin-Johnson, Blythe P.; Yap, Stanley A.; Ghosh, Paramita M.; deVere White, Ralph W.

    2016-01-01

    The identification and development of biomarkers which predict response of muscle invasive bladder cancer (MIBC) patients to neoadjuvant chemotherapy would likely increase usage of this treatment option and thereby improve patient survival rates. MiRNA array and qRT-PCR validation was used to identify miRNA which are associated with response to neoadjuvant chemotherapy. RNA was extracted from a total of 41 archival, fully annotated, MIBC patient diagnostic biopsies (20 chemo-responders and 21 non-responders (response is defined as > 5 year survival rate and being pT0 post-chemotherapy)). Microarray and qPCR identified let-7c as being differentially expressed in chemo-responder versus non-responder patients. Patients with higher let-7c expression levels had significantly higher odds of responding to chemotherapy (p = 0.023, OR 2.493, 95% CI 1.121, 5.546), and assessment of let-7c levels allowed for prediction of patient response (AUC 0.72, positive predictive value 59%). Decreased let-7c was associated with MIBC incidence (p < 0.001), and significantly correlated with other related miRNA including those that were not differentially expressed between responders and non-responders. The combined data indicate let-7c plays a role in mediating chemoresistance to neoadjuvant chemotherapy in MIBC patients, and is a modest, yet clinically meaningful, predictor of patient response. PMID:27382433

  3. Decreased expression of let-7c is associated with non-response of muscle-invasive bladder cancer patients to neoadjuvant chemotherapy.

    PubMed

    Vinall, Ruth L; Tepper, Clifford G; Ripoll, Alexandra A Z; Gandour-Edwards, Regina F; Durbin-Johnson, Blythe P; Yap, Stanley A; Ghosh, Paramita M; deVere White, Ralph W

    2016-03-01

    The identification and development of biomarkers which predict response of muscle invasive bladder cancer (MIBC) patients to neoadjuvant chemotherapy would likely increase usage of this treatment option and thereby improve patient survival rates. MiRNA array and qRT-PCR validation was used to identify miRNA which are associated with response to neoadjuvant chemotherapy. RNA was extracted from a total of 41 archival, fully annotated, MIBC patient diagnostic biopsies (20 chemo-responders and 21 non-responders (response is defined as > 5 year survival rate and being pT0 post-chemotherapy)). Microarray and qPCR identified let-7c as being differentially expressed in chemo-responder versus non-responder patients. Patients with higher let-7c expression levels had significantly higher odds of responding to chemotherapy (p = 0.023, OR 2.493, 95% CI 1.121, 5.546), and assessment of let-7c levels allowed for prediction of patient response (AUC 0.72, positive predictive value 59%). Decreased let-7c was associated with MIBC incidence (p < 0.001), and significantly correlated with other related miRNA including those that were not differentially expressed between responders and non-responders. The combined data indicate let-7c plays a role in mediating chemoresistance to neoadjuvant chemotherapy in MIBC patients, and is a modest, yet clinically meaningful, predictor of patient response. PMID:27382433

  4. Summary Report For The Analysis Of The Sludge Batch 7b (Macrobatch 9) DWPF Pour Stream Glass Sample For Canister S04023

    SciTech Connect

    Johnson, F. C.

    2013-11-18

    In order to comply with the Defense Waste Processing Facility (DWPF) Waste Form Compliance Plan for Sluldge Batch 7b, Savannah River National Laboratory (SRNL) personnel characterized the Defense Waste Processing Facility (DWPF) pour stream (PS) glass sample collected while filling canister S04023. This report summarizes the results of the compositional analysis for reportable oxides and radionuclides and the normalized Product Consistency Test (PCT) results. The PCT responses indicate that the DWPF produced glass that is significantly more durable than the Environmental Assessment glass.

  5. The influence of pressure on the phase stability of nanocomposite Fe89Zr7B4 during heating from energy dispersive x-ray diffraction

    NASA Astrophysics Data System (ADS)

    Leary, A. M.; Lucas, M. S.; Ohodnicki, P. R.; Kernion, S. J.; Mauger, L.; Park, C.; Kenney-Benson, C.; McHenry, M. E.

    2013-05-01

    Nanocomposite materials consisting of small crystalline grains embedded within an amorphous matrix show promise for many soft magnetic applications. The influence of pressure is investigated by in situ diffraction of hammer milled Fe89Zr7B4 during heating through the α → γ Fe transition at 0.5, 2.2, and 4.9 GPa. The changes in primary and secondary crystallization onset are described by diffusion and the energy to form a critical nucleus within the framework of classical nucleation theory.

  6. ORF7-encoded accessory protein 7a of feline infectious peritonitis virus as a counteragent against IFN-α-induced antiviral response.

    PubMed

    Dedeurwaerder, Annelike; Olyslaegers, Dominique A J; Desmarets, Lowiese M B; Roukaerts, Inge D M; Theuns, Sebastiaan; Nauwynck, Hans J

    2014-02-01

    The type I IFN-mediated immune response is the first line of antiviral defence. Coronaviruses, like many other viruses, have evolved mechanisms to evade this innate response, ensuring their survival. Several coronavirus accessory genes play a central role in these pathways, but for feline coronaviruses this has never to our knowledge been studied. As it has been demonstrated previously that ORF7 is essential for efficient replication in vitro and virulence in vivo of feline infectious peritonitis virus (FIPV), the role of this ORF in the evasion of the IFN-α antiviral response was investigated. Deletion of ORF7 from FIPV strain 79-1146 (FIPV-Δ7) rendered the virus more susceptible to IFN-α treatment. Given that ORF7 encodes two proteins, 7a and 7b, it was further explored which of these proteins is active in this mechanism. Providing 7a protein in trans rescued the mutant FIPV-Δ7 from IFN sensitivity, which was not achieved by addition of 7b protein. Nevertheless, addition of protein 7a to FIPV-Δ3Δ7, a FIPV mutant deleted in both ORF3 and ORF7, could no longer increase the replication capacity of this mutant in the presence of IFN. These results indicate that FIPV 7a protein is a type I IFN antagonist and protects the virus from the antiviral state induced by IFN, but it needs the presence of ORF3-encoded proteins to exert its antagonistic function. PMID:24189622

  7. Characterization of a purified thermostable xylanase from Caldicoprobacter algeriensis sp. nov. strain TH7C1(T).

    PubMed

    Amel, Bouanane-Darenfed; Nawel, Boucherba; Khelifa, Bouacem; Mohammed, Gagaoua; Manon, Joseph; Salima, Kebbouche-Gana; Farida, Nateche; Hocine, Hacene; Bernard, Ollivier; Jean-Luc, Cayol; Marie-Laure, Fardeau

    2016-01-01

    The present study investigates the purification and biochemical characterization of an extracellular thermostable xylanase (called XYN35) from Caldicoprobacter algeriensis sp. nov., strain TH7C1(T), a thermophilic, anaerobic strain isolated from the hydrothermal hot spring of Guelma (Algeria). The maximum xylanase activity recorded after 24 h of incubation at 70 °C and in an optimized medium containing 10 g/L mix birchwood- and oats spelt-xylan was 250 U/mL. The pure protein was obtained after heat treatment (1 h at 70 °C), followed by sequential column chromatographies on Sephacryl S-200 gel filtration and Mono-S Sepharose anion-exchange. Matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis indicated that the purified enzyme is a monomer with a molecular mass of 35,075.10 Da. The results from amino-acid sequence analysis revealed high homology between the 21 NH2-terminal residues of XYN35 and those of bacterial xylanases. The enzyme showed optimum activity at pH 11 and 70 °C. While XYN35 was activated by Ca(2+), Mn(2+), and Mg(2+), it was completely inhibited by Hg(2+) and Cd(2+). The xylanase showed higher specific activity on soluble oat-spelt xylan, followed by beechwood xylan. This enzyme was also noted to obey the Michaelis-Menten kinetics, with Km and kcat values on oat-spelt xylan being 1.33 mg/mL and 400 min(-1), respectively. Thin-layer chromatography soluble oat-spelt xylan (TLC) analysis showed that the final hydrolyzed products of the enzyme from birchwood xylan were xylose, xylobiose, and xylotriose. Taken together, the results indicated that the XYN35 enzyme has a number of attractive biochemical properties that make it a potential promising candidate for future application in the pulp bleaching industry. PMID:26687892

  8. Comet-like tail-formation of exospheres of hot rocky exoplanets: Possible implications for CoRoT-7b

    NASA Astrophysics Data System (ADS)

    Mura, A.; Wurz, P.; Schneider, J.; Lammer, H.; Grießmeier, J.-M.; Khodachenko, M. L.; Weingrill, J.; Guenther, E.; Cabrera, J.; Erikson, A.; Fridlund, M.; Milillo, A.; Rauer, H.; von Paris, Ph.

    2011-01-01

    In this study, the interaction of stellar wind plasma with the exosphere and possibly with the planetary magnetospheric environment of close-in rocky exoplanets is investigated. In particular, we focus on the "super-Earth" CoRoT-7b, which has been recently discovered by the CoRoT space observatory. The physical properties of such a planet, with an orbital distance of about 0.017 AU from its host star, may most likely resemble a big and more massive Mercury-type planet in the sense that it most likely releases its surface elements into space. Based on the present knowledge of CoRoT-7b and drawing on the analogy to Solar System planets, we use numerical models to simulate exospheric and magnetospheric distributions of different particle populations, among which are neutral sodium and ionised calcium and magnesium. We find that, for most species, the atmospheric loss rate in such an extreme environment can be very high, so that a neutral and an ionised tail of escaping particles will form. Depending on the planetary composition we postulate the presence of a sodium tail, similar to that of Mercury but shorter due to the shorter Na lifetime, and of an extended magnetospheric distribution of ionised calcium or magnesium. The feasibility of observation of such populations is also discussed.

  9. The silicate and carbon-rich models of CoRoT-7b, Kepler-9d and Kepler-10b

    NASA Astrophysics Data System (ADS)

    Gong, Yan-Xiang; Zhou, Ji-Lin

    2012-06-01

    Possible bulk compositions of the super-Earth exoplanets CoRoT-7b, Kepler-9d, and Kepler-10b are investigated by applying a commonly used silicate model and a non-standard carbon model. Their internal structures are deduced using a suitable equation of state for the materials. The degeneracy problems of their compositions can be partly overcome, based on the fact that all three planets are extremely close to their host stars. By analyzing the numerical results, we conclude: 1) the iron core of CoRoT-7b is not more than 27% of its total mass within 1σ mass-radius error bars, so an Earth-like composition is less likely, but its carbon rich model can be compatible with an Earth-like core/mantle mass fraction; 2) Kepler-10b is more likely to have a Mercury-like composition, with its old age implying that its high iron content may be a result of strong solar wind or giant impact; 3) the transiting-only super-Earth Kepler-9d is also discussed. Combining its possible composition with the formation theory, we can place some constraints on its mass and bulk composition.

  10. DOT-7A packaging test procedure

    SciTech Connect

    Kelly, D.L.

    1995-01-23

    This test procedure documents the steps involved with performance testing of Department of Transportation Specification 7A (DOT-7A) Type A packages. It includes description of the performance tests, the personnel involved, appropriate safety considerations, and the procedures to be followed while performing the tests. Westinghouse Hanford Company (WHC) is conducting the evaluation and testing discussed herein for the Department of Energy-Headquarters, Division of Quality Verification and Transportation Safety (EH-321). Please note that this report is not in WHC format. This report is being submitted through the Engineering Documentation System so that it may be used for reference and information purposes.

  11. Growth-arrest-specific 7C protein inhibits tumor metastasis via the N-WASP/FAK/F-actin and hnRNP U/β-TrCP/β-catenin pathways in lung cancer

    PubMed Central

    Chang, Jer-Wei; Mao, Jiou-Shan; Tsai, Charng-Dar; Wu, Pei-Chen; Lin, Cuei-Jyuan; Lu, Yi-Lin; Liao, Sheng-You; Cheng, Hung-Chi; Hsu, Han-Shui

    2015-01-01

    Growth-arrest-specific 7 (GAS7) belongs to a group of adaptor proteins that coordinate the actin cytoskeleton. Among human GAS7 isoforms, only GAS7C possesses a Src homology 3 domain. We report here that GAS7C acts as a migration suppressor and can serve as a prognostic biomarker in lung cancer. GAS7C overexpression reduces lung cancer migration, whereas GAS7C knockdown enhances cancer cell migration. Importantly, ectopically overexpressed GAS7C binds tightly with N-WASP thus inactivates the fibronectin/integrin/FAK pathway, which in turn leads to the suppression of F-actin dynamics. In addition, overexpression of GAS7C sequesters hnRNP U and thus decreases the level of β-catenin protein via the β-TrCP ubiquitin-degradation pathway. The anti-metastatic effect of GAS7C overexpression was also confirmed using lung cancer xenografts. Our clinical data indicated that 23.6% (25/106) of lung cancer patients showed low expression of GAS7C mRNA which correlated with a poorer overall survival. In addition, low GAS7C mRNA expression was detected in 60.0% of metastatic lung cancer patients, indicating an association between low GAS7C expression and cancer progression. A significant inverse correlation between mRNA expression and promoter hypermethylation was also found, which suggests that the low level of GAS7C expression was partly due to promoter hypermethylation. Our results provide novel evidence that low GAS7C correlates with poor prognosis and promotes metastasis in lung cancer. Low GAS7C increases cancer cell motility by promoting N-WASP/FAK/F-actin cytoskeleton dynamics. It also enhances β-catenin stability via hnRNP U/β-TrCP complex formation. Therefore, GAS7C acts as a metastasis suppressor in lung cancer. PMID:26506240

  12. Insights into endosomal maturation of human holo-transferrin in the enteric parasite Entamoeba histolytica: essential roles of Rab7A and Rab5 in biogenesis of giant early endocytic vacuoles.

    PubMed

    Verma, Kuldeep; Saito-Nakano, Yumiko; Nozaki, Tomoyoshi; Datta, Sunando

    2015-12-01

    The pathogenic amoeba Entamoeba histolytica is one of the causative agents of health hazards in tropical countries. It causes amoebic dysentery, colitis and liver abscesses in human. Iron is one of the essential nutritional resources for survival and chronic infection caused by the amoeba. The parasite has developed multiple ways to import, sequester and utilize iron from various iron-binding proteins from its host. In spite of its central role in pathogenesis, the mechanism of iron uptake by the parasite is largely unknown. Here, we carried out a systematic study to understand the role of some of the amoebic homologues of mammalian endocytic Rab GTPases (Rab5 and Rab21, Rab7A and Rab7B) in intracellular transport of human holo-transferrin by the parasite. Flow cytometry and quantitative microscopic image analysis revealed that Rab5 and Rab7A are required for the biogenesis of amoebic giant endocytic vacuoles (GEVs) and regulate the early phase of intracellular trafficking of transferrin. Rab7B is involved in the late phase, leading to the degradation of transferrin in the amoebic lysosome-like compartments. Using time-lapse fluorescence imaging in fixed trophozoites, we determined the kinetics of the vesicular transport of transferrin through Rab5-, Rab7A- and Rab7B-positive compartments. The involvement of Rab7A in the early phase of endocytosis by the parasite marks a significant divergence from its host in terms of spatiotemporal regulation by the Rab GTPases. PMID:26096601

  13. Nanocrystalline Fe88-2xCoxNixZr7B4Cu1 alloys: Soft magnets for vehicle electrification technologies (invited)

    NASA Astrophysics Data System (ADS)

    Knipling, K. E.; Daniil, M.; Willard, M. A.

    2015-05-01

    We report on the effect of substituting Co and Ni for Fe on the crystallization behavior, crystal structure, and magnetic properties of Fe88-2xCoxNixZr7B4Cu1 (x = 0-22.00). The magnetization generally decreases and the coercivity increases with increasing x, whereas the Curie temperature of the amorphous phase increases significantly (from 73 °C at x = 0 to 570 °C at x = 22.00). There is thus an optimum composition near x = 5.50 exhibiting excellent soft magnetic properties at 300-500 °C. The higher magnetization and Curie temperature as compared with Fe-based alloys, and smaller Co content as compared with (Fe,Co)-based alloys, make this alloy attractive as an affordable high-temperature soft magnetic material.

  14. Dipolar correlations in a nanocomposite: A neutron scattering study of Nanoperm Fe{sub 89}Zr{sub 7}B{sub 3}Cu

    SciTech Connect

    Michels, A.; Vecchini, C.; Moze, O.; Suzuki, K.; Pranzas, P. K.; Kohlbrecher, J.; Weissmueller, J.

    2006-10-01

    We present results for the magnetic-field, temperature, and neutron-polarization dependence of the small-angle neutron scattering intensity in the soft magnetic iron-based nanocomposite Nanoperm (Fe{sub 89}Zr{sub 7}B{sub 3}Cu). An unusual 'clover-leaf-shaped' intensity distribution on the detector is attributed to the dipolar stray fields around the nanosized iron particles, which are embedded in an amorphous magnetic matrix of lesser saturation magnetization. The dipole field induces spin disorder, correlating the spin misalignment of neighboring particles and matrix over several particle spacings. The clover-leaf-shaped anisotropy is observed over a wide range of applied magnetic field and momentum transfer. It persists up to several hundred degrees Kelvin above the Curie temperature of the matrix phase, indicating that some degree of magnetic coupling persists even when the matrix is paramagnetic.

  15. Sex-dependent regulation of cytochrome P450 family members Cyp1a1, Cyp2e1, and Cyp7b1 by methylation of DNA

    PubMed Central

    Penaloza, Carlos G.; Estevez, Brian; Han, Dinah M.; Norouzi, Melissa; Lockshin, Richard A.; Zakeri, Zahra

    2014-01-01

    Sexual differences are only partially attributable to hormones. Cultured male or female cells, even from embryos before sexual differentiation, differ in gene expression and sensitivity to toxins, and these differences persist in isolated primary cells. Male and female cells from Swiss Webster CWF mice manifest sex-distinct patterns of DNA methylation for X-ist and for cytochrome P450 (CYP; family members 1a1, 2e1m, and 7b1. Dnmt3l is differentially expressed but not differentially methylated, and Gapdh is neither differentially methylated nor expressed. CYP family genes differ in expression in whole tissue homogenates and cell cultures, with female Cyp expression 2- to 355-fold higher and Dnmt3l 12- to 32-fold higher in males. DNA methylation in the promoters of these genes is sex dimorphic; reducing methylation differences reduces to 1- to 6-fold differences in the expression of these genes. Stress or estradiol alters both methylation and gene expression. We conclude that different methylation patterns partially explain the sex-based differences in expression of CYP family members and X-ist, which potentially leads to inborn differences between males and females and their different responses to chronic and acute changes. Sex-differential methylation may have medical effects.—Penaloza, C.G., Estevez, B., Han, D.M., Norouzi, M., Lockshin, R.A., Zakeri, Z. Sex-dependent regulation of cytochrome P450 family members Cyp1a1, Cyp2e1, and Cyp7b1 by methylation of DNA. PMID:24161885

  16. Genome-wide screen identified let-7c/miR-99a/miR-125b regulating tumor progression and stem-like properties in cholangiocarcinoma

    PubMed Central

    Lin, K-Y; Ye, H; Han, B-W; Wang, W-T; Wei, P-P; He, B; Li, X-J; Chen, Y-Q

    2016-01-01

    Cholangiocarcinoma (CCA), which is a poor prognosis malignancy that arises from the malignant transformation of cholangiocytes, is associated with chronic inflammation of the biliary epithelium. Thus far, the molecular mechanisms of the origin and neoplastic processes of CCA that are promoted by inflammation are still unclear and need to be fully elucidated. Here using small RNA sequencing to determine the microRNA (miRNA) expression profiles in CCA, we found that let-7c, miR-99a and miR-125b, which are three miRNAs of the same cluster, were downregulated in CCA and targeted interleukin 6 (IL-6), IL-6R and type 1 insulin-like growth factor, which are important cytokines and receptors of the IL-6/signal transducer and activator 3 (STAT3) pathway and have key roles in inflammation and CCA initiation. We also found that enforced expression of let-7c, miR-99a or miR-125b could reduce the activity of STAT3 and further suppress CCA tumorigenicity in vivo and inhibit the migration and invasion of CCA cells in vitro. Surprisingly, let-7c/miR-99a/miR-125b cluster also significantly decreased the ability of CCA cells for cancer stem cell-like mammosphere generation by downregulating CD133 and CD44, which suggests the pivotal roles of let-7c, miR-99a and miR-125b in CCA by regulating both inflammation and stem-like properties. Our findings showed potential links between miRNAs and inflammation, and provide a potential treatment strategy for developing an miRNA-based therapy via IL-6/STAT3 targeting for CCA. PMID:26455324

  17. Magnetic phase diagrams and thermal equations of state of Fe7C3 and Fe3C up to the pressure-temperature conditions of Earth's core

    NASA Astrophysics Data System (ADS)

    Liu, J.; Li, Z.; Chen, B.; Li, J.; Ikuta, D.; Smith, J.; Sinogeikin, S. V.; Popov, D.; Kenney-Benson, C.

    2015-12-01

    Iron carbides Fe7C3 and Fe3C have been proposed as candidates for the dominant components of the Earth's inner core to explain its density deficit and velocity discrepancy with respect to those of pure iron at relevant pressure-temperature conditions (e.g. Chen et al., 2012; Chen et al., 2014; Gao et al., 2011). Testing the hypothesis of carbon-rich inner core requires knowledge of the thermal equations of state of the iron carbides to megabar pressures. Existing experimental data, however, are restricted to either ambient temperature or the pressures near the top of the lower mantle. In particular, the thermal expansion coefficients of the carbides under high pressures remain poorly constrained. Previous studies showed that both Fe7C3 an Fe3C are Invar-type alloys with extremely low thermal expansions in the ferromagnetic phases, and their thermal expansion coefficients more than triple across the ferromagnetic-paramagnetic transition at 1 bar (Litasov et al., 2015). On the other hand, both iron carbides experience pressure-induced spin transitions under high pressures (e.g. Chen et al., 2012; Prescher et al., 2012), but their effects on the thermal expansion are still unknown. We conducted synchrotron X-ray diffraction measurements on Fe7C3 and Fe3C up to the core's pressure and temperature conditions. High pressures up to ~140 GPa were generated by using diamond anvil cells (DAC), while high temperatures were generated using the whole-cell resistive heating device up to 700 K, and using the double-sided laser-heating system up to ~ 3500 K. The new data allow us to construct the magnetic phase diagrams of Fe7C3 and Fe3C and to assess the influences of magnetic transitions on their thermal expansion coefficients. The density profiles of appropriate magnetic phases are calculated and compared with that of the Earth's inner core to estimate its carbon content.

  18. Genome-wide screen identified let-7c/miR-99a/miR-125b regulating tumor progression and stem-like properties in cholangiocarcinoma.

    PubMed

    Lin, K-Y; Ye, H; Han, B-W; Wang, W-T; Wei, P-P; He, B; Li, X-J; Chen, Y-Q

    2016-06-30

    Cholangiocarcinoma (CCA), which is a poor prognosis malignancy that arises from the malignant transformation of cholangiocytes, is associated with chronic inflammation of the biliary epithelium. Thus far, the molecular mechanisms of the origin and neoplastic processes of CCA that are promoted by inflammation are still unclear and need to be fully elucidated. Here using small RNA sequencing to determine the microRNA (miRNA) expression profiles in CCA, we found that let-7c, miR-99a and miR-125b, which are three miRNAs of the same cluster, were downregulated in CCA and targeted interleukin 6 (IL-6), IL-6R and type 1 insulin-like growth factor, which are important cytokines and receptors of the IL-6/signal transducer and activator 3 (STAT3) pathway and have key roles in inflammation and CCA initiation. We also found that enforced expression of let-7c, miR-99a or miR-125b could reduce the activity of STAT3 and further suppress CCA tumorigenicity in vivo and inhibit the migration and invasion of CCA cells in vitro. Surprisingly, let-7c/miR-99a/miR-125b cluster also significantly decreased the ability of CCA cells for cancer stem cell-like mammosphere generation by downregulating CD133 and CD44, which suggests the pivotal roles of let-7c, miR-99a and miR-125b in CCA by regulating both inflammation and stem-like properties. Our findings showed potential links between miRNAs and inflammation, and provide a potential treatment strategy for developing an miRNA-based therapy via IL-6/STAT3 targeting for CCA. PMID:26455324

  19. Crystal structure and electronic properties of the new compounds, U 6Fe 16Si 7 and its interstitial carbide U 6Fe 16Si 7C

    NASA Astrophysics Data System (ADS)

    Berthebaud, D.; Tougait, O.; Potel, M.; Lopes, E. B.; Gonçalves, A. P.; Noël, H.

    2007-10-01

    The new compounds U6Fe16Si7 and U6Fe16Si7C were prepared by arc-melting and subsequent annealing at 1500 °C. Single-crystal X-ray diffraction showed that they crystallize in the cubic space group Fm3¯m (No. 225), with unit-cell parameters at room temperature a=11.7206(5) Å for U6Fe16Si7 and a=11.7814(2) Å for U6Fe16Si7C. Their crystal structures correspond to ordered variants of the Th6Mn23 type. U6Fe16Si7 adopts the Mg6Cu16Si7 structure type, whereas U6Fe16Si7C crystallizes with a novel "filled" quaternary variant. The inserted carbon is located in octahedral cages formed by six U atoms, with U-U interatomic distances of 3.509(1) Å. Insertion of carbon in the structure of U6Fe16Si7 has a direct influence on the U-Fe and Fe-Fe interatomic distances. The electronic properties of both compounds were investigated by means of DC susceptibility, electrical resistivity and thermopower. U6Fe16Si7 is a Pauli paramagnet. Its electrical resistivity and thermopower point out that it cannot be classified as a simple metal. The magnetic susceptibility of U 6Fe 16Si 7C is best described over the temperature range 100-300 K by using a modified Curie-Weiss law with an effective magnetic moment of 2.3(2) μB/U, a paramagnetic Weiss temperature, θp=57(2) K and a temperature-independent term χ0=0.057(1) emu/mol. Both the electrical resistivity and thermopower reveal metallic behavior.

  20. Microstructure and wear resistance of Al2O3-M7C3/Fe composite coatings produced by laser controlled reactive synthesis

    NASA Astrophysics Data System (ADS)

    Tan, Hui; Luo, Zhen; Li, Yang; Yan, Fuyu; Duan, Rui

    2015-05-01

    Based on the principle of thermite reaction of Al and Fe2O3 powders, the Al2O3 ceramic reinforced Fe-based composite coatings were fabricated on a steel substrate by laser controlled reactive synthesis and cladding. The effects of different additions of thermite reactants on the phase transition, microstructure evolution, microhardness and wear resistance of the composite coatings were investigated by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Vickers microhardness and block-on-ring wear test, respectively. The results show that Al2O3 ceramic and M7C3 carbide are in situ synthesized via the laser controlled reactive synthesis. The Al2O3 ceramic and M7C3 carbides prefer to distribute along the γ-Fe phase boundary continuously, which separates the γ-Fe matrix and is beneficial to the grain refinement. With the increase of thermite reactants, the amount of Al2O3 ceramic and M7C3 carbide in the composite coatings increases gradually. Moreover the cladding layer changes from dendritic structure to columnar structure and martensite structure in the heat affected zone becomes coarse. The increased thermite reactants improve the microhardness and wear resistance of the in situ composite coatings obviously and enhance the hardness of the heat affected zone, which should be ascribed to the grain refinement, ceramic and carbide precipitation and solid solution strengthening.

  1. Synthesis of single phase. alpha. -Fe, Fe sub 3 C and Fe sub 7 C sub 3 nano-particles by CO sub 2 laser pyrolysis technique

    SciTech Connect

    Eklund, P.C.; Bi, X.X.

    1992-01-01

    Iron-containing catalysts have been known to be useful in assisting the Fischer-Tropsch (FT) reaction for synthesizing hydrocarbons. However, it has been well recognized that iron catalyst are not stable during the reaction but converted into iron carbides. It is thus important to understand the role of the iron carbides in the catalytic reaction of the FT-synthesis. It has been found difficult to produce iron carbide nano-particles as a single phase, because iron carbide phases are only metastable under 1 atm pressure. Iron carbide bulk particles prepared so far are often contaminated with metallic iron, iron oxides and free carbon. In this study, we investigate the synthesis of iron carbide nano-particles using CO{sub 2} laser pyrolysis technique. We show that this technique is successful in synthesizing {alpha}-Fe, Fe{sub 3}C and Fe{sub 7}C{sub 3} nano-particles in their single phase with sizes in the range of 5--20nm. In particular, we have produced for the first time the Fe{sub 7}C{sub 3} which has been known to exist but unable to be produced as a single phase. Furthermore, it is interesting that Fe{sub 5}C{sub 2} which has carbon and iron ratio between Fe{sub 3}C and Fe{sub 7}C{sub 3}, is not seen in any run of our synthesis.

  2. Transiting exoplanets from the CoRoT space mission. VIII. CoRoT-7b: the first super-Earth with measured radius

    NASA Astrophysics Data System (ADS)

    Léger, A.; Rouan, D.; Schneider, J.; Barge, P.; Fridlund, M.; Samuel, B.; Ollivier, M.; Guenther, E.; Deleuil, M.; Deeg, H. J.; Auvergne, M.; Alonso, R.; Aigrain, S.; Alapini, A.; Almenara, J. M.; Baglin, A.; Barbieri, M.; Bruntt, H.; Bordé, P.; Bouchy, F.; Cabrera, J.; Catala, C.; Carone, L.; Carpano, S.; Csizmadia, Sz.; Dvorak, R.; Erikson, A.; Ferraz-Mello, S.; Foing, B.; Fressin, F.; Gandolfi, D.; Gillon, M.; Gondoin, Ph.; Grasset, O.; Guillot, T.; Hatzes, A.; Hébrard, G.; Jorda, L.; Lammer, H.; Llebaria, A.; Loeillet, B.; Mayor, M.; Mazeh, T.; Moutou, C.; Pätzold, M.; Pont, F.; Queloz, D.; Rauer, H.; Renner, S.; Samadi, R.; Shporer, A.; Sotin, Ch.; Tingley, B.; Wuchterl, G.; Adda, M.; Agogu, P.; Appourchaux, T.; Ballans, H.; Baron, P.; Beaufort, T.; Bellenger, R.; Berlin, R.; Bernardi, P.; Blouin, D.; Baudin, F.; Bodin, P.; Boisnard, L.; Boit, L.; Bonneau, F.; Borzeix, S.; Briet, R.; Buey, J.-T.; Butler, B.; Cailleau, D.; Cautain, R.; Chabaud, P.-Y.; Chaintreuil, S.; Chiavassa, F.; Costes, V.; Cuna Parrho, V.; de Oliveira Fialho, F.; Decaudin, M.; Defise, J.-M.; Djalal, S.; Epstein, G.; Exil, G.-E.; Fauré, C.; Fenouillet, T.; Gaboriaud, A.; Gallic, A.; Gamet, P.; Gavalda, P.; Grolleau, E.; Gruneisen, R.; Gueguen, L.; Guis, V.; Guivarc'h, V.; Guterman, P.; Hallouard, D.; Hasiba, J.; Heuripeau, F.; Huntzinger, G.; Hustaix, H.; Imad, C.; Imbert, C.; Johlander, B.; Jouret, M.; Journoud, P.; Karioty, F.; Kerjean, L.; Lafaille, V.; Lafond, L.; Lam-Trong, T.; Landiech, P.; Lapeyrere, V.; Larqué, T.; Laudet, P.; Lautier, N.; Lecann, H.; Lefevre, L.; Leruyet, B.; Levacher, P.; Magnan, A.; Mazy, E.; Mertens, F.; Mesnager, J.-M.; Meunier, J.-C.; Michel, J.-P.; Monjoin, W.; Naudet, D.; Nguyen-Kim, K.; Orcesi, J.-L.; Ottacher, H.; Perez, R.; Peter, G.; Plasson, P.; Plesseria, J.-Y.; Pontet, B.; Pradines, A.; Quentin, C.; Reynaud, J.-L.; Rolland, G.; Rollenhagen, F.; Romagnan, R.; Russ, N.; Schmidt, R.; Schwartz, N.; Sebbag, I.; Sedes, G.; Smit, H.; Steller, M. B.; Sunter, W.; Surace, C.; Tello, M.; Tiphène, D.; Toulouse, P.; Ulmer, B.; Vandermarcq, O.; Vergnault, E.; Vuillemin, A.; Zanatta, P.

    2009-10-01

    Aims: We report the discovery of very shallow (Δ F/F ≈ 3.4× 10-4), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as caused by a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods: We used CoRoT colours information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy, and preliminary results from radial velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star were derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. Results: We examined all conceivable cases of false positives carefully, and all the tests support the planetary hypothesis. Blends with separation >0.40´´or triple systems are almost excluded with a 8 × 10-4 risk left. We conclude that, inasmuch we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 ± 3 × 10-5 day and a radius of Rp = 1.68 ± 0.09 R_Earth. Analysis of preliminary radial velocity data yields an upper limit of 21 M_Earth for the companion mass, supporting the finding. Conclusions: CoRoT-7b is very likely the first Super-Earth with a measured radius. This object illustrates what will probably become a common situation with missions such as Kepler, namely the need to establish the planetary origin of transits in the absence of a firm radial velocity detection and mass measurement. The composition of CoRoT-7b remains loosely constrained without a precise mass. A very high surface temperature on its irradiated face, ≈1800-2600 K at the substellar point, and a very low one, ≈50 K, on its dark face assuming no atmosphere, have been derived. The CoRoT space mission, launched on 27

  3. LIN28B suppresses microRNA let-7b expression to promote CD44+/LIN28B+ human pancreatic cancer stem cell proliferation and invasion

    PubMed Central

    Shao, Yebo; Zhang, Lei; Cui, Lei; Lou, Wenhui; Wang, Dansong; Lu, Weiqi; Jin, Dayong; Liu, Te

    2015-01-01

    Although the highly proliferative, migratory, and multi-drug resistant phenotype of human pancreatic cancer stem cells (PCSCs) is well characterized, knowledge of their biological mechanisms is limited. We used CD44 and LIN28B as markers to screen, isolate, and enrich CSCs from human primary pancreatic cancer. Using flow cytometry, we identified a human primary pancreatic cancer cell (PCC) subpopulation expressing high levels of both CD44 and LIN28B. CD44+/LIN28B+ PCSCs expressed high levels of stemness marker genes and possessed higher migratory and invasive ability than CD44-/LIN28B- PCCs. CD44+/LIN28B+ PCSCs were more resistant to growth inhibition induced by the chemotherapeutic drugs cisplatin and gemcitabine hydrochloride, and readily established tumors in vivo in a relatively short time. Moreover, microarray analysis revealed significant differences between the cDNA expression patterns of CD44+/LIN28B+ PCSCs and CD44-/LIN28B- PCCs. Following siRNA interference of endogenous LIN28B gene expression in CD44+/LIN28B+ PCSCs, not only was their proliferation decreased, there was also cell cycle arrest due to suppression of cyclin D1 expression following the stimulation of miRNA let-7b expression. In conclusion, CD44+/LIN28B+ cells, which possess CSC characteristics, can be reliably sorted from human primary PCCs and represent a valuable model for studying cancer cell physiology and multi-drug resistance. PMID:26609473

  4. A Potent Derivative of Indolizino[6,7-b]Indole for Treatment of Human Non–Small Cell Lung Cancer Cells12

    PubMed Central

    Chen, Chi-Wei; Wu, Ming-Hsi; Chen, Yi-Fan; Yen, Tsai-Yi; Lin, Yi-Wen; Chao, Shu-Hsin; Tala, Satishkumar; Tsai, Tung-Hu; Su, Tsann-Long; Lee, Te-Chang

    2016-01-01

    The therapeutic effect in non–small cell lung cancer (NSCLC) patients is limited because of intrinsic and acquired resistance. Thus, an unmet need exists for the development of new drugs to improve the therapeutic efficacy in NSCLC patients. In this study, the novel small molecule indolizino[6,7-b]indole derivative BO-1978 was selected to evaluate its therapeutic effects on NSCLC and its preclinical toxicity in animal models. An in vitro cytotoxicity assay revealed that BO-1978 significantly suppressed the growth of various NSCLC cell lines with or without mutations in epidermal growth factor receptor (EGFR). Mechanistically, we demonstrated that BO-1978 exhibited multiple modes of action, including inhibition of topoisomerase I/II and induction of DNA cross-linking. Treatment of NSCLC cells with BO-1978 caused DNA damage, disturbed cell cycle progression, and triggered apoptotic cell death. Furthermore, BO-1978 significantly suppressed the growth of EGFR wild-type and mutant NSCLC tumors in xenograft tumor and orthotopic lung tumor models with negligible body weight loss. The combination of BO-1978 with gefitinib further suppressed EGFR mutant NSCLC cell growth in xenograft tumor and orthotopic lung tumor models. Preclinical toxicity studies showed that BO-1978 administration did not cause apparent toxicity in mice. Based on its significant therapeutic efficacy and low drug toxicity, BO-1978 is a potential therapeutic agent for treatment of NSCLC. PMID:27108383

  5. 2-Amino-4-(4-chloro­phen­yl)-4H-chromeno[8,7-b]pyridine-3-carbonitrile

    PubMed Central

    Amr, Abd El-Galil E.; El-Agrody, Ahmed M.; Sabry, Nermien M.; Ng, Seik Weng; Tiekink, Edward R. T.

    2013-01-01

    The asymmetric unit of the title compound, C19H12ClN3O, contains two mol­ecules with similar conformations. The 14 non-H atoms comprising the 4H-chromeno[8,7-b]pyridine residue are essentially coplanar (r.m.s. deviations = 0.037 and 0.042 Å for the two mol­ecules) and the main difference between them is seen in the twist about the bond linking the main residue to the attached chloro­benzene rings [dihedral angles = 79.01 (12) and 76.22 (11)° for the two mol­ecules]. Zigzag supra­molecular chains along the a-axis direction mediated by amino–pyridine N—H⋯N hydrogen bonds feature in the crystal packing; these are connected into a three-dimensional architecture by C—H⋯π inter­actions and Cl⋯Cl contacts [Cl⋯Cl = 3.3896 (14) Å]. PMID:23634023

  6. N,N'-Bis(2-cyclohexylethyl)naphtho[2,3-b:6,7-b']dithiophene Diimides: Effects of Substituents.

    PubMed

    Nakano, Masahiro; Hashizume, Daisuke; Takimiya, Kazuo

    2016-01-01

    Naphtho[2,3-b:6,7-b']dithiophene-4,5,9,10-tetracarboxylic diimide (NDTI) is a promising electron-deficient building block for n-type organic conductors, and the performance of NDTI-based field-effect transistors (FETs) is largely dependent on the substituents that alter the supramolecular organization in the solid state and, in turn, the intermolecular orbital overlap. For this reason, the rational selection of substituent on imide nitrogen atoms and/or thiophene α-positions is the key to developing superior n-type organic semiconductors. We here report new NDTI derivatives having N-(2-cyclohexylethyl) groups. Despite their one-dimensional packing structures in the solid state regardless of the presence or absence of chlorine groups at the thiophene α-positions, their FETs show promising performance with electron mobilities higher than 0.1 cm²·V(-1)·s(-1) under ambient conditions. We also discuss how the cyclohexylethyl groups affect the packing structure in comparison with analogous n-octyl derivatives having the same number of carbon atoms. PMID:27483217

  7. Sex-dependent regulation of cytochrome P450 family members Cyp1a1, Cyp2e1, and Cyp7b1 by methylation of DNA.

    PubMed

    Penaloza, Carlos G; Estevez, Brian; Han, Dinah M; Norouzi, Melissa; Lockshin, Richard A; Zakeri, Zahra

    2014-02-01

    Sexual differences are only partially attributable to hormones. Cultured male or female cells, even from embryos before sexual differentiation, differ in gene expression and sensitivity to toxins, and these differences persist in isolated primary cells. Male and female cells from Swiss Webster CWF mice manifest sex-distinct patterns of DNA methylation for X-ist and for cytochrome P450 (CYP; family members 1a1, 2e1m, and 7b1. Dnmt3l is differentially expressed but not differentially methylated, and Gapdh is neither differentially methylated nor expressed. CYP family genes differ in expression in whole tissue homogenates and cell cultures, with female Cyp expression 2- to 355-fold higher and Dnmt3l 12- to 32-fold higher in males. DNA methylation in the promoters of these genes is sex dimorphic; reducing methylation differences reduces to 1- to 6-fold differences in the expression of these genes. Stress or estradiol alters both methylation and gene expression. We conclude that different methylation patterns partially explain the sex-based differences in expression of CYP family members and X-ist, which potentially leads to inborn differences between males and females and their different responses to chronic and acute changes. Sex-differential methylation may have medical effects. PMID:24161885

  8. Electronic structure, magnetic properties, and stability of the binary and ternary carbides (Fe,Cr)3C and (Fe,Cr)7C3

    NASA Astrophysics Data System (ADS)

    Konyaeva, M. A.; Medvedeva, N. I.

