Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John
2012-05-11
Conjugated linolenic acids (CLNs), 18:3 Δ(9,11,13), lack the methylene groups found between the double bonds of linolenic acid (18:3 Δ(9,12,15)). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 Δ(9cis,11trans,13cis)) or α-eleostearic acid (18:3 Δ(9cis,11trans,13trans)). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly α-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of α-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation.
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Christopher R Bohl
Full Text Available The cellular E2 Sumo conjugase, Ubc9 interacts with HIV-1 Gag, and is important for the assembly of infectious HIV-1 virions. In the previous study we demonstrated that in the absence of Ubc9, a defect in virion assembly was associated with decreased levels of mature intracellular Envelope (Env that affected Env incorporation into virions and virion infectivity. We have further characterized the effect of Ubc9 knockdown on HIV Env processing and assembly. We found that gp160 stability in the endoplasmic reticulum (ER and its trafficking to the trans-Golgi network (TGN were unaffected, indicating that the decreased intracellular mature Env levels in Ubc9-depleted cells were due to a selective degradation of mature Env gp120 after cleavage from gp160 and trafficked out of the TGN. Decreased levels of Gag and mature Env were found to be associated with the plasma membrane and lipid rafts, which suggest that these viral proteins were not trafficked correctly to the assembly site. Intracellular gp120 were partially rescued when treated with a combination of lysosome inhibitors. Taken together our results suggest that in the absence of Ubc9, gp120 is preferentially degraded in the lysosomes likely before trafficking to assembly sites leading to the production of defective virions. This study provides further insight in the processing and packaging of the HIV-1 gp120 into mature HIV-1 virions.
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Ellis-Perry, B. [Univ. of British Columbia, Vancouver, British Columbia (Canada); Yogendran, Y. [NRC Inst. for Fuel Cell Innovation, Vancouver, British Columbia (Canada)
2004-07-01
reality. Demonstration projects will include a hydrogen fuelling station, solid oxide fuel cells, hydrogen powered internal combustion engine shuttle buses, and on-campus hydrogen fuel cell vehicles. The project will be promoted through an integrated communications program, building awareness and support among investors and the public, and so accelerating the early adoption of this technology on a broader scale. Yoga Yogandren and Barney Ellis-Perry will review the UBC/NRC Node, discussing the power of partnerships that are enabling this project to move from an idea to reality. (author)
International Nuclear Information System (INIS)
Ellis-Perry, B.; Yogendran, Y.
2004-01-01
. Demonstration projects will include a hydrogen fuelling station, solid oxide fuel cells, hydrogen powered internal combustion engine shuttle buses, and on-campus hydrogen fuel cell vehicles. The project will be promoted through an integrated communications program, building awareness and support among investors and the public, and so accelerating the early adoption of this technology on a broader scale. Yoga Yogandren and Barney Ellis-Perry will review the UBC/NRC Node, discussing the power of partnerships that are enabling this project to move from an idea to reality. (author)
Degradation Signals Recognized by the Ubc6p-Ubc7p Ubiquitin-Conjugating Enzyme Pair
Gilon, Tamar; Chomsky, Orna; Kulka, Richard G.
2000-01-01
Proteolysis by the ubiquitin-proteasome system is highly selective. Specificity is achieved by the cooperation of diverse ubiquitin-conjugating enzymes (Ubcs or E2s) with a variety of ubiquitin ligases (E3s) and other ancillary factors. These recognize degradation signals characteristic of their target proteins. In a previous investigation, we identified signals directing the degradation of β-galactosidase and Ura3p fusion proteins via a subsidiary pathway of the ubiquitin-proteasome system involving Ubc6p and Ubc7p. This pathway has recently been shown to be essential for the degradation of misfolded and regulated proteins in the endoplasmic reticulum (ER) lumen and membrane, which are transported to the cytoplasm via the Sec61p translocon. Mutant backgrounds which prevent retrograde transport of ER proteins (hrd1/der3Δ and sec61-2) did not inhibit the degradation of the β-galactosidase and Ura3p fusions carrying Ubc6p/Ubc7p pathway signals. We therefore conclude that the ubiquitination of these fusion proteins takes place on the cytosolic face of the ER without prior transfer to the ER lumen. The contributions of different sequence elements to a 16-amino-acid-residue Ubc6p-Ubc7p-specific signal were analyzed by mutation. A patch of bulky hydrophobic residues was an essential element. In addition, positively charged residues were found to be essential. Unexpectedly, certain substitutions of bulky hydrophobic or positively charged residues with alanine created novel degradation signals, channeling the degradation of fusion proteins to an unidentified proteasomal pathway not involving Ubc6p and Ubc7p. PMID:10982838
Ying, Shibo; Dünnebier, Thomas; Si, Jing; Hamann, Ute
2013-01-01
UBC9 encodes a protein that conjugates small ubiquitin-related modifier (SUMO) to target proteins thereby changing their functions. Recently, it was noted that UBC9 expression and activity play a role in breast tumorigenesis and response to anticancer drugs. However, the underlying mechanism is poorly understood. To investigate the transcriptional regulation of the UBC9 gene, we identified and characterized its promoter and cis-elements. Promoter activity was tested using luciferase reporter assays. The binding of transcription factors to the promoter was detected by chromatin immunoprecipitation (ChIP), and their functional role was confirmed by siRNA knockdown. UBC9 mRNA and protein levels were measured by quantitative reverse transcription PCR and Western blot analysis, respectively. An increased expression of UBC9 mRNA and protein was found in MCF-7 breast cancer cells treated with 17β-estradiol (E2). Analysis of various deletion mutants revealed a 137 bp fragment upstream of the transcription initiation site to be sufficient for reporter gene transcription. Mutations of putative estrogen receptor α (ER-α) (one imperfect estrogen response element, ERE) and/or nuclear factor Y (NF-Y) binding sites (two CCAAT boxes) markedly reduced promoter activity. Similar results were obtained in ER-negative MDA-MB-231 cells except that the ERE mutation did not affect promoter activity. Additionally, promoter activity was stimulated upon E2 treatment and overexpression of ER-α or NF-YA in MCF-7 cells. ChIP confirmed direct binding of both transcription factors to the UBC9 promoter in vivo. Furthermore, UBC9 expression was diminished by ER-α and NF-Y siRNAs on the mRNA and protein levels. In conclusion, we identified the proximal UBC9 promoter and provided evidence that ER-α and NF-Y regulate UBC9 expression on the transcriptional level in response to E2 in MCF-7 cells. These findings may contribute to a better understanding of the regulation of UBC9 in ER
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Shibo Ying
Full Text Available UBC9 encodes a protein that conjugates small ubiquitin-related modifier (SUMO to target proteins thereby changing their functions. Recently, it was noted that UBC9 expression and activity play a role in breast tumorigenesis and response to anticancer drugs. However, the underlying mechanism is poorly understood. To investigate the transcriptional regulation of the UBC9 gene, we identified and characterized its promoter and cis-elements. Promoter activity was tested using luciferase reporter assays. The binding of transcription factors to the promoter was detected by chromatin immunoprecipitation (ChIP, and their functional role was confirmed by siRNA knockdown. UBC9 mRNA and protein levels were measured by quantitative reverse transcription PCR and Western blot analysis, respectively. An increased expression of UBC9 mRNA and protein was found in MCF-7 breast cancer cells treated with 17β-estradiol (E2. Analysis of various deletion mutants revealed a 137 bp fragment upstream of the transcription initiation site to be sufficient for reporter gene transcription. Mutations of putative estrogen receptor α (ER-α (one imperfect estrogen response element, ERE and/or nuclear factor Y (NF-Y binding sites (two CCAAT boxes markedly reduced promoter activity. Similar results were obtained in ER-negative MDA-MB-231 cells except that the ERE mutation did not affect promoter activity. Additionally, promoter activity was stimulated upon E2 treatment and overexpression of ER-α or NF-YA in MCF-7 cells. ChIP confirmed direct binding of both transcription factors to the UBC9 promoter in vivo. Furthermore, UBC9 expression was diminished by ER-α and NF-Y siRNAs on the mRNA and protein levels. In conclusion, we identified the proximal UBC9 promoter and provided evidence that ER-α and NF-Y regulate UBC9 expression on the transcriptional level in response to E2 in MCF-7 cells. These findings may contribute to a better understanding of the regulation of UBC9 in ER
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Hatoh Shinji
2009-03-01
Full Text Available Abstract Background UbcH10 participates in proper metaphase to anaphase transition, and abrogation of UbcH10 results in the premature separation of sister chromatids. To assess the potential role of UbcH10 in colon cancer progression, we analyzed the clinicopathological relevance of UbcH10 in colon cancer. Methods We firstly screened the expression profile of UbcH10 in various types of cancer tissues as well as cell lines. Thereafter, using the colon cancer cells line, we manipulated the expression of UbcH10 and evaluated the cell cycle profile and cellular proliferations. Furthermore, the clinicopathological significance of UbcH10 was immunohistologically evaluated in patients with colon cancer. Statistical analysis was performed using the student's t-test and Chi-square test. Results Using the colon cancer cells, depletion of UbcH10 resulted in suppression of cellular growth whereas overexpression of UbcH10 promoted the cellular growth and oncogenic cellular growth. Mitotic population was markedly alternated by the manipulation of UbcH10 expression. Immunohistochemical analysis indicated that UbcH10 was significantly higher in colon cancer tissue compared with normal colon epithelia. Furthermore, the clinicopathological evaluation revealed that UbcH10 was associated with high-grade histological tumors. Conclusion The results show the clinicopathological significance of UbcH10 in the progression of colon cancer. Thus UbcH10 may act as a novel biomarker in patients with colon cancer.