    2009-10-01

    The structural, electronic, and magnetic properties of the binary and ternary carbides (Fe,Cr)3C and (Fe,Cr)7C3 have been investigated within the ab initio density functional theory. The crystal structure of the binary carbides has been optimized and the preferred positions for replacement of chromium or iron impurities in the corresponding carbides have been determined. The changes in the electronic structure and magnetic properties have been investigated, the formation energies of the ternary carbides as functions of the impurity concentrations have been calculated, and conclusions have been drawn regarding the influence of the impurity on the stability of the carbides under investigation.

  9. Autosomal dominant familial spastic paraplegia: reduction of the FSP1 candidate region on chromosome 14q to 7 cM and locus heterogeneity.

    PubMed Central

    Gispert, S; Santos, N; Damen, R; Voit, T; Schulz, J; Klockgether, T; Orozco, G; Kreuz, F; Weissenbach, J; Auburger, G

    1995-01-01

    Three large pedigrees of German descent with autosomal dominant "pure" familial spastic paraplegia (FSP) were characterized clinically and genetically. Haplotype and linkage analyses, with microsatellites covering the FSP region on chromosome 14q (locus FSP1), were performed. In pedigree W, we found a haplotype that cosegregates with the disease and observed three crossing-over events, reducing the FSP1 candidate region to 7 cM; in addition, the observation of apparent anticipation in this family suggests a trinucleotide repeat expansion as the mutation. In pedigrees D and S, the gene locus could be excluded from the whole FSP1 region, confirming the locus heterogeneity of autosomal dominant FSP. PMID:7825576

  10. Disruption of copper homeostasis due to a mutation of Atp7a delays the onset of prion disease

    PubMed Central

    Siggs, Owen M.; Cruite, Justin T.; Du, Xin; Rutschmann, Sophie; Masliah, Eliezer; Beutler, Bruce; Oldstone, Michael B. A.

    2012-01-01

    Copper influences the pathogenesis of prion disease, but whether it is beneficial or detrimental remains controversial. Copper homeostasis is also essential for normal physiology, as highlighted by the spectrum of diseases caused by disruption of the copper transporting enzymes ATP7A and ATP7B. Here, by using a forward genetics approach in mice, we describe the isolation of three alleles of Atp7a, each with different phenotypic consequences. The mildest of the three, Atp7abrown, was insufficient to cause lethality in hemizygotes or mottling of the coat in heterozygotes, but did lead to coat hypopigmentation and reduced copper content in the brains of hemizygous males. When challenged with Rocky Mountain Laboratory scrapie, the onset of prion disease was delayed in Atp7abrown mice, and significantly less proteinase-resistant prion protein was found in the brains of moribund Atp7abrown mice compared with WT littermates. Our results establish that ATP7A-mediated copper homeostasis is important for the formation of pathogenic proteinase-resistant prion protein. PMID:22869751

  11. Formation of linearly linked Fe clusters on Si(111)-7 × 7-C2H5OH surface

    PubMed Central

    2014-01-01

    The Fe atoms were deposited on the Si(111)-7 × 7 surface, which has been saturated with the C2H5OH molecules. Then, the Fe clusters were formed on Si(111)-7 × 7-C2H5OH surface and in situ observed by the scanning tunneling microscopy (STM). The STM images showed that with the increase of Fe clusters, the size of clusters was about 5 nm and they self-assembled in straightly linked chain crossing the step to lower or upper terrace. X-ray photoelectron spectroscopy (XPS) was in situ carried out on the surface of Fe/Si(111)-7 × 7-C2H5OH samples before and after the introduction of thin air (4.5 × 10-2 Langmuir) into the STM chamber. The XPS results showed that the Fe clusters are stable in the abovementioned thin air condition at room temperature. Based on the STM and XPS results, the driving force making one-dimensional straightly linked chain structure might be the magnetic force of the Fe clusters. The formation of straightly linked Fe clusters chains suggests the formation of single magnetic domain Fe clusters. PACS 07.79.Cz, 81.15.-z, 75.75.Fk PMID:25170327

  12. Fast lithium intercalation chemistry of the hierarchically porous Li2FeP2O7/C composite prepared by an iron-reduction method

    NASA Astrophysics Data System (ADS)

    Tan, L.; Zhang, S.; Deng, C.

    2015-02-01

    Lithium iron pyrophosphate has drawn great attention because of its interesting physical and electrochemical properties, whereas its high rate capability is far from satisfactory. We synthesize nano-Li2FeP2O7/C with hierarchical pore via a low cost method which uses iron powder instead of Vitamin C as the reducing agent. The hierarchical pore is constructed through a "combustion" mechanism according to the thermogravimetric and morphological characterizations. The phase-pure nanoparticles of Li2FeP2O7 are embedded in the three-dimensional network of amorphous carbon. The hierarchical pore together with the two-dimensional diffusion channel of lithium in Li2FeP2O7 is beneficial to lithium diffusion capability which is evaluated by the lithium diffusion coefficients calculated from the results of GITT measurements. The fast lithium intercalation chemistry facilitates the reversible de/intercalation of lithium, resulting in the high cycling stability and rate-capability. After 100 cycles at the current density of 1C, 93.8% of the initial capacity is retained. The discharge capacity is 62.1 mAh g-1 at the current density of 4C. Therefore, the hierarchically porous nano-Li2FeP2O7/C is a promising cathode material for advanced rechargeable lithium ion battery.

  13. BnaC9.SMG7b Functions as a Positive Regulator of the Number of Seeds per Silique in Brassica napus by Regulating the Formation of Functional Female Gametophytes.

    PubMed

    Li, Shipeng; Chen, Lei; Zhang, Liwu; Li, Xi; Liu, Ying; Wu, Zhikun; Dong, Faming; Wan, Lili; Liu, Kede; Hong, Dengfeng; Yang, Guangsheng

    2015-12-01

    Number of seeds per silique (NSS) is an important determinant of seed yield potential in Brassicaceae crops, and it is controlled by naturally occurring quantitative trait loci. We previously mapped a major quantitative trait locus, qSS.C9, on the C9 chromosome that controls NSS in Brassica napus. To gain a better understanding of how qSS.C9 controls NSS in B. napus, we isolated this locus through a map-based cloning strategy. qSS.C9 encodes a predicted small protein with 119 amino acids, designated as BnaC9.SMG7b, that shows homology with the Ever ShorterTelomere1 tertratricopeptide repeats and Ever Shorter Telomere central domains of Arabidopsis (Arabidopsis thaliana) SUPPRESSOR WITH MORPHOGENETIC EFFECTS ON GENITALIA7 (SMG7). BnaC9.SMG7b plays a role in regulating the formation of functional female gametophyte, thus determining the formation of functional megaspores and then mature ovules. Natural loss or artificial knockdown of BnaC9.SMG7b significantly reduces the number of functional ovules per silique and thus, results in decreased seed number, indicating that qSS.C9 is a positive regulator of NSS in B. napus. Sequence and function analyses show that BnaC9.SMG7b experiences a subfunctionalization process that causes loss of function in nonsense-mediated mRNA decay, such as in Arabidopsis SMG7. Haplotype analysis in 84 accessions showed that the favorable BnaC9.SMG7b alleles are prevalent in modern B. napus germplasms, suggesting that this locus has been a major selection target of B. napus improvement. Our results represent the first step toward unraveling the molecular mechanism that controls the natural variation of NSS in B. napus. PMID:26494121

  14. Effective treatment of a murine model of adult T-cell leukemia using 211At-7G7/B6 and its combination with unmodified anti-Tac (daclizumab) directed toward CD25.

    PubMed

    Zhang, Zhuo; Zhang, Meili; Garmestani, Kayhan; Talanov, Vladimir S; Plascjak, Paul S; Beck, Barbara; Goldman, Carolyn; Brechbiel, Martin W; Waldmann, Thomas A

    2006-08-01

    Adult T-cell leukemia (ATL) consists of an overabundance of T cells, which express CD25. Therapeutic efficacy of astatine-211 ((211)At)-labeled murine monoclonal antibody 7G7/B6 alone and in combination with daclizumab was evaluated in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice given injections of MET-1 human T-cell leukemia cells. Daclizumab and 7G7/B6 are directed toward different epitopes of CD25. Either a single dose of 12 microCi (0.444 MBq) (211)At-7G7/B6 per mouse given intravenously or receptor-saturating doses of daclizumab given at 100 microg weekly for 4 weeks intravenously inhibited tumor growth as monitored by serum levels of human beta-2 microglobulin (beta(2)mu) and by prolonged survival of leukemia-bearing mice compared with the control groups (P < .001). The combination of 2 agents enhanced the antitumor effect when compared with groups treated with 12 microCi (0.444 MBq) of (211)At-7G7/B6 (P < .05) or daclizumab alone (P < .05). The median survival duration of the PBS group was 62.6 days and 61.5 days in the radiolabeled nonspecific antibody (211)At-11F11-treated group. In contrast, 91% of mice in the combination group survived through day 94. These results that demonstrate a significantly improved therapeutic efficacy by combining (211)At-7G7/B6 with daclizumab support a clinical trial of this regimen in patients with ATL. PMID:16569769

  15. Substrate-Induced Transcriptional Activation of the MoCel7C Cellulase Gene Is Associated with Methylation of Histone H3 at Lysine 4 in the Rice Blast Fungus Magnaporthe oryzae

    PubMed Central

    Vu, Ba Van; Pham, Kieu Thi Minh

    2013-01-01

    The mechanisms involved in substrate-dependent regulation of a Magnaporthe oryzae gene encoding a cellulase which we designate MoCel7C (MGG_14954) were investigated. The levels of MoCel7C transcript were dramatically increased more than 1,000-fold, 16 to 24 h after transfer to a medium containing 2% carboxymethylcellulose (CMC), while levels were very low or undetectable in conventional rich medium. Green fluorescent protein reporter assays showed that the MoCel7C promoter was activated by cello-oligosaccharides larger than a pentamer. CMC-induced activation of the MoCel7C promoter was suppressed by glucose and cellobiose. Chromatin immunoprecipitation assays revealed that histone H3 methylation on lysine 4 (H3K4) at the MoCel7C locus was associated with activation of the gene by CMC. Consistently, CMC-induced MoCel7C gene activation was drastically diminished in a knockout (KO) mutant of the MoSET1 gene, which encodes a histone lysine methyltransferase that catalyzes H3K4 methylation in M. oryzae. Interestingly, however, MoCel7C transcript levels under noninducing conditions were significantly increased in the MoSET1 KO mutant, suggesting that MoSET1 directly or indirectly plays a role in both activation and suppression of the MoCel7C gene in response to environmental signals. In addition, gene expression and silencing vectors using the MoCel7C promoter were constructed. PMID:23995923

  16. Immunogenicity, reactogenicity, and safety of a P1.7b,4 strain-specific serogroup B meningococcal vaccine given to preteens.

    PubMed

    Hosking, Jamie; Rasanathan, Kumanan; Mow, Florina Chan; Jackson, Catherine; Martin, Diana; O'Hallahan, Jane; Oster, Philipp; Ypma, Ellen; Reid, Stewart; Aaberge, Ingeborg; Crengle, Sue; Stewart, Joanna; Lennon, Diana

    2007-11-01

    New Zealand (NZ) has experienced a Neisseria meningitidis serogroup B epidemic since 1991. MeNZB, a strain-specific outer membrane vesicle vaccine made using an NZ epidemic strain isolate, NZ98/254 (B:4:P1.7b,4), from two manufacturing sites, the Norwegian Institute of Public Health (NIPH) and Chiron Vaccines (CV; now Novartis), was evaluated for safety, immunogenicity, and reactogenicity in this observer-blind trial with 8- to 12-year-old children. In year 1, cohort A (n = 302) was randomized 4:1 for receipt of NIPH-MeNZB or MenBvac (Norwegian parent vaccine strain 44/76; B:15:P1.7,16). In year 2, cohort B (n = 313) was randomized 4:1 for receipt of CV-MeNZB or NIPH-MeNZB. Participants all received three vaccinations 6 weeks apart. Local and systemic reactions were monitored for 7 days. Seroresponse was defined as a fourfold or greater rise in the serum bactericidal antibody titer from the baseline titer as measured by a serum bactericidal assay. Those with baseline titers of <1:4 required titers of >/=1:8 to serorespond. Intention-to-treat (ITT) and per protocol (PP) analyses are presented. In cohort A, 74% (ITT) and 73% (PP) of NIPH-MeNZB recipients demonstrated seroresponses against NZ98/254 after three doses, versus 32% (ITT and PP) of MenBvac recipients. In cohort B, seroresponses against NZ98/254 after three doses occurred in 79% (ITT and PP) of CV-MeNZB versus 75% (ITT) and 76% (PP) of NIPH-MeNZB recipients. Vaccines were tolerable, with no vaccine-related serious adverse events. In conclusion, the NZ strain meningococcal B vaccine (MeNZB) from either manufacturing site was immunogenic against New Zealand epidemic vaccine strain meningococci with no safety concerns when given in three doses to these 8- to 12-year-old children. PMID:17898183

  17. Novel BCOR-MAML3 and ZC3H7B-BCOR Gene Fusions in Undifferentiated Small Blue Round Cell Sarcomas.

    PubMed

    Specht, Katja; Zhang, Lei; Sung, Yun-Shao; Nucci, Marisa; Dry, Sarah; Vaiyapuri, Sumathi; Richter, Gunther H S; Fletcher, Christopher D M; Antonescu, Cristina R

    2016-04-01

    Small blue round cell tumors (SBRCTs) are a heterogenous group of tumors that are difficult to diagnose because of overlapping morphologic, immunohistochemical, and clinical features. About two-thirds of EWSR1-negative SBRCTs are associated with CIC-DUX4-related fusions, whereas another small subset shows BCOR-CCNB3 X-chromosomal paracentric inversion. Applying paired-end RNA sequencing to an SBRCT index case of a 44-year-old man, we identified a novel BCOR-MAML3 chimeric fusion, which was validated by reverse transcription polymerase chain reaction and fluorescence in situ hybridization techniques. We then screened a total of 75 SBRCTs lacking EWSR1, FUS, SYT, CIC, and BCOR-CCNB3 abnormalities for BCOR break-apart probes by fluorescence in situ hybridization to detect potential recurrent BCOR gene rearrangements outside the typical X-chromosomal inversion. Indeed, 8/75 (11%) SBRCTs showed distinct BCOR gene rearrangements, with 2 cases each showing either a BCOR-MAML3 or the alternative ZC3H7B-BCOR fusion, whereas no fusion partner was detected in the remaining 4 cases. Gene expression of the BCOR-MAML3-positive index case showed a distinct transcriptional profile with upregulation of HOX-gene signature, compared with classic Ewing's sarcoma or CIC-DUX4-positive SBRCTs. The clinicopathologic features of the SBRCTs with alternative BCOR rearrangements were also compared with a group of BCOR-CCNB3 inversion-positive cases, combining 11 from our files with a meta-analysis of 42 published cases. The BCOR-CCNB3-positive tumors occurred preferentially in children and in bone, in contrast to alternative BCOR-rearranged SBRCTs, which presented in young adults, with a variable anatomic distribution. Furthermore, BCOR-rearranged tumors often displayed spindle cell areas, either well defined in intersecting fascicles or blending with the round cell component, which appears distinct from most other fusion-positive SBRCTs and shares histologic overlap with poorly

  18. 7 CFR 201.7a - Treated seed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Treated seed. 201.7a Section 201.7a Agriculture..., Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Records for Agricultural and Vegetable Seeds § 201.7a Treated seed. The complete record for...

  19. 7 CFR 201.7a - Treated seed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Treated seed. 201.7a Section 201.7a Agriculture..., Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Records for Agricultural and Vegetable Seeds § 201.7a Treated seed. The complete record for...

  20. 17 CFR 260.7a-4 - Calculation of time.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Calculation of time. 260.7a-4 Section 260.7a-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rules Under Section 307 § 260.7a-4 Calculation...

  1. 7 CFR 201.7a - Treated seed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Treated seed. 201.7a Section 201.7a Agriculture..., Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Records for Agricultural and Vegetable Seeds § 201.7a Treated seed. The complete record for...

  2. 7 CFR 201.7a - Treated seed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Treated seed. 201.7a Section 201.7a Agriculture..., Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Records for Agricultural and Vegetable Seeds § 201.7a Treated seed. The complete record for...

  3. 7 CFR 201.7a - Treated seed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Treated seed. 201.7a Section 201.7a Agriculture..., Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Records for Agricultural and Vegetable Seeds § 201.7a Treated seed. The complete record for...

  4. Total Syntheses of Bryostatins. Syntheses of Two Ring-Expanded Bryostatin Analogues and Development of a New-Generation Strategy to Access the C7-C27 Fragment

    PubMed Central

    Yang, Hanbiao; Dong, Guangbin

    2012-01-01

    This paper reports the synthesis of novel ring-expanded bryostatin analogues. By carefully modifying the substrate, a selective and high-yielding Ru-catalyzed tandem enyne coupling/Michael addition was employed to construct the northern fragment. A ring-closing metathesis was utilized to form the 31-membered macrocycle of the analogue. These ring-expanded bryostatin analogues possess anticancer activity against several cancer cell lines. Given the difficulty of forming the C16-17 olefin in the late stage, we also describe our development of a new-generation strategy to access the C7-C27 fragment containing both the B- and C-ring subunits. PMID:21780195

  5. LBT/LUCIFER view of star-forming galaxies in the cluster 7C 1756+6520 at z ˜ 1.4

    NASA Astrophysics Data System (ADS)

    Magrini, Laura; Sommariva, Veronica; Cresci, Giovanni; Sani, Eleonora; Galametz, Audrey; Mannucci, Filippo; Petropoulou, Vasiliki; Fumana, Marco

    2012-10-01

    Galaxy clusters are key places to study the contribution of nature (i.e. mass and morphology) and nurture (i.e. environment) in the formation and evolution of galaxies. Recently, a number of clusters at z > 1, i.e. corresponding to the first epochs of the cluster formation, have been discovered and confirmed spectroscopically. We present new observations obtained with the LBT Near Infrared Spectroscopic Utility with Camera and Integral Field Unit for Extragalactic Research (LUCIFER) spectrograph at Large Binocular Telescope (LBT) of a sample of star-forming galaxies associated with a large-scale structure around the radio galaxy 7C 1756+6520 at z = 1.42. Combining our spectroscopic data and the literature photometric data, we derived some of the properties of these galaxies: star formation rate, metallicity and stellar mass. With the aim of analysing the effect of the cluster environment on galaxy evolution, we have located the galaxies in the plane of the so-called fundamental metallicity relation (FMR), which is known not to evolve with redshift up to z = 2.5 for field galaxies, but it is still unexplored in rich environments at low and high redshifts. We found that the properties of the galaxies in the cluster 7C 1756+6520 are compatible with the FMR which suggests that the effect of the environment on galaxy metallicity at this early epoch of cluster formation is marginal. As a side study, we also report the spectroscopic analysis of a bright active galactic nucleus, belonging to the cluster, which shows a significant outflow of gas.

  6. ATP7A trafficking and mechanisms underlying the distal motor neuropathy induced by mutations in ATP7A.

    PubMed

    Yi, Ling; Kaler, Stephen

    2014-05-01

    Diverse mutations in the gene encoding the copper transporter ATP7A lead to X-linked recessive Menkes disease or occipital horn syndrome. Recently, two unique ATP7A missense mutations, T994I and P1386S, were shown to cause isolated adult-onset distal motor neuropathy. These mutations induce subtle defects in ATP7A intracellular trafficking resulting in preferential accumulation at the plasma membrane compared to wild-type ATP7A. Immunoprecipitation assays revealed abnormal interaction between ATP7A(T994I) and p97/VCP, a protein mutated in two autosomal dominant forms of motor neuron disease. Small-interfering RNA knockdown of valosin-containing protein corrected ATP7A(T994I) mislocalization. For ATP7A(P1386S) , flow cytometry documented that nonpermeabilized fibroblasts bound a C-terminal ATP7A antibody, suggesting unstable insertion of the eighth transmembrane segment due to a helix-breaker effect of the amino acid substitution. This could sabotage interaction of ATP7A(P1386S) with adaptor protein complexes. These molecular events appear to selectively disturb normal motor neuron function and lead to neurologic illness that takes years and sometimes decades to develop. PMID:24754450

  7. 17 CFR 260.7a-19 - Margin for binding.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Margin for binding. 260.7a-19...) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Formal Requirements § 260.7a-19 Margin for... and documents filed as a part thereof, shall have a back or stitching margin of at least 11/2...

  8. 17 CFR 260.7a-19 - Margin for binding.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Margin for binding. 260.7a-19...) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Formal Requirements § 260.7a-19 Margin for... and documents filed as a part thereof, shall have a back or stitching margin of at least 11/2...

  9. Sec61β Controls Sensitivity to Platinum-Containing Chemotherapeutic Agents through Modulation of the Copper-Transporting ATPase ATP7A

    PubMed Central

    Larson, Christopher A.; Manorek, Gerald; Adams, Preston; Howell, Stephen B.

    2012-01-01

    The Sec61 protein translocon is a multimeric complex that transports proteins across lipid bilayers. We discovered that the Sec61β subunit modulates cellular sensitivity to chemotherapeutic agents, particularly the platinum drugs. To investigate the mechanism, expression of Sec61β was constitutively knocked down in 2008 ovarian cancer cells. Sec61β knockdown (KD) resulted in 8-, 16.8-, and 9-fold resistance to cisplatin (cDDP), carboplatin, and oxaliplatin, respectively. Sec61β KD reduced the cellular accumulation of cDDP to 67% of that in parental cells. Baseline copper levels, copper uptake, and copper cytotoxicity were also reduced. Because copper transporters and chaperones regulate platinum drug accumulation and efflux, their expression in 2008 Sec61β-KD cells was analyzed; ATP7A was found to be 2- to 3-fold overexpressed, whereas there was no change in ATP7B, ATOX1, CTR1, or CTR2 levels. Cells lacking ATP7A did not exhibit increased cDDP resistance upon knockdown of Sec61β. Sec61β-KD cells also exhibited altered ATP7A cellular distribution. We conclude that Sec61β modulates the cytotoxicity of many chemotherapeutic agents, with the largest effect being on the platinum drugs. This modulation occurs through effects of Sec61β on the expression and distribution of ATP7A, which was shown previously to control platinum drug sequestration and cytotoxicity. PMID:22710939

  10. ZBTB7A suppresses melanoma metastasis by transcriptionally repressing MCAM

    PubMed Central

    Liu, Xue-Song; Genet, Matthew D; Haines, Jenna E; Mehanna, Elie K; Wu, Shaowei; Chen, Hung-I Harry; Chen, Yidong; Qureshi, Abrar A; Han, Jiali; Chen, Xiang; Fisher, David E; Pandolfi, Pier Paolo; Yuan, Zhi-Min

    2015-01-01

    The excessive metastatic propensity of melanoma makes it the most deadly form of skin cancer, yet the underlying mechanism of metastasis remains elusive. Here, mining of cancer genome datasets discovered a frequent loss of chromosome 19p13.3 and associated down-regulation of the zinc finger transcription factor ZBTB7A in metastatic melanoma. Functional assessment of ZBTB7A-regulated genes identified MCAM, which encodes an adhesion protein key to melanoma metastasis. Using an integrated approach, it is demonstrated that ZBTB7A directly binds to the promoter and transcriptionally represses the expression of MCAM, establishing ZBTB7A as a bona fide transcriptional repressor of MCAM. Consistently, down-regulation of ZBTB7A results in marked upregulation of MCAM and enhanced melanoma cell invasion and metastasis. An inverse correlation of ZBTB7A and MCAM expression in association with melanoma metastasis is further validated with data from analysis of human melanoma specimens. Implications Together these results uncover a previously unrecognized role of ZBTB7A in negative regulation of melanoma metastasis and have important clinical implications. PMID:25995384

  11. A sesquiterpene lactone antrocin from Antrodia camphorata negatively modulates JAK2/STAT3 signaling via microRNA let-7c and induces apoptosis in lung cancer cells.

    PubMed

    Yeh, Chi-Tai; Huang, Wen-Chien; Rao, Yerra Koteswara; Ye, Min; Lee, Wei-Hwa; Wang, Liang-Shun; Tzeng, David T W; Wu, Chih-Hsiung; Shieh, Yi-Shing; Huang, Chi-Ying F; Chen, Yu-Jen; Hsiao, Michael; Wu, Alexander T H; Yang, Zhen; Tzeng, Yew-Min

    2013-12-01

    Lung cancer is the leading cause of cancer deaths worldwide and current therapies fail to treat this disease in majority of cases. Antrodia camphorata is a medicinal mushroom being widely used as food dietary supplement for cancer prevention. The sesquiterpene lactone antrocin is the most potent among >100 secondary metabolites isolated from A. camphorata. However, the molecular mechanisms of antrocin-mediated anticancer effects remain unclear. In this study, we found that antrocin inhibited cell proliferation in two non-small-cell lung cancer cells, namely H441 (wild-type epidermal growth factor receptor, IC50 = 0.75 μM) and H1975 (gefitnib-resistant mutant T790M, IC50 = 0.83 μM). Antrocin dose dependently suppressed colony formation and induced apoptosis as evidenced by activated caspase-3 and increased Bax/Bcl2 ratio. Gene profiling studies indicated that antrocin downregulated Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. We further demonstrated that antrocin suppressed both constitutively activated and interleukin 6-induced STAT3 phosphorylation and its subsequent nuclear translocation. Such inhibition is found to be achieved through the suppression of JAK2 and interaction between STAT3 and extracellular signal-regulated kinase. Additionally, antrocin increased microRNA let-7c expression and suppressed STAT signaling. The combination of antrocin and JAK2/STAT3 gene silencing significantly increased apoptosis in H441 cells. Such dual interruption of JAK2 and STAT3 pathways also induced downregulation of antiapoptotic protein mcl-1 and increased caspase-3 expression. In vivo intraperitoneal administration of antrocin significantly suppressed the growth of lung cancer tumor xenografts. Our results indicate that antrocin may be a potential therapeutic agent for human lung cancer cells through constitutive inhibition of JAK2/STAT3 pathway. PMID:23880305

  12. Discovery of a Neuroprotective Chemical, (S)-N-(3-(3,6-Dibromo-9H-carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-amine [(−)-P7C3-S243], with Improved Druglike Properties

    PubMed Central

    2015-01-01

    (−)-P7C3-S243 is a neuroprotective aminopropyl carbazole with improved druglike properties compared with previously reported compounds in the P7C3 class. It protects developing neurons in a mouse model of hippocampal neurogenesis and protects mature neurons within the substantia nigra in a mouse model of Parkinson’s disease. A short, enantioselective synthesis provides the neuroprotective agent in optically pure form. It is nontoxic, orally bioavailable, metabolically stable, and able to cross the blood–brain barrier. As such, it represents a valuable lead compound for the development of drugs to treat neurodegenerative diseases and traumatic brain injury. PMID:24697290

  13. The influence of pressure on the phase stability of nanocomposite Fe{sub 89}Zr{sub 7}B{sub 4} during heating from energy dispersive x-ray diffraction

    SciTech Connect

    Leary, A M; Lucas, M S; Ohodnicki, P R; Kernion, S J; Mauger, L; Park, C; Kenney-Benson, C; McHenry, M E

    2013-05-07

    Nanocomposite materials consisting of small crystalline grains embedded within an amorphous matrix show promise for many soft magnetic applications. The influence of pressure is investigated by in situ diffraction of hammer milled Fe{sub 89}Zr{sub 7}B{sub 4} during heating through the α → γ Fe transition at 0.5, 2.2, and 4.9 GPa. The changes in primary and secondary crystallization onset are described by diffusion and the energy to form a critical nucleus within the framework of classical nucleation theory.

  14. The influence of pressure on the phase stability of nanocomposite Fe{sub 89}Zr{sub 7}B{sub 4} during heating from energy dispersive x-ray diffraction

    SciTech Connect

    Leary, A. M.; Kernion, S. J.; McHenry, M. E.; Lucas, M. S.; Ohodnicki, P. R.; Mauger, L.; Park, C.; Kenney-Benson, C.

    2013-05-07

    Nanocomposite materials consisting of small crystalline grains embedded within an amorphous matrix show promise for many soft magnetic applications. The influence of pressure is investigated by in situ diffraction of hammer milled Fe{sub 89}Zr{sub 7}B{sub 4} during heating through the {alpha}{yields}{gamma} Fe transition at 0.5, 2.2, and 4.9 GPa. The changes in primary and secondary crystallization onset are described by diffusion and the energy to form a critical nucleus within the framework of classical nucleation theory.

  15. DOT-7A Type A packaging design guide

    SciTech Connect

    Kelly, D.L.

    1995-01-23

    The purpose of this Design Guide is to provide instruction for designing a U.S. Department of Transportation Specification 7A (DOT-7A) Type A packaging. Another purpose for this Design Guide is to support the evaluation and testing activities that are performed on new designs by a U.S. Department of Energy (DOE) test facility. This evaluation and testing program is called the DOT-7A Program. When an applicant has determined that a DOT-7A packaging is needed and not commercially available, a design may be created according to this document. The design should include a packaging drawing, specifications, analysis report, operating instructions, and a Packaging Qualification Checklist; all of which should be forwarded to a DOE/HQ approved test facility for evaluation and testing. This report is being submitted through the Engineering Documentation System so that it may be used for reference and information purposes.

  16. Characterization of Vadose Zone Sediment: Borehole C3103 Located in the 216-B-7A Crib Near the B Tank Farm

    SciTech Connect

    Lindenmeier, Clark W.; Serne, R JEFFREY.; Bjornstad, Bruce N.; Last, George V.; Lanigan, David C.; Lindberg, Michael J.; Clayton, Ray E.; Legore, Virginia L.; Kutnyakov, Igor V.; Baum, Steven R.; Geiszler, Keith N.; Valenta, Michelle M.; Vickerman, Tanya S.

    2002-12-01

    This report summarizes data collected from samples in borehole C3103. Borehole C3103 was completed to further characterize the nature and extent of vadose zone contaminants supplied by intentional liquid discharges into the crib 216-B7A/7B between 1954 and 1967. These cribs received dilute waste streams from the bismuth phosphate fuel reprocessing program in the 1950's and decontamination waste in the 1960's. Elevated concentrations of several constituents were primarily measured at different depth intervals. The primary radionuclides present in this borehole are cesium-137 and uranium near the top of the borehole. Chemical characteristics attributed to wastewater-soil interaction at different locations within this zone are elevated pH, sodium, fluoride, carbonate nitrate, and sulphate

  17. Maturation of cortical circuits requires Semaphorin 7A.

    PubMed

    Carcea, Ioana; Patil, Shekhar B; Robison, Alfred J; Mesias, Roxana; Huntsman, Molly M; Froemke, Robert C; Buxbaum, Joseph D; Huntley, George W; Benson, Deanna L

    2014-09-23

    Abnormal cortical circuits underlie some cognitive and psychiatric disorders, yet the molecular signals that generate normal cortical networks remain poorly understood. Semaphorin 7A (Sema7A) is an atypical member of the semaphorin family that is GPI-linked, expressed principally postnatally, and enriched in sensory cortex. Significantly, SEMA7A is deleted in individuals with 15q24 microdeletion syndrome, characterized by developmental delay, autism, and sensory perceptual deficits. We studied the role that Sema7A plays in establishing functional cortical circuitry in mouse somatosensory barrel cortex. We found that Sema7A is expressed in spiny stellate cells and GABAergic interneurons and that its absence disrupts barrel cytoarchitecture, reduces asymmetrical orientation of spiny stellate cell dendrites, and functionally impairs thalamocortically evoked synaptic responses, with reduced feed-forward GABAergic inhibition. These data identify Sema7A as a regulator of thalamocortical and local circuit development in layer 4 and provide a molecular handle that can be used to explore the coordinated generation of excitatory and inhibitory cortical circuits. PMID:25201975

  18. Alleviating product inhibition in cellulase enzyme Cel7A.

    PubMed

    Atreya, Meera E; Strobel, Kathryn L; Clark, Douglas S

    2016-02-01

    Enzymes that degrade cellulose into glucose are one of the most expensive components of processes for converting cellulosic biomass to fuels and chemicals. Cellulase enzyme Cel7A is the most abundant enzyme naturally employed by fungi to depolymerize cellulose, and like other cellulases is inhibited by its product, cellobiose. There is thus great economic incentive for minimizing the detrimental effects of product inhibition on Cel7A. In this work, we experimentally generated 10 previously proposed site-directed mutant Cel7A enzymes expected to have reduced cellobiose binding energies (the majority of mutations were to alanine). We then tested their resilience to cellobiose as well as their hydrolytic activities on microcrystalline cellulose. Although every mutation tested conferred reduced product inhibition (and abolished it for some), our results confirm a trade-off between Cel7A tolerance to cellobiose and enzymatic activity: Reduced product inhibition was accompanied by lower overall enzymatic activity on crystalline cellulose for the mutants tested. The tempering effect of mutations on inhibition was nearly constant despite relatively large differences in activities of the mutants. Our work identifies an amino acid in the Cel7A product binding site of interest for further mutational studies, and highlights both the challenge and the opportunity of enzyme engineering toward improving product tolerance in Cel7A. PMID:26302366

  19. G9a/RelB regulates self-renewal and function of colon-cancer-initiating cells by silencing Let-7b and activating the K-RAS/β-catenin pathway.

    PubMed

    Cha, Shih-Ting; Tan, Ching-Ting; Chang, Cheng-Chi; Chu, Chia-Yu; Lee, Wei-Jiunn; Lin, Been-Zen; Lin, Ming-Tsan; Kuo, Min-Liang

    2016-09-01

    Epigenetic reprogramming has been associated with the functional plasticity of cancer-initiating cells (CICs); however, the regulatory pathway has yet to be elucidated. A siRNA screen targeting known epigenetic genes revealed that G9a profoundly impairs the chemo-resistance, self-renewal and metastasis of CICs obtained from patients with colorectal cancer (CRC). Patients with elevated G9a were shown to face a high risk of relapse and poor survival rates. From a mechanistic perspective, G9a binds with and stabilizes RelB, thereby recruiting DNA methyltransferase 3 on the Let-7b promoter and repressing its expression. This leads to the activation of the K-RAS/β-catenin pathway and regulates self-renewal and function of CICs. These findings indicate that the G9a/RelB/Let-7b axis acts as a critical regulator in the maintenance of CIC phenotypes and is strongly associated with negative clinical outcomes. Thus, these findings may have diagnostic as well as therapeutic implications for the treatment of chemotherapy-resistant or metastatic CRC. PMID:27525719

  20. Study on feasibility of producing an amorphous surface layer of Fe49Cr18Mo7B16C4Nb3 by pulsed Nd:YAG laser surface melting

    NASA Astrophysics Data System (ADS)

    Mojaver, Reza; Mojtahedi, Faezeh; Shahverdi, Hamid Reza; Torkamany, Mohammad Javad

    2013-01-01

    This work aims to investigate whether an amorphous surface layer can be obtained when as-cast Fe49Cr18Mo7B16C4Nb3 alloy is submitted to pulsed Nd:YAG laser surface melting. The experiments were conducted in the various laser scanning speeds. The microstructures of laser treated zones were investigated by X-ray diffraction XRD and Field Emission Scanning Electron Microscope (FESEM) and their microhardness were measured, too. The chemical composition of different points of each sample was analyzed by energy-dispersive X-ray spectroscopy EDS. Although the estimated cooling rates in surface layers were higher than the required cooling rate to achieve full amorphization, but the present experiments were unable to retain complete glassy microstructure on surface and a mixture of amorphous (low volume fraction) and ultrafine grained phases were produced in surface of samples. Based on the findings, it was understood that the overlapping of successive pulses and element redistributions occurred in pulsed laser melting could severely restrict amorphization. The influence of laser scan speed and laser power on heat input, melting ratio, compositional changes and cracking in laser treated zone were discussed separately. It is suggested that the limited range of laser variables in pulsed Nd:YAG laser melting may help to produce a sound amorphous phase of as-cast Fe49Cr18Mo7B16C4Nb3 alloy.

  1. microRNA let-7c is essential for the anisomycin-elicited apoptosis in Jurkat T cells by linking JNK1/2 to AP-1/STAT1/STAT3 signaling.

    PubMed

    Zhou, Zhiwei; Lu, Xijian; Wang, Jin; Xiao, Jia; Liu, Jing; Xing, Feiyue

    2016-01-01

    Anisomycin, an antibiotic produced by Streptomyces griseolus, strongly induces apoptosis in various tumor cells in vitro, superior dramatically to adriamycin. The present study aims to elucidate its detailed mechanistic process. The results showed that anisomycin sufficiently promoted the apoptosis in human leukemic Jurkat T cells at a quite low dose. microRNA let-7c (let-7c) contributed to the anisomycin-induced apoptosis, which could be abrogated by the inactivation of JNK signaling. The let-7c over-expression and the addition of its mimics facilitated the activation of AP-1, STAT1 and Bim by linking JNK1/2 to AP-1/STAT1, but rather inhibited the activation of STAT3 and Bcl-xL by connecting JNK1/2 to STAT3, followed by the augmented apoptosis in the cells. The let-7c deficiency reduced the AP-1, STAT1 and Bim activities, and enhanced the STAT3 and Bcl-xL, alleviating the anisomycin-induced apoptosis. The knockdown of the bim gene repressed the anisomycin-boosted apoptosis through the attenuation of the active Bak and Bax. The findings indicate for the first time that miR let-7c is essential for the anisomycin-triggered apoptosis by linking JNK1/2 to AP-1/STAT1/STAT3/Bim/Bcl-xL/Bax/Bak signaling. This provides a novel insight into the mechanism by which anisomycin leads to the tumor cell apoptosis, potentially laying the foundations for its development and clinical application. PMID:27087117

  2. microRNA let-7c is essential for the anisomycin-elicited apoptosis in Jurkat T cells by linking JNK1/2 to AP-1/STAT1/STAT3 signaling

    PubMed Central

    Zhou, Zhiwei; Lu, Xijian; Wang, Jin; Xiao, Jia; Liu, Jing; Xing, Feiyue

    2016-01-01

    Anisomycin, an antibiotic produced by Streptomyces griseolus, strongly induces apoptosis in various tumor cells in vitro, superior dramatically to adriamycin. The present study aims to elucidate its detailed mechanistic process. The results showed that anisomycin sufficiently promoted the apoptosis in human leukemic Jurkat T cells at a quite low dose. microRNA let-7c (let-7c) contributed to the anisomycin-induced apoptosis, which could be abrogated by the inactivation of JNK signaling. The let-7c over-expression and the addition of its mimics facilitated the activation of AP-1, STAT1 and Bim by linking JNK1/2 to AP-1/STAT1, but rather inhibited the activation of STAT3 and Bcl-xL by connecting JNK1/2 to STAT3, followed by the augmented apoptosis in the cells. The let-7c deficiency reduced the AP-1, STAT1 and Bim activities, and enhanced the STAT3 and Bcl-xL, alleviating the anisomycin-induced apoptosis. The knockdown of the bim gene repressed the anisomycin-boosted apoptosis through the attenuation of the active Bak and Bax. The findings indicate for the first time that miR let-7c is essential for the anisomycin-triggered apoptosis by linking JNK1/2 to AP-1/STAT1/STAT3/Bim/Bcl-xL/Bax/Bak signaling. This provides a novel insight into the mechanism by which anisomycin leads to the tumor cell apoptosis, potentially laying the foundations for its development and clinical application. PMID:27087117

  3. MicroRNA-7a regulates pancreatic β cell function

    PubMed Central

    Latreille, Mathieu; Hausser, Jean; Stützer, Ina; Zhang, Quan; Hastoy, Benoit; Gargani, Sofia; Kerr-Conte, Julie; Pattou, Francois; Zavolan, Mihaela; Esguerra, Jonathan L.S.; Eliasson, Lena; Rülicke, Thomas; Rorsman, Patrik; Stoffel, Markus

    2014-01-01

    Dysfunctional microRNA (miRNA) networks contribute to inappropriate responses following pathological stress and are the underlying cause of several disease conditions. In pancreatic β cells, miRNAs have been largely unstudied and little is known about how specific miRNAs regulate glucose-stimulated insulin secretion (GSIS) or impact the adaptation of β cell function to metabolic stress. In this study, we determined that miR-7 is a negative regulator of GSIS in β cells. Using Mir7a2 deficient mice, we revealed that miR-7a2 regulates β cell function by directly regulating genes that control late stages of insulin granule fusion with the plasma membrane and ternary SNARE complex activity. Transgenic mice overexpressing miR-7a in β cells developed diabetes due to impaired insulin secretion and β cell dedifferentiation. Interestingly, perturbation of miR-7a expression in β cells did not affect proliferation and apoptosis, indicating that miR-7 is dispensable for the maintenance of endocrine β cell mass. Furthermore, we found that miR-7a levels are decreased in obese/diabetic mouse models and human islets from obese and moderately diabetic individuals with compensated β cell function. Our results reveal an interconnecting miR-7 genomic circuit that regulates insulin granule exocytosis in pancreatic β cells and support a role for miR-7 in the adaptation of pancreatic β cell function in obesity and type 2 diabetes. PMID:24789908

  4. DOT-7A Type A packaging test and evaluation procedure

    SciTech Connect

    Kelly, D.L., Westinghouse Hanford

    1996-06-13

    The purpose of this document is to provide guidance for qualifying a DOT-7A Type A packaging for use. WHC qualifies DOT-7A packaging for two purposes. The first is to provide packages for use by WHC (manufacturer-qualified). The second is to provide a contracted service in support of DOE/EM-76 (DOE-qualified). This document includes descriptions of the performance tests, the personnel involved and their qualifications, appropriate safety and quality assurance considerations, and the procedures to be followed when WHC performs the tests (either as the manufacturer, or on behalf of the DOE`s certification program).

  5. TTC7A mutations disrupt intestinal epithelial apicobasal polarity

    PubMed Central

    Bigorgne, Amélie E.; Farin, Henner F.; Lemoine, Roxane; Mahlaoui, Nizar; Lambert, Nathalie; Gil, Marine; Schulz, Ansgar; Philippet, Pierre; Schlesser, Patrick; Abrahamsen, Tore G.; Oymar, Knut; Davies, E. Graham; Ellingsen, Christian Lycke; Leteurtre, Emmanuelle; Moreau-Massart, Brigitte; Berrebi, Dominique; Bole-Feysot, Christine; Nischke, Patrick; Brousse, Nicole; Fischer, Alain; Clevers, Hans; de Saint Basile, Geneviève

    2013-01-01

    Multiple intestinal atresia (MIA) is a rare cause of bowel obstruction that is sometimes associated with a combined immunodeficiency (CID), leading to increased susceptibility to infections. The factors underlying this rare disease are poorly understood. We characterized the immunological and intestinal features of 6 unrelated MIA-CID patients. All patients displayed a profound, generalized lymphocytopenia, with few lymphocytes present in the lymph nodes. The thymus was hypoplastic and exhibited an abnormal distribution of epithelial cells. Patients also had profound disruption of the epithelial barrier along the entire gastrointestinal tract. Using linkage analysis and whole-exome sequencing, we identified 10 mutations in tetratricopeptide repeat domain–7A (TTC7A), all of which potentially abrogate TTC7A expression. Intestinal organoid cultures from patient biopsies displayed an inversion of apicobasal polarity of the epithelial cells that was normalized by pharmacological inhibition of Rho kinase. Our data indicate that TTC7A deficiency results in increased Rho kinase activity, which disrupts polarity, growth, and differentiation of intestinal epithelial cells, and which impairs immune cell homeostasis, thereby promoting MIA-CID development. PMID:24292712

  6. 7. A DETAIL, TAKEN FROM THE EAST END OF THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. A DETAIL, TAKEN FROM THE EAST END OF THE BRIDGE. THIS IMAGE SHOWS THE MODERN, EDGE-LAID 2" X 4" DIMENSIONED LUMBER AS DECKING. - Freedom Bridge, Spanning West Fork of White River at County Road 590 South, Freedom, Owen County, IN

  7. REORGANIZED SCIENCE CURRICULUM, 7A, GRADE SEVEN SUPPLEMENT.

    ERIC Educational Resources Information Center

    Minneapolis Special School District 1, Minn.

    THE TWELFTH IN A SERIES OF 17 VOLUMES, THIS VOLUME PROVIDES THE SEVENTH GRADE TEACHER WITH A GUIDE TO THE REORGANIZED SCIENCE CURRICULUM OF THE MINNEAPOLIS PUBLIC SCHOOLS. THE MATERIALS ARE INTENDED TO BE AUGMENTED AND REVISED AS THE NEED ARISES. THE SEVENTH GRADE SUPPLEMENT IS IN TWO VOLUMES. VOLUME 7A CONTAINS INTRODUCTORY MATERIAL, A BRIEF…

  8. Two-current model of the composition dependence of resistivity in amorphous (Fe100-xCox)(89-y)Zr7B4Cuy alloys using a rigid-band assumption

    SciTech Connect

    Shen, S; Ohodnicki, PR; Kernion, SJ; McHenry, ME

    2012-11-15

    Composition dependence of resistivity is studied in amorphous (Fe100-xCox)(89-y)Zr7B4Cuy (0 <= x <= 50, y = 0, 1) alloys. The two-current model proposed by Mott for crystalline materials is extended to a disordered amorphous system where s-d scattering is dominant in electron conduction. A rigid-band assumption is made due to the small atomic number difference between Fe and Co. Band structures with a constant density of states (DOS), parabolic distributed DOS, and Gaussian distributed DOS were investigated to fit experimental data. The Gaussian distributed DOS was found to simulate the resistivity maximum and magnetic moment maximum in the Fe-rich region. The basic concepts presented here can potentially provide insight into the optimization of FeCo-based HITPERM alloys for applications at increased frequencies. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4765673

  9. In situ detection method for obtaining permeability of Fe-based amorphous alloys: ac resistance measurement for Fe{sub 84}Nb{sub 7}B{sub 9}

    SciTech Connect

    Ichitsubo, Tetsu; Matsubara, Eiichiro; Tanaka, Satoshi; Nishiyama, Nobuyuki; Amiya, Kenji

    2005-01-17

    In this letter, we propose an in situ detection method for obtaining permeability of soft magnetic Fe-based amorphous alloys. The temperature dependence of ac resistance was measured at different frequencies during heat treatment of Fe{sub 84}Nb{sub 7}B{sub 9} amorphous alloys. A significant increase in the ac ({approx}1000 kHz) resistance appears at around 920 K during the heating process, which arises from the skin effect caused by a marked increase in sample permeability. This skin effect diminishes when the sample is heated to approximately 1100 K, which corresponds to the decrease in its permeability. Consequently, we note that the ac resistance measurement is useful for quick in situ assessment to achieve the soft magnetic property of an Fe-based amorphous alloy.

  10. Tubby-RFP Balancers for Developmental Analysis: FM7c 2xTb-RFP, CyO 2xTb-RFP and TM3 2xTb-RFP

    PubMed Central

    Pina, Cara; Pignoni, Francesca

    2012-01-01

    We report here the construction of Tubby-RFP balancers for the X, 2nd and 3rd chromosomes of Drosophila melanogaster. The insertion of a 2xTb-RFP transgene on the FM7c, CyO and TM3 balancer chromosomes introduces two easily scorable, dominant, developmental markers. The strong Tb phenotype is visible to the naked eye at the larval L2, L3 and pupal stages. The RFP associated with the cuticle is easily detected at all stages from late embryo to adult with the use of a fluorescence stereomicroscope. The FM7c Bar 2xTb-RFP, CyO Cy 2xTb-RFP and TM3 Sb 2xTb-RFP balancers will greatly facilitate the analysis of lethals and other developmental mutants in L2/L3 larvae and pupae, but also provide coverage of other stages beginning in late embryogenesis through to the adult. PMID:21913310

  11. Synthesis of single phase {alpha}-Fe, Fe{sub 3}C and Fe{sub 7}C{sub 3} nano-particles by CO{sub 2} laser pyrolysis technique. Quarterly progress report, January--March, 1992

    SciTech Connect

    Eklund, P.C.; Bi, X.X.

    1992-07-01

    Iron-containing catalysts have been known to be useful in assisting the Fischer-Tropsch (FT) reaction for synthesizing hydrocarbons. However, it has been well recognized that iron catalyst are not stable during the reaction but converted into iron carbides. It is thus important to understand the role of the iron carbides in the catalytic reaction of the FT-synthesis. It has been found difficult to produce iron carbide nano-particles as a single phase, because iron carbide phases are only metastable under 1 atm pressure. Iron carbide bulk particles prepared so far are often contaminated with metallic iron, iron oxides and free carbon. In this study, we investigate the synthesis of iron carbide nano-particles using CO{sub 2} laser pyrolysis technique. We show that this technique is successful in synthesizing {alpha}-Fe, Fe{sub 3}C and Fe{sub 7}C{sub 3} nano-particles in their single phase with sizes in the range of 5--20nm. In particular, we have produced for the first time the Fe{sub 7}C{sub 3} which has been known to exist but unable to be produced as a single phase. Furthermore, it is interesting that Fe{sub 5}C{sub 2} which has carbon and iron ratio between Fe{sub 3}C and Fe{sub 7}C{sub 3}, is not seen in any run of our synthesis.

  12. SULFATE SOLUBILITY LIMIT VERIFICATION FOR DWPF SLUDGE BATCH 7A

    SciTech Connect

    Billings, A.

    2011-04-19

    During processing at the Defense Waste Processing Facility (DWPF), high sulfate concentrations in the feed are a concern to DWPF as it can lead to the formation of a detrimental, sulfate-rich, molten salt phase on the surface of the glass melt pool. To avoid these issues, a sulfate concentration limit was implemented into the Product Composition Control System (PCCS). Related to SB7a frit development efforts, the Savannah River National Laboratory (SRNL) assessed the viability of using the current 0.6 wt % SO{sub 4}{sup 2-} limit set for SB6 (in glass) and the possibility of increasing the SO{sub 4}{sup 2-} solubility limit in PCCS to account for anticipated sulfur concentrations, targeted waste loadings, and inclusion of secondary streams (e.g., Actinide Removal Process (ARP)) with two recommended frits (Frit 418 and Frit 702) for SB7a processing. For a nominal SB7a blend with a 63 inch SB6 heel remaining in Tank 40 (projection SB7a-63), a 0.60 wt% SO{sub 4}{sup 2-} in glass limit was determined for waste loadings of 34 wt% up to 40 wt% with Frit 418 based on crucible melts with batched chemicals. SRNL also examined the inclusion of ARP for the same blending scenario (SB7a-63-ARP) with Frit 418 and at least a 0.6 wt% SO{sub 4}{sup 2-} level, and waste loadings of 34 wt% to 40 wt% were also acceptable. When a visible yellow and/or white sulfate salt layer was visible on the surface of any cooled glass, it was assumed to have surpassed the solubility limit of SO{sub 4}{sup 2-} for that particular composition. All of the glasses fabricated at these concentrations did not exhibit a sulfate rich salt layer on the surface of the glass melt and retained the majority of the batched SO{sub 4}{sup 2-}. At higher levels of SO{sub 4}{sup 2-} 'spiked' into the projected sludge compositions over the aforementioned interval of waste loadings, with Frit 418, low viscosity sulfur layers were observed on the surface of glass melts which confirm exceeding the solubility limit. The

  13. The Lumenal Loop M672-P707 of the Menkes Protein (ATP7A) Transfers Copper to Peptidylglycine Monooxygenase

    PubMed Central

    Otoikhian, Adenike; Barry, Amanda N.; Mayfield, Mary; Nilges, Mark; Huang, Yiping; Lutsenko, Svetlana; Blackburn, Ninian J.

    2012-01-01

    Copper transfer to cuproproteins located in vesicular compartments of the secretory pathway depends on activity of the copper translocating ATPase (ATP7A or ATP7B) but the mechanism of transfer is largely unexplored. Copper-ATPase ATP7A is unique in having a sequence rich in histidine and methionine residues located on the lumenal side of the membrane. The corresponding fragment binds Cu(I) when expressed as a chimera with a scaffold protein, and mutations or deletions of His and/or Met residues in its sequence inhibit dephosphorylation of the ATPase, a catalytic step associated with copper release. Here we present evidence for a potential role of this lumenal region of ATP7A in copper transfer to cuproenzymes. Both Cu(II) and Cu(I) forms were investigated since the form in which copper is transferred to acceptor proteins is currently unknown. Analysis of Cu(II) using EPR demonstrated that at Cu:P ratios below 1:1, 15N-substituted protein had Cu(II) bound by 4 His residues, but this coordination changed as the Cu(II) to protein ratio increased towards 2:1. XAS confirmed this coordination via analysis of the intensity of outer-shell scattering from imidazole residues. The Cu(II) complexes could be reduced to their Cu(I) counterparts by ascorbate, but here again, as shown by EXAFS and XANES spectroscopy, the coordination was dependent on copper loading. At low copper Cu(I) was bound by a mixed ligand set of His + Met while at higher ratios His coordination predominated. The copper-loaded loop was able to transfer either Cu(II) or Cu(I) to peptidylglycine monooxygenase in the presence of chelating resin, generating catalytically active enzyme in a process that appeared to involve direct interaction between the two partners. The variation of coordination with copper loading suggests copper-dependent conformational change which in turn could act as a signal for regulating copper release by the ATPase pump. PMID:22577880

  14. The lumenal loop M672-P707 of the Menkes protein (ATP7A) transfers copper to peptidylglycine monooxygenase

    SciTech Connect

    Otoikhian, Adenike; Barry, Amanda N.; Mayfield, Mary; Nilges, Mark; Huang, Yiping; Lutsenko, Svetlana; Blackburn, Ninian

    2012-05-14

    Copper transfer to cuproproteins located in vesicular compartments of the secretory pathway depends on activity of the copper translocating ATPase (ATP7A or ATP7B) but the mechanism of transfer is largely unexplored. Copper-ATPase ATP7A is unique in having a sequence rich in histidine and methionine residues located on the lumenal side of the membrane. The corresponding fragment binds Cu(I) when expressed as a chimera with a scaffold protein, and mutations or deletions of His and/or Met residues in its sequence inhibit dephosphorylation of the ATPase, a catalytic step associated with copper release. Here we present evidence for a potential role of this lumenal region of ATP7A in copper transfer to cuproenzymes. Both Cu(II) and Cu(I) forms were investigated since the form in which copper is transferred to acceptor proteins is currently unknown. Analysis of Cu(II) using EPR demonstrated that at Cu:P ratios below 1:1, 15N-substituted protein had Cu(II) bound by 4 His residues, but this coordination changed as the Cu(II) to protein ratio increased towards 2:1. XAS confirmed this coordination via analysis of the intensity of outer-shell scattering from imidazole residues. The Cu(II) complexes could be reduced to their Cu(I) counterparts by ascorbate, but here again, as shown by EXAFS and XANES spectroscopy, the coordination was dependent on copper loading. At low copper Cu(I) was bound by a mixed ligand set of His + Met while at higher ratios His coordination predominated. The copper-loaded loop was able to transfer either Cu(II) or Cu(I) to peptidylglycine monooxygenase in the presence of chelating resin, generating catalytically active enzyme in a process that appeared to involve direct interaction between the two partners. The variation of coordination with copper loading suggests copper-dependent conformational change which in turn could act as a signal for regulating copper release by the ATPase pump.

  15. Crystal structure and electronic properties of the new compounds, U{sub 6}Fe{sub 16}Si{sub 7} and its interstitial carbide U{sub 6}Fe{sub 16}Si{sub 7}C

    SciTech Connect

    Berthebaud, D.; Tougait, O. Potel, M.; Lopes, E.B.; Goncalves, A.P.

    2007-10-15

    The new compounds U6Fe16Si7 and U6Fe16Si7C were prepared by arc-melting and subsequent annealing at 1500 deg. C. Single-crystal X-ray diffraction showed that they crystallize in the cubic space group Fm3-barm (No. 225), with unit-cell parameters at room temperature a=11.7206(5) A for U6Fe16Si7 and a=11.7814(2) A for U6Fe16Si7C. Their crystal structures correspond to ordered variants of the Th6Mn23 type. U6Fe16Si7 adopts the Mg6Cu16Si7 structure type, whereas U6Fe16Si7C crystallizes with a novel 'filled' quaternary variant. The inserted carbon is located in octahedral cages formed by six U atoms, with U-U interatomic distances of 3.509(1) A. Insertion of carbon in the structure of U6Fe16Si7 has a direct influence on the U-Fe and Fe-Fe interatomic distances. The electronic properties of both compounds were investigated by means of DC susceptibility, electrical resistivity and thermopower. U6Fe16Si7 is a Pauli paramagnet. Its electrical resistivity and thermopower point out that it cannot be classified as a simple metal. The magnetic susceptibility of U{sub 6}Fe{sub 16}Si{sub 7}C is best described over the temperature range 100-300 K by using a modified Curie-Weiss law with an effective magnetic moment of 2.3(2) {mu}{sub B}/U, a paramagnetic Weiss temperature, {theta}{sub p}=57(2) K and a temperature-independent term {chi}{sub 0}=0.057(1) emu/mol. Both the electrical resistivity and thermopower reveal metallic behavior. - Graphical abstract: The new compounds U{sub 6}Fe{sub 16}Si{sub 7} and U{sub 6}Fe{sub 16}Si{sub 7}C crystallize with the ternary ordered variant of the Th{sub 6}Mn{sub 23} type, commonly referred as Mg{sub 6}Cu{sub 16}Si7 and with a novel 'filled' variant of this type of structure, respectively.

  16. 40 CFR Table 3 of Subpart Aaaa of... - Requirements for Validating Continuous Emission Monitoring Systems (CEMS)

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... Nitrogen Oxides (Class I units only) a Method 7, 7A, 7B, 7C, 7D, or 7E Method 3 or 3A. 2. Sulfur Dioxide... combustion plants with an aggregate plant combustion capacity more than 250 tons per day of municipal...

  17. 40 CFR Table 3 of Subpart Aaaa of... - Requirements for Validating Continuous Emission Monitoring Systems (CEMS)

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... Nitrogen Oxides (Class I units only) a Method 7, 7A, 7B, 7C, 7D, or 7E Method 3 or 3A. 2. Sulfur Dioxide... combustion plants with an aggregate plant combustion capacity more than 250 tons per day of municipal...

  18. Effect of the external field on the soft magnetic properties and microstructure of directly cast Fe75P8.7B5C7Si4.3 nanocrystalline sheets

    NASA Astrophysics Data System (ADS)

    Shih, C. W.; Lin, Y. Y.; Chang, H. W.; Lee, Y. I.; Chang, W. C.; Yang, C. C.

    2015-05-01

    A new method to fabricate soft magnetic bulk metallic glasses (BMGs) by an injection casting with applying external magnetic field during solidification has been developed. The effect of applying magnetic fields (Ha) on soft magnetic properties and microstructure of Fe75P8.7B5C7Si4.3 alloy sheets with dimension of t × 4 mm × 15 mm (t = 1-3 mm) have been studied. The microstructure shows that the fully amorphous is attained by the applying magnetic field even at the core region of the thicker sheets with t = 3 mm. All studied sheets exhibit similar saturation magnetization of 1.23-1.25 T, but the coercivity and resistivity are strongly dependent on the thickness t and the strength of magnetic field Ha, where Hc increases with t, the slope of Hc versus t decreases with the increase of Ha, and the resistivity increases with the increase of Ha. The changes of coercivity and resistivity are strongly related to the fully amorphous induced by Ha. The external magnetic field has significant improvement in glass forming ability, and thus coercivity and resistivity for the studied sheet, especially for larger t = 3 mm. This study suggests that applying a magnetic field during the casting process provides a useful way to produce high-performance magnetically soft Fe-based BMGs.

  19. Integrative Analyses of miRNA-mRNA Interactions Reveal let-7b, miR-128 and MAPK Pathway Involvement in Muscle Mass Loss in Sex-Linked Dwarf Chickens

    PubMed Central

    Luo, Wen; Lin, Shumao; Li, Guihuan; Nie, Qinghua; Zhang, Xiquan

    2016-01-01

    The sex-linked dwarf (SLD) chicken is an ideal model system for understanding growth hormone (GH)-action and growth hormone receptor (GHR) function because of its recessive mutation in the GHR gene. Skeletal muscle mass is reduced in the SLD chicken with a smaller muscle fiber diameter. Our previous study has presented the mRNA and miRNA expression profiles of the SLD chicken and normal chicken between embryo day 14 and seven weeks of age. However, the molecular mechanism of GHR-deficient induced muscle mass loss is still unclear, and the key molecules and pathways underlying the GHR-deficient induced muscle mass loss also remain to be illustrated. Here, by functional network analysis of the differentially expressed miRNAs and mRNAs between the SLD and normal chickens, we revealed that let-7b, miR-128 and the MAPK pathway might play key roles in the GHR-deficient induced muscle mass loss, and that the reduced cell division and growth are potential cellular processes during the SLD chicken skeletal muscle development. Additionally, we also found some genes and miRNAs involved in chicken skeletal muscle development, through the MAPK, PI3K-Akt, Wnt and Insulin signaling pathways. This study provides new insights into the molecular mechanism underlying muscle mass loss in the SLD chickens, and some regulatory networks that are crucial for chicken skeletal muscle development. PMID:26927061

  20. Surface magnetic properties and magnetoimpedance of Co-rich amorphous and nanocrystalline (Co1-xFex)89 Zr7B4 ribbons with oxide layer formed by long-term exposure to air

    NASA Astrophysics Data System (ADS)

    Eggers, Tatiana; Leary, Alex; McHenry, Michael; Skorvanek, Ivan; Srikanth, Hariharan; Phan, Manh-Huong

    The surface magnetic properties and magnetoimpedance (MI) of amorphous and nanocrystalline (Co1-xFex)89 Zr7B4 melt-spun ribbons with x = 0, 0.025, 0.05 & 0.1 was investigated. A 540°C heat treatment for 1 hour under a 2 T transverse field formed a large volume fraction of nanocrystalline phases in the ribbons, in addition to a well-defined transverse anisotropy indicated by x-ray diffraction and magneto-optical Kerr effect microscopy. After the heat treatment, the ribbon samples were exposed to open air for an extended period of time producing a visible oxide layer on the surfaces. High frequency magnetoimpedance measurements in the driving frequency range of 1-1000 MHz were made to characterize the potential impact of the surface oxide layer on the ac magnetization process. Unique field-dependent behavior of the real and imaginary components of the MI was found in nanocrystalline ribbons with higher Co content (x >= 0.05), showing multiple peaks above 50 MHz driving current.

  1. Optical study of SrAl 1.7B 0.3O 4:Eu, R ( R=Nd, Dy) pigments with long-lasting phosphorescence for industrial uses

    NASA Astrophysics Data System (ADS)

    Sánchez-Benítez, J.; de Andrés, A.; Marchal, M.; Cordoncillo, E.; Regi, M. Vallet; Escribano, P.

    2003-02-01

    We have studied and compared the optical properties of SrAl 1.7B 0.3O 4:Eu, R ( R=Nd, Dy) pigments that present long-lasting phosphorescence obtained by different synthesis techniques. Samples obtained by ceramic methods, in our laboratories and by an industrial process, present better phosphorescent properties than those obtained by sol-gel technique. Raman spectra show that grinding produces severe damage of the lattice. We have obtained and analyzed the Eu 3+ crystal field luminescence indicating that Eu 3+ is found in quite different sites comparing ceramic and sol-gel samples. Codoping, with Nd or Dy is necessary in order to reduce the Eu 3+ content, in all cases. The green luminescence band, obtained under UV illumination, can be fitted to two and three components in ceramic and sol-gel samples, respectively, due to different Eu 2+ sites. Eu-Dy samples present the longest and the most efficient phosphorescence. The time evolution of the afterglow is well described by a t-1 law, up to about 2 h, indicating that the recombination process is achieved by electron-hole tunneling.

  2. Giant magnetoimpedance and field sensitivity in amorphous and nanocrystalline (Co1-xFex)89Zr7B4 (x = 0, 0.025, 0.05, 0.1) ribbons

    NASA Astrophysics Data System (ADS)

    Chaturvedi, Anurag; Laurita, Nicholas; Leary, Alex; Phan, Manh-Huong; McHenry, Michael E.; Srikanth, Hariharan

    2011-04-01

    We report on the giant magnetoimpedance (GMI) effect and its field sensitivity (η) in amorphous and nanocrystalline (Co1-xFex)89Zr7B4 ribbons with x = 0, 0.025, 0.05, and 0.10. The nanocrystalline samples were obtained by annealing amorphous ribbons in a field of 2 T applied perpendicular to the ribbon axis. We find that for the amorphous samples the GMI ratio tends to decrease with Fe doping, while the largest value of η is achieved for the x = 0.025 composition. For the nanocrystalline samples, the GMI ratio and η first decrease with increase of Fe-doped content from x = 0 to x = 0.05 and then increase for x = 0.1. The field annealing significantly enhances the GMI ratio and η in the nanocrystalline samples with x = 0 and 0.1, but decreases the η in the nanocrystalline samples with x = 0.025 and 0.05. The variations of the GMI ratio and the field-induced magnetic anisotropy field (HK) upon Fe doping are correlated with the microstructural changes in the nanocrystalline samples.

  3. REPORTABLE RADIONUCLIDES IN DWPF SLUDGE BATCH 7A (MACROBATCH 8)

    SciTech Connect

    Reboul, S.; Diprete, D.; Click, D.; Bannochie, C.

    2011-12-20

    The Waste Acceptance Product Specifications (WAPS) 1.2 require that the waste producer 'shall report the curie inventory of radionuclides that have half-lives longer than 10 years and that are, or will be, present in concentrations greater than 0.05 percent of the total inventory for each waste type indexed to the years 2015 and 3115.' As part of the strategy to meet WAPS 1.2, the Defense Waste Processing Facility (DWPF) will report for each waste type all radionuclides that have half-lives longer than 10 years and contribute greater than 0.01 percent of the total curie inventory from the time of production through the 1100 year period from 2015 through 3115. The initial list of radionuclides to be reported is based on the design-basis glass identified in the Waste Form Compliance Plan (WCP) and Waste Form Qualification Report. However, it is required that the list be expanded if other radionuclides with half-lives greater than 10 years are identified that meet the 'greater than 0.01% of the curie inventory' criterion. Specification 1.6 of the WAPS, International Atomic Energy Agency Safeguards Reporting for High Level Waste (HLW), requires that the ratio by weights of the following uranium and plutonium isotopes be reported: U-233, U-234, U-235, U-236, and U-238; and Pu-238, Pu-239, Pu-240, Pu-241, and Pu-242. Therefore, the complete list of reportable radionuclides must also include these sets of U and Pu isotopes - and the U and Pu isotopic mass distributions must be identified. The DWPF receives HLW sludge slurry from Savannah River Site (SRS) Tank 40. For Sludge Batch 7a (SB7a), the waste in Tank 40 contained a blend of the heel from Sludge Batch 6 (SB6) and the Sludge Batch 7 (SB7) material transferred to Tank 40 from Tank 51. This sludge blend is also referred to as Macrobatch 8. Laboratory analyses of a Tank 40 sludge sample were performed to quantify the concentrations of pertinent radionuclides in the SB7a waste. Subsequently, radiological decay and in

  4. FalconSAT-7: a membrane space telescope

    NASA Astrophysics Data System (ADS)

    Andersen, Geoff; Asmolova, Olha; Dickinson, Thomas

    2014-06-01

    The USAF Academy Department of Physics is building FalconSAT-7, a membrane solar telescope to be deployed from a 3U CubeSat in LEO. The primary optic is a 0.2m photon sieve.—a diffractive element consisting of billions of tiny holes in an otherwise opaque polymer sheet. The membrane, its support structure, secondary optics, two imaging cameras and associated control/recording electronics are all packaged within half the CubeSat volume. Once in space the supporting pantograph structure is deployed, pulling the membrane flat under tension. The telescope will then be steered towards the Sun to gather images at H-alpha for transmission to the ground. Due for launch in 2016, FalconSAT-7 will serve as a pathfinder for future surveillance missions.

  5. Projection map of aquaporin-9 at 7 A resolution.

    PubMed

    Viadiu, Hector; Gonen, Tamir; Walz, Thomas

    2007-03-16

    Aquaporin-9, an aquaglyceroporin present in diverse tissues, is unique among aquaporins because it is not only permeable to water, urea and glycerol, but also allows passage of larger uncharged solutes. Single particle analysis of negatively stained recombinant rat aquaporin-9 revealed a particle size characteristic of the tetrameric organization of all members of the aquaporin family. Reconstitution of aquaporin-9 into two-dimensional crystals enabled us to calculate a projection map at 7 A resolution. The projection structure indicates a tetrameric structure, similar to GlpF, with each square-like monomer forming a pore. A comparison of the pore-lining residues between the crystal structure of GlpF and a homology model of aquaporin-9 locates substitutions in these residues predominantly to the hydrophobic edge of the tripathic pore of GlpF, providing first insights into the structural basis for the broader substrate specificity of aquaporin-9. PMID:17239399

  6. Structure of chymopapain at 1.7 A resolution.

    PubMed

    Maes, D; Bouckaert, J; Poortmans, F; Wyns, L; Looze, Y

    1996-12-17

    The X-ray structure of chymopapain, a cysteine proteinase isolated from the latex of the fruits of Carica papaya L., has been determined by molecular replacement methods and refined to a conventional R factor of 0.19 for all observed reflections in the range from 9.5 to 1.7 A resolution. The crystals used in this study contained a unique molecular species of chymopapain with two moles of thiomethyl attached to the two free cysteines per mole of enzyme. A comparison is made with the other known papaya proteinase X-ray structures: papain, caricain, and glycyl endopeptidase. Their backbone conformations are extremely similar except for two loop regions. Both regions are located at the surface of the protein and far away of the active site cleft. In each X-ray structure the same water network was found at the interface between the two domains of the enzyme. A close examination of the active site groove showed that the specificity restrictions dictated by the S2 subsite did not differ significantly among the four proteinases. PMID:8973203

  7. Feige 7 - A hot, rotating magnetic white dwarf

    NASA Technical Reports Server (NTRS)

    Liebert, J.; Angel, J. R. P.; Stockman, H. S.; Spinrad, H.; Beaver, E. A.

    1977-01-01

    Results are reported for image-tube-scanner and digicon observations of Feige 7, a faint blue star identified as a probable white dwarf. It is found that this star is a magnetic white dwarf showing a very rich spectrum with Zeeman subcomponents of both hydrogen and neutral helium as well as periodic spectrum and circular-polarization variations. A polarization period of 2.2 hr is computed, and a surface magnetic-field strength of about 18 MG is determined by matching features of the absorption spectrum to Zeeman components. It is suggested that the only reasonable explanation for the periodic variations in circular polarization is an oblique rotator with the spin axis approximately in the plane of the sky and tilted by about 24 deg to the magnetic axis. An effective temperature in the range from 20,000 to 25,000 K is estimated, an absolute magnitude of about 10.5 is derived, and the atmosphere is shown to be helium-dominated. The evolution of Feige 7 is discussed in terms of possible magnetic-field effects on atmospheric composition, rotation velocity (5.5 km/s for a radius of 7000 km), and the origin of white-dwarf magnetic fields.

  8. FalconSAT-7: a membrane space telescope

    NASA Astrophysics Data System (ADS)

    Andersen, Geoff P.; Asmolova, Olha

    2014-08-01

    The USAF Academy Department of Physics has built FalconSAT-7, a membrane solar telescope to be deployed from a 3U CubeSat in LEO. The primary optic is a 0.2m photon sieve - a diffractive element consisting of billions of tiny circular dimples etched into a Kapton sheet. The membrane, its support structure, secondary optics, two imaging cameras and associated control/recording electronics are all packaged within half the CubeSat volume. Once in space, the supporting pantograph structure is deployed, extending out and pulling the membrane flat under tension. The telescope will then be directed at the Sun to gather images at H-alpha for transmission to the ground. Due for launch in 2015, FalconSAT-7 will serve as a pathfinder for future surveillance missions consisting of a 0.3m aperture deployed from a 12U satellite. Such a telescope would be capable of providing sub-meter resolution of ground-based objects.

  9. 75 FR 3468 - Revised Jurisdictional Thresholds For Section 7A of the Clayton Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-21

    ... follows: SUBSECTION OF 7A ORIGINAL THRESHOLD ADJUSTED THRESHOLD 7A(a)(2)(A) $200 million $253.7 million 7A(a)(2)(B)(i) $50 million $63.4 million 7A(a)(2)(B)(i) $200 million $253.7 million 7A(a)(2)(B)(ii)(I... million $200 million $253.7 million $500 million $634.4 million $1 billion $1,268.7 million...

  10. High frequency of the c.3207C>A (p.H1069Q) mutation in ATP7B gene of Lithuanian patients with hepatic presentation of Wilson’s disease

    PubMed Central

    Kucinskas, Laimutis; Jeroch, Jolanta; Vitkauskiene, Astra; Sakalauskas, Raimundas; Petrenkiene, Vitalija; Kucinskas, Vaidutis; Naginiene, Rima; Schmidt, Hartmut; Kupcinskas, Limas

    2008-01-01

    AIM: To investigate the prevalence of the ATP7B gene mutation in patients with hepatic presentation of Wilson’s disease (WD) in Lithuania. METHODS: Eleven unrelated Lithuanian families, including 13 WD patients were tested. Clinically WD diagnosis was established in accordance to the Leipzig scoring system. Genomic DNA was extracted from whole venous blood using a salt precipitation method. Firstly, the semi-nested polymerase chain reaction (PCR) technique was used to detect the c.3207C>A (p.H1069Q) mutation. Patients not homozygous for the c.3207C>A (p.H1069Q) mutation were further analyzed. The 21 exons of the WD gene were amplified in a thermal cycler (Biometra T3 Thermocycler, Göttingen, Germany). Direct sequencing of the amplified PCR products was performed by cycle sequencing using fluorescent dye terminators in an automatic sequencer (Applied Biosystems, Darmstadt, Germany). RESULTS: Total of 13 WD patients (mean age 26.4 years; range 17-40; male/female 3/10) presented with hepatic disorders and 16 their first degree relatives (including 12 siblings) were studied. Some of WD patients, in addition to hepatic symptoms, have had extrahepatic disorders (hemolytic anemia 3; Fanconi syndrome 1; neuropsychiatric and behavioural disorder 2). Liver biopsy specimens were available in all of 13 WD patients (8 had cirrhosis; 1-chronic hepatitis; 3-acute liver failure, 1-liver steatosis). Twelve of 13 (92.3%) WD patients had the c.3207C>A (p.H1069Q) mutation, 6 of them in both chromosomes, 6 were presented as compound heterozygotes with additional c.3472-82delGGTTTAACCAT, c.3402delC, c.3121C>T (p.R1041W) or unknown mutations. For one patient with liver cirrhosis and psychiatric disorder (Leipzig score 6), no mutations were found. Out of 16 first degree WD relatives, 11 (68.7%) were heterozygous for the c.3207C>A (p.H1069Q) mutation. Two patients with fulminant WD died from acute liver failure and 11 are in full remission under penicillamine or zinc acetate treatment

  11. Ab initio studies on cyanoacetylenes of astrochemical interest: [Y(Ctbnd C)CN, Y dbnd C2H5, C3H7, C4H9, F, Cl, Br and CN

    NASA Astrophysics Data System (ADS)

    Kodi Ramanah, D.; Surajbali, P.; Rhyman, L.; Alswaidan, I. A.; Fun, H.-K.; Somanah, R.; Ramasami, P.

    2016-01-01

    Theoretical studies were performed on seven potential interstellar and circumstellar substituted cyanoacetylenes, Y(Ctbnd C)CN [Y = C2H5, C3H7, C4H9, F, Cl, Br and CN]. Geometry optimizations were carried out using the DFT/B3LYP, the CCSD and CCSD(T) levels of theory. The cc-pVTZ basis set was used for all atoms. Frequency computations were also carried out at the same level of theory as for the optimization to check the nature of the stationary points. The molecular and spectroscopic parameters of the cyanoacetylenes were computed. An analysis of these parameters is in line with the satisfactory performance of the B3LYP/cc-pVTZ level compared to the golden standard, the CCSD(T) level. The theoretical data reported in this work should facilitate future identifications of these cyanoacetylenes in extraterrestrial locations. Plausible mechanisms for the formation of these molecules have been proposed.

  12. Test plan for the M-100 container, (model M-101/7A/12/90) docket 96-43-7A, type A container. Revision 1

    SciTech Connect

    Kelly, D.L.

    1997-07-22

    This report concerns the packaging configurations being tested by the U.S. DOE and its contractors, and according to U.S. DOT specification 7A Type A (DOT-7A) requirements. The objective of this Test Plan is to describe the testing for the qualification of the M-100 Container, Model M-101/7A/12/90 as a DOT-7A Type A packaging. This packaging system is designed to ship Type A solid radioactive materials, normal form, Form Number 1, Form Number 2, and Form Number 3.

  13. Sol-gel synthesis of Na4Fe3(PO4)2(P2O7)/C nanocomposite for sodium ion batteries and new insights into microstructural evolution during sodium extraction

    NASA Astrophysics Data System (ADS)

    Wu, Xuehang; Zhong, Guiming; Tang, Zheng; Yang, Yong

    2016-09-01

    A mixed polyanionic Na4Fe3(PO4)2(P2O7)/C nanocomposite is synthesized via a sol-gel route. The phosphate raw material is transformed to the mixed phosphate-pyrophosphate with high phase purity via a self-condensation reaction at 500 °C. Na4Fe3(PO4)2(P2O7)/C can deliver an initial capacity of 110 mAh g-1 at 0.05C with the average discharge voltage approaching 3.1 V. The nanocomposite shows excellent rate capability because of the presence of an in-situ formed 3-D network of carbon. At 10 C rate, the nanocomposite delivers a discharge capacity of 78 mAh g-1 at 25 mAh °C and 82 mAh g-1 at 55 °C. The nanocomposite has a good long-term cycling stability, retaining 89% of the initial discharge capacity after 300 cycles. In-situ XRD results demonstrate that the sodium insertion/extraction process in Na4Fe3(PO4)2(P2O7) is an imperfect solid-solution reaction with an obvious local lattice distortion instead of an ideal solid-solution reaction. Using a solid-state NMR technique, it is further found that the sodium extraction from the Na1, Na3, and Na4 sites causes an obvious change in local structure. However, the local structure of Na2 remains unchanged, which may aid the stability of the host structure.

  14. 77 FR 4323 - Revised Jurisdictional Thresholds for Section 7A of the Clayton Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-27

    ... Revised Jurisdictional Thresholds for Section 7A of the Clayton Act AGENCY: Federal Trade Commission...-Rodino Antitrust Improvements Act of 1976 required by the 2000 amendment of Section 7A of the Clayton Act... Pennsylvania Avenue NW, Washington, DC 20580. SUPPLEMENTARY INFORMATION: Section 7A of the Clayton Act, 15...

  15. 76 FR 4349 - Revised Jurisdictional Thresholds for Section 7a of The Clayton Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-25

    ... Revised Jurisdictional Thresholds for Section 7a of The Clayton Act AGENCY: Federal Trade Commission...-Rodino Antitrust Improvements Act of 1976 required by the 2000 amendment of Section 7A of the Clayton Act. Section 7A of the Clayton Act, 15 U.S.C. 18a, as added by the Hart-Scott-Rodino ] Antitrust...

  16. 13 CFR 120.520 - Purchase of 7(a) loan guarantees.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Purchase of 7(a) loan guarantees. 120.520 Section 120.520 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Servicing, Liquidation and Debt Collection Litigation of 7(a) and 504 Loans Sba's Purchase of A Guaranteed Portion § 120.520 Purchase of 7(a)...