Ree, J.H.; Jeganathan, K.B.; Malureanu, L.; Deursen, J.M.A. van
2010-01-01
The anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase functions with the E2 ubiquitin-conjugating enzyme UbcH10 in the orderly progression through mitosis by marking key mitotic regulators for destruction by the 26-S proteasome. UbcH10 is overexpressed in many human cancer types and
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Imura, Yoshiyuki; Molho, Melissa; Chuang, Chingkai; Nagy, Peter D.
2015-01-01
Mono- and multi-ubiquitination alters the functions and subcellular localization of many cellular and viral proteins. Viruses can co-opt or actively manipulate the ubiquitin network to support viral processes or suppress innate immunity. Using yeast (Saccharomyces cerevisiae) model host, we show that the yeast Rad6p (radiation sensitive 6) E2 ubiquitin-conjugating enzyme and its plant ortholog, AtUbc2, interact with two tombusviral replication proteins and these E2 ubiquitin-conjugating enzymes could be co-purified with the tombusvirus replicase. We demonstrate that TBSV RNA replication and the mono- and bi-ubiquitination level of p33 is decreased in rad6Δ yeast. However, plasmid-based expression of AtUbc2p could complement both defects in rad6Δ yeast. Knockdown of UBC2 expression in plants also decreases tombusvirus accumulation and reduces symptom severity, suggesting that Ubc2p is critical for virus replication in plants. We provide evidence that Rad6p is involved in promoting the subversion of Vps23p and Vps4p ESCRT proteins for viral replicase complex assembly. - Highlights: • Tombusvirus p33 replication protein interacts with cellular RAD6/Ubc2 E2 enzymes. • Deletion of RAD6 reduces tombusvirus replication in yeast. • Silencing of UBC2 in plants inhibits tombusvirus replication. • Mono- and bi-ubiquitination of p33 replication protein in yeast and in vitro. • Rad6p promotes the recruitment of cellular ESCRT proteins into the tombusvirus replicase
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Imura, Yoshiyuki, E-mail: imura@brs.nihon-u.ac.jp; Molho, Melissa; Chuang, Chingkai; Nagy, Peter D., E-mail: pdnagy2@uky.edu
2015-10-15
Mono- and multi-ubiquitination alters the functions and subcellular localization of many cellular and viral proteins. Viruses can co-opt or actively manipulate the ubiquitin network to support viral processes or suppress innate immunity. Using yeast (Saccharomyces cerevisiae) model host, we show that the yeast Rad6p (radiation sensitive 6) E2 ubiquitin-conjugating enzyme and its plant ortholog, AtUbc2, interact with two tombusviral replication proteins and these E2 ubiquitin-conjugating enzymes could be co-purified with the tombusvirus replicase. We demonstrate that TBSV RNA replication and the mono- and bi-ubiquitination level of p33 is decreased in rad6Δ yeast. However, plasmid-based expression of AtUbc2p could complement both defects in rad6Δ yeast. Knockdown of UBC2 expression in plants also decreases tombusvirus accumulation and reduces symptom severity, suggesting that Ubc2p is critical for virus replication in plants. We provide evidence that Rad6p is involved in promoting the subversion of Vps23p and Vps4p ESCRT proteins for viral replicase complex assembly. - Highlights: • Tombusvirus p33 replication protein interacts with cellular RAD6/Ubc2 E2 enzymes. • Deletion of RAD6 reduces tombusvirus replication in yeast. • Silencing of UBC2 in plants inhibits tombusvirus replication. • Mono- and bi-ubiquitination of p33 replication protein in yeast and in vitro. • Rad6p promotes the recruitment of cellular ESCRT proteins into the tombusvirus replicase.
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Park, Hyejin; Yoon, Min-Sik; Ryu, Kwon-Yul, E-mail: kyryu@uos.ac.kr
2013-06-07
Highlights: •Proliferation capacity of Ubc{sup −/−} FLCs was reduced during culture in vitro. •Ubc is required for proliferation of both hepatocytes and bipotent FLEPCs. •Bipotent FLEPCs exhibit highest Ubc transcription and proliferation capacity. •Cell types responsible for Ubc{sup −/−} fetal liver developmental defect were identified. -- Abstract: We have previously demonstrated that disruption of polyubiquitin gene Ubc leads to mid-gestation embryonic lethality most likely due to a defect in fetal liver development, which can be partially rescued by ectopic expression of Ub. In a previous study, we assessed the cause of embryonic lethality with respect to the fetal liver hematopoietic system. We confirmed that Ubc{sup −/−} embryonic lethality could not be attributed to impaired function of hematopoietic stem cells, which raises the question of whether or not FLECs such as hepatocytes and bile duct cells, the most abundant cell types in the liver, are affected by disruption of Ubc and contribute to embryonic lethality. To answer this, we isolated FLCs from E13.5 embryos and cultured them in vitro. We found that proliferation capacity of Ubc{sup −/−} cells was significantly reduced compared to that of control cells, especially during the early culture period, however we did not observe the increased number of apoptotic cells. Furthermore, levels of Ub conjugate, but not free Ub, decreased upon disruption of Ubc expression in FLCs, and this could not be compensated for by upregulation of other poly- or mono-ubiquitin genes. Intriguingly, the highest Ubc expression levels throughout the entire culture period were observed in bipotent FLEPCs. Hepatocytes and bipotent FLEPCs were most affected by disruption of Ubc, resulting in defective proliferation as well as reduced cell numbers in vitro. These results suggest that defective proliferation of these cell types may contribute to severe reduction of fetal liver size and potentially mid
Observation of an E2 (Ubc9-homodimer by crystallography
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Aileen Y. Alontaga
2016-06-01
Full Text Available Post-translational modifications by the small ubiquitin-like modifiers (SUMO, in particular the formation of poly-SUMO-2 and -3 chains, regulates essential cellular functions and its aberration leads to life-threatening diseases (Geoffroy and Hay, 2009 [1]. It was shown previously that the non-covalent interaction between SUMO and the conjugating enzyme (E2 for SUMO, known as Ubc9, is required for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007 [2]. However, the structure of SUMO-Ubc9 non-covalent complex, by itself, could not explain how the poly-SUMO-2/3 chain forms and consequently a Ubc9 homodimer, although never been observed, was proposed for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007 [2]. Here, we solved the crystal structure of a heterotrimer containing a homodimer of Ubc9 and the RWD domain from RWDD3. The asymmetric Ubc9 homodimer is mediated by the N-terminal region of one Ubc9 molecule and a surface near the catalytic Cys of the second Ubc9 molecule (Fig. 1A. This N-terminal surface of Ubc9 that is involved in the homodimer formation also interacts with the RWD domain, the ubiquitin-fold domain of the SUMO activating enzyme (E1, SUMO, and the E3 ligase, RanBP2 (Knipscheer et al., 2007; Tong et al.. 1997; Tatham et al., 2005; Reverter and Lima, 2005; Capili and Lima, 2007; Wang et al., 2009, 2010; Wang and Chen, 2010; Alontaga et al., 2015 [2–10]. The existence of the Ubc9 homodimer in solution is supported by previously published solution NMR studies of rotational correlation time and chemical shift perturbation (Alontaga et al., 2015; Yuan et al., 1999 [10,11]. Site-directed mutagenesis and biochemical analysis suggests that this dimeric arrangement of Ubc9 is likely important for poly-SUMO chain formation (Fig. 1B and C. The asymmetric Ubc9 homodimer described for the first time in this work could provide the critical missing link in the poly-SUMO chain formation mechanism. The data presented here are related
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Cheng Wang
2015-03-01
Full Text Available Breast cancer is one of the most common and lethal cancers in women. As a hub gene involved in a diversity of tumors, the ubiquitin-conjugating enzyme H10 (UbcH10, may also play some roles in the genesis and development of breast cancer. In the current study, we found that the expression of UbcH10 was up-regulated in some breast cancer tissues and five cell lines. We established a dual drug resistant cell line MCF-7/EPB (epirubicin/TXT (docetaxel and a lentiviral system expressing UbcH10 shRNA to investigate the effects of UbcH10 knockdown on the chemosensitivity of MCF-7/EPB/TXT cells to epirubicin and docetaxel. The knockdown of UbcH10 inhibited the proliferation of both MCF-7 and MCF-7/EPB/TXT cells, due to the G1 phase arrest in cell cycle. Furthermore, UbcH10 knockdown increased the sensitivity of MCF-7/EPB/TXT cells to epirubicin and docetaxel and promoted the apoptosis induced by these two drugs. Protein detection showed that, in addition to inhibiting the expression of Ki67 and cyclin D1, UbcH10 RNAi also impaired the increased BCL-2 and MDR-1 expression levels in MCF-7/EPB/TXT cells, which may contribute to abating the drug resistance in the breast cancer cells. Our research in the current study demonstrated that up-regulation of UbcH10 was involved in breast cancer and its knockdown can inhibit the growth of cancer cells and increase the chemosensitivity of the dual drug resistant breast cancer cells to epirubicin and docetaxel, suggesting that UbcH10 may be a promising target for the therapy of breast cancer.