  17. 17 CFR 260.7a-31 - Incorporation by reference of contested material.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... contested material. 260.7a-31 Section 260.7a-31 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... § 260.7a-31 Incorporation by reference of contested material. Notwithstanding any particular provision... the Trust Indenture Act of 1939, or otherwise) or to an order entered under either of those sections....

  18. 17 CFR 260.7a-31 - Incorporation by reference of contested material.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... contested material. 260.7a-31 Section 260.7a-31 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... § 260.7a-31 Incorporation by reference of contested material. Notwithstanding any particular provision... the Trust Indenture Act of 1939, or otherwise) or to an order entered under either of those sections....

  19. 17 CFR 260.7a-31 - Incorporation by reference of contested material.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... contested material. 260.7a-31 Section 260.7a-31 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... § 260.7a-31 Incorporation by reference of contested material. Notwithstanding any particular provision... the Trust Indenture Act of 1939, or otherwise) or to an order entered under either of those sections....

  20. 17 CFR 260.7a-31 - Incorporation by reference of contested material.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... contested material. 260.7a-31 Section 260.7a-31 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... § 260.7a-31 Incorporation by reference of contested material. Notwithstanding any particular provision... the Trust Indenture Act of 1939, or otherwise) or to an order entered under either of those sections....

  1. 17 CFR 260.7a-31 - Incorporation by reference of contested material.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... contested material. 260.7a-31 Section 260.7a-31 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... § 260.7a-31 Incorporation by reference of contested material. Notwithstanding any particular provision... the Trust Indenture Act of 1939, or otherwise) or to an order entered under either of those sections....

  2. 17 CFR 260.7a-32 - Incorporation by reference rendering document incomplete, unclear, or confusing.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Incorporation by reference rendering document incomplete, unclear, or confusing. 260.7a-32 Section 260.7a-32 Commodity and Securities... OF 1939 Incorporation by Reference § 260.7a-32 Incorporation by reference rendering...

  3. 17 CFR 260.7a-32 - Incorporation by reference rendering document incomplete, unclear, or confusing.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Incorporation by reference rendering document incomplete, unclear, or confusing. 260.7a-32 Section 260.7a-32 Commodity and Securities... OF 1939 Incorporation by Reference § 260.7a-32 Incorporation by reference rendering...

  4. 17 CFR 260.7a-32 - Incorporation by reference rendering document incomplete, unclear, or confusing.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Incorporation by reference rendering document incomplete, unclear, or confusing. 260.7a-32 Section 260.7a-32 Commodity and Securities... OF 1939 Incorporation by Reference § 260.7a-32 Incorporation by reference rendering...

  5. 17 CFR 260.7a-32 - Incorporation by reference rendering document incomplete, unclear, or confusing.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Incorporation by reference rendering document incomplete, unclear, or confusing. 260.7a-32 Section 260.7a-32 Commodity and Securities... OF 1939 Incorporation by Reference § 260.7a-32 Incorporation by reference rendering...

  6. 17 CFR 260.7a-32 - Incorporation by reference rendering document incomplete, unclear, or confusing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Incorporation by reference rendering document incomplete, unclear, or confusing. 260.7a-32 Section 260.7a-32 Commodity and Securities... OF 1939 Incorporation by Reference § 260.7a-32 Incorporation by reference rendering...

  7. 17 CFR 260.7a-25 - Words relating to the future.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Words relating to the future. 260.7a-25 Section 260.7a-25 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... § 260.7a-25 Words relating to the future. Unless the context clearly shows otherwise, whenever...

  8. 17 CFR 260.7a-24 - Words relating to periods of time in the past.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Words relating to periods of time in the past. 260.7a-24 Section 260.7a-24 Commodity and Securities Exchanges SECURITIES AND... Requirements As to Contents § 260.7a-24 Words relating to periods of time in the past. Unless the...

  9. 17 CFR 260.7a-24 - Words relating to periods of time in the past.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Words relating to periods of time in the past. 260.7a-24 Section 260.7a-24 Commodity and Securities Exchanges SECURITIES AND... Requirements As to Contents § 260.7a-24 Words relating to periods of time in the past. Unless the...

  10. 17 CFR 260.7a-24 - Words relating to periods of time in the past.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Words relating to periods of time in the past. 260.7a-24 Section 260.7a-24 Commodity and Securities Exchanges SECURITIES AND... Requirements As to Contents § 260.7a-24 Words relating to periods of time in the past. Unless the...

  11. 17 CFR 260.7a-24 - Words relating to periods of time in the past.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Words relating to periods of time in the past. 260.7a-24 Section 260.7a-24 Commodity and Securities Exchanges SECURITIES AND... Requirements As to Contents § 260.7a-24 Words relating to periods of time in the past. Unless the...

  12. Pri-let-7a-1 rs10739971 polymorphism is associated with gastric cancer prognosis and might affect mature let-7a expression

    PubMed Central

    Li, Ying; Xu, Qian; Liu, Jingwei; He, Caiyun; Yuan, Quan; Xing, Chengzhong; Yuan, Yuan

    2016-01-01

    The relationship between the pri-let-7a-1 rs10739971 polymorphism and gastric cancer (GC) risk has been reported. However, the role of this polymorphism in the prognosis of GC remains largely elusive. Sequenom MassARRAY platform method and the polymerase chain reaction (PCR)-restriction fragment length polymorphism were used to investigate pri-let-7a-1 rs10739971 G→A in 334 GC patients. Real-time PCR detected expression of mature let-7a in serum and tissue. Patients with AA or GA+AA genotypes of the pri-let-7a-1 rs10739971 polymorphism demonstrated significantly longer survival time than those with the wild GG genotype. Stratified analysis indicated that survival time was significantly longer in women with AA or GA+AA genotypes and in Borrmann type I/II patients with GA heterozygote or GA+AA genotypes. AA genotype was more frequent in the lymphatic-metastasis-negative subgroup. Serum mature let-7a expression in healthy people with the GA heterozygote and the GA+AA genotype was higher than in those with the GG genotype, and the difference remained significant in the female healthy subgroup. Pri-let-7a-1 rs10739971 polymorphism might be a biomarker for GC prognosis, especially for female and Borrmann type I/II patients. The pri-let-7a-1 rs10739971 polymorphism might affect serum mature let-7a expression, and partly explain the mechanism of the relationship between the pri-let-7a-1 rs10739971 polymorphism and GC survival. PMID:27445488

  13. Proteomic analysis reveals that COP9 signalosome complex subunit 7A (CSN7A) is essential for the phase transition of migratory locust.

    PubMed

    Tong, Xi-Wen; Chen, Bing; Huang, Li-Hua; Feng, Qi-Li; Kang, Le

    2015-01-01

    The migratory locust displays a reversible, density-dependent transition between the two phases of gregaria and solitaria. This phenomenon is a typical kind of behavior plasticity. Here, we report that COP9 signalosome complex subunit 7A (CSN7A) is involved in the regulation of locust phase transition. Firstly, 90 proteins were identified to express differentially between the two phases by quantitative proteomic analysis. Gregaria revealed higher levels in proteins related to structure formation, melanism and energy metabolism, whereas solitaria had more abundant proteins related to digestion, absorption and chemical sensing. Subsequently, ten proteins including CSN7A were found to reveal differential mRNA expression profiles between the two phases. The CSN7A had higher mRNA level in the gregaria as compared with the solitaria, and the mRNA amount in the gregaria decreased remarkably during the 32 h-isolation. However, the mRNA level in the solitaria kept constant during the crowding rearing. Finally and importantly, RNA interference of CSN7A in gregaria resulted in obvious phase transition towards solitaria within 24 h. It suggests that CSN7A plays an essential role in the transition of gregaria towards solitaria in the migratory locust. To our knowledge, it's the first time to report the role of CSN in behavior plasticity of animals. PMID:26212173

  14. Proteomic analysis reveals that COP9 signalosome complex subunit 7A (CSN7A) is essential for the phase transition of migratory locust

    PubMed Central

    Tong, Xi-Wen; Chen, Bing; Huang, Li-Hua; Feng, Qi-Li; Kang, Le

    2015-01-01

    The migratory locust displays a reversible, density-dependent transition between the two phases of gregaria and solitaria. This phenomenon is a typical kind of behavior plasticity. Here, we report that COP9 signalosome complex subunit 7A (CSN7A) is involved in the regulation of locust phase transition. Firstly, 90 proteins were identified to express differentially between the two phases by quantitative proteomic analysis. Gregaria revealed higher levels in proteins related to structure formation, melanism and energy metabolism, whereas solitaria had more abundant proteins related to digestion, absorption and chemical sensing. Subsequently, ten proteins including CSN7A were found to reveal differential mRNA expression profiles between the two phases. The CSN7A had higher mRNA level in the gregaria as compared with the solitaria, and the mRNA amount in the gregaria decreased remarkably during the 32 h-isolation. However, the mRNA level in the solitaria kept constant during the crowding rearing. Finally and importantly, RNA interference of CSN7A in gregaria resulted in obvious phase transition towards solitaria within 24 h. It suggests that CSN7A plays an essential role in the transition of gregaria towards solitaria in the migratory locust. To our knowledge, it’s the first time to report the role of CSN in behavior plasticity of animals. PMID:26212173

  15. Somatic human ZBTB7A zinc finger mutations promote cancer progression.

    PubMed

    Liu, X-S; Liu, Z; Gerarduzzi, C; Choi, D E; Ganapathy, S; Pandolfi, P P; Yuan, Z-M

    2016-06-01

    We recently reported that ZBTB7A is a bona fide transcription repressor of key glycolytic genes and its downregulation in human cancer contributes to tumor metabolism. As reduced expression of ZBTB7A is found only in a subset of human cancers, we explored alternative mechanisms of its inactivation by mining human cancer genome databases. We discovered recurrent somatic mutations of ZBTB7A in multiple types of human cancers with a marked enrichment of mutations within the zinc finger domain. Functional characterization of the mutants demonstrated that mutations within the zinc finger region of ZBTB7A invariably resulted in loss of function. As a consequence, the glycolytic genes were markedly upregulated in cancer cells harboring ZBTB7A zinc finger mutation, leading to increased glycolysis and proliferation. Our study uncovers the loss-of-function mutation in ZBTB7A as a novel mechanism causing elevated glycolysis in human cancer, which carries important therapeutic implication. PMID:26455326

  16. ANALYSIS OF DWPF SLUDGE BATCH 7A (MACROBATCH 8) POUR STREAM SAMPLES

    SciTech Connect

    Johnson, F.

    2012-05-01

    The Defense Waste Processing Facility (DWPF) began processing Sludge Batch 7a (SB7a), also referred to as Macrobatch 8 (MB8), in June 2011. SB7a is a blend of the heel of Tank 40 from Sludge Batch 6 (SB6) and the SB7a material that was transferred to Tank 40 from Tank 51. SB7a was processed using Frit 418. During processing of each sludge batch, the DWPF is required to take at least one glass sample to meet the objectives of the Glass Product Control Program (GPCP), which is governed by the DWPF Waste Compliance Plan, and to complete the necessary Production Records so that the final glass product may be disposed of at a Federal Repository. Three pour stream glass samples and two Melter Feed Tank (MFT) slurry samples were collected while processing SB7a. These additional samples were taken during SB7a to understand the impact of antifoam and the melter bubblers on glass redox chemistry. The samples were transferred to the Savannah River National Laboratory (SRNL) where they were analyzed. The following conclusions were drawn from the analytical results provided in this report: (1) The sum of oxides for the official SB7a pour stream glass is within the Product Composition Control System (PCCS) limits (95-105 wt%). (2) The average calculated Waste Dilution Factor (WDF) for SB7a is 2.3. In general, the measured radionuclide content of the official SB7a pour stream glass is in good agreement with the calculated values from the Tank 40 dried sludge results from the SB7a Waste Acceptance Program Specification (WAPS) sample. (3) As in previous pour stream samples, ruthenium and rhodium inclusions were detected by Scanning Electron Microscopy-Electron Dispersive Spectroscopy (SEM-EDS) in the official SB7a pour stream sample. (4) The Product Consistency Test (PCT) results indicate that the official SB7a pour stream glass meets the waste acceptance criteria for durability with a normalized boron release of 0.64 g/L, which is an order of magnitude less than the Environmental

  17. Overexpressed let-7a-3 is associated with poor outcome in acute myeloid leukemia.

    PubMed

    Li, Yun; Lin, Jiang; Yang, Jing; Qian, Jun; Qian, Wei; Yao, Dong-Ming; Deng, Zhao-Qun; Liu, Qing; Chen, Xing-Xing; Xie, Dong; An, Cui; Tang, Chun-Yan

    2013-12-01

    Dysregulation of microRNA let-7a-3 has been identified in several solid tumors and is associated with prognosis of patients. However, the pattern of let-7a-3 expression and the impact on prognosis has not yet been studied in acute myeloid leukemia (AML). The purpose of this study is to investigate the expression status of let-7a-3 and its clinical significance in AML patients using real-time quantitative PCR. Overexpression of let-7a-3 was identified in 25 of 102 (25%) de novo AML. There was no significant difference in age, blood parameters, FAB/WHO subtypes, karyotype risks and nine gene mutations (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, C/EBPA and N/K-RAS) between patients with and without let-7a-3 overexpression (P>0.05). The patients with let-7a-3 overexpression had similar rates of complete remission (CR) as those without let-7a-3 overexpression (50% vs. 56%, P=0.693). Although the overall survival (OS) of AML patients with let-7a-3 overexpression (median 12 months,) was shorter than those without overexpression (median 25 months), the difference was not statistically significant (P=0.228). However, among those 51 obtained CR, patients with let-7a-3 overexpression had significantly shorter OS than those without let-7a-3 overexpression (P=0.029). The difference in relapse-free survival (RFS) was also significant between two groups (P=0.005). These findings suggest that let-7a-3 overexpression is a common event and is associated with poor clinical outcome in AML. PMID:24138945

  18. 49 CFR 178.350 - Specification 7A; general packaging, Type A.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Specification 7A; general packaging, Type A. 178... FOR PACKAGINGS Specifications for Packagings for Class 7 (Radioactive) Materials § 178.350 Specification 7A; general packaging, Type A. (a) Each packaging must meet all applicable requirements of...

  19. Let7a involves in neural stem cell differentiation relating with TLX level

    SciTech Connect

    Song, Juhyun; Cho, Kyoung Joo; Oh, Yumi; Lee, Jong Eun

    2015-07-10

    Neural stem cells (NSCs) have the potential for differentiation into neurons known as a groundbreaking therapeutic solution for central nervous system (CNS) diseases. To resolve the therapeutic efficiency of NSCs, recent researchers have focused on the study on microRNA's role in CNS. Some micro RNAs have been reported significant functions in NSC self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. MicroRNA-Let7a (Let7a) has known as the regulator of diverse cellular mechanisms including cell differentiation and proliferation. In present study, we investigated whether Let7a regulates NSC differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal, proliferation and differentiation. We performed the following experiments: western blot analysis, TaqMan assay, RT-PCR, and immunocytochemistry to confirm the alteration of NSCs. Our data showed that let7a play important roles in controlling NSC fate determination. Thus, manipulating Let-7A and TLX could be a novel strategy to enhance the efficiency of NSC's neuronal differentiation for CNS disorders. - Highlights: • Let7a influences on NSC differentiation and proliferation. • Let7a involves in mainly NSC differentiation rather than proliferation. • Let7a positively regulates the TLX expression.

  20. 13 CFR 120.520 - Purchase of 7(a) loan guarantees.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Registered Holder, Lenders must provide SBA with a loan status report within 15 business days of such... Servicing, Liquidation and Debt Collection Litigation of 7(a) and 504 Loans Sba's Purchase of A Guaranteed Portion § 120.520 Purchase of 7(a) loan guarantees. (a) When SBA will purchase—(1) For loans approved...

  1. 49 CFR 178.350 - Specification 7A; general packaging, Type A.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Specification 7A; general packaging, Type A. 178... Specification 7A; general packaging, Type A. (a) Each packaging must meet all applicable requirements of subpart... of §§ 173.403, 173.410, 173.412, 173.415 and 173.465 of this subchapter for Type A packaging....

  2. 17 CFR 260.7a-17 - Quality, color and size of paper.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Quality, color and size of paper. 260.7a-17 Section 260.7a-17 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Quality, color and size of paper. The application, statement or report, including all amendments...

  3. Construction of an adenovirus type 7a E1A- vector.

    PubMed Central

    Abrahamsen, K; Kong, H L; Mastrangeli, A; Brough, D; Lizonova, A; Crystal, R G; Falck-Pedersen, E

    1997-01-01

    A strategy for constructing replication-defective adenovirus vectors from non-subgroup C viruses has been successfully demonstrated with adenovirus type 7 strain a (Ad7a) as the prototype. An E1A-deleted Ad7a reporter virus expressing the chloramphenicol acetyltransferase (CAT) gene from the cytomegalovirus promoter enhancer was constructed with DNA fragments isolated from Ad7a, an Ad7a recombination reporter plasmid, and the 293 cell line. The Ad7a-CAT virus particle transduces A549 cells as efficiently as Ad5-based vectors. Intravenous infections in a murine model indicate that the Ad7a-CAT virus infects a variety of tissues, with maximal levels of CAT gene expression found in the liver. The duration of Ad7a-CAT transgene expression in the liver was maximally maintained 2 weeks postinfection, with a decline to baseline activity by the week 4 postinfection. Ad7a-CAT represents the first example of a non-subgroup C E1A- adenovirus gene transfer vector. PMID:9343264

  4. 49 CFR 178.350 - Specification 7A; general packaging, Type A.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Specification 7A; general packaging, Type A. 178... FOR PACKAGINGS Specifications for Packagings for Class 7 (Radioactive) Materials § 178.350 Specification 7A; general packaging, Type A. (a) Each packaging must meet all applicable requirements of...

  5. 49 CFR 178.350 - Specification 7A; general packaging, Type A.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Specification 7A; general packaging, Type A. 178... FOR PACKAGINGS Specifications for Packagings for Class 7 (Radioactive) Materials § 178.350 Specification 7A; general packaging, Type A. (a) Each packaging must meet all applicable requirements of...

  6. 17 CFR 260.7a-17 - Quality, color and size of paper.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... paper. 260.7a-17 Section 260.7a-17 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Quality, color and size of paper. The application, statement or report, including all amendments and, where practicable, all papers and documents filed as a part thereof, shall be on good quality,...

  7. ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis

    PubMed Central

    Liu, Xue-Song; Haines, Jenna E.; Mehanna, Elie K.; Genet, Matthew D.; Ben-Sahra, Issam; Asara, John M.; Manning, Brendan D.

    2014-01-01

    Elevated glycolysis is a common metabolic trait of cancer, but what drives such metabolic reprogramming remains incompletely clear. We report here a novel transcriptional repressor-mediated negative regulation of glycolysis. ZBTB7A, a member of the POK (POZ/BTB and Krüppel) transcription repressor family, directly binds to the promoter and represses the transcription of critical glycolytic genes, including GLUT3, PFKP, and PKM. Analysis of The Cancer Genome Atlas (TCGA) data sets reveals that the ZBTB7A locus is frequently deleted in many human tumors. Significantly, reduced ZBTB7A expression correlates with up-regulation of the glycolytic genes and poor survival in colon cancer patients. Remarkably, while ZBTB7A-deficient tumors progress exceedingly fast, they exhibit an unusually heightened sensitivity to glycolysis inhibition. Our study uncovers a novel tumor suppressor role of ZBTB7A in directly suppressing glycolysis. PMID:25184678

  8. Computational and anti-tumor studies of 7a-Aza-B-homostigmast-5-eno [7a, 7-d] tetrazole-3β-yl chloride

    NASA Astrophysics Data System (ADS)

    Alam, Mahboob; Alam, Mohammad Jane; Nami, Shahab A. A.; Lee, Dong-Ung; Azam, Mohammad; Ahmad, Shabbir

    2016-03-01

    The present paper reports the detailed computational study including molecular docking of a biologically active steroidal tetrazole, 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole-3β-yl chloride. The molecular structure, IR and NMR (13C and 1H) spectra of the tetrazole were interpreted by comparing the experimental results with the theoretical, B3LYP/6-311G(d,p) calculations. The vibrational bands appearing in the FTIR are assigned with great accuracy using animated modes. Molecular properties like HOMO-LUMO analysis, chemical reactivity descriptors, MEP mapping, dipole moment and natural atomic charges have been presented at the same level of theory. The theoretical results are found in good correlation with the experimental data. Moreover, the Hirshfeld analysis was carried out to ascertain the secondary interactions and associated 2D fingerprint plots. The in vitro anti-tumor activity of 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole-3β-yl chloride has also been carried out against five human tumor cell lines. Doxorubicin is used as a standard drug for the in vitro anti-tumor screening.

  9. DFT, Hirshfeld surfaces, spectral and in vivo cytotoxic studies of 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole

    NASA Astrophysics Data System (ADS)

    Alam, Mahboob; Alam, Mohammad Jane; Nami, Shahab A. A.; Khan, Mohd Shoeb; Ahmad, Shabbir; Lee, Dong-Ung

    2015-11-01

    The DFT (B3LYP) calculations on a synthetic steroidal molecule 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole, C29H48N4, have been performed. The molecular structure, IR and NMR (13C and 1H) spectra of the present compound were interpreted using experiments (XRD, FTIR, NMR) as well as theoretical, B3LYP/6-311 + G(2d,p), calculations. The vibrational bands appearing in FTIR are assigned with great accuracy using animated modes. Molecular properties like HOMO-LUMO analysis, chemical reactivity descriptors, MEP mapping, dipole moment and Mullikan's atomic charges have been presented at the same level of theory. The theoretical results are found in good correlation with experimental data. Moreover, the Hirshfeld analysis was carried out to ascertain the secondary interactions and associated 2D fingerprint plots. The in vivo cytotoxicity of 7a-Aza-B-homostigmast-5-eno [7a,7-d] has also been carried out against brine shrimp nauplii by lethality bioassay.

  10. ZBTB7A mutations in acute myeloid leukaemia with t(8;21) translocation.

    PubMed

    Hartmann, Luise; Dutta, Sayantanee; Opatz, Sabrina; Vosberg, Sebastian; Reiter, Katrin; Leubolt, Georg; Metzeler, Klaus H; Herold, Tobias; Bamopoulos, Stefanos A; Bräundl, Kathrin; Zellmeier, Evelyn; Ksienzyk, Bianka; Konstandin, Nikola P; Schneider, Stephanie; Hopfner, Karl-Peter; Graf, Alexander; Krebs, Stefan; Blum, Helmut; Middeke, Jan Moritz; Stölzel, Friedrich; Thiede, Christian; Wolf, Stephan; Bohlander, Stefan K; Preiss, Caroline; Chen-Wichmann, Linping; Wichmann, Christian; Sauerland, Maria Cristina; Büchner, Thomas; Berdel, Wolfgang E; Wörmann, Bernhard J; Braess, Jan; Hiddemann, Wolfgang; Spiekermann, Karsten; Greif, Philipp A

    2016-01-01

    The t(8;21) translocation is one of the most frequent cytogenetic abnormalities in acute myeloid leukaemia (AML) and results in the RUNX1/RUNX1T1 rearrangement. Despite the causative role of the RUNX1/RUNX1T1 fusion gene in leukaemia initiation, additional genetic lesions are required for disease development. Here we identify recurring ZBTB7A mutations in 23% (13/56) of AML t(8;21) patients, including missense and truncating mutations resulting in alteration or loss of the C-terminal zinc-finger domain of ZBTB7A. The transcription factor ZBTB7A is important for haematopoietic lineage fate decisions and for regulation of glycolysis. On a functional level, we show that ZBTB7A mutations disrupt the transcriptional repressor potential and the anti-proliferative effect of ZBTB7A. The specific association of ZBTB7A mutations with t(8;21) rearranged AML points towards leukaemogenic cooperativity between mutant ZBTB7A and the RUNX1/RUNX1T1 fusion. PMID:27252013

  11. ZBTB7A mutations in acute myeloid leukaemia with t(8;21) translocation

    PubMed Central

    Hartmann, Luise; Dutta, Sayantanee; Opatz, Sabrina; Vosberg, Sebastian; Reiter, Katrin; Leubolt, Georg; Metzeler, Klaus H.; Herold, Tobias; Bamopoulos, Stefanos A.; Bräundl, Kathrin; Zellmeier, Evelyn; Ksienzyk, Bianka; Konstandin, Nikola P.; Schneider, Stephanie; Hopfner, Karl-Peter; Graf, Alexander; Krebs, Stefan; Blum, Helmut; Middeke, Jan Moritz; Stölzel, Friedrich; Thiede, Christian; Wolf, Stephan; Bohlander, Stefan K.; Preiss, Caroline; Chen-Wichmann, Linping; Wichmann, Christian; Sauerland, Maria Cristina; Büchner, Thomas; Berdel, Wolfgang E.; Wörmann, Bernhard J.; Braess, Jan; Hiddemann, Wolfgang; Spiekermann, Karsten; Greif, Philipp A.

    2016-01-01

    The t(8;21) translocation is one of the most frequent cytogenetic abnormalities in acute myeloid leukaemia (AML) and results in the RUNX1/RUNX1T1 rearrangement. Despite the causative role of the RUNX1/RUNX1T1 fusion gene in leukaemia initiation, additional genetic lesions are required for disease development. Here we identify recurring ZBTB7A mutations in 23% (13/56) of AML t(8;21) patients, including missense and truncating mutations resulting in alteration or loss of the C-terminal zinc-finger domain of ZBTB7A. The transcription factor ZBTB7A is important for haematopoietic lineage fate decisions and for regulation of glycolysis. On a functional level, we show that ZBTB7A mutations disrupt the transcriptional repressor potential and the anti-proliferative effect of ZBTB7A. The specific association of ZBTB7A mutations with t(8;21) rearranged AML points towards leukaemogenic cooperativity between mutant ZBTB7A and the RUNX1/RUNX1T1 fusion. PMID:27252013

  12. Homocysteine induces cardiac hypertrophy by up-regulating ATP7a expression

    PubMed Central

    Cao, Zhanwei; Zhang, Yanzhou; Sun, Tongwen; Zhang, Shuguang; Yu, Weiya; Zhu, Jie

    2015-01-01

    Aims: The aim of the study is to investigate the molecular mechanism by which homocysteine (Hcy) induces cardiac hypertrophy. Methods: Primary cardiomyocytes were obtained from baby Sprague-Dawley rats within 3 days after birth. Flow cytometry was used to measure cell sizes. Quantitative real-time polymerase chain reaction was performed to measure the expression of β-myosin heavy chain and atrial natriuretic peptide genes. Western blotting assay was employed to determine ATP7a protein expression. Cytochrome C oxidase (COX) activity test was used to evaluate the activity of COX. Atomic absorption spectroscopy was performed to determine copper content. siRNAs were used to target-silence the expression of ATP7a. Results: Hcy induced cardiac hypertrophy and increased the expression of cardiac hypertrophy-related genes. ATP7a was a key factor in cardiac hypertrophy induced by Hcy. Reduced ATP7a expression inhibited cardiac hypertrophy induced by Hcy. Elevated ATP7a expression induced by Hcy inhibited COX activity. Enhanced ATP7a expression inhibited COX activity by lowering intracellular copper content. Conclusions: Hcy elevates ATP7a protein expression, reduces copper content, and lowers COX activity, finally leading to cardiac hypertrophy. PMID:26722473

  13. The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria*

    PubMed Central

    Bhattacharjee, Ashima; Yang, Haojun; Duffy, Megan; Robinson, Emily; Conrad-Antoville, Arianrhod; Lu, Ya-Wen; Capps, Tony; Braiterman, Lelita; Wolfgang, Michael; Murphy, Michael P.; Yi, Ling; Kaler, Stephen G.; Lutsenko, Svetlana; Ralle, Martina

    2016-01-01

    Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria, whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia). PMID:27226607

  14. SARS coronavirus protein 7a interacts with human Ap4A-hydrolase

    PubMed Central

    2010-01-01

    The SARS coronavirus (SARS-CoV) open reading frame 7a (ORF 7a) encodes a 122 amino acid accessory protein. It has no significant sequence homology with any other known proteins. The 7a protein is present in the virus particle and has been shown to interact with several host proteins; thereby implicating it as being involved in several pathogenic processes including apoptosis, inhibition of cellular protein synthesis, and activation of p38 mitogen activated protein kinase. In this study we present data demonstrating that the SARS-CoV 7a protein interacts with human Ap4A-hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17). Ap4A-hydrolase is responsible for metabolizing the "allarmone" nucleotide Ap4A and therefore likely involved in regulation of cell proliferation, DNA replication, RNA processing, apoptosis and DNA repair. The interaction between 7a and Ap4A-hydrolase was identified using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation from cultured human cells transiently expressing V5-His tagged 7a and HA tagged Ap4A-hydrolase. Human tissue culture cells transiently expressing 7a and Ap4A-hydrolase tagged with EGFP and Ds-Red2 respectively show these proteins co-localize in the cytoplasm. PMID:20144233

  15. The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria.

    PubMed

    Bhattacharjee, Ashima; Yang, Haojun; Duffy, Megan; Robinson, Emily; Conrad-Antoville, Arianrhod; Lu, Ya-Wen; Capps, Tony; Braiterman, Lelita; Wolfgang, Michael; Murphy, Michael P; Yi, Ling; Kaler, Stephen G; Lutsenko, Svetlana; Ralle, Martina

    2016-08-01

    Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria, whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia). PMID:27226607

  16. Analysis Of DWPF Sludge Batch 7a (Macrobatch 8) Pour Stream Samples

    SciTech Connect

    Johnson, F. C.; Pareizs, J. M.

    2012-10-24

    The Defense Waste Processing Facility (DWPF) began processing Sludge Batch 7a (SB7a), also referred to as Macrobatch 8 (MB8), in June 2011. SB7a is a blend of the heel of Tank 40 from Sludge Batch 6 (SB6) and the SB7a material that was transferred to Tank 40 from Tank 51. SB7a was processed using Frit 418. During processing of each sludge batch, the DWPF is required to take at least one glass sample to meet the objectives of the Glass Product Control Program (GPCP), which is governed by the DWPF Waste Compliance Plan, and to complete the necessary Production Records so that the final glass product may be disposed of at a Federal Repository. Three pour stream glass samples and two Melter Feed Tank (MFT) slurry samples were collected while processing SB7a. These additional samples were taken during SB7a to understand the impact of antifoam and the melter bubblers on glass redox chemistry. The samples were transferred to the Savannah River National Laboratory (SRNL) where they were analyzed.

  17. Unexpected role of the copper transporter ATP7A in PDGF-induced vascular smooth

    SciTech Connect

    Ashino, T.; Varadarajan, S.; Urao, N.; Oshikawa, J.; Chen, G. -F.; Wang, H.; Huo, Y.; Finney, L.; Vogt, S.; McKinney, R. D.; Maryon, E. B.; Kaplan, J. H.; Ushio-Fukai, M.; Fukai, T.

    2010-09-09

    Copper, an essential nutrient, has been implicated in vascular remodeling and atherosclerosis with unknown mechanism. Bioavailability of intracellular copper is regulated not only by the copper importer CTR1 (copper transporter 1) but also by the copper exporter ATP7A (Menkes ATPase), whose function is achieved through copper-dependent translocation from trans-Golgi network (TGN). Platelet-derived growth factor (PDGF) promotes vascular smooth muscle cell (VSMC) migration, a key component of neointimal formation. To determine the role of copper transporter ATP7A in PDGF-induced VSMC migration. Depletion of ATP7A inhibited VSMC migration in response to PDGF or wound scratch in a CTR1/copper-dependent manner. PDGF stimulation promoted ATP7A translocation from the TGN to lipid rafts, which localized at the leading edge, where it colocalized with PDGF receptor and Rac1, in migrating VSMCs. Mechanistically, ATP7A small interfering RNA or CTR small interfering RNA prevented PDGF-induced Rac1 translocation to the leading edge, thereby inhibiting lamellipodia formation. In addition, ATP7A depletion prevented a PDGF-induced decrease in copper level and secretory copper enzyme precursor prolysyl oxidase (Pro-LOX) in lipid raft fraction, as well as PDGF-induced increase in LOX activity. In vivo, ATP7A expression was markedly increased and copper accumulation was observed by synchrotron-based x-ray fluorescence microscopy at neointimal VSMCs in wire injury model. These findings suggest that ATP7A plays an important role in copper-dependent PDGF-stimulated VSMC migration via recruiting Rac1 to lipid rafts at the leading edge, as well as regulating LOX activity. This may contribute to neointimal formation after vascular injury. Our findings provide insight into ATP7A as a novel therapeutic target for vascular remodeling and atherosclerosis.

  18. Wnt7A is a putative prognostic and chemosensitivity marker in human malignant pleural mesothelioma

    PubMed Central

    HIRATA, TOMOMI; ZHENG, QINGFENG; CHEN, ZHAO; KINOSHITA, HIROYASU; OKAMOTO, JUNICHI; KRATZ, JOHANNES; LI, HUI; LUI, NATALIE; DO, HANH; CHENG, TIFFANY; TSENG, HSIN-HUI KATTY; KOIZUMI, KIYOSHI; SHIMIZU, KAZUO; ZHOU, HAI-MENG; JABLONS, DAVID; HE, BIAO

    2015-01-01

    Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that has a poor prognosis, limited treatment options, and a worldwide incidence that is expected to increase in the next decade. We evaluated Wnt7A expression in 50 surgically resected tumor specimens using quantitative PCR. The expression values, were assessed by clinicopathological factors and K-M and Cox’s regression with OS. The mean level of Wnt7A expression had a significant correlation with International Mesothelioma Interest Group (IMIG) stage (P<0.034), gender, smoking history and ethnicity, respectively (P=0.020, P=0.014, P=0.039). In the univariate analysis, low Wnt7A expression was a significant negative factor for overall survival (P=0.043, HR=2.30). However, multivariate Cox’s regression revealed no significant factors for overall survival (low Wnt7A: P=0.051, HR=2.283; non-epithelioid subtype: P=0.050, HR=2.898). In patients with epithelioid tumors, those with low Wnt7A expression had significantly worse prognosis (P=0.019, HR=2.98). In patients with epithelioid tumors, females had significantly better prognosis than males (P=0.035). In patients who did not have neoadjuvant chemotherapy, prognosis was significantly more favorable for patients with high Wnt7A expression than for those with low Wnt7A expression (P=0.031). Among the patients with low Wnt7A-expressing tumors, those who received neoadjuvant chemotherapy had better prognosis than those who did not (P=0.024). The results of our study suggest that Wnt7A expression is a putative prognostic factor and a predictor of chemosensitivity. PMID:25632963

  19. Small amounts of functional ATP7A protein permit mild phenotype.

    PubMed

    Møller, Lisbeth Birk

    2015-01-01

    Mutations in ATP7A lead to at least three allelic disorders: Menkes disease (MD), Occipital horn syndrome and X-linked distal motor neuropathy. These disorders are mainly seen in male individuals, but a few affected females have been described. More than 400 different mutations have been identified in the ATP7A gene. We have conducted several studies in the hope of uncovering the relationship between genotype and phenotype. We have examined the X-inactivation pattern in affected females, the effect of exon-deletions and--duplications, and splice-site mutations on the composition and amount of ATP7A transcript, and we have examined the structural location of missense mutations. The X-inactivation pattern did not fully explain the manifestation of MD in a small fraction of carriers. Most of the affected females had preferential inactivation of the X-chromosome with the normal ATP7A gene, but a few individuals exhibited preferential inactivation of the X-chromosome with the mutated ATP7A gene. The observed mild phenotype in some patients with mutations that effect the composition of the ATP7A transcript, seems to be explained by the presence of a small amount of normal ATP7A transcript. The location of missense mutations on structural models of the ATP7A protein suggests that affected conserved residues generally lead to a severe phenotype. The ATP7A protein traffics within the cells. At low copper levels, ATP7A locates to the Trans-Golgi Network (TGN) to load cuproenzymes with copper, whereas at higher concentrations, ATP7A shifts to the post-Golgi compartments or to the plasma membrane to export copper out of the cell. Impaired copper-regulation trafficking has been observed for ATP7A mutants, but its impact on the clinical outcome is not clear. The major problem in patients with MD seems to be insufficient amounts of copper in the brain. In fact, prenatal treatment of mottled mice as a model for human MD with a combination of chelator and copper, produces a slight

  20. Derivatives of 1,5-diamino-1H-tetrazole: a new family of energetic heterocyclic-based salts.

    PubMed

    Gálvez-Ruiz, Juan Carlos; Holl, Gerhard; Karaghiosoff, Konstantin; Klapötke, Thomas M; Löhnwitz, Karolin; Mayer, Peter; Nöth, Heinrich; Polborn, Kurt; Rohbogner, Christoph J; Suter, Max; Weigand, Jan J

    2005-06-13

    1,5-Diamino-1H-tetrazole (2, DAT) can easily be protonated by reaction with strong mineral acids, yielding the poorly investigated 1,5-diaminotetrazolium nitrate (2a) and perchlorate (2b). A new synthesis for 2 is introduced that avoids lead azide as a hazardous byproduct. The reaction of 1,5-diamino-1H-tetrazole with iodomethane (7a) followed by the metathesis of the iodide (7a) with silver nitrate (7b), silver dinitramide (7c), or silver azide (7d) leads to a new family of heterocyclic-based salts. In all cases, stable salts were obtained and fully characterized by vibrational (IR, Raman) spectroscopy, multinuclear NMR spectroscopy, mass spectrometry, elemental analysis, X-ray structure determination, and initial safety testing (impact and friction sensitivity). Most of the salts exhibit good thermal stabilities, and both the perchlorate (2b) and the dinitramide (7c) have melting points well below 100 degrees C, yet high decomposition onsets, defining them as new (7c), highly energetic ionic liquids. Preliminary sensitivity testing of the crystalline compounds indicates rather low impact sensitivities for all compounds, the highest being that of the perchlorate (2b) and the dinitramide (7c) with a value of 7 J. In contrast, the friction sensitivities of the perchlorate (2b, 60 N) and the dinitramide (7c, 24 N) are relatively high. The enthalpies of combustion (Delta(c)H degrees ) of 7b-d were determined experimentally using oxygen bomb calorimetry: Delta(c)H degrees (7b) = -2456 cal g(-)(1), Delta(c)H degrees (7c) = -2135 cal g(-)(1), and Delta(c)H degrees (7d) = -3594 cal g(-)(1). The standard enthalpies of formation (Delta(f)H degrees ) of 7b-d were obtained on the basis of quantum chemical computations using the G2 (G3) method: Delta(f)H degrees (7b) = 41.7 (41.2) kcal mol(-)(1), Delta(f)H degrees (7c) = 92.1 (91.1) kcal mol(-)(1), and Delta(f)H degrees (7d) = 161.6 (161.5) kcal mol(-)(1). The detonation velocities (D) and detonation pressures (P) of 2b and 7b

  1. Glass forming ability and magnetic properties of Co(40.2-x)Fe(20.1+x)Ni6.7B22.7Si5.3Nb5 (x=0-10) bulk metallic glasses produced by suction casting

    NASA Astrophysics Data System (ADS)

    Sarlar, Kagan; Kucuk, Ilker

    2015-01-01

    The effect of Fe concentration on the glass forming ability (GFA) and magnetic properties in Co(40.2-x)Fe(20.1+x)Ni6.7B22.7Si5.3Nb5 (x=0-10) bulk metallic glasses were investigated. By suction casting method, the bulk metallic glasses with diameters up to 2 mm were produced. We try to find out which Fe concentration makes an influence on Co based system's magnetic properties and glass forming ability. The curves of thermal analysis, obtained using differential scanning calorimetry (DSC), show that the Co(40.2-x)Fe(20.1+x)Ni6.7B22.7Si5.3Nb5 (x=0-10) have a supercooled liquid region (∆Tx) of about 44 K. The saturation magnetizations (Js) for as-cast BMG alloys were in the range of 0.62 T-0.81 T.