Physical and functional interactions between ZIP kinase and UbcH5
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Ohbayashi, Norihiko; Okada, Katsuya; Kawakami, Shiho; Togi, Sumihito; Sato, Noriko; Ikeda, Osamu; Kamitani, Shinya; Muromoto, Ryuta; Sekine, Yuichi; Kawai, Taro; Akira, Shizuo; Matsuda, Tadashi
2008-01-01
Zipper-interacting protein kinase (ZIPK) is a widely expressed serine/threonine kinase that has been implicated in cell death and transcriptional regulation, but its mechanism of regulation remains unknown. In our previous study, we showed that leukemia inhibitory factor stimulated threonine-265 phosphorylation of ZIPK, thereby leading to phosphorylation and activation of signal transducer and activator of transcription 3. Here, we identified UbcH5c as a novel ZIPK-binding partner by yeast two-hybrid screening. Importantly, we found that UbcH5c induced ubiquitination of ZIPK. Small-interfering RNA-mediated reduction of endogenous UbcH5 expression decreased ZIPK ubiquitination. Furthermore, coexpression of UbcH5c with ZIPK influenced promyelocytic leukemia protein nuclear body (PML-NB) formation. These results suggest that UbcH5 regulates ZIPK accumulation in PML-NBs by interacting with ZIPK and stimulating its ubiquitination
Zoledronate induces apoptosis in cells from fibro-cellular membrane of unicameral bone cyst (UBC).
Yu, John; Chang, Seong-Sil; Suratwala, Sanjeev; Chung, Woo-Sik; Abdelmessieh, Peter; Lee, Hahn-Jun; Yang, Jay; Lee, Francis Young-In
2005-09-01
Unicameral bone cyst (UBC) is a benign cystic lesion in children which is prone to fracture. Various treatments are available, but recurrence after different types of percutaneous injection therapy can cause bone destruction and pathologic fracture. The potential therapeutic effects of anti-resorptive agents, such as bisphosphonates, have not been investigated for UBC. The objective of this study was to characterize the cells from the fibro-cellular membrane of unicameral bone cyst (UBC cells) and to determine whether zoledronate, a nitrogen-containing bisphosphonate, could induce apoptosis in UBC cells. Flow cytometry and immunoblotting were performed in order to determine whether zoledronate induced apoptosis. Cells derived from normal human trabecular bones were used as controls against UBC cells to compare the effect of zoledronate in inducing apoptosis. Immunohisto/cytochemistry (IHC/ICC) and mini-array analyses were performed on tissues and cultured cells. Isolated peripheral blood mononuclear cells were incubated with conditioned media from the UBC cells to determine whether they are capable of inducing osteoclastogenesis. UBC membrane is composed of cells staining positively with CD68, SDF-1, STRO-1 and RANKL, but in vitro cells showed no staining with antibodies to CD68 and STRO-1, suggesting that there was a clonal selection of stromal cells during cell culture. UBC cells also express RUNX2 (runt-related transcription factor-2, core binding factor-1), a key transcription factor for osteoblastic differentiation. In addition, media collected from UBC cells induced a generation of multi-nucleated osteoclast-like cells of peripheral blood mononuclear cells. Zoledronate induced apoptosis of UBC cells in a dose-dependent manner. Apoptosis was evidenced by induction of the active cleaved form of caspase-3. The baseline apoptotic fractions were similar in UBC cells and trabecular bone cells. However, in the overall apoptotic fractions in this study, trabecular
U.B.C.: Past, present and future
International Nuclear Information System (INIS)
Wall, W.D.
1993-01-01
This report documents the involvement of the International Conference of Building Officials (ICBO) in hazard mitigation, particularly in relation to earthquakes. It encompasses the history of the Uniform Building Code TM (U.B.C) provisions as they apply to earthquake hazard mitigation. Also discussed is Executive Order 12699. Conference membership services and benefits are reviewed and the future of ICBO, building codes and hazard mitigation are examined. The U.B.C. seismic provisions make a vast contribution to the design of buildings for seismic safety
Enhanced SUMOylation of proteins containing a SUMO-interacting motif by SUMO-Ubc9 fusion
International Nuclear Information System (INIS)
Kim, Eui Tae; Kim, Kyeong Kyu; Matunis, Mike J.; Ahn, Jin-Hyun
2009-01-01
Identifying new targets for SUMO and understanding the function of protein SUMOylation are largely limited by low level of SUMOylation. It was found recently that Ubc9, the SUMO E2 conjugating enzyme, is covalently modified by SUMO at a lysine 14 in the N-terminal alpha helix, and that SUMO-modified Ubc9 has enhanced conjugation activity for certain target proteins containing a SUMO-interacting motif (SIM). Here, we show that, compared to intact Ubc9, the SUMO-Ubc9 fusion protein has higher conjugating activity for SIM-containing targets such as Sp100 and human cytomegalovirus IE2. Assays using an IE2 SIM mutant revealed the requirement of SIM for the enhanced IE2 SUMOylation by SUMO-Ubc9. In pull-down assays with cell extracts, the SUMO-Ubc9 fusion protein bound to more diverse cellular proteins and interacted with some SIM-containing proteins with higher affinities than Ubc9. Therefore, the devised SUMO-Ubc9 fusion will be useful for identifying SIM-containing SUMO targets and producing SUMO-modified proteins.
Inhibition of Ubc13-mediated Ubiquitination by GPS2 Regulates Multiple Stages of B Cell Development.
Lentucci, Claudia; Belkina, Anna C; Cederquist, Carly T; Chan, Michelle; Johnson, Holly E; Prasad, Sherry; Lopacinski, Amanda; Nikolajczyk, Barbara S; Monti, Stefano; Snyder-Cappione, Jennifer; Tanasa, Bogdan; Cardamone, M Dafne; Perissi, Valentina
2017-02-17
Non-proteolytic ubiquitin signaling mediated by Lys 63 ubiquitin chains plays a critical role in multiple pathways that are key to the development and activation of immune cells. Our previous work indicates that GPS2 (G-protein Pathway Suppressor 2) is a multifunctional protein regulating TNFα signaling and lipid metabolism in the adipose tissue through modulation of Lys 63 ubiquitination events. However, the full extent of GPS2-mediated regulation of ubiquitination and the underlying molecular mechanisms are unknown. Here, we report that GPS2 is required for restricting the activation of TLR and BCR signaling pathways and the AKT/FOXO1 pathway in immune cells based on direct inhibition of Ubc13 enzymatic activity. Relevance of this regulatory strategy is confirmed in vivo by B cell-targeted deletion of GPS2, resulting in developmental defects at multiple stages of B cell differentiation. Together, these findings reveal that GPS2 genomic and non-genomic functions are critical for the development and cellular homeostasis of B cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Structure of human ubiquitin-conjugating enzyme E2 G2 (UBE2G2/UBC7)
International Nuclear Information System (INIS)
Arai, Ryoichi; Yoshikawa, Seiko; Murayama, Kazutaka; Imai, Yuzuru; Takahashi, Ryosuke; Shirouzu, Mikako; Yokoyama, Shigeyuki
2006-01-01
The crystal structure of human UBE2G2/UBC7 was solved at 2.56 Å resolution. The superimposition of UBE2G2 on UbcH7 in a c-Cbl–UbcH7–ZAP70 ternary complex suggested that the two loop regions of UBE2G2 interact with the RING domain in a similar way as UbcH7. The human ubiquitin-conjugating enzyme E2 G2 (UBE2G2/UBC7) is involved in protein degradation, including a process known as endoplasmic reticulum-associated degradation (ERAD). The crystal structure of human UBE2G2/UBC7 was solved at 2.56 Å resolution. The UBE2G2 structure comprises a single domain consisting of an antiparallel β-sheet with four strands, five α-helices and two 3 10 -helices. Structural comparison of human UBE2G2 with yeast Ubc7 indicated that the overall structures are similar except for the long loop region and the C-terminal helix. Superimposition of UBE2G2 on UbcH7 in a c-Cbl–UbcH7–ZAP70 ternary complex suggested that the two loop regions of UBE2G2 interact with the RING domain in a similar way to UbcH7. In addition, the extra loop region of UBE2G2 may interact with the RING domain or its neighbouring region and may be involved in the binding specificity and stability
International Nuclear Information System (INIS)
Nuvoli, S.; Spanu, A.; Masia, A.; Mulas, A.; Falchi, A.; Solinas, M.E.; Marrosu, A.; Madeddu, G.; Mocci, A.
2002-01-01
Aim: We evaluated BTA and UBC clinical utility in TCC diagnosis and follow-up. Materials and Methods: We enrolled consecutively 96 untreated TCC, 73 other genitourinary carcinomas (OC), 106 benign genitourinary diseases (BD) and 75 normal controls (C). After trans-urethral resection (TUR), TCC were classified by clinical staging (9 Ta, 27 T1, 32 T2, 20 T3 and 8 T4) and pathological grading (14 G1, 28 G2, 41 G3 and 13 G4). Urine BTA and UBC were assayed by monoclonal antibody methods, IEMA and IRMA, respectively (cut-off:14 U/ml and 8 μg/l, respectively). Results: Sensitivity, specificity, PPV, NPV and accuracy were 83.6%, 75.1%, 64.6%, 89.% and 72.4%, respectively for BTA and 53.1%, 89.4%, 72.8%, 78% and 75.6%, respectively for UBC. BTA and UBC specificities were determined combining OC and BD data, although UBC reached the highest value in OC (93.15%). Sensitivity and specificity differences between the two markers were significant (p<0.00001). BTA and UBC sensitivity and mean values significantly increased with progressive staging and grading. Moreover, marker levels were significantly higher in TCC compared to OC, BD and C. Seventy-one high stage and/or grade TCC underwent radical cystectomy, while 25 were monitored after TUR (14 cases: group A) or segmental cystectomy (11 cases: group B) for 8-32 months by periodical clinical examination, cystoscopy and urinary BTA and UBC assays. During follow-up, 9 group A cases developed recurrences and 5 were NED. BTA was elevated in 8/9 cases (88.8%) with recurrence, while borderline in the remaining one. UBC was above cut-off in 6/9 cases (66.6%) all with high BTA, while low in the remaining 3, confirming first observation data. Both marker increases preceded by several months the cystoscopic evidence of recurrence. In NED patients, BTA was low in all cases (100%), while UBC was under cut-off in 4/5 cases (80%) and slightly high in the remaining asymptomatic patient. Ten group B patients developed local recurrences
Distinct Functional Domains of Ubc9 Dictate Cell Survival and Resistance to Genotoxic Stress
van Waardenburg, Robert C. A. M.; Duda, David M.; Lancaster, Cynthia S.; Schulman, Brenda A.; Bjornsti, Mary-Ann
2006-01-01
Covalent modification with SUMO alters protein function, intracellular localization, or protein-protein interactions. Target recognition is determined, in part, by the SUMO E2 enzyme, Ubc9, while Siz/Pias E3 ligases may facilitate select interactions by acting as substrate adaptors. A yeast conditional Ubc9P123L mutant was viable at 36°C yet exhibited enhanced sensitivity to DNA damage. To define functional domains in Ubc9 that dictate cellular responses to genotoxic stress versus those necessary for cell viability, a 1.75-Å structure of yeast Ubc9 that demonstrated considerable conservation of backbone architecture with human Ubc9 was solved. Nevertheless, differences in side chain geometry/charge guided the design of human/yeast chimeras, where swapping domains implicated in (i) binding residues within substrates that flank canonical SUMOylation sites, (ii) interactions with the RanBP2 E3 ligase, and (iii) binding of the heterodimeric E1 and SUMO had distinct effects on cell growth and resistance to DNA-damaging agents. Our findings establish a functional interaction between N-terminal and substrate-binding domains of Ubc9 and distinguish the activities of E3 ligases Siz1 and Siz2 in regulating cellular responses to genotoxic stress. PMID:16782883
International Nuclear Information System (INIS)
Fradet-Turcotte, Amelie; Brault, Karine; Titolo, Steve; Howley, Peter M.; Archambault, Jacques
2009-01-01
The E1 helicase from BPV and HPV16 interacts with Ubc9 to facilitate viral genome replication. We report that HPV11 E1 also interacts with Ubc9 in vitro and in the yeast two-hybrid system. Residues in E1 involved in oligomerization (353-435) were sufficient for binding to Ubc9 in vitro, but the origin-binding and ATPase domains were additionally required in yeast. Nuclear accumulation of BPV E1 was shown previously to depend on its interaction with Ubc9 and sumoylation on lysine 514. In contrast, HPV11 and HPV16 E1 mutants defective for Ubc9 binding remained nuclear even when the SUMO pathway was inhibited. Furthermore, we found that K514 in BPV E1 and the analogous K559 in HPV11 E1 are not essential for nuclear accumulation of E1. These results suggest that the interaction of E1 with Ubc9 is not essential for its nuclear accumulation but, rather, depends on its oligomerization and binding to DNA and ATP.
Ecke, Thorsten H; Arndt, Christian; Stephan, Carsten; Hallmann, Steffen; Lux, Oliver; Otto, Thomas; Ruttloff, Jürgen; Gerullis, Holger
2015-05-01
UBC Rapid is a test detecting fragments of cytokeratins 8 and 18 in urine. These are cytokeratins frequently overexpressed in tumor cells. We present the first results of a multi-centre study using UBC Rapid in patients with bladder cancer and healthy controls. Clinical urine samples from 92 patients with tumors of the urinary bladder (45 low-grade and 47 high-grade tumors) and from 33 healthy controls were used. Urine samples were analyzed by the UBC Rapid point-of-care (POC) system and evaluated both visually and quantitatively using a concile Omega 100 POC reader. For visual evaluation, different thresholds of band intensity for considering a test as positive were applied. Sensitivities and specificities were calculated by contingency analyses. We found that pathological concentrations by UBC Rapid are detectable in urine of patients with bladder cancer. The calculated diagnostic sensitivity of UBC Rapid in urine was 68.1% for high-grade, but only 46.2% for low-grade tumors. The specificity was 90.9%. The area under the curve (AUC) after receiver-operated curve (ROC) analysis was 0.733. Pathological levels of UBC Rapid in urine are higher in patients with bladder cancer in comparison to the control group (pbladder cancer and controls. Further studies with a greater number of patients will show how valuable these results are. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
The mechanism of OTUB1-mediated inhibition of ubiquitination
Energy Technology Data Exchange (ETDEWEB)
Wiener, Reuven; Zhang, Xiangbin; Wang, Tao; Wolberger, Cynthia (JHU)
2013-04-08
Histones are ubiquitinated in response to DNA double-strand breaks (DSB), promoting recruitment of repair proteins to chromatin. UBC13 (also known as UBE2N) is a ubiquitin-conjugating enzyme (E2) that heterodimerizes with UEV1A (also known as UBE2V1) and synthesizes K63-linked polyubiquitin (K63Ub) chains at DSB sites in concert with the ubiquitin ligase (E3), RNF168 (ref. 3). K63Ub synthesis is regulated in a non-canonical manner by the deubiquitinating enzyme, OTUB1 (OTU domain-containing ubiquitin aldehyde-binding protein 1), which binds preferentially to the UBC13-Ub thiolester. Residues amino-terminal to the OTU domain, which had been implicated in ubiquitin binding, are required for binding to UBC13-Ub and inhibition of K63Ub synthesis. Here we describe structural and biochemical studies elucidating how OTUB1 inhibits UBC13 and other E2 enzymes. We unexpectedly find that OTUB1 binding to UBC13-Ub is allosterically regulated by free ubiquitin, which binds to a second site in OTUB1 and increases its affinity for UBC13-Ub, while at the same time disrupting interactions with UEV1A in a manner that depends on the OTUB1 N terminus. Crystal structures of an OTUB1-UBC13 complex and of OTUB1 bound to ubiquitin aldehyde and a chemical UBC13-Ub conjugate show that binding of free ubiquitin to OTUB1 triggers conformational changes in the OTU domain and formation of a ubiquitin-binding helix in the N terminus, thus promoting binding of the conjugated donor ubiquitin in UBC13-Ub to OTUB1. The donor ubiquitin thus cannot interact with the E2 enzyme, which has been shown to be important for ubiquitin transfer. The N-terminal helix of OTUB1 is positioned to interfere with UEV1A binding to UBC13, as well as with attack on the thiolester by an acceptor ubiquitin, thereby inhibiting K63Ub synthesis. OTUB1 binding also occludes the RING E3 binding site on UBC13, thus providing a further component of inhibition. The general features of the inhibition mechanism explain how OTUB1
Telomerase reverse transcriptase promoter mutations in bladder cancer
DEFF Research Database (Denmark)
Allory, Yves; Beukers, Willemien; Sagrera, Ana
2014-01-01
for detection of recurrences in urine in patients with urothelial bladder cancer (UBC). DESIGN, SETTING, AND PARTICIPANTS: A set of 111 UBCs of different stages was used to assess TERT promoter mutations by Sanger sequencing and TERT messenger RNA (mRNA) expression by reverse transcription...... surveillance after diagnosis of non-muscle-invasive UBC (n=194), was tested using a SNaPshot assay. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Association of mutation status with age, sex, tobacco, stage, grade, fibroblast growth factor receptor 3 (FGFR3) mutation, progression-free survival, disease...... frequent among FGFR3 mutant tumors (p=0.0002). There was no association between TERT mutations and mRNA expression (p=0.3). Mutations were not associated with clinical outcome. In urine, TERT mutations had 90% specificity in subjects with hematuria but no bladder tumor, and 73% in recurrence-free UBC...