  2. THE SLUDGE BATCH 7A GLASS VARIABILITY STUDY WITH FRIT 418 AND FRIT 702

    SciTech Connect

    Peeler, D; Edwards, T

    2011-03-24

    The Defense Waste Processing Facility (DWPF) is preparing to initiate processing of Sludge Batch 7a (SB7a) in May 2011. To support qualification of SB7a, the Savannah River National Laboratory (SRNL) was requested to execute a variability study (VS) to assess the applicability of the current Product Composition Control System (PCCS) durability models for the Frit 418-SB7a compositional region of interest. The objective of this study was to demonstrate applicability of the current durability models to the SB7a compositional region of interest and acceptability of the SB7a glasses with respect to the Environmental Assessment (EA) glass in terms of durability as defined by the Product Consistency Test (PCT). To support programmatic objectives, twenty-eight SB7a glasses were selected based on the nominal sludge projections used to support the frit recommendation. Twenty-three of the SB7a VS glasses were based on the use of Frit 418, while 5 glasses were based on the use of Frit 702. Frit 702 was also identified as a viable candidate for SB7a, especially if SO{sub 4} concentrations are found to be higher than anticipated. Frit 702 has shown a higher SO{sub 4} retention capability as compared to Frit 418. With respect to acceptability, the PCT results of the SB7a-VS glasses are acceptable relative to the EA glass regardless of thermal history (quenched or canister centerline cooled) or compositional view (target or measured). More specifically, all of the SB7a glasses have normalized boron release values (NL [B]) less than 0.9 g/L as compared to the benchmark NL [B] value for EA of 16.695 g/L. With respect to the applicability of the current durability models to the SB7a VS compositional region of interest, all of the study glasses (based on target compositions) lie within the 95% confidence intervals of the model predictions. When model applicability is based on the measured compositions, all of the SB7a VS glasses are predictable with the exception of SB7aVS-02 and SB7

  3. miR-Let7A Modulates Autophagy Induction in LPS-Activated Microglia

    PubMed Central

    Song, Juhyun; Oh, Yumi

    2015-01-01

    Microglia regulate the secretion of various immunomediators in central nervous system diseases. Microglial autophagy is the crucial process for cell's survival and cytokine productions. Recent studies have reported that several microRNAs are involved in the autophagy system. miR-Let7A is such a microRNA that plays a role in various inflammation responses, and is magnified as a key modulator particularly in the autophagy system. In present study, we investigated whether miR-Let7A is involved in autophagy in activating microglia. Overexpression of miR-Let7A in LPS-stimulated BV2 microglial cells promoted the induction of the autophagy related factors such as LC3II, Beclin1, and ATG3. Our results suggest a potential role of miR-Let7A in the autophagy process of microglia during CNS inflammation. PMID:26113790

  4. Let7a inhibits the growth of endometrial carcinoma cells by targeting Aurora-B.

    PubMed

    Liu, Ping; Qi, Meiyan; Ma, Chengbin; Lao, Guoying; Liu, Yu; Liu, Yan; Liu, Yingzi

    2013-08-19

    MicroRNAs negatively regulate target gene expression at the post-transcriptional level during carcinogenesis. Recent advances revealed that the expression levels of several miRNAs are up- or down-regulated in endometrial carcinoma (EC). Here we identify dysregulated miRNAs in EC and we elucidate the essential role of let-7a. The expression of 86 miRNAs in EC was found to be different from adjacent normal endometrial tissues. Moreover, miR-let-7 members are down-regulated in EC and let-7 miRNAs are highly associated with endometrial cancer. A functional investigation revealed that let-7a suppressed proliferation of HeLa cells by targeting Aurora-B. Let-7a also antagonizes Aurora-B functions in promoting carcinoma cell proliferation by down-regulating Aurora-B protein level. Let-7a could be applied for gene therapy against endometrial carcinogenesis. PMID:23769985

  5. 13 CFR 120.423 - Which 7(a) loans may a Lender securitize?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Lender may only securitize 7(a) loans that will be fully disbursed within 90 days of the securitization's closing date. If the amount of a fully disbursed loan increases after a securitization settles, the...

  6. Regulatory compliance guide for DOT-7A type A packaging design

    SciTech Connect

    Kelly, D.L.

    1996-06-04

    The purpose of this guide is to provide instruction for assuring that the regulatory design requirements for a DOT-7A Type A packaging are met. This guide also supports the testing and evaluation activities that are performed on new packaging designs by a DOE-approved test facility through the DOE`s DOT-7A Test Program. This Guide was updated to incorporate regulatory changes implemented by HM-169A (49 CFR, `Transportation`).

  7. MicroRNA-Let-7a regulates the function of microglia in inflammation.

    PubMed

    Cho, Kyoung Joo; Song, Juhyun; Oh, Yumi; Lee, Jong Eun

    2015-09-01

    Microglia have multiple functions in cerebrovascular and neurodegenerative diseases. Regulation of microglial function during inflammatory stress is important for treatment of central nervous system (CNS) diseases because microglia secrete various substances that affect neurons and glia. MicroRNA-Let-7a (miR-Let-7a) is a tumor suppressor miRNA that has been reported to target transcripts that encode proteins involved in apoptosis. In the present study, we examined the essential role of miR-Let-7a in inflammatory stress by over-expressing miR-Let-7a to investigate its role in determining the BV2 microglial phenotype, a cell line often used as a model of activated microglia. We found that inflammatory factors and Reactive Oxygen Species (ROS) production levels were altered according to miR-Let-7a expression level as measured by Western blot analysis, reverse transcription PCR, quantitative real time PCR, the measurement of nitrite (indicative of the nitric oxide (NO) pathway), and immunocytochemistry (ICC). Our results suggest that miR-Let-7a is involved in the function of microglia in the setting of inflammatory injury. In response to inflammation, miR-Let-7a participates in the reduction of nitrite production and the expression of inducible nitric oxide synthase (iNOS), interleukin (IL)-6 and is involved in increased expression of brain derived neurotrophic factor (BDNF), interleukin (IL)-10, and IL-4 in microglia. Thus, miRNA-Let-7a could act as a regulator of the function of microglia in inflammation. PMID:26221772

  8. Test plan for the M-100 container model M-101/7A/12/90 Docket 96-43-7A, type A container

    SciTech Connect

    Kelly, D.L.

    1997-05-30

    This document describes the test plan for the M-100 Container, Model M-101/7A/12/90. This packaging system is designed to ship Type A solid, radioactive materials, normal form, Form Nos. 1, 2, and 3. The nominal overall dimensions, including risers, of the M-100 Container are 79 x 54 x 42 inches. The capacity of the container is approximately 89.9 ft. The estimated gross weight of the packaging and contents is 9,000 lb.

  9. PDZD7-MYO7A complex identified in enriched stereocilia membranes

    PubMed Central

    Morgan, Clive P; Krey, Jocelyn F; Grati, M'hamed; Zhao, Bo; Fallen, Shannon; Kannan-Sundhari, Abhiraami; Liu, Xue Zhong; Choi, Dongseok; Müller, Ulrich; Barr-Gillespie, Peter G

    2016-01-01

    While more than 70 genes have been linked to deafness, most of which are expressed in mechanosensory hair cells of the inner ear, a challenge has been to link these genes into molecular pathways. One example is Myo7a (myosin VIIA), in which deafness mutations affect the development and function of the mechanically sensitive stereocilia of hair cells. We describe here a procedure for the isolation of low-abundance protein complexes from stereocilia membrane fractions. Using this procedure, combined with identification and quantitation of proteins with mass spectrometry, we demonstrate that MYO7A forms a complex with PDZD7, a paralog of USH1C and DFNB31. MYO7A and PDZD7 interact in tissue-culture cells, and co-localize to the ankle-link region of stereocilia in wild-type but not Myo7a mutant mice. Our data thus describe a new paradigm for the interrogation of low-abundance protein complexes in hair cell stereocilia and establish an unanticipated link between MYO7A and PDZD7. DOI: http://dx.doi.org/10.7554/eLife.18312.001 PMID:27525485

  10. PDZD7-MYO7A complex identified in enriched stereocilia membranes.

    PubMed

    Morgan, Clive P; Krey, Jocelyn F; Grati, M'hamed; Zhao, Bo; Fallen, Shannon; Kannan-Sundhari, Abhiraami; Liu, Xue Zhong; Choi, Dongseok; Müller, Ulrich; Barr-Gillespie, Peter G

    2016-01-01

    While more than 70 genes have been linked to deafness, most of which are expressed in mechanosensory hair cells of the inner ear, a challenge has been to link these genes into molecular pathways. One example is Myo7a (myosin VIIA), in which deafness mutations affect the development and function of the mechanically sensitive stereocilia of hair cells. We describe here a procedure for the isolation of low-abundance protein complexes from stereocilia membrane fractions. Using this procedure, combined with identification and quantitation of proteins with mass spectrometry, we demonstrate that MYO7A forms a complex with PDZD7, a paralog of USH1C and DFNB31. MYO7A and PDZD7 interact in tissue-culture cells, and co-localize to the ankle-link region of stereocilia in wild-type but not Myo7a mutant mice. Our data thus describe a new paradigm for the interrogation of low-abundance protein complexes in hair cell stereocilia and establish an unanticipated link between MYO7A and PDZD7. PMID:27525485

  11. Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy

    PubMed Central

    Yan, Ning; Peng, Rui; Li, Hongmei; Liu, Handeng; Peng, Huimin; Sun, Yan; Wu, Tianhui; Chen, Lei; Duan, Qingrui; Sun, Yixuan; Zhou, Qin; Wei, Lijiang

    2016-01-01

    Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus (DM). However, the exact mechanism is not clearly understood. In this study, our results showed that 24 h urinary protein, kidney index, and glomerular area were decreased, while creatinine clearance ratio was increased in DN rats when the rats were treated with NAR 50 mg/d for 6 weeks. Mesangial cell (MMCs) proliferation was inhibited in the NAR group by 3,(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and the cell cycle analysis showed that cells stayed in G2 phase in NAR group. And NAR treatment attenuated the deposition of ECM in DN rats and MMCs. Moreover, our data showed that let-7a was downexpressed in both DN rats and MMCs under high glucose condition. Surprisingly, NAR affected the expressions of Col4 and FN through upregulating let-7a in MMCs. In addition, we found that let-7a negatively regulated the expression of transforming growth factor-β1 receptor 1 (TGFBR1), and TGFBR1 was required for the let-7a-mediated downregulation of TGF-β1/smad signaling. Interestingly, NAR inhibited TGF-β1/smads signaling activation by upregulating let-7a. Therefore, our findings indicated that NAR ameliorated kidney injury by regulating let-7a/TGFBR1 signaling. PMID:27446963

  12. WNT7A Regulation by miR-15b in Ovarian Cancer.

    PubMed

    MacLean, James A; King, Mandy L; Okuda, Hiroshi; Hayashi, Kanako

    2016-01-01

    WNT signaling is well known to play an important role in the regulation of development, cell proliferation and cell differentiation in a wide variety of normal and cancerous tissues. Despite the wealth of knowledge concerning when and where various WNT genes are expressed and downstream events under their control, there is surprisingly little published evidence of how they are regulated. We have recently reported that aberrant WNT7A is observed in serous ovarian carcinomas, and WNT7A is the sole ligand accelerating ovarian tumor progression through CTNNB1 (β-catenin)/TCF signaling in the absence of CTNNB1 mutations. In the present study, we report that WNT7A is a direct target of miR-15b in ovarian cancer. We showed that a luciferase reporter containing the putative binding site of miR-15b in the WNT7A 3'-UTR was significantly repressed by miR-15b. Mutation of the putative binding site of miR-15b in the WNT7A 3'-UTR restored luciferase activity. Furthermore, miR-15b was able to repress increased levels of TOPFLASH activity by WNT7A, but not those induced by S33Y. Additionally, miR-15b dose-dependently decreased WNT7A expression. When we evaluated the prognostic impact of WNT7A and miR-15b expression using TCGA datasets, a significant inverse correlation in which high-expression of WNT7A and low-expression of miR-15b was associated with reduced survival rates of ovarian cancer patients. Treatment with decitabine dose-dependently increased miR-15b expression, and silencing of DNMT1 significantly increased miR-15b expression. These results suggest that WNT7A is post-transcriptionally regulated by miR-15b, which could be down-regulated by promoter hypermethylation, potentially via DNMT1, in ovarian cancer. PMID:27195958

  13. WNT7A Regulation by miR-15b in Ovarian Cancer

    PubMed Central

    MacLean, James A.; King, Mandy L.; Okuda, Hiroshi

    2016-01-01

    WNT signaling is well known to play an important role in the regulation of development, cell proliferation and cell differentiation in a wide variety of normal and cancerous tissues. Despite the wealth of knowledge concerning when and where various WNT genes are expressed and downstream events under their control, there is surprisingly little published evidence of how they are regulated. We have recently reported that aberrant WNT7A is observed in serous ovarian carcinomas, and WNT7A is the sole ligand accelerating ovarian tumor progression through CTNNB1 (β-catenin)/TCF signaling in the absence of CTNNB1 mutations. In the present study, we report that WNT7A is a direct target of miR-15b in ovarian cancer. We showed that a luciferase reporter containing the putative binding site of miR-15b in the WNT7A 3’-UTR was significantly repressed by miR-15b. Mutation of the putative binding site of miR-15b in the WNT7A 3’-UTR restored luciferase activity. Furthermore, miR-15b was able to repress increased levels of TOPFLASH activity by WNT7A, but not those induced by S33Y. Additionally, miR-15b dose-dependently decreased WNT7A expression. When we evaluated the prognostic impact of WNT7A and miR-15b expression using TCGA datasets, a significant inverse correlation in which high-expression of WNT7A and low-expression of miR-15b was associated with reduced survival rates of ovarian cancer patients. Treatment with decitabine dose-dependently increased miR-15b expression, and silencing of DNMT1 significantly increased miR-15b expression. These results suggest that WNT7A is post-transcriptionally regulated by miR-15b, which could be down-regulated by promoter hypermethylation, potentially via DNMT1, in ovarian cancer. PMID:27195958

  14. New metal-organic frameworks of [M(C{sub 6}H{sub 5}O{sub 7})(C{sub 6}H{sub 6}O{sub 7})(C{sub 6}H{sub 7}O{sub 7})(H{sub 2}O)] . H{sub 2}O (M=La, Ce) and [Ce{sub 2}(C{sub 2}O{sub 4})(C{sub 6}H{sub 6}O{sub 7}){sub 2}] . 4H{sub 2}O

    SciTech Connect

    Weng Shengfeng; Wang, Yun-Hsin; Lee, Chi-Shen

    2012-04-15

    Two novel materials, [M(C{sub 6}H{sub 5}O{sub 7})(C{sub 6}H{sub 6}O{sub 7})(C{sub 6}H{sub 7}O{sub 7})(H{sub 2}O)] . H{sub 2}O (M=La(1a), Ce(1b)) and [Ce{sub 2}(C{sub 2}O{sub 4})(C{sub 6}H{sub 6}O{sub 7}){sub 2}] . 4H{sub 2}O (2), with a metal-organic framework (MOF) were prepared with hydrothermal reactions and characterized with photoluminescence, magnetic susceptibility, thermogravimetric analysis and X-ray powder diffraction in situ. The crystal structures were determined by single-crystal X-ray diffraction. Compound 1 crystallized in triclinic space group P1-bar (No. 2); compound 2 crystallized in monoclinic space group P2{sub 1}/c (No. 14). The structure of 1 is built from a 1D MOF, composed of deprotonated citric ligands of three kinds. Compound 2 contains a 2D MOF structure consisting of citrate and oxalate ligands; the oxalate ligand arose from the decomposition in situ of citric acid in the presence of Cu{sup II} ions. Photoluminescence spectra of compounds 1b and 2 revealed transitions between the 5d{sup 1} excited state and two levels of the 4f{sup 1} ground state ({sup 2}F{sub 5/2} and {sup 2}F{sub 7/2}). Compounds 1b and 2 containing Ce{sup III} ion exhibit a paramagnetic property with weak antiferromagnetic interactions between the two adjacent magnetic centers. - Graphical Abstract: [M(C{sub 6}H{sub 5}O{sub 7})(C{sub 6}H{sub 6}O{sub 7})(C{sub 6}H{sub 7}O{sub 7})(H{sub 2}O)] . H{sub 2}O (M=La(1a), Ce(1b)) and [Ce{sub 2}(C{sub 2}O{sub 4})(C{sub 6}H{sub 6}O{sub 7}){sub 2}] . 4H{sub 2}O (2)-with 1D and 2D structures were synthesized and characterized. Highlights: Black-Right-Pointing-Pointer Two MOF - [M(C{sub 6}H{sub 5}O{sub 7})(C{sub 6}H{sub 6}O{sub 7})(C{sub 6}H{sub 7}O{sub 7})(H{sub 2}O)] . H{sub 2}O (M=La(1a), Ce(1b)) and [Ce{sub 2}(C{sub 2}O{sub 4})(C{sub 6}H{sub 6}O{sub 7}){sub 2}] . 4H{sub 2}O (2) - with 1D and 2D structures. Black-Right-Pointing-Pointer The adjacent chains of the 1D framework were correlated with each other through an oxalate

  15. Structural Basis of Substrate Recognition by Aldehyde Dehydrogenase 7A1.

    PubMed

    Luo, Min; Tanner, John J

    2015-09-01

    Aldehyde dehydrogenase 7A1 (ALDH7A1) is part of lysine catabolism and catalyzes the NAD(+)-dependent oxidation of α-aminoadipate semialdehyde to α-aminoadipate. Herein, we describe a structural study of human ALDH7A1 focused on substrate recognition. Five crystal structures and small-angle X-ray scattering data are reported, including the first crystal structure of any ALDH7 family member complexed with α-aminoadipate. The product binds with the ε-carboxylate in the oxyanion hole, the aliphatic chain packed into an aromatic box, and the distal end of the product anchored by electrostatic interactions with five conserved residues. This binding mode resembles that of glutamate bound to the proline catabolic enzyme ALDH4A1. Analysis of ALDH7A1 and ALDH4A1 structures suggests key interactions that underlie substrate discrimination. Structures of apo ALDH7A1 reveal dramatic conformational differences from the product complex. Product binding is associated with a 16 Å movement of the C-terminus into the active site, which stabilizes the active conformation of the aldehyde substrate anchor loop. The fact that the C-terminus is part of the active site was hitherto unknown. Interestingly, the C-terminus and aldehyde anchor loop are disordered in a new tetragonal crystal form of the apoenzyme, implying that these parts of the enzyme are highly flexible. Our results suggest that the active site of ALDH7A1 is disassembled when the aldehyde site is vacant, and the C-terminus is a mobile element that forms quaternary structural interactions that aid aldehyde binding. These results are relevant to the c.1512delG genetic deletion associated with pyridoxine-dependent epilepsy, which alters the C-terminus of ALDH7A1. PMID:26260980

  16. Wnt7a stimulates myogenic stem cell motility and engraftment resulting in improved muscle strength.

    PubMed

    Bentzinger, C Florian; von Maltzahn, Julia; Dumont, Nicolas A; Stark, Danny A; Wang, Yu Xin; Nhan, Kevin; Frenette, Jérôme; Cornelison, D D W; Rudnicki, Michael A

    2014-04-14

    Wnt7a/Fzd7 signaling stimulates skeletal muscle growth and repair by inducing the symmetric expansion of satellite stem cells through the planar cell polarity pathway and by activating the Akt/mTOR growth pathway in muscle fibers. Here we describe a third level of activity where Wnt7a/Fzd7 increases the polarity and directional migration of mouse satellite cells and human myogenic progenitors through activation of Dvl2 and the small GTPase Rac1. Importantly, these effects can be exploited to potentiate the outcome of myogenic cell transplantation into dystrophic muscles. We observed that a short Wnt7a treatment markedly stimulated tissue dispersal and engraftment, leading to significantly improved muscle function. Moreover, myofibers at distal sites that fused with Wnt7a-treated cells were hypertrophic, suggesting that the transplanted cells deliver activated Wnt7a/Fzd7 signaling complexes to recipient myofibers. Taken together, we describe a viable and effective ex vivo cell modulation process that profoundly enhances the efficacy of stem cell therapy for skeletal muscle. PMID:24711502

  17. Wnt7a stimulates myogenic stem cell motility and engraftment resulting in improved muscle strength

    PubMed Central

    Bentzinger, C. Florian; von Maltzahn, Julia; Dumont, Nicolas A.; Stark, Danny A.; Wang, Yu Xin; Nhan, Kevin; Frenette, Jérôme; Cornelison, DDW

    2014-01-01

    Wnt7a/Fzd7 signaling stimulates skeletal muscle growth and repair by inducing the symmetric expansion of satellite stem cells through the planar cell polarity pathway and by activating the Akt/mTOR growth pathway in muscle fibers. Here we describe a third level of activity where Wnt7a/Fzd7 increases the polarity and directional migration of mouse satellite cells and human myogenic progenitors through activation of Dvl2 and the small GTPase Rac1. Importantly, these effects can be exploited to potentiate the outcome of myogenic cell transplantation into dystrophic muscles. We observed that a short Wnt7a treatment markedly stimulated tissue dispersal and engraftment, leading to significantly improved muscle function. Moreover, myofibers at distal sites that fused with Wnt7a-treated cells were hypertrophic, suggesting that the transplanted cells deliver activated Wnt7a/Fzd7 signaling complexes to recipient myofibers. Taken together, we describe a viable and effective ex vivo cell modulation process that profoundly enhances the efficacy of stem cell therapy for skeletal muscle. PMID:24711502

  18. Test and evaluation document for DOT Specification 7A type A packaging. Volume 1

    SciTech Connect

    Kelly, D L

    1997-08-04

    The US Department of Energy (DOE) has been conducting, through several of its operating contractors, an evaluation and testing program to qualify Type A radioactive material packagings per US Department of Transportation (DOT) Specification 7A (DOT-7A) of the Code of Federal Regulations (CFR), Title 49, Part 178 (49 CFR 178). This document summarizes the evaluation and testing performed for all of the packagings successfully qualified in this program. This document supersedes DOE Evaluation Document for DOT-7A Type A Packaging (Edling 1987), originally issued in 1987 by Monsanto Research Corporation Mound Laboratory (MLM), Miamisburg, Ohio, for the Department of Energy, Security Evaluation Program (I)P-4. Mound Laboratory issued four revisions to the document between November 1988 and December 1989. In September 1989, the program was transferred to Westinghouse Hanford Company (Westinghouse Hanford) in Richland, Washington. One additional revision was issued in March 1990 by Westinghouse Hanford. This revision reflects the earlier material and incorporates a number of changes. Evaluation and testing activities on 1208 three DOT-7A Program Dockets resulted in the qualification of three new packaging configurations, which are incorporated herein and summarized. This document presents approximately 300 different packagings that have been determined to meet the requirements for a DOT-7A, type A packaging per 49 CFR 178.350.

  19. Two-current model of the composition dependence of resistivity in amorphous (Fe{sub 100-x}Co{sub x}){sub 89-y}Zr{sub 7}B{sub 4}Cu{sub y} alloys using a rigid-band assumption

    SciTech Connect

    Shen, S.; Ohodnicki, P. R.; Kernion, S. J.; McHenry, M. E.

    2012-11-15

    Composition dependence of resistivity is studied in amorphous (Fe{sub 100−x}Co{sub x}){sub 89−y}Zr{sub 7}B{sub 4}Cu{sub y} (0 ≤ x ≤ 50, y = 0, 1) alloys. The two-current model proposed by Mott for crystalline materials is extended to a disordered amorphous system where s-d scattering is dominant in electron conduction. A rigid-band assumption is made due to the small atomic number difference between Fe and Co. Band structures with a constant density of states (DOS), parabolic distributed DOS, and Gaussian distributed DOS were investigated to fit experimental data. The Gaussian distributed DOS was found to simulate the resistivity maximum and magnetic moment maximum in the Fe-rich region. The basic concepts presented here can potentially provide insight into the optimization of FeCo-based HITPERM alloys for applications at increased frequencies.

  20. Translational research investigations on ATP7A, an important human copper ATPase

    PubMed Central

    Kaler, Stephen G.

    2014-01-01

    In the more than 40 years since copper deficiency was delineated in pediatric subjects with Menkes disease, remarkable advances in our understanding of the clinical, biochemical, and molecular aspects of the human copper transporter ATP7A have emerged. Mutations in the gene encoding this multitasking molecule are now implicated in at least two other distinctive phenotypes: occipital horn syndrome and ATP7A-related isolated distal motor neuropathy. Several other novel inherited disorders of copper metabolism have been identified in the past several years, aided by advances in human gene mapping and sequencing. In this paper, I review the history and evolution of our understanding of disorders caused by impaired ATP7A function, and outline future challenges. PMID:24735419

  1. Xylan oligosaccharides and cellobiohydrolase I (TrCel7A) interaction and effect on activity

    PubMed Central

    2011-01-01

    Background The well-studied cellulase mixture secreted by Trichoderma reesei (anamorph to Hypocrea jecorina) contains two cellobiohydolases (CBHs), cellobiohydrolase I (TrCel7A) and cellobiohydrolase II (TrCeI6A), that are core enzymes for the solubilisation of cellulose. This has attracted significant research interest because of the role of the CBHs in the conversion of biomass to fermentable sugars. However, the CHBs are notoriously slow and susceptible to inhibition, which presents a challenge for the commercial utilisation of biomass. The xylans and xylan fragments that are also present in the biomass have been suggested repeatedly as one cause of the reduced activity of CHBs. Yet, the extent and mechanisms of this inhibition remain poorly elucidated. Therefore, we studied xylan oligosaccharides (XOSs) of variable lengths with respect to their binding and inhibition of both TrCel7A and an enzyme variant without the cellulose-binding domain (CBM). Results We studied the binding of XOSs to TrCel7A by isothermal titration calorimetry. We found that XOSs bind to TrCel7A and that the affinity increases commensurate with XOS length. The CBM, on the other hand, did not affect the affinity significantly, which suggests that XOSs may bind to the active site. Activity assays of TrCel7A clearly demonstrated the negative effect of the presence of XOSs on the turnover number. Conclusions On the basis of these binding data and a comparison of XOS inhibition of the activity of the two enzyme variants towards, respectively, soluble and insoluble substrates, we propose a competitive mechanism for XOS inhibition of TrCel7A with phosphoric swollen cellulose as a substrate. PMID:22035059

  2. Test and evaluation document for DOT Specification 7A Type A Packaging. Revision 3

    SciTech Connect

    1996-01-30

    The US Department of Energy (DOE) has been conducting, through several of its operating contractors, an evaluation and testing program to qualify Type A radioactive material packagings per US Department of Transportation (DOT) Specification 7A (DOT-7A) of the Code of Federal Regulations (CFR), Title 49, Part 178 (49 CFR 178). The program is currently administered by the DOE, Office of Facility Safety Analysis, DOE/EH-32, at DOE-Headquarters (DOE-HQ) in Germantown, Maryland. This document summarizes the evaluation and testing performed for all of the packagings successfully qualified in this program.

  3. 17 CFR 260.7a-16 - Inclusion of items, differentiation between items and answers, omission of instructions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Inclusion of items, differentiation between items and answers, omission of instructions. 260.7a-16 Section 260.7a-16 Commodity and... INDENTURE ACT OF 1939 Formal Requirements § 260.7a-16 Inclusion of items, differentiation between items...

  4. 40 CFR 60.482-7a - Standards: Valves in gas/vapor service and in light liquid service.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... and in light liquid service. 60.482-7a Section 60.482-7a Protection of Environment ENVIRONMENTAL...-7a Standards: Valves in gas/vapor service and in light liquid service. (a)(1) Each valve shall be... service or light liquid service after the initial startup date for the process unit must be...

  5. 17 CFR 260.7a-16 - Inclusion of items, differentiation between items and answers, omission of instructions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Inclusion of items, differentiation between items and answers, omission of instructions. 260.7a-16 Section 260.7a-16 Commodity and... INDENTURE ACT OF 1939 Formal Requirements § 260.7a-16 Inclusion of items, differentiation between items...

  6. A novel quantitative trait locus for Fusarium head blight resistance in chromosome 7A of wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A Chinese Spring-Sumai 3 chromosome 7A disomic substitution line (CS-Sumai 3-7ADSL) was reported to have a high level of Fusarium head blight (FHB) resistance for symptom spread within a spike (Type II) and low deoxynivalenol accumulation in infected kernels (Type III), but quantitative trait locus ...

  7. 17 CFR 260.7a-25 - Words relating to the future.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Words relating to the future... § 260.7a-25 Words relating to the future. Unless the context clearly shows otherwise, whenever words relate to the future, they have reference solely to present intention....

  8. 19 CFR 4.7a - Inward manifest; information required; alternative forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... the Immigration and Naturalization Service, United States Department of Justice (8 CFR part 251). (e... requirements of the Immigration and Naturalization Service, U.S. Department of Justice (8 CFR part 231), and... § 4.7a, see the List of CFR Sections Affected, which appears in the Finding Aids section of...

  9. Documentation and analysis for packaging for surface moisture measurement system 7A containers

    SciTech Connect

    Clem, D.K.

    1996-06-17

    This documentation and analysis for packaging documents that two, procured, carbon steel 5-gal drums meet all applicable U.S.Department of Transportation-7A requirements. One container will be used to transport a 0.009 Ci 252 Cf source and the other to transport a 1.7 Ci Am-Be source to and from various 200 Area tank farms.

  10. SLC7A5 act as a potential leukemic transformation target gene in myelodysplastic syndrome

    PubMed Central

    Ma, Yan; Song, Jing; Chen, Bobin; Xu, Xiaoping; Lin, Guowei

    2016-01-01

    Objective Myelodysplastic syndromes (MDS) are a heterogenous group of clonal hematopoietic stem cell disorders characterized by increased risk of leukemic transformation. This study identifies microRNAs(miRNA) and miRNA targets that might represent leukemic transformation markers for MDS. Methods Based on our previously established nested case-control study cohort of MDS patients, we chose paired patients to undergo Angilent 8 × 15K human miRNA microarrays. Target prediction analysis was administrated using targetscan 5.1 software. We further investigated the function of target gene in MDS cell line using siRNA method, including cell proliferation, cell apoptosis, cell cycle and electron microscope. Results Finally we screened a subset of 7 miRNAs to be significantly differentially expressed between the case (at the end of follow up with leukemic transformation) and control group (at the end of follow up without leukemic transformation). Target prediction analysis revealed SLC7A5 was the common target gene of these 7 miRNAs. Further study on the function of SLC7A5 gene in SKM-1 cell line showed that downregulation of SLC7A5 inhibited SKM-1 cells proliferation, increased apoptosis and caused cell cycle arrest in the G0/G1 stage. Conclusion Our data indicate that SLC7A5 gene may act as a potential leukemic transformation target gene in MDS. PMID:26657287

  11. Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness

    PubMed Central

    Avgustinova, Alexandra; Iravani, Marjan; Robertson, David; Fearns, Antony; Gao, Qiong; Klingbeil, Pamela; Hanby, Andrew M.; Speirs, Valerie; Sahai, Erik; Calvo, Fernando; Isacke, Clare M.

    2016-01-01

    Stromal fibroblast recruitment to tumours and activation to a cancer-associated fibroblast (CAF) phenotype has been implicated in promoting primary tumour growth and progression to metastatic disease. However, the mechanisms underlying the tumour:fibroblast crosstalk that drive the intertumoural stromal heterogeneity remain poorly understood. Using in vivo models we identify Wnt7a as a key factor secreted exclusively by aggressive breast tumour cells, which induces CAF conversion. Functionally, this results in extracellular matrix remodelling to create a permissive environment for tumour cell invasion and promotion of distant metastasis. Mechanistically, Wnt7a-mediated fibroblast activation is not dependent on classical Wnt signalling. Instead, we demonstrate that Wnt7a potentiates TGFβ receptor signalling both in 3D in vitro and in vivo models, thus highlighting the interaction between two of the key signalling pathways in development and disease. Importantly, in clinical breast cancer cohorts, tumour cell Wnt7a expression correlates with a desmoplastic, poor-prognosis stroma and poor patient outcome. PMID:26777421

  12. Semaphorin7A regulates neuroglial plasticity in the adult hypothalamic median eminence

    PubMed Central

    Parkash, Jyoti; Messina, Andrea; Langlet, Fanny; Cimino, Irene; Loyens, Anne; Mazur, Danièle; Gallet, Sarah; Balland, Eglantine; Malone, Samuel A.; Pralong, François; Cagnoni, Gabriella; Schellino, Roberta; De Marchis, Silvia; Mazzone, Massimiliano; Pasterkamp, R. Jeroen; Tamagnone, Luca; Prevot, Vincent; Giacobini, Paolo

    2015-01-01

    Reproductive competence in mammals depends on the projection of gonadotropin-releasing hormone (GnRH) neurons to the hypothalamic median eminence (ME) and the timely release of GnRH into the hypothalamic–pituitary–gonadal axis. In adult rodents, GnRH neurons and the specialized glial cells named tanycytes periodically undergo cytoskeletal plasticity. However, the mechanisms that regulate this plasticity are still largely unknown. We demonstrate that Semaphorin7A, expressed by tanycytes, plays a dual role, inducing the retraction of GnRH terminals and promoting their ensheathment by tanycytic end feet via the receptors PlexinC1 and Itgb1, respectively. Moreover, Semaphorin7A expression is regulated during the oestrous cycle by the fluctuating levels of gonadal steroids. Genetic invalidation of Semaphorin7A receptors in mice induces neuronal and glial rearrangements in the ME and abolishes normal oestrous cyclicity and fertility. These results show a role for Semaphorin7A signalling in mediating periodic neuroglial remodelling in the adult ME during the ovarian cycle. PMID:25721933

  13. Semaphorin7A regulates neuroglial plasticity in the adult hypothalamic median eminence.

    PubMed

    Parkash, Jyoti; Messina, Andrea; Langlet, Fanny; Cimino, Irene; Loyens, Anne; Mazur, Danièle; Gallet, Sarah; Balland, Eglantine; Malone, Samuel A; Pralong, François; Cagnoni, Gabriella; Schellino, Roberta; De Marchis, Silvia; Mazzone, Massimiliano; Pasterkamp, R Jeroen; Tamagnone, Luca; Prevot, Vincent; Giacobini, Paolo

    2015-01-01

    Reproductive competence in mammals depends on the projection of gonadotropin-releasing hormone (GnRH) neurons to the hypothalamic median eminence (ME) and the timely release of GnRH into the hypothalamic-pituitary-gonadal axis. In adult rodents, GnRH neurons and the specialized glial cells named tanycytes periodically undergo cytoskeletal plasticity. However, the mechanisms that regulate this plasticity are still largely unknown. We demonstrate that Semaphorin7A, expressed by tanycytes, plays a dual role, inducing the retraction of GnRH terminals and promoting their ensheathment by tanycytic end feet via the receptors PlexinC1 and Itgb1, respectively. Moreover, Semaphorin7A expression is regulated during the oestrous cycle by the fluctuating levels of gonadal steroids. Genetic invalidation of Semaphorin7A receptors in mice induces neuronal and glial rearrangements in the ME and abolishes normal oestrous cyclicity and fertility. These results show a role for Semaphorin7A signalling in mediating periodic neuroglial remodelling in the adult ME during the ovarian cycle. PMID:25721933

  14. 17 CFR 260.7a-25 - Words relating to the future.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Words relating to the future... § 260.7a-25 Words relating to the future. Unless the context clearly shows otherwise, whenever words relate to the future, they have reference solely to present intention....

  15. 17 CFR 260.7a-25 - Words relating to the future.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Words relating to the future... § 260.7a-25 Words relating to the future. Unless the context clearly shows otherwise, whenever words relate to the future, they have reference solely to present intention....

  16. 17 CFR 260.7a-25 - Words relating to the future.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Words relating to the future... § 260.7a-25 Words relating to the future. Unless the context clearly shows otherwise, whenever words relate to the future, they have reference solely to present intention....

  17. Genome Sequence of Streptomyces viridosporus Strain T7A ATCC 39115, a Lignin-Degrading Actinomycete

    SciTech Connect

    Davis, Jennifer R.; Goodwin, Lynne A.; Teshima, Hazuki; Detter, J. Chris; Tapia, Roxanne; Han, Cliff; Huntemann, Marcel; Wei, Chia-Lin; Han, James; Chen, Amy; Kyrpides, Nikos C; Mavromatis, K; Szeto, Ernest; Markowitz, Victor; Ivanova, N; Mikhailova, Natalia; Ovchinnikova, Galina; Pagani, Ioanna; Pati, Amrita; Woyke, Tanja; Pitluck, Sam; Peters, Lin; Nolan, Matt; Land, Miriam L; Sello, Jason K.

    2013-01-01

    We announce the availability of the genome sequence of Streptomyces viridosporus strain T7A ATCC 39115, a plant biomass- degrading actinomycete. This bacterium is of special interest because of its capacity to degrade lignin, an underutilized compo- nent of plants in the context of bioenergy. It has a full complement of genes for plant biomass catabolism.

  18. Pipe Nebula (B59, B65-7, B79)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    A large dark nebula in the constellation Scorpius, resembling a tobacco pipe. E E Barnard assigned five separate catalog numbers to sections of the nebula. B78 is the `bowl', about 3½° by 2½°, with approximate position RA 17 h 33 m, dec. -26°, while B59 and B65-7 comprise the `stem', 5° by 1°, with approximate position RA 17 h 21 m, dec. -27°....

  19. Evidence on Private Sector Training. Background Paper No. 7b.

    ERIC Educational Resources Information Center

    Mangum, Stephen L.

    Today's postindustrial or information age requires a different mix and a more advanced level of basic employability skills than those needed in the industrial age. As a result, the workplace is now demanding a higher entrance level of employability skills than the schools have previously been asked to provide. In addition, information technology…

  20. Cystinuria Associated with Different SLC7A9 Gene Variants in the Cat

    PubMed Central

    Raj, Karthik; Osborne, Carl; Giger, Urs

    2016-01-01

    Cystinuria is a classical inborn error of metabolism characterized by a selective proximal renal tubular defect affecting cystine, ornithine, lysine, and arginine (COLA) reabsorption, which can lead to uroliths and urinary obstruction. In humans, dogs and mice, cystinuria is caused by variants in one of two genes, SLC3A1 and SLC7A9, which encode the rBAT and bo,+AT subunits of the bo,+ basic amino acid transporter system, respectively. In this study, exons and flanking regions of the SLC3A1 and SLC7A9 genes were sequenced from genomic DNA of cats (Felis catus) with COLAuria and cystine calculi. Relative to the Felis catus-6.2 reference genome sequence, DNA sequences from these affected cats revealed 3 unique homozygous SLC7A9 missense variants: one in exon 5 (p.Asp236Asn) from a non-purpose-bred medium-haired cat, one in exon 7 (p.Val294Glu) in a Maine Coon and a Sphinx cat, and one in exon 10 (p.Thr392Met) from a non-purpose-bred long-haired cat. A genotyping assay subsequently identified another cystinuric domestic medium-haired cat that was homozygous for the variant originally identified in the purebred cats. These missense variants result in deleterious amino acid substitutions of highly conserved residues in the bo,+AT protein. A limited population survey supported that the variants found were likely causative. The remaining 2 sequenced domestic short-haired cats had a heterozygous variant at a splice donor site in intron 10 and a homozygous single nucleotide variant at a branchpoint in intron 11 of SLC7A9, respectively. This study identifies the first SLC7A9 variants causing feline cystinuria and reveals that, as in humans and dogs, this disease is genetically heterogeneous in cats. PMID:27404572

  1. Cystinuria Associated with Different SLC7A9 Gene Variants in the Cat.

    PubMed

    Mizukami, Keijiro; Raj, Karthik; Osborne, Carl; Giger, Urs

    2016-01-01

    Cystinuria is a classical inborn error of metabolism characterized by a selective proximal renal tubular defect affecting cystine, ornithine, lysine, and arginine (COLA) reabsorption, which can lead to uroliths and urinary obstruction. In humans, dogs and mice, cystinuria is caused by variants in one of two genes, SLC3A1 and SLC7A9, which encode the rBAT and bo,+AT subunits of the bo,+ basic amino acid transporter system, respectively. In this study, exons and flanking regions of the SLC3A1 and SLC7A9 genes were sequenced from genomic DNA of cats (Felis catus) with COLAuria and cystine calculi. Relative to the Felis catus-6.2 reference genome sequence, DNA sequences from these affected cats revealed 3 unique homozygous SLC7A9 missense variants: one in exon 5 (p.Asp236Asn) from a non-purpose-bred medium-haired cat, one in exon 7 (p.Val294Glu) in a Maine Coon and a Sphinx cat, and one in exon 10 (p.Thr392Met) from a non-purpose-bred long-haired cat. A genotyping assay subsequently identified another cystinuric domestic medium-haired cat that was homozygous for the variant originally identified in the purebred cats. These missense variants result in deleterious amino acid substitutions of highly conserved residues in the bo,+AT protein. A limited population survey supported that the variants found were likely causative. The remaining 2 sequenced domestic short-haired cats had a heterozygous variant at a splice donor site in intron 10 and a homozygous single nucleotide variant at a branchpoint in intron 11 of SLC7A9, respectively. This study identifies the first SLC7A9 variants causing feline cystinuria and reveals that, as in humans and dogs, this disease is genetically heterogeneous in cats. PMID:27404572

  2. Let-7a inhibits tumor cell growth and metastasis by directly targeting RTKN in human colon cancer.

    PubMed

    Li, Bin; Chen, Peng; Chang, Yanxiang; Qi, Jingpeng; Fu, Hui; Guo, Huifang

    2016-09-16

    Colorectal cancer (CRC) is the third most common cancer worldwide, with high morbidity. MicroRNAs (miRNAs) are endogenous small RNAs that play important roles in regulating multiple biological and pathologic processes. The differential expression of miRNAs in CRC was first reported in 2003. Accumulated evidence indicates that lethal-7a (let-7a, miRNA) generally functions as a tumor suppressor in several human cancers. However, the role of let-7a in human colon cancer remains unclear. The aim of this study was to investigate the biological functions of let-7a and its potential role in colon cancer. We first discovered that let-7a level was significantly decreased in colon cancer tissues and cell lines (HT-29, HCT-116, LoVo, SW480, and SW620). To explore the effects of let-7a on colon cancer, let-7a over-expressed HCT-116 and SW620 cells were constructed. Further studies demonstrated that over-expressed let-7a could remarkably inhibit HCT-116 and SW620 cell growth and metastasis by directly down-regulating Rhotekin (RTKN). When RTKN was reintroduced into let-7a mimic transfected HCT-116 or SW620 cells, the inhibition effects of let-7a on colon cancer cell growth and metastasis were markedly reversed. In conclusion, our research shows that let-7a can inhibit tumor cell growth and metastasis by directly targeting RTKN in human colon cancer. PMID:27498032

  3. The SLC7A7 Transporter Identifies Microglial Precursors prior to Entry into the Brain.

    PubMed

    Rossi, Federico; Casano, Alessandra Maria; Henke, Katrin; Richter, Kerstin; Peri, Francesca

    2015-05-19

    During development, macrophages invade organs to establish phenotypically and transcriptionally distinct tissue-resident populations. How they invade and colonize these organs is unclear. In particular, it remains to be established whether they arise from naive equivalents that colonize organs randomly or whether there are committed macrophages that follow pre-determined migration paths. Here, by using a combination of genetics and imaging approaches in the zebrafish embryo, we have addressed how macrophages colonize the brain to become microglia. Identification and cloning of a mutant that lacks microglia has shown that Slc7a7, a Leucine/Arginine transporter, defines a restricted macrophage sub-lineage and is necessary for brain colonization. By taking a photoconversion approach, we show that these macrophages give rise to microglia. This study provides direct experimental evidence for the existence of sub-lineages among embryonic macrophages. PMID:25959825

  4. A COL7A1 Mutation Causes Dystrophic Epidermolysis Bullosa in Rotes Höhenvieh Cattle

    PubMed Central

    Menoud, Annie; Welle, Monika; Tetens, Jens; Lichtner, Peter; Drögemüller, Cord

    2012-01-01

    We identified a congenital mechanobullous skin disorder in six calves on a single farm of an endangered German cattle breed in 2010. The condition presented as a large loss of skin distal to the fetlocks and at the mucosa of the muzzle. All affected calves were euthanized on humane grounds due to the severity, extent and progression of the skin and oral lesions. Examination of skin samples under light microscopy revealed detachment of the epidermis from the dermis at the level of the dermo epidermal junction, leading to the diagnosis of a subepidermal bullous dermatosis such as epidermolysis bullosa. The pedigree was consistent with monogenic autosomal recessive inheritance. We localized the causative mutation to an 18 Mb interval on chromosome 22 by homozygosity mapping. The COL7A1 gene encoding collagen type VII alpha 1 is located within this interval and COL7A1 mutations have been shown to cause inherited dystrophic epidermolysis bullosa (DEB) in humans. A SNP in the bovine COL7A1 exon 49 (c.4756C>T) was perfectly associated with the observed disease. The homozygous mutant T/T genotype was exclusively present in affected calves and their parents were heterozygous C/T confirming the assumed recessive mode of inheritance. All known cases and genotyped carriers were related to a single cow, which is supposed to be the founder animal. The mutant T allele was absent in 63 animals from 24 cattle breeds. The identified mutation causes a premature stop codon which leads to a truncated protein representing a complete loss of COL7A1 function (p.R1586*). We thus have identified a candidate causative mutation for this genetic disease using only three cases to unravel its molecular basis. Selection against this mutation can now be used to eliminate the mutant allele from the Rotes Höhenvieh breed. PMID:22715415

  5. A truncated Wnt7a retains full biological activity in skeletal muscle

    NASA Astrophysics Data System (ADS)

    von Maltzahn, Julia; Zinoviev, Radoslav; Chang, Natasha C.; Bentzinger, C. Florian; Rudnicki, Michael A.

    2013-11-01

    Wnt signaling has essential roles during embryonic development and tissue homoeostasis. Wnt proteins are post-translationally modified and the attachment of a palmitate moiety at two conserved residues is believed to be a prerequisite for the secretion and function of Wnt proteins. Here we demonstrate that a mammalian Wnt protein can be fully functional without palmitoylation. We generate a truncated Wnt7a variant, consisting of the C-terminal 137 amino acids lacking the conserved palmitoylation sites and show that it retains full biological activity in skeletal muscle. This includes binding to and signaling through its receptor Fzd7 to stimulate symmetric expansion of satellite stem cells by activating the planar-cell polarity pathway and inducing myofibre hypertrophy by signaling through the AKT/mTOR pathway. Furthermore, this truncated Wnt7a shows enhanced secretion and dispersion compared with the full-length protein. Together, these findings open important new avenues for the development of Wnt7a as a treatment for muscle-wasting diseases and have broad implications for the therapeutic use of Wnts as biologics.

  6. The respiratory chain supercomplex organization is independent of COX7a2l isoforms.

    PubMed

    Mourier, Arnaud; Matic, Stanka; Ruzzenente, Benedetta; Larsson, Nils-Göran; Milenkovic, Dusanka

    2014-12-01

    The organization of individual respiratory chain complexes into supercomplexes or respirasomes has attracted great interest because of the implications for cellular energy conversion. Recently, it was reported that commonly used mouse strains harbor a short COX7a2l (SCAFI) gene isoform that supposedly precludes the formation of complex IV-containing supercomplexes. This claim potentially has serious implications for numerous mouse studies addressing important topics in metabolism, including adaptation to space flights. Using several complementary experimental approaches, we show that mice with the short COX7a2l isoform have normal biogenesis and steady-state levels of complex IV-containing supercomplexes and consequently have normal respiratory chain function. Furthermore, we use a mouse knockout of Lrpprc and show that loss of complex IV compromises respirasome formation. We conclude that the presence of the short COX7a2l isoform in the commonly used C57BL/6 mouse strains does not prevent their use in metabolism research. PMID:25470551

  7. The Respiratory Chain Supercomplex Organization Is Independent of COX7a2l Isoforms

    PubMed Central

    Mourier, Arnaud; Matic, Stanka; Ruzzenente, Benedetta; Larsson, Nils-Göran; Milenkovic, Dusanka

    2014-01-01

    Summary The organization of individual respiratory chain complexes into supercomplexes or respirasomes has attracted great interest because of the implications for cellular energy conversion. Recently, it was reported that commonly used mouse strains harbor a short COX7a2l (SCAFI) gene isoform that supposedly precludes the formation of complex IV-containing supercomplexes. This claim potentially has serious implications for numerous mouse studies addressing important topics in metabolism, including adaptation to space flights. Using several complementary experimental approaches, we show that mice with the short COX7a2l isoform have normal biogenesis and steady-state levels of complex IV-containing supercomplexes and consequently have normal respiratory chain function. Furthermore, we use a mouse knockout of Lrpprc and show that loss of complex IV compromises respirasome formation. We conclude that the presence of the short COX7a2l isoform in the commonly used C57BL/6 mouse strains does not prevent their use in metabolism research. PMID:25470551

  8. Structural insights into the affinity of Cel7A carbohydrate-binding module for lignin.

    PubMed

    Strobel, Kathryn L; Pfeiffer, Katherine A; Blanch, Harvey W; Clark, Douglas S

    2015-09-11

    The high cost of hydrolytic enzymes impedes the commercial production of lignocellulosic biofuels. High enzyme loadings are required in part due to their non-productive adsorption to lignin, a major component of biomass. Despite numerous studies documenting cellulase adsorption to lignin, few attempts have been made to engineer enzymes to reduce lignin binding. In this work, we used alanine-scanning mutagenesis to elucidate the structural basis for the lignin affinity of Trichoderma reesei Cel7A carbohydrate binding module (CBM). T. reesei Cel7A CBM mutants were produced with a Talaromyces emersonii Cel7A catalytic domain and screened for their binding to cellulose and lignin. Mutation of aromatic and polar residues on the planar face of the CBM greatly decreased binding to both cellulose and lignin, supporting the hypothesis that the cellulose-binding face is also responsible for lignin affinity. Cellulose and lignin affinity of the 31 mutants were highly correlated, although several mutants displayed selective reductions in lignin or cellulose affinity. Four mutants with increased cellulose selectivity (Q2A, H4A, V18A, and P30A) did not exhibit improved hydrolysis of cellulose in the presence of lignin. Further reduction in lignin affinity while maintaining a high level of cellulose affinity is thus necessary to generate an enzyme with improved hydrolysis capability. This work provides insights into the structural underpinnings of lignin affinity, identifies residues amenable to mutation without compromising cellulose affinity, and informs engineering strategies for family one CBMs. PMID:26209638

  9. Myosin7a Deficiency Results in Reduced Retinal Activity Which Is Improved by Gene Therapy

    PubMed Central

    Colella, Pasqualina; Sommella, Andrea; Marrocco, Elena; Di Vicino, Umberto; Polishchuk, Elena; Garrido, Marina Garcia; Seeliger, Mathias W.; Polishchuk, Roman; Auricchio, Alberto

    2013-01-01

    Mutations in MYO7A cause autosomal recessive Usher syndrome type IB (USH1B), one of the most frequent conditions that combine severe congenital hearing impairment and retinitis pigmentosa. A promising therapeutic strategy for retinitis pigmentosa is gene therapy, however its pre-clinical development is limited by the mild retinal phenotype of the shaker1 (sh1−/−) murine model of USH1B which lacks both retinal functional abnormalities and degeneration. Here we report a significant, early-onset delay of sh1−/− photoreceptor ability to recover from light desensitization as well as a progressive reduction of both b-wave electroretinogram amplitude and light sensitivity, in the absence of significant loss of photoreceptors up to 12 months of age. We additionally show that subretinal delivery to the sh1−/− retina of AAV vectors encoding the large MYO7A protein results in significant improvement of sh1−/− photoreceptor and retinal pigment epithelium ultrastructural anomalies which is associated with improvement of recovery from light desensitization. These findings provide new tools to evaluate the efficacy of experimental therapies for USH1B. In addition, although AAV vectors expressing large genes might have limited clinical applications due to their genome heterogeneity, our data show that AAV-mediated MYO7A gene transfer to the sh1−/− retina is effective. PMID:23991031

  10. Structural Insights into the Affinity of Cel7A Carbohydrate-binding Module for Lignin*

    PubMed Central

    Strobel, Kathryn L.; Pfeiffer, Katherine A.; Blanch, Harvey W.; Clark, Douglas S.

    2015-01-01

    The high cost of hydrolytic enzymes impedes the commercial production of lignocellulosic biofuels. High enzyme loadings are required in part due to their non-productive adsorption to lignin, a major component of biomass. Despite numerous studies documenting cellulase adsorption to lignin, few attempts have been made to engineer enzymes to reduce lignin binding. In this work, we used alanine-scanning mutagenesis to elucidate the structural basis for the lignin affinity of Trichoderma reesei Cel7A carbohydrate binding module (CBM). T. reesei Cel7A CBM mutants were produced with a Talaromyces emersonii Cel7A catalytic domain and screened for their binding to cellulose and lignin. Mutation of aromatic and polar residues on the planar face of the CBM greatly decreased binding to both cellulose and lignin, supporting the hypothesis that the cellulose-binding face is also responsible for lignin affinity. Cellulose and lignin affinity of the 31 mutants were highly correlated, although several mutants displayed selective reductions in lignin or cellulose affinity. Four mutants with increased cellulose selectivity (Q2A, H4A, V18A, and P30A) did not exhibit improved hydrolysis of cellulose in the presence of lignin. Further reduction in lignin affinity while maintaining a high level of cellulose affinity is thus necessary to generate an enzyme with improved hydrolysis capability. This work provides insights into the structural underpinnings of lignin affinity, identifies residues amenable to mutation without compromising cellulose affinity, and informs engineering strategies for family one CBMs. PMID:26209638

  11. Effect of cation substitution at the B site on the oxygen semi-permeation flux in La0.5Ba0.5Fe0.7B0.3O3-δ dense perovskite membranes with B = Al, Co, Cu, Mg, Mn, Ni, Sn, Ti and Zn (part II)

    NASA Astrophysics Data System (ADS)

    Reichmann, M.; Geffroy, P.-M.; Fouletier, J.; Richet, N.; Del Gallo, P.; Chartier, T.

    2015-03-01

    The aim of this paper is to provide insight into the effect of cation substitution at the B site on the oxygen semi-permeation performances. Particular attention is given here to identify the impact of cation substitution at the B site on oxygen diffusion and oxygen surface-exchange kinetics in the La0.5Ba0.5Fe0.7B0.3O3-δ perovskite membrane series with B = Al, Co, Cu, Mg, Mn, Ni, Sn, Ti and Zn. This study clearly shows that the prediction of the oxygen semi-permeation performances of membrane materials from the nature of cation at the A or B sites in perovskite structure is quite complex. The cation substitution at the B-site has a low impact on the nature of rate-determining step and a significant impact on oxygen semi-permeation performances, contrary to the cation substitution at A-site. Unfortunately, it is not possible to establish a relevant trend about the effect of the nature of cation in the A or B sites in perovskite structure on oxygen diffusion and the oxygen surface-exchange kinetics.

  12. Nanogranular Fe{sub x}Ni{sub 23-x}B{sub 6} phase formation during devitrification of nickel-rich Ni{sub 64}Fe{sub 16}Zr{sub 7}B{sub 12}Au{sub 1} amorphous alloy

    SciTech Connect

    Idzikowski, B.; Szajek, A.; Greneche, J.-M.; Kovac, J.

    2004-08-23

    Nickel-rich amorphous precursors with chemical composition of Ni{sub 64}Fe{sub 16}Zr{sub 7}B{sub 12}Au{sub 1} were produced by melt-spinning technique and then heat treated at temperatures ranging from 435 to 600 deg. C for 1 h to form a nanostructure. Properties of the amorphous and the nanocrystalline samples were investigated by the differential scanning calorimetry, the x-ray diffraction (XRD), the vibrating sample magnetometry, and Moessbauer techniques. The annealing favors the emergence of cubic Fe{sub x}Ni{sub 23-x}B{sub 6} crystalline grains (10-25 nm in diameter). Magnetic measurements made at 4.2-1100 K reveal rather high value of saturation magnetization (nearly 60 and 40 Am{sup 2}/kg at 4.2 K and room temperature, respectively) in amorphous as well as in nanocrystalline states. These facts are consistent with 300 K {sup 57}Fe Moessbauer effect results which are well supported by the calculations of Ni and Fe magnetic moments in Ni{sub 23}B{sub 6} and Fe{sub 23}B{sub 6} phases, using the spin polarized tight binding linear muffin-tin orbital method. However, anomalous high magnetic moments of Fe atoms were found in some inequivalent positions in the crystal structure.

  13. 26 CFR 1.482-7A - Methods to determine taxable income in connection with a cost sharing arrangement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Methods to determine taxable income in connection with a cost sharing arrangement. 1.482-7A Section 1.482-7A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Regulations Applicable on Or Before January 4, 2009. § 1.482-7A...

  14. The brown and brite adipocyte marker Cox7a1 is not required for non-shivering thermogenesis in mice

    PubMed Central

    Maurer, Stefanie F.; Fromme, Tobias; Grossman, Lawrence I.; Hüttemann, Maik; Klingenspor, Martin

    2015-01-01

    The cytochrome c oxidase subunit isoform Cox7a1 is highly abundant in skeletal muscle and heart and influences enzyme activity in these tissues characterised by high oxidative capacity. We identified Cox7a1, well-known as brown adipocyte marker gene, as a cold-responsive protein of brown adipose tissue. We hypothesised a mechanistic relationship between cytochrome c oxidase activity and Cox7a1 protein levels affecting the oxidative capacity of brown adipose tissue and thus non-shivering thermogenesis. We subjected wildtype and Cox7a1 knockout mice to different temperature regimens and tested characteristics of brown adipose tissue activation. Cytochrome c oxidase activity, uncoupling protein 1 expression and maximal norepinephrine-induced heat production were gradually increased during cold-acclimation, but unaffected by Cox7a1 knockout. Moreover, the abundance of uncoupling protein 1 competent brite cells in white adipose tissue was not influenced by presence or absence of Cox7a1. Skin temperature in the interscapular region of neonates was lower in uncoupling protein 1 knockout pups employed as a positive control, but not in Cox7a1 knockout pups. Body mass gain and glucose tolerance did not differ between wildtype and Cox7a1 knockout mice fed with high fat or control diet. We conclude that brown adipose tissue function in mice does not require the presence of Cox7a1. PMID:26635001

  15. Mechanism of product inhibition for cellobiohydrolase Cel7A during hydrolysis of insoluble cellulose.

    PubMed

    Olsen, Johan P; Alasepp, Kadri; Kari, Jeppe; Cruys-Bagger, Nicolaj; Borch, Kim; Westh, Peter

    2016-06-01

    The cellobiohydrolase cellulase Cel7A is extensively utilized in industrial treatment of lignocellulosic biomass under conditions of high product concentrations, and better understanding of inhibition mechanisms appears central in attempts to improve the efficiency of this process. We have implemented an electrochemical biosensor assay for product inhibition studies of cellulases acting on their natural substrate, cellulose. Using this method we measured the hydrolytic rate of Cel7A as a function of both product (inhibitor) concentration and substrate load. This data enabled analyses along the lines of conventional enzyme kinetic theory. We found that the product cellobiose lowered the maximal rate without affecting the Michaelis constant, and this kinetic pattern could be rationalized by two fundamentally distinct molecular mechanisms. One was simple reversibility, that is, an increasing rate of the reverse reaction, lowering the net hydrolytic velocity as product concentrations increase. Strictly this is not a case of inhibition, as no catalytically inactive is formed. The other mechanism that matched the kinetic data was noncompetitive inhibition with an inhibition constant of 490 ± 40 μM. Noncompetitive inhibition implies that the inhibitor binds with comparable strength to either free enzyme or an enzymesubstrate complex, that is, that association between enzyme and substrate has no effect on the binding of the inhibitor. This mechanism is rarely observed, but we argue, that the special architecture of Cel7A with numerous subsites for binding of both substrate and product could give rise to a true noncompetitive inhibition mechanism. Biotechnol. Bioeng. 2016;113: 1178-1186. © 2015 Wiley Periodicals, Inc. PMID:26636743

  16. WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis.

    PubMed

    Ouyang, Hong; Xue, Yuanchao; Lin, Ying; Zhang, Xiaohui; Xi, Lei; Patel, Sherrina; Cai, Huimin; Luo, Jing; Zhang, Meixia; Zhang, Ming; Yang, Yang; Li, Gen; Li, Hairi; Jiang, Wei; Yeh, Emily; Lin, Jonathan; Pei, Michelle; Zhu, Jin; Cao, Guiqun; Zhang, Liangfang; Yu, Benjamin; Chen, Shaochen; Fu, Xiang-Dong; Liu, Yizhi; Zhang, Kang

    2014-07-17

    The surface of the cornea consists of a unique type of non-keratinized epithelial cells arranged in an orderly fashion, and this is essential for vision by maintaining transparency for light transmission. Cornea epithelial cells (CECs) undergo continuous renewal from limbal stem or progenitor cells (LSCs), and deficiency in LSCs or corneal epithelium--which turns cornea into a non-transparent, keratinized skin-like epithelium--causes corneal surface disease that leads to blindness in millions of people worldwide. How LSCs are maintained and differentiated into corneal epithelium in healthy individuals and which key molecular events are defective in patients have been largely unknown. Here we report establishment of an in vitro feeder-cell-free LSC expansion and three-dimensional corneal differentiation protocol in which we found that the transcription factors p63 (tumour protein 63) and PAX6 (paired box protein PAX6) act together to specify LSCs, and WNT7A controls corneal epithelium differentiation through PAX6. Loss of WNT7A or PAX6 induces LSCs into skin-like epithelium, a critical defect tightly linked to common human corneal diseases. Notably, transduction of PAX6 in skin epithelial stem cells is sufficient to convert them to LSC-like cells, and upon transplantation onto eyes in a rabbit corneal injury model, these reprogrammed cells are able to replenish CECs and repair damaged corneal surface. These findings suggest a central role of the WNT7A-PAX6 axis in corneal epithelial cell fate determination, and point to a new strategy for treating corneal surface diseases. PMID:25030175

  17. Simulation evaluation of transition and hover flying qualities of the E-7A STOVL aircraft

    NASA Technical Reports Server (NTRS)

    Franklin, James A.; Stortz, Michael W.; Gerdes, Ronald M.; Hardy, Gordon H.; Martin, James L.; Engelland, Shawn A.

    1988-01-01

    The generalized simulation model developed for the E-7A STOVL fighter-type aircraft configuration has attempted to define the limits of acceptibility for a vertical-to-horizontal-to-vertical flight transition envelope. An effort was also made to determine the control power required during hover and transition, and to evaluate whether the integration of flight and propulsion controls thus far effected achieves good flying qualities throughout the low-speed flight envelope. The results thus obtained furnish a general view of the acceptable transition corridor, expressed in terms of the minimum-climb capability.

  18. Cloning, expression, purification and crystallization of Schizosaccharomyces pombe Set7, a putative histone methyltransferase.

    PubMed

    Mevius, Damiaan E H F; Shen, Yunpeng; Morishita, Masayo; di Luccio, Eric

    2016-04-01

    Dysfunction of histone-modifying enzymes affects chromatin regulation and is involved in carcinogenesis, tumour progression and other diseases. Histone methyltransferases are a family of key histone-modifying enzymes, but their structures, functions and mechanisms are incompletely understood, thus constraining drug-design efforts. Here, preliminary steps towards structure-function studies of Schizosaccharomyces pombe Set7, a putative histone methyltransferase and the first yeast full-length SET-domain-containing protein to be studied using X-ray crystallography, are reported. The methods from cloning to X-ray diffraction and phasing are discussed and the results will aid in prospective studies of histone-modifying enzymes. PMID:27050258

  19. Expression of WNT genes in cervical cancer-derived cells: Implication of WNT7A in cell proliferation and migration

    SciTech Connect

    Ramos-Solano, Moisés; Meza-Canales, Ivan D.; Torres-Reyes, Luis A.; Alvarez-Zavala, Monserrat; and others

    2015-07-01

    According to the multifactorial model of cervical cancer (CC) causation, it is now recognized that other modifications, in addition to Human papillomavirus (HPV) infection, are necessary for the development of this neoplasia. Among these, it has been proposed that a dysregulation of the WNT pathway might favor malignant progression of HPV-immortalized keratinocytes. The aim of this study was to identify components of the WNT pathway differentially expressed in CC vs. non-tumorigenic, but immortalized human keratinocytes. Interestingly, WNT7A expression was found strongly downregulated in cell lines and biopsies derived from CC. Restoration of WNT7A in CC-derived cell lines using a lentiviral gene delivery system or after adding a recombinant human protein decreases cell proliferation. Likewise, WNT7A silencing in non-tumorigenic cells markedly accelerates proliferation. Decreased WNT7A expression was due to hypermethylation at particular CpG sites. To our knowledge, this is the first study reporting reduced WNT7A levels in CC-derived cells and that ectopic WNT7A restoration negatively affects cell proliferation and migration. - Highlights: • WNT7A is expressed in normal keratinocytes or cervical cells without lesion. • WNT7A is significantly reduced in cervical cancer-derived cells. • Restoration of WNT7A expression in HeLa decreases proliferation and cell migration. • Silencing of WNT7A in HaCaT induces an increased proliferation and migration rate. • Decreased WNT7A expression in this model is due to hypermethylation.

  20. Human cholesterol 7alpha-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype.

    PubMed

    Pullinger, Clive R; Eng, Celeste; Salen, Gerald; Shefer, Sarah; Batta, Ashok K; Erickson, Sandra K; Verhagen, Andrea; Rivera, Christopher R; Mulvihill, Sean J; Malloy, Mary J; Kane, John P

    2002-07-01

    Bile acid synthesis plays a critical role in the maintenance of mammalian cholesterol homeostasis. The CYP7A1 gene encodes the enzyme cholesterol 7alpha-hydroxylase, which catalyzes the initial step in cholesterol catabolism and bile acid synthesis. We report here a new metabolic disorder presenting with hyperlipidemia caused by a homozygous deletion mutation in CYP7A1. The mutation leads to a frameshift (L413fsX414) that results in loss of the active site and enzyme function. High levels of LDL cholesterol were seen in three homozygous subjects. Analysis of a liver biopsy and stool from one of these subjects revealed double the normal hepatic cholesterol content, a markedly deficient rate of bile acid excretion, and evidence for upregulation of the alternative bile acid pathway. Two male subjects studied had hypertriglyceridemia and premature gallstone disease, and their LDL cholesterol levels were noticeably resistant to 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. One subject also had premature coronary and peripheral vascular disease. Study of the kindred, which is of English and Celtic background, revealed that individuals heterozygous for the mutation are also hyperlipidemic, indicating that this is a codominant disorder. PMID:12093894

  1. TEST & EVALUATION REPORT FOR THE HEDGEHOG-II PACKAGING SYSTEMS DOT-7A TYPE A CONTAINER

    SciTech Connect

    KELLY, D.L.

    2003-12-29

    This report documents the US. Department of Transportation Specification 7A (DOT-7A) Type A compliance test and evaluation results for the Hedgehog-II packaging systems. The approved Hedgehog-II packaging configurations provide primary and secondary containment. The approved packaging configurations described within this report are designed to ship Type A quantities of radioactive materials, normal form. Contents may be in solid or liquid form. Liquids transported in the approved 1 L glass bottle assembly shall have a specific gravity of less than or equal to 1.6. Liquids transported in all other approved configurations shall have a specific gravity of less than or equal to 2.0. The solid contents, including packaging, are limited in weight to the gross weight of the as-tested liquids and bottles. The approved Hedgehog-II packaging configurations described in this report may be transported by air, and have been evaluated as meeting the applicable International Air Transport Association/International Civil Aviation Organization (IATA/ICAO) Dangerous Goods Regulations in addition to the DOT requirements.

  2. Crystal structure of cytochrome c3 from Desulfovibrio desulfuricans Norway at 1.7 A resolution.

    PubMed

    Czjzek, M; Payan, F; Guerlesquin, F; Bruschi, M; Haser, R

    1994-11-01

    The crystal structure of cytochrome c3 (M(r) 13,000) from Desulfovibrio desulfuricans (118 residues, four heme groups) has been crystallographically refined to 1.7 A resolution using a simulated annealing method, based on the structure-model at 2.5 A resolution, already published. The final R-factor for 10,549 reflections was 0.198 covering the range from 5.5 to 1.7 A resolution. The individual temperature factors were refined for a total of 1059 protein atoms, together with 126 bound solvent molecules. The structure has been analyzed with respect to its detailed conformational properties, secondary structure features, temperature factor behaviour, bound solvent sites and heme geometry and ligation. The characteristic secondary structures of the polypeptide chain of this molecule are one extended alpha-helix, a short beta-strand and 13 reverse turns. The four heme groups are located in different structural environments, all highly exposed to solvent. The particular structural features of the heme environments are compared to the four hemes of the cytochrome c3 from Desulfovibrio vulgaris Miyazaki. PMID:7966289

  3. Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin

    PubMed Central

    Long, K.; Moss, L.; Laursen, L.; Boulter, L.; ffrench-Constant, C.

    2016-01-01

    Development of the cerebral cortex requires regulation of proliferation and differentiation of neural stem cells and a diverse range of progenitors. Recent work suggests a role for extracellular matrix (ECM) and the major family of ECM receptors, the integrins. Here we show that enhancing integrin beta-1 signalling, by expressing a constitutively active integrin beta-1 (CA*β1) in the embryonic chick mesencephalon, enhances neurogenesis and increases the number of mitotic cells dividing away from the ventricular surface, analogous to sub-apical progenitors in mouse. Only non-integrin-expressing neighbouring cells (lacking CA*β1) contributed to the increased neurogenesis. Transcriptome analysis reveals upregulation of Wnt7a within the CA*β1 cells and upregulation of the ECM protein Decorin in the neighbouring non-expressing cells. Experiments using inhibitors in explant models and genetic knock-downs in vivo reveal an integrin-Wnt7a-Decorin pathway that promotes proliferation and differentiation of neuroepithelial cells, and identify Decorin as a novel neurogenic factor in the central nervous system. PMID:26838601

  4. Binding and Movement of Individual Cel7A Cellobiohydrolases on Crystalline Cellulose Surfaces Revealed by Single-molecule Fluorescence Imaging*

    PubMed Central

    Jung, Jaemyeong; Sethi, Anurag; Gaiotto, Tiziano; Han, Jason J.; Jeoh, Tina; Gnanakaran, Sandrasegaram; Goodwin, Peter M.

    2013-01-01

    The efficient catalytic conversion of biomass to bioenergy would meet a large portion of energy requirements in the near future. A crucial step in this process is the enzyme-catalyzed hydrolysis of cellulose to glucose that is then converted into fuel such as ethanol by fermentation. Here we use single-molecule fluorescence imaging to directly monitor the movement of individual Cel7A cellobiohydrolases from Trichoderma reesei (TrCel7A) on the surface of insoluble cellulose fibrils to elucidate molecular level details of cellulase activity. The motion of multiple, individual TrCel7A cellobiohydrolases was simultaneously recorded with ∼15-nm spatial resolution. Time-resolved localization microscopy provides insights on the activity of TrCel7A on cellulose and informs on nonproductive binding and diffusion. We measured single-molecule residency time distributions of TrCel7A bound to cellulose both in the presence of and absence of cellobiose the major product and a potent inhibitor of Cel7A activity. Combining these results with a kinetic model of TrCel7A binding provides microscopic insight into interactions between TrCel7A and the cellulose substrate. PMID:23818525

  5. Wnt7a Activates the Planar Cell Polarity Pathway to Drive the Symmetric Expansion of Satellite Stem Cells

    PubMed Central

    Le Grand, Fabien; Jones, Andrew E.; Seale, Vanessa; Scimè, Anthony; Rudnicki, Michael A.

    2009-01-01

    Summary Satellite cells in skeletal muscle are a heterogeneous population of stem cells and committed progenitors. We found that quiescent satellite stem cells expressed the Wnt-receptor Fzd7, and that its candidate ligand Wnt7a was upregulated during regeneration. Notably, Wnt7a markedly stimulated the symmetric expansion of satellite stem cells but did not affect the growth or differentiation of myoblasts. Silencing of Fzd7 abrogated Wnt7a binding and stimulation of stem cell expansion. Wnt7a signaling induced the polarized distribution of the planar cell polarity effector Vangl2. Silencing of Vangl2 inhibited Wnt7a action on satellite stem cell expansion. Wnt7a overexpression enhanced muscle regeneration and increased both the number of satellite cells and the proportion of satellite stem cells. Muscle lacking Wnt7a exhibited a marked decrease in satellite cell number following regeneration. Therefore, Wnt7a signaling through the planar cell polarity pathway controls the homeostatic level of satellite stem cells and hence regulates the regenerative potential of muscle. PMID:19497282

  6. Binding and movement of individual Cel7A cellobiohydrolases on crystalline cellulose surfaces revealed by single-molecule fluorescence imaging.

    PubMed

    Jung, Jaemyeong; Sethi, Anurag; Gaiotto, Tiziano; Han, Jason J; Jeoh, Tina; Gnanakaran, Sandrasegaram; Goodwin, Peter M

    2013-08-16

    The efficient catalytic conversion of biomass to bioenergy would meet a large portion of energy requirements in the near future. A crucial step in this process is the enzyme-catalyzed hydrolysis of cellulose to glucose that is then converted into fuel such as ethanol by fermentation. Here we use single-molecule fluorescence imaging to directly monitor the movement of individual Cel7A cellobiohydrolases from Trichoderma reesei (TrCel7A) on the surface of insoluble cellulose fibrils to elucidate molecular level details of cellulase activity. The motion of multiple, individual TrCel7A cellobiohydrolases was simultaneously recorded with ∼15-nm spatial resolution. Time-resolved localization microscopy provides insights on the activity of TrCel7A on cellulose and informs on nonproductive binding and diffusion. We measured single-molecule residency time distributions of TrCel7A bound to cellulose both in the presence of and absence of cellobiose the major product and a potent inhibitor of Cel7A activity. Combining these results with a kinetic model of TrCel7A binding provides microscopic insight into interactions between TrCel7A and the cellulose substrate. PMID:23818525

  7. Hypoxic repression of CYP7A1 through a HIF-1α- and SHP-independent mechanism

    PubMed Central

    Moon, Yunwon; Park, Bongju; Park, Hyunsung

    2016-01-01

    Liver cells experience hypoxic stress when drug-metabolizing enzymes excessively consume O2 for hydroxylation. Hypoxic stress changes the transcription of several genes by activating a heterodimeric transcription factor called hypoxia-inducible factor-1α/β (HIF-1α/β). We found that hypoxic stress (0.1% O2) decreased the expression of cytochrome P450 7A1 (CYP7A1), a rate-limiting enzyme involved in bile acid biosynthesis. Chenodeoxycholic acid (CDCA), a major component of bile acids, represses CYP7A1 by activating a transcriptional repressor named small heterodimer partner (SHP). We observed that hypoxia decreased the levels of both CDCA and SHP, suggesting that hypoxia repressed CYP7A1 without inducing SHP. The finding that overexpression of HIF-1α increased the activity of the CYP7A1 promoter suggested that hypoxia decreased the expression of CYP7A1 in a HIF-1-independent manner. Thus, the results of this study suggested that hypoxia decreased the activity of CYP7A1 by limiting its substrate O2, and by decreasing the transcription of CYP7A1. [BMB Reports 2016; 49(3): 173-178] PMID:26521940

  8. 26 CFR 1.482-7A - Methods to determine taxable income in connection with a cost sharing arrangement.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 6 2011-04-01 2011-04-01 false Methods to determine taxable income in connection with a cost sharing arrangement. 1.482-7A Section 1.482-7A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Regulations Applicable on Or Before January 4, 2009....

  9. 26 CFR 1.482-7A - Methods to determine taxable income in connection with a cost sharing arrangement.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 6 2012-04-01 2012-04-01 false Methods to determine taxable income in connection with a cost sharing arrangement. 1.482-7A Section 1.482-7A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Regulations Applicable on Or Before January 4, 2009....

  10. 26 CFR 1.482-7A - Methods to determine taxable income in connection with a cost sharing arrangement.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 6 2014-04-01 2014-04-01 false Methods to determine taxable income in connection with a cost sharing arrangement. 1.482-7A Section 1.482-7A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Regulations Applicable on Or Before January 4, 2009....

  11. 26 CFR 1.482-7A - Methods to determine taxable income in connection with a cost sharing arrangement.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 6 2013-04-01 2013-04-01 false Methods to determine taxable income in connection with a cost sharing arrangement. 1.482-7A Section 1.482-7A Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Regulations Applicable on Or Before January 4, 2009....

  12. Test Plan for Westinghouse Hanford Company`s Hedgehog Shielded Container, Docket 94-39-7A, Type A Container

    SciTech Connect

    Kelly, D.L.

    1995-02-27

    This report documents the US Department of Transportation Specification 7A Type A (DOT-7A) compliance testing to be followed for qualification of the Westinghouse Hanford Company`s Hedgehog Shielded Container for use as a Type A packaging. The packaging configurations being tested are intended for liquids and solids, and for air transportation.

  13. Hypoxia-inducible miR-210 contributes to preeclampsia via targeting thrombospondin type I domain containing 7A

    PubMed Central

    Luo, Rongcan; Wang, Yongqing; Xu, Peng; Cao, Guangming; Zhao, Yangyu; Shao, Xuan; Li, Yu-xia; Chang, Cheng; Peng, Chun; Wang, Yan-ling

    2016-01-01

    Preeclampsia, a relatively common pregnancy disorder, is a major contributor to maternal mortality and morbidity worldwide. An elevation in microRNA-210 (miR-210) expression in the placenta has been reported to be associated with preeclampsia. Our bioinformatic analysis showed that thrombospondin type I domain containing 7A (THSD7A) is a predicted target for miR-210. The aim of this study was to determine whether miR-210 is involved in preeclampsia through its targeting of THSD7A in human placental trophoblasts. In preeclamptic placental tissues, THSD7A levels were significantly downregulated, and were inversely correlated with the levels of miR-210. THSD7A was validated as a direct target of miR-210 using quantitative real time PCR (qRT-PCR), Western blotting, and dual luciferase assays in HTR8/SVneo cells. Transwell insert invasion assays showed that THSD7A mediated the invasion-inhibitory effect of miR-210 in HTR8/SVneo cells. Interestingly, hypoxia markedly increased miR-210 expression while suppressing THSD7A expression in a time-dependent manner in HTR8/SVneo cells. This study provides novel data on the function of THSD7A in human placental cells, and extends our knowledge of how miR-210 is involved in the development of the preeclampsia. PMID:26796133

  14. 40 CFR 60.482-7a - Standards: Valves in gas/vapor service and in light liquid service.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 7 2012-07-01 2012-07-01 false Standards: Valves in gas/vapor service and in light liquid service. 60.482-7a Section 60.482-7a Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Equipment...

  15. TEF-7A, a transcript elongation factor gene, influences yield-related traits in bread wheat (Triticum aestivum L.)

    PubMed Central

    Zheng, Jun; Liu, Hong; Wang, Yuquan; Wang, Lanfen; Chang, Xiaoping; Jing, Ruilian; Hao, Chenyang; Zhang, Xueyong

    2014-01-01

    In this study, TaTEF-7A, a member of the transcript elongation factor gene family, and its flanking sequences were isolated. TaTEF-7A was located on chromosome 7A and was flanked by markers Xwmc83 and XP3156.3. Subcellular localization revealed that TaTEF-7A protein was localized in the nucleus. This gene was expressed in all organs, but the highest expression occurred in young spikes and developing seeds. Overexpression of TaTEF-7A in Arabidopsis thaliana produced pleiotropic effects on vegetative and reproductive development that enhanced grain length, silique number, and silique length. No diversity was found in the coding region of TaTEF-7A, but 16 single nucleotide polymorphisms and Indels were detected in the promoter regions of different cultivars. Markers based on sequence variations in the promoter regions (InDel-629 and InDel-604) were developed, and three haplotypes were identified based on those markers. Haplotype–trait association analysis of the Chinese wheat mini core collection revealed that TaTEF-7A was significantly associated with grain number per spike. Phenotyping of near-isogenic lines (NILs) confirmed that TaTEF-7A increases potential grain yield and yield-related traits. Frequency changes in favoured haplotypes gradually increased in cultivars released in China from the 1940s. Geographic distributions of favoured haplotypes were characterized in six major wheat production regions worldwide. The presence of Hap-7A-3, the favoured haplotype, showed a positive correlation with yield in a global set of breeding lines. These results suggest that TaTEF-7A is a functional regulatory factor for grain number per spike and provide a basis for marker-assisted selection. PMID:25056774

  16. Unsteady blade pressure measurements for the SR-7A propeller at cruise conditions

    NASA Technical Reports Server (NTRS)

    Heidelberg, L. J.; Nallasamy, M.