International Nuclear Information System (INIS)
Jeon, En Hee; Pak, Jung Hun; Kim, Mi Jin; Kim, Hye Jeong; Shin, Sang Hyun; Lee, Jai Heon; Kim, Doh Hoon; Oh, Ju Sung; Oh, Boung-Jun; Jung, Ho Won; Chung, Young Soo
2012-01-01
Highlights: ► We isolated a novel E2 ubiquitin-conjugating enzyme from leaves of wild rice plants. ► The OgUBC1 was highly expressed in leaves treated with SA and UV-B radiation. ► The recombinant OgUBC1 has an enzymatic activity of E2 in vitro. ► The OgUBC1 could protect disruption of plant cells by UV-B radiation. ► OgUBC1 confers disease resistance and UV-B tolerance in transgenic Arabidopsis plants. -- Abstract: A previously unidentified gene encoding ubiquitin-conjugating enzyme was isolated from leaves of wild rice plant treated with wounding and microbe-associated molecular patterns. The OgUBC1 gene was composed of 148 amino acids and contained a typical active site and 21 ubiquitin thioester intermediate interaction residues and 4 E3 interaction residues. Both exogenous application of salicylic acid and UV-B irradiation triggered expression of OgUBC1 in leaves of wild rice. Recombinant OgUBC1 proteins bound to ubiquitins in vitro, proposing that the protein might act as E2 enzyme in planta. Heterologous expression of the OgUBC1 in Arabidopsis thaliana protected plants from cellular damage caused by an excess of UV-B radiation. A stable expression of chalcone synthase gene was detected in leaves of OgUBC1-expressing Arabidopsis, resulting in producing higher amounts of anthocyanin than those in wild-type Col-0 plants. Additionally, both pathogenesis-related gene1 and 5 were transcribed in the transgenic Arabidopsis in the absence of pathogen infection. The OgUBC1-expressing plants were resistant to the infection of Botrytis cinerea. Taken together, we suggested that the OgUBC1 is involved in ubiquitination process important for cellular response against biotic and abiotic stresses in plants.
Energy Technology Data Exchange (ETDEWEB)
Jeon, En Hee; Pak, Jung Hun; Kim, Mi Jin; Kim, Hye Jeong [Department of Genetic Engineering, Dong-A University, Busan 604-714 (Korea, Republic of); Shin, Sang Hyun [National Crop Experiment Station, Rural Development Administration, Suwon 441-100 (Korea, Republic of); Lee, Jai Heon; Kim, Doh Hoon; Oh, Ju Sung [Department of Genetic Engineering, Dong-A University, Busan 604-714 (Korea, Republic of); Oh, Boung-Jun [BioControl Center, Jeonnam 516-942 (Korea, Republic of); Jung, Ho Won, E-mail: hwjung@dau.ac.kr [Department of Genetic Engineering, Dong-A University, Busan 604-714 (Korea, Republic of); Chung, Young Soo, E-mail: chungys@dau.ac.kr [Department of Genetic Engineering, Dong-A University, Busan 604-714 (Korea, Republic of)
2012-10-19
Highlights: Black-Right-Pointing-Pointer We isolated a novel E2 ubiquitin-conjugating enzyme from leaves of wild rice plants. Black-Right-Pointing-Pointer The OgUBC1 was highly expressed in leaves treated with SA and UV-B radiation. Black-Right-Pointing-Pointer The recombinant OgUBC1 has an enzymatic activity of E2 in vitro. Black-Right-Pointing-Pointer The OgUBC1 could protect disruption of plant cells by UV-B radiation. Black-Right-Pointing-Pointer OgUBC1 confers disease resistance and UV-B tolerance in transgenic Arabidopsis plants. -- Abstract: A previously unidentified gene encoding ubiquitin-conjugating enzyme was isolated from leaves of wild rice plant treated with wounding and microbe-associated molecular patterns. The OgUBC1 gene was composed of 148 amino acids and contained a typical active site and 21 ubiquitin thioester intermediate interaction residues and 4 E3 interaction residues. Both exogenous application of salicylic acid and UV-B irradiation triggered expression of OgUBC1 in leaves of wild rice. Recombinant OgUBC1 proteins bound to ubiquitins in vitro, proposing that the protein might act as E2 enzyme in planta. Heterologous expression of the OgUBC1 in Arabidopsis thaliana protected plants from cellular damage caused by an excess of UV-B radiation. A stable expression of chalcone synthase gene was detected in leaves of OgUBC1-expressing Arabidopsis, resulting in producing higher amounts of anthocyanin than those in wild-type Col-0 plants. Additionally, both pathogenesis-related gene1 and 5 were transcribed in the transgenic Arabidopsis in the absence of pathogen infection. The OgUBC1-expressing plants were resistant to the infection of Botrytis cinerea. Taken together, we suggested that the OgUBC1 is involved in ubiquitination process important for cellular response against biotic and abiotic stresses in plants.
Fox, Joanne; Birol, Gülnur; Han, Andrea; Cassidy, Alice; Nakonechny, Joanne; Berger, Jim; Peacock, Simon; Samuels, Lacey
2014-01-01
The First Year Seminar in Science (SCIE113) was developed during 2009/2010 academic year through an exemplary collaboration between faculty, administrators and educational support staff in the Faculty of Science at the University of British Columbia (UBC). SCIE113 reflects the vision and values of the Faculty of Science and UBC by offering an…
MEL-18 interacts with HSF2 and the SUMO E2 UBC9 to inhibit HSF2 sumoylation.
Zhang, Jie; Goodson, Michael L; Hong, Yiling; Sarge, Kevin D
2008-03-21
In a previous study we found that sumoylation of the DNA-binding protein heat shock factor 2 (HSF2) is up-regulated during mitosis, but the mechanism that mediates this regulation was unknown. Here we show that HSF2 interacts with the polycomb protein MEL-18, that this interaction decreases during mitosis, and that overexpression and RNA interference-mediated reduction of MEL-18 result in decreased and increased HSF2 sumoylation, respectively. Other results suggest that MEL-18 may also function to inhibit the sumoylation of other cellular proteins. The results also show that MEL-18 is able to interact with the small ubiquitin-like modifier (SUMO) ubiquitin carrier protein (E2) enzyme UBC9 and that MEL-18 inhibits the ability of UBC9 to transfer the SUMO protein to target proteins. Together, the results in this work suggest a mechanism in which MEL-18 bound to HSF2 inhibits its sumoylation by binding to and inhibiting the activity of UBC9 enzymes in the vicinity of HSF2. These results provide an explanation for how mitotic HSF2 sumoylation is regulated and suggest that MEL-18, in contrast to the sumoylation-stimulating activities of the polycomb protein PC2, actually functions like an anti-SUMO ubiquitin-protein isopeptide ligase (E3), interacting both with HSF2 and the SUMO E2 UBC9 but acting to inhibit UBC9 activity to decrease sumoylation of a target protein, in this case that of HSF2.