    1990-01-01

    The unsteady blade surface pressures were measured on the SR-7A propeller. The freestream Mach number, inflow angle, and advance ratio were varied while measurements were made at nine blade stations. At a freestream Mach number of 0.8, the data in terms of unsteady pressure coefficient versus azimuth angle are compared to an unsteady three-dimensional Euler solution, yielding very encouraging results. The code predicts the shape (phase) of the waveform very well, while the magnitude is over-predicted in many cases. At tunnel Mach numbers below 0.6, an unusually large response on the suction surface at 0.15 chord and 0.88 radius was observed. The behavior of this response suggests the presence of a leading-edge vortex.

  17. Unsteady blade pressure measurements for the SR-7A propeller at cruise conditions

    NASA Technical Reports Server (NTRS)

    Heidelberg, L. J.; Nallasamy, M.

    1990-01-01

    The unsteady blade surface pressures were measured on the SR-7A propeller. The freestream Mach no., inflow angle, and advance ratio were varied while measurements were made at nine blade stations. At a freestream Mach no. of 0.8, the data in terms of unsteady pressure coefficient vs. azimuth angle are compared to an unsteady 3-D Euler solution, yielding very encouraging results. The code predicts the shape (phase) of the waveform very well, while the magnitude is over-predicted in many cases. At tunnel Mach nos. below 0.6, an unusually large response on the suction surface at 0.15 chord and 0.88 radius was observed. The behavior of this response suggests the presence of a leading edge vortex. The midchord measuring stations on the suction surface exhibit a response that leads the forcing function while most other locations show a phase lag.

  18. Engineering Cel7A carbohydrate binding module and linker for reduced lignin inhibition.

    PubMed

    Strobel, Kathryn L; Pfeiffer, Katherine A; Blanch, Harvey W; Clark, Douglas S

    2016-06-01

    Non-productive binding of cellulases to lignin inhibits enzymatic hydrolysis of biomass, increasing enzyme requirements and the cost of biofuels. This study used site-directed mutagenesis of the Trichoderma Cel7A carbohydrate binding module (CBM) and linker to investigate the mechanisms of adsorption to lignin and engineer a cellulase with increased binding specificity for cellulose. CBM mutations that added hydrophobic or positively charged residues decreased the specificity for cellulose, while mutations that added negatively charged residues increased the specificity. Linker mutations that altered predicted glycosylation patterns selectively impacted lignin affinity. Beneficial mutations were combined to generate a mutant with 2.5-fold less lignin affinity while fully retaining cellulose affinity. This mutant was uninhibited by added lignin during hydrolysis of Avicel and generated 40% more glucose than the wild-type enzyme from dilute acid-pretreated Miscanthus. Biotechnol. Bioeng. 2016;113: 1369-1374. © 2015 Wiley Periodicals, Inc. PMID:26616493

  19. Structural insights into human Kif7, a kinesin involved in Hedgehog signalling

    PubMed Central

    Klejnot, Marta; Kozielski, Frank

    2012-01-01

    Kif7, a member of the kinesin 4 superfamily, is implicated in a variety of diseases including Joubert, hydrolethalus and acrocallosal syndromes. It is also involved in primary cilium formation and the Hedgehog signalling pathway and may play a role in cancer. Its activity is crucial for embryonic development. Kif7 and Kif27, a closely related kinesin in the same subfamily, are orthologues of the Drosophila melano­gaster kinesin-like protein Costal-2 (Cos2). In vertebrates, they work together to fulfil the role of the single Cos2 gene in Drosophila. Here, the high-resolution structure of the human Kif7 motor domain is reported and is compared with that of conventional kinesin, the founding member of the kinesin superfamily. These data are a first step towards structural characterization of a kinesin-4 family member and of this interesting molecular motor of medical significance. PMID:22281744

  20. Class II Analphoid Chromosome in a Child with Aberrant Chromosome 7: A Rare Cytogenetic Association.

    PubMed

    Kumar, Madhavan Jeevan; Kumar, Rangasamy Ashok; Subhashree, Venugopal; Jayasudha, Thanikachalam; Hemagowri, Venkatasubramanian; Koshy, Teena; Gowrishankar, Kalpana

    2015-01-01

    A neocentromere is a functional centromere that has arisen within a region not known to have a centromere. We present a case with a very rarely reported class II neocentromere formation in an aberrant chromosome 7. A 22-month-old male was referred because of dysmorphic features. Banding cytogenetics was performed, and a ring 7 and a supernumerary marker chromosome along with a normal chromosome 7 were found. In situ hybridization using a centromeric probe revealed 46 signals, of which 2 signals for chromosome 7 were observed, one on the normal and one on the ring chromosome. Further analysis using FISH revealed that the linear acentric fragment was part of the 7q region, which suggests that there could be a possible McClintock mechanism. PMID:26226839

  1. Detailed noise measurements on the SR-7A propeller: Tone behavior with helical tip Mach number

    NASA Technical Reports Server (NTRS)

    Dittmar, James H.; Hall, David G.

    1991-01-01

    Detailed noise measurements were taken on the SR-7A propeller to investigate the behavior of the noise with helical tip Mach number and then to level off as Mach number was increased further. This behavior was further investigated by obtaining detailed pressure-time histories of data. The pressure-time histories indicate that a portion of the primary pressure pulse is progressively cancelled by a secondary pulse which results in the noise leveling off as the helical tip Mach number is increased. This second pulse appears to originate on the same blade as the primary pulse and is in some way connected to the blade itself. This leaves open the possibility of redesigning the blade to improve the cancellation; thereby, the propeller noise is reduced.

  2. Synthesis and properties of lignin peroxidase from Streptomyces viridosporus T7A

    SciTech Connect

    Lodha, S.J.; Korus, R.A.; Crawford, D.L.

    1991-12-31

    The production of lignin peroxidase by Streptomyces viridosporus T7A was studied in shake flasks and under aerobic conditions in a 7.5-L batch fermentor. Lignin peroxidase synthesis was found to be strongly affected by catabolite repression. Lignin peroxidase was a non-growth-associated, secondary metabolite. The maximum lignin peroxidase activity was 0.064 U/mL at 36 h. In order to maximize lignin peroxidase activity, optimal conditions were determined. The optimal incubation temperature, pH, and substrate (2,4-dichlorophenol) concentration for the enzyme assays were 45{degrees}C, 6, and 3 m-M, respectively. Stability of lignin peroxidase was determined at 37, 45, and 60{degrees}C, and over the pH range 4-9.

  3. VERIFICATION OF THE DEFENSE WASTE PROCESSING FACILITY'S (DWPF) PROCESS DIGESTION METHOD FOR THE SLUDGE BATCH 7A QUALIFICATION SAMPLE

    SciTech Connect

    Click, D.; Edwards, T.; Jones, M.; Wiedenman, B.

    2011-03-14

    For each sludge batch that is processed in the Defense Waste Processing Facility (DWPF), the Savannah River National Laboratory (SRNL) performs confirmation of the applicability of the digestion method to be used by the DWPF lab for elemental analysis of Sludge Receipt and Adjustment Tank (SRAT) receipt samples and SRAT product process control samples. DWPF SRAT samples are typically dissolved using a room temperature HF-HNO{sub 3} acid dissolution (i.e., DWPF Cold Chem Method, see DWPF Procedure SW4-15.201) and then analyzed by inductively coupled plasma - atomic emission spectroscopy (ICP-AES). This report contains the results and comparison of data generated from performing the Aqua Regia (AR), Sodium peroxide/Hydroxide Fusion (PF) and DWPF Cold Chem (CC) method digestions of Sludge Batch 7a (SB7a) SRAT Receipt and SB7a SRAT Product samples. The SB7a SRAT Receipt and SB7a SRAT Product samples were prepared in the SRNL Shielded Cells, and the SRAT Receipt material is representative of the sludge that constituates the SB7a Batch or qualification composition. This is the sludge in Tank 51 that is to be transferred into Tank 40, which will contain the heel of Sludge Batch 6 (SB6), to form the Sb7a Blend composition.

  4. WNT7A/β-catenin signaling induces FGF1 and influences sensitivity to niclosamide in ovarian cancer.

    PubMed

    King, M L; Lindberg, M E; Stodden, G R; Okuda, H; Ebers, S D; Johnson, A; Montag, A; Lengyel, E; MacLean Ii, J A; Hayashi, K

    2015-06-01

    We previously characterized the link between WNT7A and the progression of ovarian cancer. Other groups have identified FGF1 as a relevant risk factor in ovarian cancer. Here, we show a linkage between these two signaling pathways that may be exploited to improve treatment and prognosis of patients with ovarian cancer. High expression of WNT7A and FGF1 are correlated in ovarian carcinomas and poor overall patient survival. A chromatin immunoprecipitation assay demonstrated that WNT7A/β-catenin signaling directly regulates FGF1 expression via TCF binding elements in the FGF1-1C promoter locus. In vitro gene manipulation studies revealed that FGF1 is sufficient to drive the tumor-promoting effects of WNT7A. In vivo xenograft studies confirmed that the stable overexpression of WNT7A or FGF1 induced a significant increase in tumor incidence, whereas FGF1 knockdown in WNT7A overexpressing cells caused a significant reduction in tumor size. Niclosamide most efficiently abrogated WNT7A/β-catenin signaling in our model, inhibited β-catenin transcriptional activity and cell viability, and increased cell death. Furthermore, niclosamide decreased cell migration following an increase in E-cadherin subsequent to decreased levels of SLUG. The effects of niclosamide on cell functions were more potent in WNT7A-overexpressing cells. Oral niclosamide inhibited tumor growth and progression in an intraperitoneal xenograft mouse model representative of human ovarian cancer. Collectively, these results indicate that FGF1 is a direct downstream target of WNT7A/β-catenin signaling and this pathway has potential as a therapeutic target in ovarian cancer. Moreover, niclosamide is a promising inhibitor of this pathway and may have clinical relevance. PMID:25174399

  5. Mutations in Tetratricopeptide Repeat Domain 7A Result in a Severe Form of Very Early Onset Inflammatory Bowel Disease

    PubMed Central

    Avitzur, Yaron; Guo, Conghui; Mastropaolo, Lucas A; Bahrami, Ehsan; Chen, Hannah; Zhao, Zhen; Elkadri, Abdul; Dhillon, Sandeep; Murchie, Ryan; Fattouh, Ramzi; Huynh, Hien; Walker, Jennifer L; Wales, Paul W; Cutz, Ernest; Kakuta, Yoichi; Dudley, Joel; Kammermeier, Jochen; Powrie, Fiona; Shah, Neil; Walz, Christoph; Nathrath, Michaela; Kotlarz, Daniel; Puchaka, Jacek; Krieger, John; Racek, Tomas; Kirchner, Thomas; Walters, Thomas D; Brumell, John H; Griffiths, Anne M; Rezaei, Nima; Rashtian, Parisa; Najafi, Mehri; Monajemzadeh, Maryam; Pelsue, Stephen; McGovern, Dermot PB; Uhlig, Holm H; Schadt, Eric; Klein, Christoph; Snapper, Scott B; Muise, Aleixo M

    2014-01-01

    Background & Aims Very early onset inflammatory bowel diseases (VEOIBD), including infant disorders, are a diverse group of diseases found in children less than 6 years of age. They have been associated with several gene variants. We aimed to identify genes that cause VEOIBD. Methods We performed whole-exome sequencing of DNA from 1 infants with severe enterocolitis and her parents. Candidate gene mutations were validated in 40 pediatric patients and functional studies were carried out using intestinal samples and human intestinal cell lines. Results We identified compound heterozygote mutations in the tetratricopeptide repeat domain 7 (TTC7A) gene in an infant from non-consanguineous parents with severe exfoliative apoptotic enterocolitis; we also detected the mutations in 2 unrelated families, each with 2 affected siblings. TTC7A interacts with EFR3 homolog B (EFR3B) to regulate phosphatidylinositol 4-kinase (PI4KA) at the plasma membrane. Functional studies demonstrated that TTC7A is expressed in human enterocytes. The mutations we identified in TTC7A result in either mislocalization or reduced expression of TTC7A. PI4KA was found to co-immunoprecipitate with TTC7A; the identified TTC7A mutations reduced this binding. Knockdown of TTC7A in human intestinal-like cell lines reduced their adhesion, increased apoptosis, and decreased production of phosphatidylinositol 4-phosphate. Conclusion In a genetic analysis, we identified loss of function mutations in TTC7A in 5 infants with VEOIBD. Functional studies demonstrated that the mutations cause defects in enterocytes and T cells that lead to severe apoptotic enterocolitis. Defects in the PI4KA–TTC7A–EFR3B pathway are involved in the pathogenesis of VEOIBD. PMID:24417819

  6. TP53 and Let-7a micro-RNA Regulate K-Ras Activity in HCT116 Colorectal Cancer Cells

    PubMed Central

    Luu, Carrie; Heinrich, Eileen L.; Duldulao, Marjun; Arrington, Amanda K.; Fakih, Marwan; Garcia-Aguilar, Julio; Kim, Joseph

    2013-01-01

    Recent reports have indicated that KRAS and TP53 mutations predict response to therapy in colorectal cancer. However, little is known about the relationship between these two common genetic alterations. Micro-RNAs (miRNAs), a class of noncoding RNA implicated in cellular processes, have been increasingly linked to KRAS and TP53. We hypothesized that lethal-7a (let-7a) miRNA regulates KRAS through TP53. To investigate the relationship between KRAS, TP53, and let-7a, we used HCT116 KRASmut human colorectal cancer cells with four different genotypic modifications in TP53 (TP53−/−, TP53+/−, TP53mut/+, and TP53mut/−). Using these cells we observed that K-Ras activity was higher in cells with mutant or knocked out TP53 alleles, suggesting that wild-type TP53 may suppress K-Ras activity. Let-7a was present in HCT116 KRASmut cells, though there was no correlation between let-7a level and TP53 genotype status. To explore how let-7a may regulate K-Ras in the different TP53 genotype cells we used let-7a inhibitor and demonstrated increased K-Ras activity across all TP53, thus corroborating prior reports that let-7a regulates K-Ras. To assess potential clinical implications of this regulatory network, we examined the influence of TP53 genotype and let-7a inhibition on colon cancer cell survival following chemoradiation therapy (CRT). We observed that cells with complete loss of wild-type TP53 alleles (−/− or −/mut) were resistant to CRT following treatment with 5-fluorouracil and radiation. Further increase in K-Ras activity with let-7a inhibition did not impact survival in these cells. In contrast, cells with single or double wild-type TP53 alleles were moderately responsive to CRT and exhibited resistance when let-7a was inhibited. In summary, our results show a complex regulatory system involving TP53, KRAS, and let-7a. Our results may provide clues to understand and target these interactions in colorectal cancer. PMID:23936455

  7. X-ray crystallographic characterization of new soluble endohedral fullerenes utilizing the popular C82 bucky cage. Isolation and structural characterization of Sm@C3v(7)-C82, Sm@C(s)(6)-C82, and Sm@C2(5)-C82.

    PubMed

    Yang, Hua; Jin, Hongxiao; Wang, Xinqing; Liu, Ziyang; Yu, Meilan; Zhao, Fukun; Mercado, Brandon Q; Olmstead, Marilyn M; Balch, Alan L

    2012-08-29

    Three isomers of Sm@C(82) that are soluble in organic solvents were obtained from the carbon soot produced by vaporization of hollow carbon rods doped with Sm(2)O(3)/graphite powder in an electric arc. These isomers were numbered as Sm@C(82)(I), Sm@C(82)(II), and Sm@C(82)(III) in order of their elution times from HPLC chromatography on a Buckyprep column with toluene as the eluent. The identities of isomers, Sm@C(82)(I) as Sm@C(s)(6)-C(82), Sm@C(82)(II) as Sm@C(3v)(7)-C(82), and Sm@C(82)(III) as Sm@C(2)(5)-C(82), were determined by single-crystal X-ray diffraction on cocrystals formed with Ni(octaethylporphyrin). For endohedral fullerenes like La@C(82), which have three electrons transferred to the cage to produce the M(3+)@(C(82))(3-) electronic distribution, generally only two soluble isomers (e.g., La@C(2v)(9)-C(82) (major) and La@C(s)(6)-C(82) (minor)) are observed. In contrast, with samarium, which generates the M(2+)@(C(82))(2-) electronic distribution, five soluble isomers of Sm@C(82) have been detected, three in this study, the other two in two related prior studies. The structures of the four Sm@C(82) isomers that are currently established are Sm@C(2)(5)-C(82), Sm@C(s)(6)-C(82), Sm@C(3v)(7)-C(82), and Sm@C(2v)(9)-C(82). All of these isomers obey the isolated pentagon rule (IPR) and are sequentially interconvertable through Stone-Wales transformations. PMID:22860880

  8. Final evaluation & test report for the standard waste box (docket 01-53-7A) type A packaging

    SciTech Connect

    KELLY, D L

    2001-10-15

    This report documents the U.S. Department of Transportation Specification 7A Type A compliance test and evaluation results of the Standard Waste Box. Testing and evaluation activities documented herein are on behalf of the U.S. Department of Energy-Headquarters, Office of Safety, Health and Security (EM-5), Germantown, Maryland. Duratek Federal Services, Inc., Northwest Operations performed an evaluation of the changes as documented herein under Docket 01-53-7A.

  9. slc7a6os Gene Plays a Critical Role in Defined Areas of the Developing CNS in Zebrafish

    PubMed Central

    Benini, Anna; Cignarella, Francesca; Calvarini, Laura; Mantovanelli, Silvia; Giacopuzzi, Edoardo; Zizioli, Daniela; Borsani, Giuseppe

    2015-01-01

    The aim of this study is to shed light on the functional role of slc7a6os, a gene highly conserved in vertebrates. The Danio rerio slc7a6os gene encodes a protein of 326 amino acids with 46% identity to human SLC7A6OS and 14% to Saccharomyces cerevisiae polypeptide Iwr1. Yeast Iwr1 specifically binds RNA pol II, interacts with the basal transcription machinery and regulates the transcription of specific genes. In this study we investigated for the first time the biological role of SLC7A6OS in vertebrates. Zebrafish slc7a6os is a maternal gene that is expressed throughout development, with a prevalent localization in the developing central nervous system (CNS). The gene is also expressed, although at different levels, in various tissues of the adult fish. To determine the functional role of slc7a6os during zebrafish development, we knocked-down the gene by injecting a splice-blocking morpholino. At 24 hpf morphants show morphological defects in the CNS, particularly the interface between hindbrain and midbrain is not well-defined. At 28 hpf the morpholino injected embryos present an altered somite morphology and appear partially or completely immotile. At this stage the midbrain, hindbrain and cerebellum are compromised and not well defined compared with control embryos. The observed alterations persist at later developmental stages. Consistently, the expression pattern of two markers specifically expressed in the developing CNS, pax2a and neurod, is significantly altered in morphants. The co-injection of embryos with synthetic slc7a6os mRNA, rescues the morphant phenotype and restores the wild type expression pattern of pax2a and neurod. Our data suggest that slc7a6os might play a critical role in defined areas of the developing CNS in vertebrates, probably by regulating the expression of key genes. PMID:25803583

  10. Role of DNA Methylation on the Expression of the Anthracycline Metabolizing Enzyme AKR7A2 in Human Heart.

    PubMed

    Hoefer, Carrie C; Quiñones-Lombraña, Adolfo; Blair, Rachael Hageman; Blanco, Javier G

    2016-04-01

    The intracardiac synthesis of anthracycline alcohol metabolites by aldo-keto reductases (AKRs) contributes to the pathogenesis of anthracycline-related cardiotoxicity. AKR7A2 is the most abundant anthracycline reductase in hearts from donors with and without Down syndrome (DS), and its expression varies between individuals (≈tenfold). We investigated whether DNA methylation impacts AKR7A2 expression in hearts from donors with (n = 11) and without DS (n = 30). Linear models were used to test for associations between methylation status and cardiac AKR7A2 expression. In hearts from donors without DS, DNA methylation status at CpG site -865 correlated with AKR7A2 mRNA (Pearson's regression coefficient, r = -0.4051, P = 0.0264) and AKR7A2 protein expression (r = -0.5818, P = 0.0071). In heart tissue from donors with DS, DNA methylation status at CpG site -232 correlated with AKR7A2 protein expression (r = 0.8659, P = 0.0025). Multiple linear regression modeling revealed that methylation at several CpG sites is associated with the synthesis of cardiotoxic daunorubicinol. AKR7A2 methylation status in lymphoblastoid cell lines from donors with and without DS was examined to explore potential parallelisms between cardiac tissue and lymphoid cells. These results suggest that DNA methylation impacts AKR7A2 expression and the synthesis of cardiotoxic daunorubicinol. PMID:25962911

  11. Lentiviral Engineered Fibroblasts Expressing Codon-Optimized COL7A1 Restore Anchoring Fibrils in RDEB

    PubMed Central

    Georgiadis, Christos; Syed, Farhatullah; Petrova, Anastasia; Abdul-Wahab, Alya; Lwin, Su M.; Farzaneh, Farzin; Chan, Lucas; Ghani, Sumera; Fleck, Roland A.; Glover, Leanne; McMillan, James R.; Chen, Mei; Thrasher, Adrian J.; McGrath, John A.; Di, Wei-Li; Qasim, Waseem

    2016-01-01

    Cells therapies, engineered to secrete replacement proteins, are being developed to ameliorate otherwise debilitating diseases. Recessive dystrophic epidermolysis bullosa (RDEB) is caused by defects of type VII collagen, a protein essential for anchoring fibril formation at the dermal-epidermal junction. Whereas allogeneic fibroblasts injected directly into the dermis can mediate transient disease modulation, autologous gene-modified fibroblasts should evade immunological rejection and support sustained delivery of type VII collagen at the dermal-epidermal junction. We demonstrate the feasibility of such an approach using a therapeutic grade, self-inactivating-lentiviral vector, encoding codon-optimized COL7A1, to transduce RDEB fibroblasts under conditions suitable for clinical application. Expression and secretion of type VII collagen was confirmed with transduced cells exhibiting supranormal levels of protein expression, and ex vivo migration of fibroblasts was restored in functional assays. Gene-modified RDEB fibroblasts also deposited type VII collagen at the dermal-epidermal junction of human RDEB skin xenografts placed on NOD-scid IL2Rgammanull recipients, with reconstruction of human epidermal structure and regeneration of anchoring fibrils at the dermal-epidermal junction. Fibroblast-mediated restoration of protein and structural defects in this RDEB model strongly supports proposed therapeutic applications in man. PMID:26763448

  12. Lentiviral Engineered Fibroblasts Expressing Codon-Optimized COL7A1 Restore Anchoring Fibrils in RDEB.

    PubMed

    Georgiadis, Christos; Syed, Farhatullah; Petrova, Anastasia; Abdul-Wahab, Alya; Lwin, Su M; Farzaneh, Farzin; Chan, Lucas; Ghani, Sumera; Fleck, Roland A; Glover, Leanne; McMillan, James R; Chen, Mei; Thrasher, Adrian J; McGrath, John A; Di, Wei-Li; Qasim, Waseem

    2016-01-01

    Cells therapies, engineered to secrete replacement proteins, are being developed to ameliorate otherwise debilitating diseases. Recessive dystrophic epidermolysis bullosa (RDEB) is caused by defects of type VII collagen, a protein essential for anchoring fibril formation at the dermal-epidermal junction. Whereas allogeneic fibroblasts injected directly into the dermis can mediate transient disease modulation, autologous gene-modified fibroblasts should evade immunological rejection and support sustained delivery of type VII collagen at the dermal-epidermal junction. We demonstrate the feasibility of such an approach using a therapeutic grade, self-inactivating-lentiviral vector, encoding codon-optimized COL7A1, to transduce RDEB fibroblasts under conditions suitable for clinical application. Expression and secretion of type VII collagen was confirmed with transduced cells exhibiting supranormal levels of protein expression, and ex vivo migration of fibroblasts was restored in functional assays. Gene-modified RDEB fibroblasts also deposited type VII collagen at the dermal-epidermal junction of human RDEB skin xenografts placed on NOD-scid IL2Rgamma(null) recipients, with reconstruction of human epidermal structure and regeneration of anchoring fibrils at the dermal-epidermal junction. Fibroblast-mediated restoration of protein and structural defects in this RDEB model strongly supports proposed therapeutic applications in man. PMID:26763448

  13. An epidemic of adenovirus 7a infection in a neonatal nursery: course, morbidity, and management.

    PubMed

    Finn, A; Anday, E; Talbot, G H

    1988-09-01

    An epidemic of adenovirus 7a in our neonatal intensive care nursery and intermediate care nursery in July and August 1987 caused the death of two patients. Significant symptomatic infection possibly due to the virus occurred in nine patients, ten staff, and three parents, of whom three patients, three staff, and one parent were positive by culture. As a direct consequence of the outbreak, 58 staff days of work were lost; the intensive care nursery had to be closed to admissions for 19 days and the intermediate care nursery for 14 days. Seventeen newborns were transferred to other hospitals and four mothers were sent elsewhere for delivery. Control measures, which included cohorting of patients, use of gloves, gowns and goggles, and exclusion of symptomatic staff from the unit, appeared effective. Rapid immunofluorescence testing of virological specimens was of little use in monitoring the outbreak, largely because of poor specimen quality. This outbreak further underlines the ease of transmission and high morbidity of neonatal adenovirus infection. PMID:2844886

  14. G 87-7: A White Dwarf with a Strange Core Composition?

    NASA Astrophysics Data System (ADS)

    Fontaine, G.; Bergeron, P.; Brassard, P.

    2007-09-01

    We present the results of an analysis of G 87-7, a DA star which has been previously suggested as a potential iron core white dwarf. This suggestion rests critically not only on the accuracy of the parallax measurements available for that star, but also on the accuracy of the atmospheric parameters deduced from optical spectroscopy. We therefore gathered additional high S/N ratio spectra for G 87-7 for the specific purpose of pinning down better its estimated atmospheric parameters. On the basis of these improved values of the effective temperature and surface gravity, we constructed families of full stellar models for G 87-7 assuming a variety of core compositions from pure C to pure Fe, and different envelope layering from ``thick'' to ``thin''. We also considered the possibility that G 87-7 could be made, in part, of strange matter, an idea that has come out recently as an alternative to white dwarf cores with heavy elements. We report on some of the results of our calculations in this short communication.

  15. Lignin Peroxidase from Streptomyces viridosporus T7A: Enzyme Concentration Using Ultrafiltration

    NASA Astrophysics Data System (ADS)

    Gottschalk, Leda M. F.; Bon, Elba P. S.; Nobrega, Ronaldo

    It is well known that lignin degradation is a key step in the natural process of biomass decay whereby oxidative enzymes such as laccases and high redox potential ligninolytic peroxidases and oxidases play a central role. More recently, the importance of these enzymes has increased because of their prospective industrial use for the degradation of the biomass lignin to increase the accessibility of the cellulose and hemicellulose moieties to be used as renewable material for the production of fuels and chemicals. These biocatalysts also present potential application on environmental biocatalysis for the degradation of xenobiotics and recalcitrant pollutants. However, the cost for these enzymes production, separation, and concentration must be low to permit its industrial use. This work studied the concentration of lignin peroxidase (LiP), produced by Streptomyces viridosporus T7A, by ultrafiltration, in a laboratory-stirred cell, loaded with polysulfone (PS) or cellulose acetate (CA) membranes with molecular weight cutoffs (MWCO) of 10, 20, and 50 KDa. Experiments were carried out at 25 °C and pH 7.0 in accordance to the enzyme stability profile. The best process conditions and enzyme yield were obtained using a PS membrane with 10 KDa MWCO, whereby it was observed a tenfold LiP activity increase, reaching 1,000 U/L and 90% enzyme activity upholding.

  16. Structural insights into human Kif7, a kinesin involved in Hedgehog signalling

    SciTech Connect

    Klejnot, Marta Kozielski, Frank

    2012-02-01

    The human Kif7 motor domain structure provides insights into a kinesin of medical significance. Kif7, a member of the kinesin 4 superfamily, is implicated in a variety of diseases including Joubert, hydrolethalus and acrocallosal syndromes. It is also involved in primary cilium formation and the Hedgehog signalling pathway and may play a role in cancer. Its activity is crucial for embryonic development. Kif7 and Kif27, a closely related kinesin in the same subfamily, are orthologues of the Drosophila melano@@gaster kinesin-like protein Costal-2 (Cos2). In vertebrates, they work together to fulfil the role of the single Cos2 gene in Drosophila. Here, the high-resolution structure of the human Kif7 motor domain is reported and is compared with that of conventional kinesin, the founding member of the kinesin superfamily. These data are a first step towards structural characterization of a kinesin-4 family member and of this interesting molecular motor of medical significance.

  17. Premature termination codons in the Type VII collagen gene (COL7A1) underlie severe, mutilating recessive dystrophic epidermolysis bullosa

    SciTech Connect

    Christiano, A.M.; Uitto, J. ); Anhalt, G. ); Gibbons, S.; Bauer, E.A. )

    1994-05-01

    Epidermolysis bullosa (EB) is a group of heritable mechano-bullous skin diseases classified into three major categories on the basis of the level of tissue separation within the dermal-epidermal basement membrane zone. The most severe, dystrophic (scarring) forms of EB demonstrate blister formation below the cutaneous basement membrane at the level of the anchoring fibrils. Ultrastructural observations of altered anchoring fibrils and genetic linkage to the gene encoding type VII collagen (COL7A1), the major component of anchoring fibrils, have implicated COL7A1 as the candidate gene in the dystrophic forms of EB. The authors have recently cloned the entire cDNA and gene for human COL7A1, which has been mapped to 3p21. In this study, they describe mutations in four COL7A1 alleles in three patients with severe, mutilating recessive dystrophic EB (Hallopeau-Siemens type, HS-RDEB). Each of these mutations resulted in a premature termination codon (PTC) in the amino-terminal portion of COL7A1. One of the patients was a compound heterozygote for two different mutations. The heterozygous carriers showed an [approximately] 50% reduction in anchoring fibrils, yet were clinically unaffected. Premature termination codons in both alleles of COL7A1 may thus be a major underlying cause of the severe, recessive dystrophic forms of EB. 40 refs., 8 figs.

  18. Involvement of CTR1 and ATP7A in lead (Pb)-induced copper (Cu) accumulation in choroidal epithelial cells.

    PubMed

    Zheng, Gang; Zhang, Jieqiong; Xu, Yan; Shen, Xuefeng; Song, Han; Jing, Jinfei; Luo, Wenjing; Zheng, Wei; Chen, Jingyuan

    2014-02-10

    The blood-cerebrospinal fluid barrier (BCB) plays a key role in maintaining copper (Cu) homeostasis in the brain. Cumulative evidences indicate that lead (Pb) exposure alters cerebral Cu homeostasis, which may underlie the development of neurodegenerative diseases. This study investigated the roles of Cu transporter 1 (CTR1) and ATP7A, two Cu transporters, in Pb-induced Cu accumulation in the choroidal epithelial cells. Pb exposure resulted in increased intracellular (64)Cu retention, accompanying with up-regulated CTR1 level. Knockdown of CTR1 using siRNA before Pb exposure diminished the Pb-induced increase of (64)Cu uptake. The expression level of ATP7A was down-regulated following the Pb exposure. ATP7A siRNA knockdown, or PCMB treatment, inhibited the (64)Cu efflux from the cells, while the following additional incubation with Pb failed to further increase the intracellular (64)Cu retention. Cu exposure, or intracellular Cu accumulation following the tetracycline (Tet)-induced overexpression of CTR1, did not result in significant change in ATP7A expression. Taken together, these data indicate that CTR1 and ATP7A play important roles in Cu transport in choroidal epithelial cells, and the Pb-induced intracellular Cu accumulation appears to be mediated, at least in part, via the alteration of CTR1 and ATP7A expression levels following Pb exposure. PMID:24316150

  19. Bovine CLEC7A genetic variants and their association with seropositivity in Johne's disease ELISA.

    PubMed

    Pant, S D; Verschoor, C P; Schenkel, F S; You, Q; Kelton, D F; Karrow, N A

    2014-03-10

    Mycobacterium avium ssp. paratuberculosis (MAP) infection in cattle causes significant economic losses to the dairy and beef industries resulting from reduced productivity, premature culling and mortality. Bovine Dectin-1, an important pattern recognition molecule that is able to generate a proinflammatory response by acting alongside Toll like receptor (TLR) signaling, is known to co-operate with TLR2 to specifically activate a macrophage proinflammatory response against mycobacterial infections. Therefore, the goal of this study was to identify single nucleotide polymorphisms (SNPs) in the gene encoding bovine Dectin-1 (CLEC7A) and to assess their association with susceptibility to MAP infection in dairy cattle. Blood and milk samples, collected from commercial dairy operations, were tested for MAP infection using blood and milk ELISAs and a resource population consisting of 197 infected and 242 healthy cattle was constructed. Pooled DNA was used for sequencing and eight single nucleotide polymorphisms (SNPs) were identified. Identified SNPs were genotyped on the resource population using the iPLEX MassARRAY system and statistical analysis was performed using logistic regression fitting the additive and dominance effects of each SNP in the model. Out of a total of eight identified SNPs, five were successfully genotyped, and three out of these five SNPs were found to be in complete linkage. Statistical analysis revealed a strong association between a non-synonymous SNP c.589A>G (p=0.008), and MAP infection status of the resource population inferred by seropositivity in MAP antibody specific ELISAs. This SNP c.589A>G was located in the geneic region that encodes the carbohydrate recognition domain of bovine Dectin-1. Therefore, further investigation of its functional relevance is warranted. PMID:24393710

  20. Cyclopalladated Compound 7a Induces Apoptosis- and Autophagy-Like Mechanisms in Paracoccidioides and Is a Candidate for Paracoccidioidomycosis Treatment

    PubMed Central

    Arruda, Denise C.; Matsuo, Alisson L.; Silva, Luiz S.; Real, Fernando; Leitão, Natanael P.; Pires, Jhon H. S.; Caires, Antonio Carlos F.; Garcia, Daniel M.; Cunha, Fernanda F. M.; Longo, Larissa V. G.

    2015-01-01

    Paracoccidioidomycosis (PCM), caused by Paracoccidioides species, is the main cause of death due to systemic mycoses in Brazil and other Latin American countries. Therapeutic options for PCM and other systemic mycoses are limited and time-consuming, and there are high rates of noncompliance, relapses, toxic side effects, and sequelae. Previous work has shown that the cyclopalladated 7a compound is effective in treating several kinds of cancer and parasitic Chagas disease without significant toxicity in animals. Here we show that cyclopalladated 7a inhibited the in vitro growth of Paracoccidioides lutzii Pb01 and P. brasiliensis isolates Pb18 (highly virulent), Pb2, Pb3, and Pb4 (less virulent) in a dose-response manner. Pb18 was the most resistant. Opportunistic Candida albicans and Cryptococcus neoformans were also sensitive. BALB/c mice showed significantly lighter lung fungal burdens when treated twice a day for 20 days with a low cyclopalladated 7a dose of 30 μg/ml/day for 30 days after intratracheal infection with Pb18. Electron microscopy images suggested that apoptosis- and autophagy-like mechanisms are involved in the fungal killing mechanism of cyclopalladated 7a. Pb18 yeast cells incubated with the 7a compound showed remarkable chromatin condensation, DNA degradation, superoxide anion production, and increased metacaspase activity suggestive of apoptosis. Autophagy-related killing mechanisms were suggested by increased autophagic vacuole numbers and acidification, as indicated by an increase in LysoTracker and monodansylcadaverine (MDC) staining in cyclopalladated 7a-treated Pb18 yeast cells. Considering that cyclopalladated 7a is highly tolerated in vivo and affects yeast fungal growth through general apoptosis- and autophagy-like mechanisms, it is a novel promising drug for the treatment of PCM and other mycoses. PMID:26349827

  1. Transcriptional activation of the cholesterol 7alpha-hydroxylase gene (CYP7A) by nuclear hormone receptors.

    PubMed

    Crestani, M; Sadeghpour, A; Stroup, D; Galli, G; Chiang, J Y

    1998-11-01

    The gene encoding cholesterol 7alpha-hydroxylase (CYP7A), the rate-limiting enzyme in bile acid synthesis, is transcriptionally regulated by bile acids and hormones. Previously, we have identified two bile acid response elements (BARE) in the promoter of the CYP7A gene. The BARE II is located in nt -149/-118 region and contains three hormone response element (HRE)-like sequences that form two overlapping nuclear receptor binding sites. One is a direct repeat separated by one nucleotide DR1 (-146- TGGACTtAGTTCA-134) and the other is a direct repeat separated by five nucleotides DR5 (-139-AGTTCAaggccGGG TAA-123). Mutagenesis of these HRE sequences resulted in lower transcriptional activity of the CYP7A promoter/reporter genes in transient transfection assay in HepG2 cells. The orphan nuclear receptor, hepatocyte nuclear factor 4 (HNF-4)1, binds to the DR1 sequence as assessed by electrophoretic mobility shift assay, and activates the CYP7A promoter/reporter activity by about 9-fold. Cotransfection of HNF-4 plasmid with another orphan nuclear receptor, chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), synergistically activated the CYP7A transcription by 80-fold. The DR5 binds the RXR/RAR heterodimer. A hepatocyte nuclear factor-3 (HNF-3) binding site (-175-TGTTTGTTCT-166) was identified. HNF-3 was required for both basal transcriptional activity and stimulation of the rat CYP7A promoter activity by retinoic acid. Combinatorial interactions and binding of these transcription factors to BAREs may modulate the promoter activity and also mediate bile acid repression of CYP7A gene transcription. PMID:9799805

  2. Cyclopalladated Compound 7a Induces Apoptosis- and Autophagy-Like Mechanisms in Paracoccidioides and Is a Candidate for Paracoccidioidomycosis Treatment.

    PubMed

    Arruda, Denise C; Matsuo, Alisson L; Silva, Luiz S; Real, Fernando; Leitão, Natanael P; Pires, Jhon H S; Caires, Antonio Carlos F; Garcia, Daniel M; Cunha, Fernanda F M; Puccia, Rosana; Longo, Larissa V G

    2015-12-01

    Paracoccidioidomycosis (PCM), caused by Paracoccidioides species, is the main cause of death due to systemic mycoses in Brazil and other Latin American countries. Therapeutic options for PCM and other systemic mycoses are limited and time-consuming, and there are high rates of noncompliance, relapses, toxic side effects, and sequelae. Previous work has shown that the cyclopalladated 7a compound is effective in treating several kinds of cancer and parasitic Chagas disease without significant toxicity in animals. Here we show that cyclopalladated 7a inhibited the in vitro growth of Paracoccidioides lutzii Pb01 and P. brasiliensis isolates Pb18 (highly virulent), Pb2, Pb3, and Pb4 (less virulent) in a dose-response manner. Pb18 was the most resistant. Opportunistic Candida albicans and Cryptococcus neoformans were also sensitive. BALB/c mice showed significantly lighter lung fungal burdens when treated twice a day for 20 days with a low cyclopalladated 7a dose of 30 μg/ml/day for 30 days after intratracheal infection with Pb18. Electron microscopy images suggested that apoptosis- and autophagy-like mechanisms are involved in the fungal killing mechanism of cyclopalladated 7a. Pb18 yeast cells incubated with the 7a compound showed remarkable chromatin condensation, DNA degradation, superoxide anion production, and increased metacaspase activity suggestive of apoptosis. Autophagy-related killing mechanisms were suggested by increased autophagic vacuole numbers and acidification, as indicated by an increase in LysoTracker and monodansylcadaverine (MDC) staining in cyclopalladated 7a-treated Pb18 yeast cells. Considering that cyclopalladated 7a is highly tolerated in vivo and affects yeast fungal growth through general apoptosis- and autophagy-like mechanisms, it is a novel promising drug for the treatment of PCM and other mycoses. PMID:26349827

  3. Dynamic Regulation of Wnt7a Expression in the Primate Endometrium: Implications for Postmenstrual Regeneration and Secretory Transformation

    PubMed Central

    Fan, Xiujun; Krieg, Sacha; Hwang, Jong Yun; Dhal, Sabita; Kuo, Calvin J.; Lasley, Bill L.; Brenner, Robert M.