Zimnik, Susan; Gaestel, Matthias; Niedenthal, Rainer
2009-03-01
Post-translational modifications control the physiological activity of the signal transducer and activator of transcription STAT1. While phosphorylation at tyrosine Y701 is a prerequisite for STAT1 dimerization, its SUMOylation represses the transcriptional activity. Recently, we have demonstrated that SUMOylation at lysine K703 inhibits the phosphorylation of nearby localized Y701 of STAT1. Here, we analysed the influence of phosphorylation of Y701 on SUMOylation of K703 in vivo. For that reason, an Ubc9/substrate dimerization-dependent SUMOylation (USDDS) system was developed, which consists of fusions of the SUMOylation substrate and of the SUMO-conjugating enzyme Ubc9 to the chemically activatable heterodimerization domains FKBP and FRB, respectively. When FKBP fusion proteins of STAT1, p53, CRSP9, FOS, CSNK2B, HES1, TCF21 and MYF6 are coexpressed with Ubc9-FRB, treatment of HEK293 cells with the rapamycin-related dimerizer compound AP21967 induces SUMOylation of these proteins in vivo. For STAT1-FKBP and p53-FKBP we show that this SUMOylation takes place at their specific SUMOylation sites in vivo. Using USDDS, we then demonstrate that STAT1 phosphorylation at Y701 induced by interferon-beta treatment inhibits SUMOylation of K703 in vivo. Thus, pY701 and SUMO-K703 of STAT1 represent mutually exclusive modifications, which prevent signal integration at this molecule and probably ensure the existence of differentially modified subpopulations of STAT1 necessary for its regulated nuclear cytoplasmic activation/inactivation cycle.
DEFF Research Database (Denmark)
Nielsen, Inga Sig; Nielsen, Olaf; Murray, Johanne M
2002-01-01
Genes transcribed by RNA polymerase II are silenced when introduced near the mat2 or mat3 mating-type loci of the fission yeast Schizosaccharomyces pombe. Silencing is mediated by a number of gene products and cis-acting elements. We report here the finding of novel trans-acting factors identified...... was not suppressed by a mutation in the 26S proteasome, suggesting that loss of silencing is not due to an increased degradation of silencing factors but rather to the posttranslational modification of proteins by ubiquitination. We discuss the implications of these results for the possible modes of action of UbcP3...
Are We Doing Any Good? A Value-Added Analysis of UBC's Science One Program
Directory of Open Access Journals (Sweden)
Chris Waltham
2012-12-01
Full Text Available Science One is a full academic year interdisciplinary alternative to the traditional first-year experience in the Faculty of Science at the University of British Columbia (UBC. Anecdotal reports suggest that alumni/ae of the program do very well in upper-level classes and many become successful graduate and medical students. The high faculty/student ratio makes the program an expensive one, however, and thus we have sought rigorous evidence of the benefits to our students. Our approach has been a value-added one; we have compared high-school and upper-level undergraduate grades for students in all UBC's first-year science programs. We have found a clear signal that there is a large benefit to participating in Science One, and conclude that this arises from a combination of the recruitment of enthusiastic students who are up for a challenge, the Science One admissions process, and taking the program itself.Science One consiste en une année scolaire interdisciplinaire complète qui représente une variante de l’expérience traditionnelle vécue en première année à la Faculté des sciences de l’Université de la Colombie-Britannique (UBC. Des rapports isolés suggèrent que les anciens étudiants du programme obtiennent de très bons résultats dans les cours de niveau supérieur et plusieurs obtiennent leur diplôme avec succès et étudient en médecine. Cependant, le ratio élevé enseignant/étudiant fait en sorte que le programme coûte cher, c’est pourquoi les auteurs ont cherché à obtenir des données probantes sur les avantages qu’il présente pour leurs étudiants. Ils ont employé la méthode de la valeur ajoutée; ont comparé les notes obtenues au secondaire et celles des étudiants de premier cycle inscrits à des cours de niveau supérieur dans tous les programmes scientifiques offerts à l’UBC. Ils ont découvert que la participation à Science One est très bénéfique et ont conclu que cela résulte d
Conjugated Fatty Acid Synthesis
Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John
2012-01-01
Conjugated linolenic acids (CLNs), 18:3 Δ9,11,13, lack the methylene groups found between the double bonds of linolenic acid (18:3 Δ9,12,15). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 Δ9cis,11trans,13cis) or α-eleostearic acid (18:3 Δ9cis,11trans,13trans). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly α-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of α-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation. PMID:22451660
Duda, David M.; van Waardenburg, Robert C. A. M.; Borg, Laura A.; McGarity, Sierra; Nourse, Amanda; Waddell, M. Brett; Bjornsti, Mary-Ann; Schulman, Brenda A.
2007-01-01
Summary The SUMO ubiquitin-like proteins play regulatory roles in cell division, transcription, DNA repair, and protein subcellular localization. Paralleling other ubiquitin-like proteins, SUMO proteins are proteolytically processed to maturity, conjugated to targets by E1-E2-E3 cascades, and subsequently recognized by specific downstream effectors containing a SUMO-binding motif (SBM). SUMO and its E2 from the budding yeast S. cerevisiae, Smt3p and Ubc9p, are encoded by essential genes. Here we describe the 1.9 Å resolution crystal structure of a noncovalent Smt3p–Ubc9p complex. Unexpectedly, a heterologous portion of the crystallized complex derived from the expression construct mimics an SBM, and binds Smt3p in a manner resembling SBM binding to human SUMO family members. In the complex, Smt3p binds a surface distal from Ubc9's catalytic cysteine. The structure implies that a single molecule of Smt3p cannot bind concurrently to both the noncovalent binding site and the catalytic cysteine of a single Ubc9p molecule. However, formation of higher-order complexes can occur, where a single Smt3p covalently linked to one Ubc9p's catalytic cysteine also binds noncovalently to another molecule of Ubc9p. Comparison with other structures from the SUMO pathway suggests that formation of the noncovalent Smt3p–Ubc9p complex occurs mutually exclusively with many other Smt3p and Ubc9p interactions in the conjugation cascade. By contrast, high-resolution insights into how Smt3p–Ubc9p can also interact with downstream recognition machineries come from contacts with the SBM mimic. Interestingly, the overall architecture of the Smt3p–Ubc9p complex is strikingly similar to recent structures from the ubiquitin pathway. The results imply that noncovalent ubiquitin-like protein–E2 complexes are conserved platforms, which function as parts of larger assemblies involved many protein post-translational regulatory pathways. PMID:17475278
International Nuclear Information System (INIS)
Synowiec, Ewelina; Krupa, Renata; Morawiec, Zbigniew; Wasylecka, Maja; Dziki, Lukasz; Morawiec, Jan; Blasiak, Janusz; Wozniak, Katarzyna
2010-01-01
UBC9 (E2) SUMO conjugating enzyme plays an important role in the maintenance of genome stability and integrity. In the present work we examined the association between the c.73G>A (Val25Met) polymorphism of the UBC9 gene (rs11553473) and efficacy of DNA double-strand breaks (DSBs) repair (DRE) in breast cancer patients. We determined the level of endogenous (basal) and exogenous (induced by γ-irradiation) DSBs and efficacy of their repair in peripheral blood lymphocytes of 57 breast cancer patients and 70 healthy individuals. DNA damage and repair were studied by neutral comet assay. Genotypes were determined in DNA from peripheral blood lymphocytes by allele-specific PCR (ASO-PCR). We also correlated genotypes with the clinical characteristics of breast cancer patients. We observed a strong association between breast cancer occurrence and the variant allele carried genotypes in patients with elevated level of basal as well as induced DNA damage (OR 6.74, 95% CI 2.27-20.0 and OR 5.33, 95% CI 1.81-15.7, respectively). We also found statistically significant (p A polymorphism of the UBC9 gene in breast cancer patients. Carriers of variant allele have decreased DNA DRE as compared to wild type genotype carriers. We did not find any association with the UBC9 gene polymorphism and estrogen and progesterone receptor status. The variant allele of the UBC9 gene polymorphism was strongly inversely related to HER negative breast cancer patients (OR 0.03, 95% CI 0.00-0.23). Our results suggest that the c.73G>A polymorphism of the UBC9 gene may affect DNA DSBs repair efficacy in breast cancer patients.
Caspase recruitment domain of procaspase-2 could be a target for SUMO-1 modification through Ubc9
International Nuclear Information System (INIS)
Shirakura, Hiromi; Hayashi, Naoko; Ogino, Shin-ichi; Tsuruma, Kazuhiro; Uehara, Takashi; Nomura, Yasuyuki
2005-01-01
To identify the binding proteins that regulate the function of procaspase-2, we screened for proteins using the yeast two-hybrid method and isolated human Ubc9 and SUMO-1 as the candidates. Ubc9 and SUMO-1 interacted with the caspase recruitment domain of procaspase-2 in its N-terminal. We elucidated the covalent modification of procaspase-2 by SUMO-1 in mammalian cells by immunoprecipitation followed by Western blot analysis. Procaspase-2 and SUMO-1 were co-localized by dot-like structures in the nucleus that are related to promyelocytic leukemia bodies. Interestingly, a conjugation-deficient mutant (K60R) procaspase-2 resulted in a delay of its enzyme maturation (appearance of p12 subunit) compared to that of wild-type. Thus, the modification with SUMO-1 may play a critical role in the nuclear localization and the activation (maturation) of procaspase-2
Energy Technology Data Exchange (ETDEWEB)
Synowiec, Ewelina [Department of Molecular Genetics, University of Lodz, Lodz (Poland); Krupa, Renata [Laboratory of DNA Repair, Department of Molecular Genetics, University of Lodz, Banacha 12/16, Lodz (Poland); Morawiec, Zbigniew; Wasylecka, Maja [Department of Surgical Oncology, N. Copernicus Hospital, Lodz (Poland); Dziki, Lukasz; Morawiec, Jan [Department of General and Colorectal Surgery, Medical University of Lodz, Lodz (Poland); Blasiak, Janusz [Department of Molecular Genetics, University of Lodz, Lodz (Poland); Wozniak, Katarzyna, E-mail: wozniak@biol.uni.lodz.pl [Laboratory of DNA Repair, Department of Molecular Genetics, University of Lodz, Banacha 12/16, Lodz (Poland)
2010-12-10
UBC9 (E2) SUMO conjugating enzyme plays an important role in the maintenance of genome stability and integrity. In the present work we examined the association between the c.73G>A (Val25Met) polymorphism of the UBC9 gene (rs11553473) and efficacy of DNA double-strand breaks (DSBs) repair (DRE) in breast cancer patients. We determined the level of endogenous (basal) and exogenous (induced by {gamma}-irradiation) DSBs and efficacy of their repair in peripheral blood lymphocytes of 57 breast cancer patients and 70 healthy individuals. DNA damage and repair were studied by neutral comet assay. Genotypes were determined in DNA from peripheral blood lymphocytes by allele-specific PCR (ASO-PCR). We also correlated genotypes with the clinical characteristics of breast cancer patients. We observed a strong association between breast cancer occurrence and the variant allele carried genotypes in patients with elevated level of basal as well as induced DNA damage (OR 6.74, 95% CI 2.27-20.0 and OR 5.33, 95% CI 1.81-15.7, respectively). We also found statistically significant (p < 0.05) difference in DRE related to the c.73G>A polymorphism of the UBC9 gene in breast cancer patients. Carriers of variant allele have decreased DNA DRE as compared to wild type genotype carriers. We did not find any association with the UBC9 gene polymorphism and estrogen and progesterone receptor status. The variant allele of the UBC9 gene polymorphism was strongly inversely related to HER negative breast cancer patients (OR 0.03, 95% CI 0.00-0.23). Our results suggest that the c.73G>A polymorphism of the UBC9 gene may affect DNA DSBs repair efficacy in breast cancer patients.
Directory of Open Access Journals (Sweden)
Stefania Correale
Full Text Available UbcH10 is a component of the Ubiquitin Conjugation Enzymes (Ubc; E2 involved in the ubiquitination cascade controlling the cell cycle progression, whereby ubiquitin, activated by E1, is transferred through E2 to the target protein with the involvement of E3 enzymes. In this work we propose the first three dimensional model of the tetrameric complex formed by the human UbA1 (E1, two ubiquitin molecules and UbcH10 (E2, leading to the transthiolation reaction. The 3D model was built up by using an experimentally guided incremental docking strategy that combined homology modeling, protein-protein docking and refinement by means of molecular dynamics simulations. The structural features of the in silico model allowed us to identify the regions that mediate the recognition between the interacting proteins, revealing the active role of the ubiquitin crosslinked to E1 in the complex formation. Finally, the role of these regions involved in the E1-E2 binding was validated by designing short peptides that specifically interfere with the binding of UbcH10, thus supporting the reliability of the proposed model and representing valuable scaffolds for the design of peptidomimetic compounds that can bind selectively to Ubcs and inhibit the ubiquitylation process in pathological disorders.
International Nuclear Information System (INIS)
De Souza, S.C.
1988-01-01
Four different enzyme treatments-conjugase alone, conjugase and alpha-amylase, conjugase and Pronase reg-sign and a triple enzyme combination of conjugase, Pronase reg-sign and alpha-amylase were applied in the extraction of total folate from infant formula, baby foods and various other foods by microbiological and radioassay methods. Significant increases (P < 0.05) in measurable folate were obtained using the triple enzyme system in spinach, Camembert cheese, soy-based infant formula and cereal-based, meat-based and fruit-based infant foods over the use of conjugase alone by the microbiological method. Increases were also observed in many of the same foods using Pronase reg-sign or alpha-amylase in addition to conjugase alone. Increases obtained by microbiological assay were confirmed by radioassay in a number of foods studied
Energy Technology Data Exchange (ETDEWEB)
Deng, Hua; Lin, Yingbo; Badin, Margherita; Vasilcanu, Daiana; Stroemberg, Thomas [Department of Oncology and Pathology, The Karolinska Institute, Cancer Center Karolinska, SE-17176 Stockholm (Sweden); Jernberg-Wiklund, Helena [Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala (Sweden); Sehat, Bita [Department of Oncology and Pathology, The Karolinska Institute, Cancer Center Karolinska, SE-17176 Stockholm (Sweden); Larsson, Olle, E-mail: olle.larsson@ki.se [Department of Oncology and Pathology, The Karolinska Institute, Cancer Center Karolinska, SE-17176 Stockholm (Sweden)
2011-01-14
Research highlights: {yields} SUMOylation mediates nuclear translocation of IGF-1R which activates transcription. {yields} Here we show that nuclear IGF-1R over-accumulates in tumor cells. {yields} This requires overexpression of the receptor that is a common feature in tumor cells. {yields} An increased expression of the SUMO ligase Ubc9 seems to be an involved mechanism too. -- Abstract: The insulin-like growth factor 1 receptor (IGF-1R) plays crucial roles in tumor cell growth and is overexpressed in many cancers. IGF-1R's trans-membrane kinase signaling pathways have been well characterized. Very recently, we showed that SUMOylation mediates nuclear translocation of the IGF-1R, and that nuclear IGF-1R (nIGF-1R) binds to enhancer regions and activates transcription. We identified three lysine residues in the {beta}-subunit of the receptor and that mutation of these blocks nuclear translocation and gene activation. Furthermore, accumulation of nIGF-1R was proven strongly dependent on the specific SUMO-conjugating enzyme Ubc9. Here we show that nIGF-1R originates solely from the cell membrane and that phosphorylation of the core tyrosine residues of the receptor kinase is crucial for nuclear accumulation. We also compared the levels of nIGF-1R, measured as nuclear/membrane ratios, in tumor and normal cells. We found that the breast cancer cell line MCF-7 has 13-fold higher amounts of nIGF-1R than breast epithelial cells (IME) which showed only a small amount of nIGF-1R. In comparison, the total expression of IGF-1R was only 3.7- higher in MCF-7. Comparison of several other tumor and normal cell lines showed similar tumor cell over-accumulation of nIGF-1R, exceeding the total receptor expression substantially. Ectopic overexpression (>10-fold) of the receptor increased nIGF-1R in IME cells but not to that high level as in wild type MCF-7. The levels of Ubc9 were higher in all tumor cell lines, compared to the normal cells, and this probably contributes to over
International Nuclear Information System (INIS)
Deng, Hua; Lin, Yingbo; Badin, Margherita; Vasilcanu, Daiana; Stroemberg, Thomas; Jernberg-Wiklund, Helena; Sehat, Bita; Larsson, Olle
2011-01-01
Research highlights: → SUMOylation mediates nuclear translocation of IGF-1R which activates transcription. → Here we show that nuclear IGF-1R over-accumulates in tumor cells. → This requires overexpression of the receptor that is a common feature in tumor cells. → An increased expression of the SUMO ligase Ubc9 seems to be an involved mechanism too. -- Abstract: The insulin-like growth factor 1 receptor (IGF-1R) plays crucial roles in tumor cell growth and is overexpressed in many cancers. IGF-1R's trans-membrane kinase signaling pathways have been well characterized. Very recently, we showed that SUMOylation mediates nuclear translocation of the IGF-1R, and that nuclear IGF-1R (nIGF-1R) binds to enhancer regions and activates transcription. We identified three lysine residues in the β-subunit of the receptor and that mutation of these blocks nuclear translocation and gene activation. Furthermore, accumulation of nIGF-1R was proven strongly dependent on the specific SUMO-conjugating enzyme Ubc9. Here we show that nIGF-1R originates solely from the cell membrane and that phosphorylation of the core tyrosine residues of the receptor kinase is crucial for nuclear accumulation. We also compared the levels of nIGF-1R, measured as nuclear/membrane ratios, in tumor and normal cells. We found that the breast cancer cell line MCF-7 has 13-fold higher amounts of nIGF-1R than breast epithelial cells (IME) which showed only a small amount of nIGF-1R. In comparison, the total expression of IGF-1R was only 3.7- higher in MCF-7. Comparison of several other tumor and normal cell lines showed similar tumor cell over-accumulation of nIGF-1R, exceeding the total receptor expression substantially. Ectopic overexpression (>10-fold) of the receptor increased nIGF-1R in IME cells but not to that high level as in wild type MCF-7. The levels of Ubc9 were higher in all tumor cell lines, compared to the normal cells, and this probably contributes to over-accumulation of nIGF-1R
Exploring strain-promoted 1,3-dipolar cycloadditions of end functionalized polymers
Ledin, Petr A; Kolishetti, Nagesh; Hudlikar, Manish S; Boons, Geert-Jan
2014-01-01
Strain-promoted 1,3-dipolar cycloaddition of cyclooctynes with 1,3-dipoles such as azides, nitrones, and nitrile oxides, are of interest for the functionalization of polymers. In this study, we have explored the use of a 4-dibenzocyclooctynol (DIBO)-containing chain transfer agent in reversible
CD13-positive bone marrow-derived myeloid cells promote angiogenesis, tumor growth, and metastasis.