    2012-01-01

    Despite the vital physiological role of endometrial regeneration during the menstrual cycle and the various pathological implications of abnormal growth of endometrial epithelial cells, the local factors and regulatory mechanisms involved in endometrial regeneration and growth have not been well characterized. Here, we examine the pattern, hormone dependence, and potential functions of Wnt7a (wingless-type MMTV integration site family member 7a), which is known to play a critical role in the formation of the mouse endometrial epithelium during embryonic development, in both human and artificially cycling rhesus macaque endometrium, and using a potent Wnt-antagonist in a mouse model of endometrial regeneration. Wnt7a transcript levels were examined using quantitative real-time PCR and in situ hybridization, and immunohistochemistry was performed to detect Ki-67 and 3,5-bromodeoxyuridine. Stringent, fully conditional Wnt inhibition was achieved by adenoviral expression of Dickkopf-1 during artificial endometrial regeneration in mice. In macaques, Wnt7a expression was confined to the newly formed luminal epithelium (LE) and upper glands during the postmenstrual repair phase. The signal increased in the LE during the proliferative phase but decreased in the upper glands and was undetectable in the glands by the late proliferative phase. Interestingly, Wnt7a was completely suppressed in the LE and remained undetectable in other cell types after 7 d of progesterone treatment. The pattern of Wnt7a expression in the human endometrium was similar to that in macaques. Blockade of Wnt signaling during endometrial regeneration in mice resulted in a dramatic delay in reepithelialization and degeneration of glands and LE. These results strongly suggest, for the first time, a role for Wnt7a in postmenstrual regeneration and proliferation of endometrial glands and LE in primates, and its dramatic suppression by progesterone is likely essential for secretory transformation of the

  4. Wnt7a is a novel inducer of β-catenin-independent tumor-suppressive cellular senescence in lung cancer

    PubMed Central

    Bikkavilli, R K; Avasarala, S; Van Scoyk, M; Arcaroli, J; Brzezinski, C; Zhang, W; Edwards, M G; Rathinam, M K K; Zhou, T; Tauler, J; Borowicz, S; Lussier, Y A; Parr, B A; Cool, C D; Winn, R A

    2015-01-01

    Cellular senescence is an initial barrier for carcinogenesis. However, the signaling mechanisms that trigger cellular senescence are incompletely understood, particularly in vivo. Here we identify Wnt7a as a novel upstream inducer of cellular senescence. In two different mouse strains (C57Bl/6J and FVB/NJ), we show that the loss of Wnt7a is a major contributing factor for increased lung tumorigenesis owing to reduced cellular senescence, and not reduced apoptosis, or autophagy. Wnt7a-null mice under de novo conditions and in both the strains display E-cadherin-to-N-cadherin switch, reduced expression of cellular senescence markers and reduced expression of senescence-associated secretory phenotype, indicating a genetic predisposition of these mice to increased carcinogen-induced lung tumorigenesis. Interestingly, Wnt7a induced an alternate senescence pathway, which was independent of β-catenin, and distinct from that of classical oncogene-induced senescence mediated by the well-known p16INK4a and p19ARF pathways. Mechanistically, Wnt7a induced cellular senescence via inactivation of S-phase kinase-associated protein 2, an important alternate regulator of cellular senescence. Additionally, we identified Iloprost, a prostacyclin analog, which initiates downstream signaling cascades similar to that of Wnt7a, as a novel inducer of cellular senescence, presenting potential future clinical translational strategies. Thus pro-senescence therapies using either Wnt7a or its mimic, Iloprost, might represent a new class of therapeutic treatments for lung cancer. PMID:25728679

  5. Effects of ATP7A overexpression in mice on copper transport and metabolism in lactation and gestation

    PubMed Central

    Wadwa, Jarrod; Chu, Yu‐Hsiang; Nguyen, Nhu; Henson, Thomas; Figueroa, Alyssa; Llanos, Roxana; Ackland, Margaret Leigh; Michalczyk, Agnes; Fullriede, Hendrik; Brennan, Grant; Mercer, Julian F. B.; Linder, Maria C.

    2014-01-01

    Abstract Placentae and mammary epithelial cells are unusual in robustly expressing two copper “pumps”, ATP7A and B, raising the question of their individual roles in these tissues in pregnancy and lactation. Confocal microscopic evidence locates ATP7A to the fetal side of syncytiotrophoblasts, suggesting a role in pumping Cu towards the fetus; and to the basolateral (blood) side of lactating mammary epithelial cells, suggesting a role in recycling Cu to the blood. We tested these concepts in wild‐type C57BL6 mice and their transgenic counterparts that expressed hATP7A at levels 10–20× those of endogenous mAtp7a. In lactation, overexpression of ATP7A reduced the Cu concentrations of the mammary gland and milk ~50%. Rates of transfer of tracer 64Cu to the suckling pups were similarly reduced over 30–48 h, as was the total Cu in 10‐day ‐old pups. During the early and middle periods of gestation, the transgenic litters had higher Cu concentrations than the wild‐type, placental Cu showing the reverse trend; but this difference was lost by the first postnatal day. The transgenic mice expressed ATP7A in some hepatocytes, so we investigated the possibility that metalation of ceruloplasmin (Cp) might be enhanced. Rates of 64Cu incorporation into Cp, oxidase activity, and ratios of holo to apoceruloplasmin were unchanged. We conclude that in the lactating mammary gland, the role of ATP7A is to return Cu to the blood, while in the placenta it mediates Cu delivery to the fetus and is the rate‐limiting step for fetal Cu nutrition during most of gestation in mice. PMID:24744874

  6. Synthesis and structural characterization of Al{sub 7}C{sub 3}N{sub 3}-homeotypic aluminum silicon oxycarbonitride, (Al{sub 7-x}Si{sub x})(O{sub y}C{sub z}N{sub 6-y-z}) (x{approx}1.2, y{approx}1.0 and z{approx}3.5)

    SciTech Connect

    Urushihara, Daisuke; Kaga, Motoaki; Asaka, Toru; Nakano, Hiromi; Fukuda, Koichiro

    2011-08-15

    A new aluminum silicon oxycarbonitride, (Al{sub 5.8}Si{sub 1.2})(O{sub 1.0}C{sub 3.5}N{sub 1.5}), has been synthesized and characterized by X-ray powder diffraction (XRPD), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX) and electron energy loss spectroscopy (EELS). The title compound is hexagonal with space group P6{sub 3}/mmc and unit-cell dimensions a=0.322508(4) nm, c=3.17193(4) nm and V=0.285717(6) nm{sup 3}. The atom ratios of Al:Si and those of O:C:N were, respectively, determined by EDX and EELS. The initial structural model was successfully derived from the XRPD data by the direct methods and further refined by the Rietveld method. The crystal is most probably composed of four types of domains with nearly the same fraction, each of which is isotypic to Al{sub 7}C{sub 3}N{sub 3} with space group P6{sub 3}mc. The existence of another new oxycarbonitride (Al{sub 6.6}Si{sub 1.4})(O{sub 0.7}C{sub 4.3}N{sub 2.0}), which must be homeotypic to Al{sub 8}C{sub 3}N{sub 4}, has been also demonstrated by XRPD and TEM. - Graphical abstract: A new oxycarbonitride discovered in the Al-Si-O-C-N system, (Al{sub 7-x}Si{sub x})(O{sub y}C{sub z}N{sub 6-y-z}) (x{approx}1.2, y{approx}1.0 and z{approx}3.5). The crystal is composed of four types of domains (I, II, III and IV), and hence the structure is represented by a split-atom model. Individual crystal structures can be regarded as layered structures, which consist of A-type [(Al, Si){sub 4}(O, C, N){sub 4}] unit layers and B-type [(Al, Si)(O, C, N){sub 2}] single layers. Highlights: > (Al{sub 5.8}Si{sub 1.2})(O{sub 1.0}C{sub 3.5}N{sub 1.5}) as a new aluminum silicon oxycarbonitride. > Crystal structure is determined and represented by a split-atom model. > Existence of another new oxycarbonitride (Al{sub 6.6}Si{sub 1.4})(O{sub 0.7}C{sub 4.3}N{sub 2.0}) is demonstrated. > Both new materials are formed by oxidation and nitridation of (Al, Si){sub 6}(O, C){sub 5}.

  7. ASK1 modulates the expression of microRNA Let7A in microglia under high glucose in vitro condition

    PubMed Central

    Song, Juhyun; Lee, Jong Eun

    2015-01-01

    Hyperglycemia results in oxidative stress and leads to neuronal apoptosis in the brain. Diabetes studies show that microglia participate in the progression of neuropathogenesis through their involvement in inflammation in vivo and in vitro. In high-glucose-induced inflammation, apoptosis signal regulating kinase 1 (ASK1) triggers the release of apoptosis cytokines and apoptotic gene expression. MicroRNA-Let7A (miR-Let7A) is reported to be a regulator of inflammation. In the present study, we investigated whether miR-Let7A regulates the function of microglia by controlling ASK1 in response to high-glucose-induced oxidative stress. We performed reverse transcription (RT) polymerase chain reaction, Taqman assay, real-time polymerase chain reaction, and immunocytochemistry to confirm the alteration of microglia function. Our results show that miR-Let7A is associated with the activation of ASK1 and the expression of anti-inflammatory cytokine (interleukin (IL)-10) and Mycs (c-Myc and N-Myc). Thus, the relationship between Let-7A and ASK1 could be a novel target for enhancing the beneficial function of microglia in central nervous system (CNS) disorders. PMID:26041997

  8. A Gene Gun-mediated Nonviral RNA trans-splicing Strategy for Col7a1 Repair.

    PubMed

    Peking, Patricia; Koller, Ulrich; Hainzl, Stefan; Kitzmueller, Sophie; Kocher, Thomas; Mayr, Elisabeth; Nyström, Alexander; Lener, Thomas; Reichelt, Julia; Bauer, Johann W; Murauer, Eva M

    2016-01-01

    RNA trans-splicing represents an auspicious option for the correction of genetic mutations at RNA level. Mutations within COL7A1 causing strong reduction or absence of type VII collagen are associated with the severe skin blistering disease dystrophic epidermolysis bullosa. The human COL7A1 mRNA constitutes a suitable target for this RNA therapy approach, as only a portion of the almost 9 kb transcript has to be delivered into the target cells. Here, we have proven the feasibility of 5' trans-splicing into the Col7a1 mRNA in vitro and in vivo. We designed a 5' RNA trans-splicing molecule, capable of replacing Col7a1 exons 1-15 and verified it in a fluorescence-based trans-splicing model system. Specific and efficient Col7a1 trans-splicing was confirmed in murine keratinocytes. To analyze trans-splicing in vivo, we used gene gun delivery of a minicircle expressing a FLAG-tagged 5' RNA trans-splicing molecule into the skin of wild-type mice. Histological and immunofluorescence analysis of bombarded skin sections revealed vector delivery and expression within dermis and epidermis. Furthermore, we have detected trans-spliced type VII collagen protein using FLAG-tag antibodies. In conclusion, we describe a novel in vivo nonviral RNA therapy approach to restore type VII collagen expression for causative treatment of dystrophic epidermolysis bullosa. PMID:26928235

  9. Innexin7a forms junctions that stabilize the basal membrane during cellularization of the blastoderm in Tribolium castaneum.

    PubMed

    van der Zee, Maurijn; Benton, Matthew A; Vazquez-Faci, Tania; Lamers, Gerda E M; Jacobs, Chris G C; Rabouille, Catherine

    2015-06-15

    In insects, the fertilized egg undergoes a series of rapid nuclear divisions before the syncytial blastoderm starts to cellularize. Cellularization has been extensively studied in Drosophila melanogaster, but its thick columnar blastoderm is unusual among insects. We therefore set out to describe cellularization in the beetle Tribolium castaneum, the embryos of which exhibit a thin blastoderm of cuboidal cells, like most insects. Using immunohistochemistry, live imaging and transmission electron microscopy, we describe several striking differences to cellularization in Drosophila, including the formation of junctions between the forming basal membrane and the yolk plasmalemma. To identify the nature of this novel junction, we used the parental RNAi technique for a small-scale screen of junction proteins. We find that maternal knockdown of Tribolium innexin7a (Tc-inx7a), an ortholog of the Drosophila gap junction gene Innexin 7, leads to failure of cellularization. In Inx7a-depleted eggs, the invaginated plasma membrane retracts when basal cell closure normally begins. Furthermore, transiently expressed tagged Inx7a localizes to the nascent basal membrane of the forming cells in wild-type eggs. We propose that Inx7a forms the newly identified junctions that stabilize the forming basal membrane and enable basal cell closure. We put forward Tribolium as a model for studying a more ancestral mode of cellularization in insects. PMID:26015545

  10. Molecular structure of leucine aminopeptidase at 2.7-A resolution.

    PubMed Central

    Burley, S K; David, P R; Taylor, A; Lipscomb, W N

    1990-01-01

    The three-dimensional structure of bovine lens leucine aminopeptidase (EC 3.4.11.1) complexed with bestatin, a slow-binding inhibitor, has been solved to 3.0-A resolution by the multiple isomorphous replacement method with phase combination and density modification. In addition, the structure of the isomorphous native enzyme has been refined at 2.7-A resolution, and the current crystallographic R factor is 0.169 for a model that includes the two zinc ions and all 487 amino acid residues comprising the asymmetric unit. The enzyme is physiologically active as a hexamer, which has 32 symmetry and is triangular in shape with a triangle edge length of 115 A and maximal thickness of 90 A. The monomers are crystallographically equivalent and each is folded into two unequal alpha/beta domains connected by an alpha-helix to give a comma-like shape with approximate maximal dimensions of 90 x 55 x 55 A3. The secondary structural composition is 40% alpha-helix and 19% beta-strand. The N-terminal domain (160 amino acids) mediates trimer-trimer interactions and does not appear to participate directly in catalysis. The C-terminal domain (327 amino acids) is responsible for catalysis and binds the two zinc ions, which are 2.88 A apart. The pair of metal ions is located near the edge of an eight-stranded, saddle-shaped beta-sheet. One zinc ion is coordinated by carboxylate oxygen atoms of Asp-255, Asp-332, and Glu-334 and the carbonyl oxygen of Asp-332. The other zinc ion is coordinated by the carboxylate oxygen atoms of Asp-255, Asp-273, and Glu-334. The active site also contains two positively charged residues, Lys-250 and Arg-336. The six active sites are themselves located in the interior of the hexamer, where they line a disk-shaped cavity of radius 15 A and thickness 10 A. Access to this cavity is provided by solvent channels that run along the twofold symmetry axes. Images PMID:2395881

  11. First cases of pyridoxine-dependent epilepsy in Bulgaria: novel mutation in the ALDH7A1 gene.

    PubMed

    Tincheva, Savina; Todorov, Tihomir; Todorova, Albena; Georgieva, Ralica; Stamatov, Dimitar; Yordanova, Iglika; Kadiyska, Tanya; Georgieva, Bilyana; Bojidarova, Maria; Tacheva, Genoveva; Litvinenko, Ivan; Mitev, Vanyo

    2015-12-01

    Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder characterized by intractable seizures in neonates and infants. The seizures cannot be controlled with antiepileptic medications but respond both clinically and electrographically to large daily supplements of pyridoxine (vitamin B6). PDE is caused by mutations in the ALDH7A1 gene. Molecular genetic analysis of the ALDH7A1 gene was performed in seven patients, referred with clinical diagnosis of PDE. Mutations were detected in a dizygotic twin pair and a non-related boy with classical form of PDE. Direct sequencing of the ALDH7A1 gene revealed one novel (c.297delG, p.Trp99*) and two already reported (c.328C>T, p.Arg110*; c.584A>G, p.Asn195Ser) mutations. Here, we report the first genetically proven cases of PDE in Bulgaria. PMID:26232297

  12. Novel SLC7A7 large rearrangements in lysinuric protein intolerance patients involving the same AluY repeat

    PubMed Central

    Font-Llitjós, Mariona; Rodríguez-Santiago, Benjamín; Espino, Meritxell; Sillué, Ruth; Mañas, Sandra; Gómez, Laia; Pérez-Jurado, Luis A; Palacín, Manuel; Nunes, Virginia

    2009-01-01

    Lysinuric protein intolerance (LPI) is a rare autosomal inherited disease caused by defective cationic aminoacid transport 4F2hc/y+LAT-1 at the basolateral membrane of epithelial cells in the intestine and kidney. LPI is a multisystemic disease with a variety of clinical symptoms such as hepatosplenomegaly, osteoporosis, hypotonia, developmental delay, pulmonary insufficiency or end-stage renal disease. The SLC7A7 gene, which encodes the y+LAT-1 protein, is mutated in LPI patients. Mutation analysis of the promoter localized in intron 1 and all exons of the SLC7A7 gene was performed in 11 patients from 9 unrelated LPI families. Point mutation screening was performed by exon direct sequencing and a new multiplex ligation probe amplification (MLPA) assay was set up for large rearrangement analysis. Eleven SLC7A7-specific mutations were identified, seven of them were novel: p.L124P, p.C425R, p.R468X, p.Y274fsX21, c.625+1G>C, DelE4-E11 and DelE6-E11. The novel large deletions originated by the recombination of Alu repeats at introns 3 and 5, respectively, with the same AluY sequence localized at the SLC7A7 3′ region. The novel MLPA assay is robust and valuable for LPI molecular diagnosis. Our results suggest that genomic rearrangements of SLC7A7 play a more important role in LPI than has been reported, increasing the detection rate from 5.1 to 21.4%. Moreover, the 3′ region AluY repeat could be a recombination hot spot as it is involved in 38% of all SLC7A7 rearranged chromosomes described so far. PMID:18716612

  13. Expression, crystal structure and cellulase activity of the thermostable cellobiohydrolase Cel7A from the fungus Humicola grisea var. thermoidea.

    PubMed

    Momeni, Majid Haddad; Goedegebuur, Frits; Hansson, Henrik; Karkehabadi, Saeid; Askarieh, Glareh; Mitchinson, Colin; Larenas, Edmundo A; Ståhlberg, Jerry; Sandgren, Mats

    2014-09-01

    Glycoside hydrolase family 7 (GH7) cellobiohydrolases (CBHs) play a key role in biomass recycling in nature. They are typically the most abundant enzymes expressed by potent cellulolytic fungi, and are also responsible for the majority of hydrolytic potential in enzyme cocktails for industrial processing of plant biomass. The thermostability of the enzyme is an important parameter for industrial utilization. In this study, Cel7 enzymes from different fungi were expressed in a fungal host and assayed for thermostability, including Hypocrea jecorina Cel7A as a reference. The most stable of the homologues, Humicola grisea var. thermoidea Cel7A, exhibits a 10°C higher melting temperature (T(m) of 72.5°C) and showed a 4-5 times higher initial hydrolysis rate than H. jecorina Cel7A on phosphoric acid-swollen cellulose and showed the best performance of the tested enzymes on pretreated corn stover at elevated temperature (65°C, 24 h). The enzyme shares 57% sequence identity with H. jecorina Cel7A and consists of a GH7 catalytic module connected by a linker to a C-terminal CBM1 carbohydrate-binding module. The crystal structure of the H. grisea var. thermoidea Cel7A catalytic module (1.8 Å resolution; R(work) and R(free) of 0.16 and 0.21, respectively) is similar to those of other GH7 CBHs. The deviations of several loops along the cellulose-binding path between the two molecules in the asymmetric unit indicate higher flexibility than in the less thermostable H. jecorina Cel7A. PMID:25195749

  14. Immobilization of sodium and phosphorus-bearing PW-7a waste in SYNROC. Progress report. [SYNROC C

    SciTech Connect

    Ringwood, A.E.

    1982-08-09

    The phosphorus, sodium and gadolinium-rich PW-7a waste can be successfully incorporated in SYNROC-C. However, a new accessory phase, a Ca,Na,Ba phosphate isostructural with Ca/sub 5/Na/sub 2/(PO/sub 4/)/sub 4/ apppears in the SYNROC mineralogy. There is no evidence for the partition of key radionuclides (e.g. Sr, REE and hence actinides) into this phosphate. Its poor resistance to groundwater dissolution, whilst hardly desirable, may therefore not have a serious effect on the leaching performance of SYNROC containing PW-7a. 9 tables.

  15. Marker Assisted Transfer of Two Powdery Mildew Resistance Genes PmTb7A.1 and PmTb7A.2 from Triticum boeoticum (Boiss.) to Triticum aestivum (L.)

    PubMed Central

    Elkot, Ahmed Fawzy Abdelnaby; Chhuneja, Parveen; Kaur, Satinder; Saluja, Manny; Keller, Beat; Singh, Kuldeep

    2015-01-01

    Powdery mildew (PM), caused by Blumeria graminis f. sp. tritici, is one of the important wheat diseases, worldwide. Two PM resistance genes, designated as PmTb7A.1 and PmTb7A.2, were identified in T. boeoticum acc. pau5088 and mapped on chromosome 7AL approximately 48cM apart. Two resistance gene analogue (RGA)-STS markers Ta7AL-4556232 and 7AL-4426363 were identified to be linked to the PmTb7A.1 and PmTb7A.2, at a distance of 0.6cM and 6.0cM, respectively. In the present study, following marker assisted selection (MAS), the two genes were transferred to T. aestivum using T. durum as bridging species. As many as 12,317 florets of F1 of the cross T. durum /T. boeoticum were pollinated with T. aestivum lines PBW343-IL and PBW621 to produce 61 and 65 seeds, respectively, of three-way F1. The resulting F1s of the cross T. durum/T. boeoticum//T. aestivum were screened with marker flanking both the PM resistance genes PmTb7A.1 and PmTb7A.2 (foreground selection) and the selected plants were backcrossed to generate BC1F1. Marker assisted selection was carried both in BC1F1 and the BC2F1 generations. Introgression of alien chromatin in BC2F1 plants varied from 15.4 - 62.9 percent. Out of more than 110 BC2F1 plants showing introgression for markers linked to the two PM resistance genes, 40 agronomically desirable plants were selected for background selection for the carrier chromosome to identify the plants with minimum of the alien introgression. Cytological analysis showed that most plants have chromosome number ranging from 40-42. The BC2F2 plants homozygous for the two genes have been identified. These will be crossed to generate lines combining both the PM resistance genes but with minimal of the alien introgression. The PM resistance gene PmTb7A.1 maps in a region very close to Sr22, a stem rust resistance gene effective against the race Ug99. Analysis of selected plants with markers linked to Sr22 showed introgression of Sr22 from T. boeoticum in several BC2F1 plants

  16. Engineering of a glycosidase Family 7 cellobiohydrolase to more alkaline pH optimum: the pH behaviour of Trichoderma reesei Cel7A and its E223S/ A224H/L225V/T226A/D262G mutant.

    PubMed Central

    Becker, D; Braet, C; Brumer , H; Claeyssens, M; Divne, C; Fagerström, B R; Harris, M; Jones, T A; Kleywegt, G J; Koivula, A; Mahdi, S; Piens, K; Sinnott, M L; Ståhlberg, J; Teeri, T T; Underwood, M; Wohlfahrt, G

    2001-01-01

    The crystal structures of Family 7 glycohydrolases suggest that a histidine residue near the acid/base catalyst could account for the higher pH optimum of the Humicola insolens endoglucanase Cel7B, than the corresponding Trichoderma reesei enzymes. Modelling studies indicated that introduction of histidine at the homologous position in T. reesei Cel7A (Ala(224)) required additional changes to accommodate the bulkier histidine side chain. X-ray crystallography of the catalytic domain of the E223S/A224H/L225V/T226A/D262G mutant reveals that major differences from the wild-type are confined to the mutations themselves. The introduced histidine residue is in plane with its counterpart in H. insolens Cel7B, but is 1.0 A (=0.1 nm) closer to the acid/base Glu(217) residue, with a 3.1 A contact between N(epsilon2) and O(epsilon1). The pH variation of k(cat)/K(m) for 3,4-dinitrophenyl lactoside hydrolysis was accurately bell-shaped for both wild-type and mutant, with pK(1) shifting from 2.22+/-0.03 in the wild-type to 3.19+/-0.03 in the mutant, and pK(2) shifting from 5.99+/-0.02 to 6.78+/-0.02. With this poor substrate, the ionizations probably represent those of the free enzyme. The relative k(cat) for 2-chloro-4-nitrophenyl lactoside showed similar behaviour. The shift in the mutant pH optimum was associated with lower k(cat)/K(m) values for both lactosides and cellobiosides, and a marginally lower stability. However, k(cat) values for cellobiosides are higher for the mutant. This we attribute to reduced non-productive binding in the +1 and +2 subsites; inhibition by cellobiose is certainly relieved in the mutant. The weaker binding of cellobiose is due to the loss of two water-mediated hydrogen bonds. PMID:11336632

  17. 13 CFR 120.431 - Which Lenders may sell, sell participations in, or pledge 7(a) loans?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Which Lenders may sell, sell participations in, or pledge 7(a) loans? 120.431 Section 120.431 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Lenders Other Conveyances § 120.431 Which Lenders may sell, sell participations...

  18. Regulation of diurnal variation of cholesterol 7alpha-hydroxylase (CYP7A1) activity in healthy subjects.

    PubMed

    Kovár, J; Lenícek, M; Zimolová, M; Vítek, L; Jirsa, M; Pitha, J

    2010-01-01

    Cholesterol 7alpha-hydroxylase (CYP7A1), the key regulatory enzyme of bile acid synthesis, displays a pronounced diurnal variation. To better understand the regulation of CYP7A1 activity, three day-long examinations were carried out in 12 healthy men. The concentrations of 7alpha-hydroxycholest-4-en-3-one (C4), a surrogate marker of CYP7A1 activity, bile acids (BA), insulin, glucose, nonesterified fatty acids, triglycerides, and cholesterol were measured in serum in 90-min intervals from 7 AM till 10 PM. To lower and to increase BA concentration during the study, the subjects received cholestyramine and chenodeoxycholic acid (CDCA), respectively, in two examinations. No drug was used in the control examination. There was a pronounced diurnal variation of C4 concentration with a peak around 1 PM in most of the subjects. The area under the curve (AUC) of C4 concentration was five times higher and three times lower when subjects were treated with cholestyramine and CDCA, respectively. No relationship was found between AUC of C4 and AUC of BA concentration, but AUC of C4 correlated positively with that of insulin. Moreover, short-term treatment with cholestyramine resulted in about 10 % suppression of glycemia throughout the day. Our results suggest that insulin is involved in the regulation of diurnal variation of CYP7A1 activity in humans. PMID:19537927

  19. [Expression levels of Slc7a11 in the skin of Kazakh sheep with different coat colors].

    PubMed

    Li, Hong-Tao; He, Xin; Zhou, Zhi-Yong; Zhao, Song-Hua; Zhang, Wen-Xiang; Liu, Gang; Zhao, Zong-Sheng; Jia, Bin

    2012-10-01

    Slc7a11 belongs to solute transporter gene family, encoding cystine/glutamate transporter xCT. It regulates switching between eumelanin and pheomelanin synthesis. In the present study, Real-time PCR was used to detect the mRNA expression levels of Slc7a11 in the skin of Kazakh lambs with different coat colors (black, brown and white), and then the prokaryotic expression plasmid PET-32a-sxCT was constructed to induce the expression of fusion protein. The target pro-tein was purified by Ni-NTA affinity chromatographic separation, and then was used to immunize rabbit in order to produce rabbit anti-sxCT polyclonal antibody. Finally, the expression levels of sxCT were detected in the skin of Kazakh lambs with different hair colors by Western blotting analysis. Results showed that the mRNA expression levels of Slc7a11 differed significantly in the skin of Kazakh lambs with different coat colors, with the highest level in brown coat color, followed by the black, and then the white. The sxCT protein was also detected in the skin of different coat colors by polyclonal antibody, with the highest level in brown coat color, followed by the black, and then the white. It is, therefore, concluded that slc7a11 gene might be associated with the phenotype of coat color in Kazakh sheep. PMID:23099788

  20. BMP-2-enhanced chondrogenesis involves p38 MAPK-mediated down-regulation of Wnt-7a pathway.

    PubMed

    Jin, Eun-Jung; Lee, Sun-Young; Choi, Young-Ae; Jung, Jae-Chang; Bang, Ok-Sun; Kang, Shin-Sung

    2006-12-31

    The bone morphogenetic protein (BMP) family has been implicated in control of cartilage development. Here, we demonstrate that BMP-2 promotes chondrogenesis by activating p38 mitogen-activated protein kinase (MAPK), which in turn downregulates Wnt-7a/b-catenin signaling responsible for proteasomal degradation of Sox9. Exposure of mesenchymal cells to BMP-2 resulted in upregulation of Sox9 protein and a concomitant decrease in the level of b-catenin protein and Wnt-7a signaling. In agreement with this, the interaction of Sox9 with b-catenin was inhibited in the presence of BMP-2. Inhibition of the p38 MAPK pathway using a dominant negative mutant led to sustained Wnt-7a signaling and decreased Sox9 expression, with consequent inhibition of precartilage condensation and chondrogenic differentiation. Moreover, overexpression of b-catenin caused degradation of Sox9 via the ubiquitin/26S proteasome pathway. Our results collectively indicate that the increase in Sox9 protein resulting from downregulation of b-catenin/Wnt-7a signaling is mediated by p38 MAPK during BMP-2 induced chondrogenesis in chick wing bud mesenchymal cells. PMID:17202865

  1. Semaphorin-7a reverses the ERF-induced inhibition of EMT in Ras-dependent mouse mammary epithelial cells.

    PubMed

    Allegra, Maryline; Zaragkoulias, Andreas; Vorgia, Elena; Ioannou, Marina; Litos, Gabriele; Beug, Hartmut; Mavrothalassitis, George

    2012-10-01

    Epithelial-to-mesenchymal transition (EMT) is a key process in cancer progression and metastasis, requiring cooperation of the epidermal growth factor/Ras with the transforming growth factor-β (TGF-β) signaling pathway in a multistep process. The molecular mechanisms by which Ras signaling contributes to EMT, however, remain elusive to a large extent. We therefore examined the transcriptional repressor Ets2-repressor factor (ERF)-a bona fide Ras-extracellular signal-regulated kinase/mitogen-activated protein kinase effector-for its ability to interfere with TGF-β-induced EMT in mammary epithelial cells (EpH4) expressing oncogenic Ras (EpRas). ERF-overexpressing EpRas cells failed to undergo TGF-β-induced EMT, formed three-dimensional tubular structures in collagen gels, and retained expression of epithelial markers. Transcriptome analysis indicated that TGF-β signaling through Smads was mostly unaffected, and ERF suppressed the TGF-β-induced EMT via Semaphorin-7a repression. Forced expression of Semaphorin-7a in ERF-overexpressing EpRas cells reestablished their ability to undergo EMT. In contrast, inhibition of Semaphorin-7a in the parental EpRas cells inhibited their ability to undergo TGF-β-induced EMT. Our data suggest that oncogenic Ras may play an additional role in EMT via the ERF, regulating Semaphorin-7a and providing a new interconnection between the Ras- and the TGF-β-signaling pathways. PMID:22875994

  2. CYP7A1 Gene Polymorphism Located in the 5′ Upstream Region Modifies the Risk of Coronary Artery Disease

    PubMed Central

    Iwanicki, Tomasz; Balcerzyk, Anna; Niemiec, Pawel; Nowak, Tomasz; Ochalska-Tyka, Anna; Krauze, Jolanta; Kosiorz-Gorczynska, Sylwia; Grzeszczak, Wladyslaw; Zak, Iwona

    2015-01-01

    Background. 7-Alpha cholesterol hydroxylase (CYP7A1), the first enzyme of classic conversion pathway leading from cholesterol to bile acids synthesis, is encoded by CYP7A1 gene. Its single nucleotide polymorphisms (SNPs) influence serum lipid levels and may be related to impaired lipid profile leading to coronary artery disease (CAD). The aim of the present study was to analyze the possible association between the rs7833904 CYP7A1 polymorphism and premature CAD. Material and Methods. Serum lipid levels and rs7833904 SNP were determined in 419 subjects: 200 patients with premature CAD and 219 age and sex matched controls. Results. The A allele carrier state was associated with CAD (OR = 1.76, 95% CI; 1.14–2.71, P = 0.014). The effect was even stronger in the male subgroups (OR = 2.16, 95% CI; 1.28–3.65, P = 0.003). There was no effect in the females. Risk factors of CAD and clinical phenotype of atherosclerosis were not associated with genotype variants of the rs7833904 SNP. Lipid profiles also did not differ significantly between individual genotypes. Conclusion. The CYP7A1 rs7833904 polymorphism may modify the risk of CAD. This effect is especially strong in male subjects. The studied polymorphism does not significantly influence serum lipid levels, in the present study. PMID:25944972

  3. Direct interactions of adaptor protein complexes 1 and 2 with the copper transporter ATP7A mediate its anterograde and retrograde trafficking

    PubMed Central

    Yi, Ling; Kaler, Stephen G.

    2015-01-01

    ATP7A is a P-type ATPase in which diverse mutations lead to X-linked recessive Menkes disease or occipital horn syndrome. Recently, two previously unknown ATP7A missense mutations, T994I and P1386S, were shown to cause an isolated distal motor neuropathy without clinical or biochemical features of other ATP7A disorders. These mutant alleles cause subtle defects in ATP7A intracellular trafficking, resulting in preferential plasma membrane localization compared with wild-type ATP7A. We reported previously that ATP7AP1386S causes unstable insertion of the eighth and final transmembrane segment, preventing proper position of the carboxyl-terminal tail in a proportion of mutant molecules. Here, we utilize this and other naturally occurring and engineered mutant ATP7A alleles to identify mechanisms of normal ATP7A trafficking. We show that adaptor protein (AP) complexes 1 and 2 physically interact with ATP7A and that binding is mediated in part by a carboxyl-terminal di-leucine motif. In contrast to other ATP7A missense mutations, ATP7AP1386S partially disturbs interactions with both APs, leading to abnormal axonal localization in transfected NSC-34 motor neurons and altered calcium-signaling following glutamate stimulation. Our results imply that AP-1 normally tethers ATP7A at the trans-Golgi network in the somatodendritic segments of motor neurons and that alterations affecting the ATP7A carboxyl-terminal tail induce release of the copper transporter to the axons or axonal membranes. The latter effects are intensified by diminished interaction with AP-2, impeding ATP7A retrograde trafficking. Taken together, these findings further illuminate the normal molecular mechanisms of ATP7A trafficking and suggest a pathophysiological basis for ATP7A-related distal motor neuropathy. PMID:25574028

  4. Molecular Docking and In Silico ADMET Study Reveals Acylguanidine 7a as a Potential Inhibitor of β-Secretase.

    PubMed

    Nisha, Chaluveelaveedu Murleedharan; Kumar, Ashwini; Nair, Prateek; Gupta, Nityasha; Silakari, Chitrangda; Tripathi, Timir; Kumar, Awanish

    2016-01-01

    Amyloidogenic pathway in Alzheimer's disease (AD) involves breakdown of APP by β-secretase followed by γ-secretase and results in formation of amyloid beta plaque. β-secretase has been a promising target for developing novel anti-Alzheimer drugs. To test different molecules for this purpose, test ligands like acylguanidine 7a, rosiglitazone, pioglitazone, and tartaric acid were docked against our target protein β-secretase enzyme retrieved from Protein Data Bank, considering MK-8931 (phase III trial, Merck) as the positive control. Docking revealed that, with respect to their free binding energy, acylguanidine 7a has the lowest binding energy followed by MK-8931 and pioglitazone and binds significantly to β-secretase. In silico ADMET predictions revealed that except tartaric acid all other compounds had minimal toxic effects and had good absorption as well as solubility characteristics. These compounds may serve as potential lead compound for developing new anti-Alzheimer drug. PMID:27190510

  5. Molecular Docking and In Silico ADMET Study Reveals Acylguanidine 7a as a Potential Inhibitor of β-Secretase

    PubMed Central

    Nisha, Chaluveelaveedu Murleedharan; Kumar, Ashwini; Nair, Prateek; Gupta, Nityasha; Silakari, Chitrangda; Tripathi, Timir; Kumar, Awanish

    2016-01-01

    Amyloidogenic pathway in Alzheimer's disease (AD) involves breakdown of APP by β-secretase followed by γ-secretase and results in formation of amyloid beta plaque. β-secretase has been a promising target for developing novel anti-Alzheimer drugs. To test different molecules for this purpose, test ligands like acylguanidine 7a, rosiglitazone, pioglitazone, and tartaric acid were docked against our target protein β-secretase enzyme retrieved from Protein Data Bank, considering MK-8931 (phase III trial, Merck) as the positive control. Docking revealed that, with respect to their free binding energy, acylguanidine 7a has the lowest binding energy followed by MK-8931 and pioglitazone and binds significantly to β-secretase. In silico ADMET predictions revealed that except tartaric acid all other compounds had minimal toxic effects and had good absorption as well as solubility characteristics. These compounds may serve as potential lead compound for developing new anti-Alzheimer drug. PMID:27190510

  6. Corrosion Behavior of Field-Exposed 7A04 Aluminum Alloy in the Xisha Tropical Marine Atmosphere

    NASA Astrophysics Data System (ADS)

    Cui, Z. Y.; Li, X. G.; Man, C.; Xiao, K.; Dong, C. F.; Wang, X.; Liu, Z. Y.

    2015-08-01

    Atmospheric corrosion behavior of 7A04 aluminum alloy exposed to a tropical marine environment for 4 years was investigated by weight loss test, morphology observation, and electrochemical impendence spectroscopy (EIS). The results showed that the weight loss of 7A04 alloy in the log-log coordinates can be approximately fitted with two liner segments, in which the slope value of the second segment is significantly lower than that of the first segment. This was mainly attributed to the protectiveness of the corrosion product layer formed on the specimen exposed for 12 and 24 months, which was further confirmed by the EIS results. Corrosion rate presented a significant fluctuation during the exposure test which is due to the deterioration effect caused by chloride ions and time of wetness and the stabilization process of the corrosion product layer. Intergranular corrosion occurred on the 7A04 alloy and then transformed into exfoliation corrosion because of the synergetic effect of the hydrogen-assisted crack initiation and the wedge effect-induced matrix delamination.

  7. Effects of Different Filler Metals on the Mechanical Behaviors of GTA Welded AA7A52(T6)

    NASA Astrophysics Data System (ADS)

    Shu, Fengyuan; Lv, Yaohui; Liu, Yuxin; Lin, Jianjun; Sun, Zhe; Xu, Binshi; He, Peng

    2014-06-01

    ER4043, ER5356, and AA7A52 on behalf of the Al-Si, Al-Mg, and Al-Zn-Mg-based welding material, respectively, were chosen as the filler metal to weld AA7A52(T6) plates by GTAW. The variance in mechanical performances of the joints caused by the various filler materials was investigated with reference to the SEM and EDS test results for the weld seam and the fracture surface. Failure was found in the seam for all the welded joints. With regard to the joint obtained with ER4043 welding wire, the total elongation was limited by the brittle intergranular compound Mg2Si of which Mg was introduced by convection mass transfer. As for the other two welds, the content ratio of Zn and Mg was found to play the dominant role in deciding the mechanical properties of the intergranular Mg-Zn compounds which were responsible for the tensile behavior of the joints. The content ratio (wt.%) of beyond 2:1 gave birth to the strengthening phase MgZn2 leading to a ductile fracture. Cr in the seam obtained with AA7A52 filler metal was found to enhance the strength of the joint through isolated particles.

  8. Gene Editing for the Efficient Correction of a Recurrent COL7A1 Mutation in Recessive Dystrophic Epidermolysis Bullosa Keratinocytes.

    PubMed

    Chamorro, Cristina; Mencía, Angeles; Almarza, David; Duarte, Blanca; Büning, Hildegard; Sallach, Jessica; Hausser, Ingrid; Del Río, Marcela; Larcher, Fernando; Murillas, Rodolfo

    2016-01-01

    Clonal gene therapy protocols based on the precise manipulation of epidermal stem cells require highly efficient gene-editing molecular tools. We have combined adeno-associated virus (AAV)-mediated delivery of donor template DNA with transcription activator-like nucleases (TALE) expressed by adenoviral vectors to address the correction of the c.6527insC mutation in the COL7A1 gene, causing recessive dystrophic epidermolysis bullosa in a high percentage of Spanish patients. After transduction with these viral vectors, high frequencies of homology-directed repair were found in clones of keratinocytes derived from a recessive dystrophic epidermolysis bullosa (RDEB) patient homozygous for the c.6527insC mutation. Gene-edited clones recovered the expression of the COL7A1 transcript and collagen VII protein at physiological levels. In addition, treatment of patient keratinocytes with TALE nucleases in the absence of a donor template DNA resulted in