Dondossola, Eleonora; Rangel, Roberto; Guzman-Rojas, Liliana; Barbu, Elena M; Hosoya, Hitomi; St John, Lisa S; Molldrem, Jeffrey J; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata
2013-12-17
Angiogenesis is fundamental to tumorigenesis and an attractive target for therapeutic intervention against cancer. We have recently demonstrated that CD13 (aminopeptidase N) expressed by nonmalignant host cells of unspecified types regulate tumor blood vessel development. Here, we compare CD13 wild-type and null bone marrow-transplanted tumor-bearing mice to show that host CD13(+) bone marrow-derived cells promote cancer progression via their effect on angiogenesis. Furthermore, we have identified CD11b(+)CD13(+) myeloid cells as the immune subpopulation directly regulating tumor blood vessel development. Finally, we show that these cells are specifically localized within the tumor microenvironment and produce proangiogenic soluble factors. Thus, CD11b(+)CD13(+) myeloid cells constitute a population of bone marrow-derived cells that promote tumor progression and metastasis and are potential candidates for the development of targeted antiangiogenic drugs.
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Zhu Shanshan; Zhang Hong; Matunis, Michael J.
2006-01-01
SUMOs (small ubiquitin-related modifiers) are eukaryotic proteins that are covalently conjugated to other proteins and thereby regulate a wide range of important cellular processes. The molecular mechanisms by which SUMO modification influences the functions of most target proteins and cellular processes, however, remain poorly defined. A major obstacle to investigating the effects of SUMO modification is the availability of a system for selectively inducing the modification or demodification of an individual protein. To address this problem, we have developed a procedure using the rapamycin heterodimerizer system. This procedure involves co-expression of rapamycin-binding domain fusion proteins of SUMO and candidate SUMO substrates in living cells. Treating cells with rapamycin induces a tight association between SUMO and a single SUMO substrate, thereby allowing specific downstream effects to be analyzed. Using RanGAP1 as a model SUMO substrate, the heterodimerizer system was used to investigate the molecular mechanism by which SUMO modification targets RanGAP1 from the cytoplasm to nuclear pore complexes (NPCs). Our results revealed a dual role for Ubc9 in targeting RanGAP1 to NPCs: In addition to conjugating SUMO-1 to RanGAP1, Ubc9 is also required to form a stable ternary complex with SUMO-1 modified RanGAP1 and Nup358. As illustrated by our studies, the rapamycin heterodimerizer system represents a novel tool for studying the molecular effects of SUMO modification
Tsai, Ching-Yi; Li, Faith C H; Wu, Carol H Y; Chang, Alice Y W; Chan, Samuel H H
2016-09-22
Small ubiquitin-related modifier (SUMO) is a group of proteins that participates in post-translational modifications. One known SUMO target is the transcription factor nuclear factor-kB (NF-kB) that plays a pivotal role in many disease processes; sumoylation inactivates NF-kB by conjugation with inhibitors of NF-kB (IkB). Our laboratory demonstrated previously that transcriptional upregulation of nitric oxide synthase II (NOS II) by NF-kB, leading to nitrosative stress by the formation of peroxynitrite in the rostral ventrolateral medulla (RVLM), underpins the defunct brain stem cardiovascular regulation that precedes brain death. Based on an experimental endotoxemia model, this study evaluated the hypothesis that sumoylation plays a pro-life role in brain death by interacting with the NF-kB/NOS II/peroxynitrite signaling pathway in the RVLM. In Sprague-Dawley rats, intravenous administration of Escherichia coli lipopolysaccharide (LPS; 10 mg kg -1 ) elicited an augmentation of SUMO-1 and ubiquitin-conjugase 9 (Ubc9) mRNA or protein levels, alongside SUMO-1-conjugated proteins in the RVLM. Immunoneutralization of SUMO-1 or Ubc9 in the RVLM significantly potentiated the already diminished sumoylation of IkBα and intensified NF-kB activation and NOS II/peroxynitrite expression in this brain stem substrate, together with exacerbated fatality, cardiovascular depression and reduction of an experimental index of a life-and-death signal detected from arterial pressure that disappears in comatose patients signifying failure of brain stem cardiovascular regulation before brain death. We conclude that sumoylation of IkB in the RVLM ameliorates the defunct brain stem cardiovascular regulation that underpins brain death in our experimental endotoxemia modal by reducing nitrosative stress via inhibition of IkB degradation that diminishes the induction of the NF-kB/NOS II/peroxynitrite signaling cascade.
ABERRANT METHYLATION OF THE PROMOTER OF APC, CDH13 AND MGMT GENES IN COLORECTAL CANCER PATIENTS
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O. I. Kit
2016-01-01
Full Text Available Aberrant methylation of gene promoter regions is the main epigenetic change characterizing colorectal cancer. Methylation levels of 42 CpG-sites of promoter regions of the MGMT, APC and CDH13 genes in colorectal cancer were studied in comparison with methylation levels of the adjacent normal tissue in 25 patients. Pyrosequencing showed an increase in methylation levels of promoter regions of the MGMT, APC and CDH13 genes in tumor samples by 3 to 5 times. These tumor samples were screened for activating SNP-mutations in the KRAS (40 %, NRAS (0 % and BRAF (0 % oncogenes. SNP-mutations in the KRAS gene were accompanied by hypermethylation of one or more promoters of the studied genes. Association of this epigenetic index with tumor metastasis was proved. The data on an increase in methylation of the promoter regions of oncosupressor genes can be used as sensitive prognostic markers of progression and metastasis of colorectal cancer.
ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site.
Abbruzzese, Genevieve; Becker, Sarah F; Kashef, Jubin; Alfandari, Dominique
2016-07-15
The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell-cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. Copyright © 2015. Published by Elsevier Inc.
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Dengwei Jue
2018-03-01
Full Text Available Ubiquitin-conjugating enzymes (E2s or UBC enzymes play vital roles in plant development and combat various biotic and abiotic stresses. Longan (Dimocarpus longan Lour. is an important fruit tree in the subtropical region of Southeast Asia and Australia; however the characteristics of the UBC gene family in longan remain unknown. In this study, 40 D. longan UBC genes (DlUBCs, which were classified into 15 groups, were identified in the longan genome. An RNA-seq based analysis showed that DlUBCs showed distinct expression in nine longan tissues. Genome-wide RNA-seq and qRT-PCR based gene expression analysis revealed that 11 DlUBCs were up- or down-regualted in the cultivar “Sijimi” (SJ, suggesting that these genes may be important for flower induction. Finally, qRT-PCR analysis showed that the mRNA levels of 13 DlUBCs under SA (salicylic acid treatment, seven under methyl jasmonate (MeJA treatment, 27 under heat treatment, and 16 under cold treatment were up- or down-regulated, respectively. These results indicated that the DlUBCs may play important roles in responses to abiotic stresses. Taken together, our results provide a comprehensive insight into the organization, phylogeny, and expression patterns of the longan UBC genes, and therefore contribute to the greater understanding of their biological roles in longan.
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Kun-Peng Xie
2017-05-01
Full Text Available AIM: To investigate the effects of apelin-13 on proliferation, migration and capillary-like tube formation of a monkey choroid / retinal endothelial cell line, RF/6A, to clarify whether apelin-13 could promote retinal angiogenesis in vitro.METHODS: RF/6A cells in good conditions were administrated with DMSO(the control group, apelin-13 at 0.1μmol/L(low dose groupor apelin-13 at 1μmol/L(high dose group. Cell proliferation, migration and capillary-like tube formation were detected by using the MTT assay, scratch assay and matrigel assay, respectively, at 24h after plating the cells. RESULTS: Cell proliferation was promoted in both low and high dose apelin-13 groups compared to the control cells(PPPCONCLUSION: Apelin-13 could obviously promote the angiogenesis capacity of RF/6A cells, suggesting that apelin-13 was an important pro-angiogenic factor in retinal endothelial cells.
Ho, Yik-Khuan; Zhi, Huijun; Bowlin, Tara; Dorjbal, Batsukh; Philip, Subha; Zahoor, Muhammad Atif; Shih, Hsiu-Ming; Semmes, Oliver John; Schaefer, Brian; Glover, J N Mark; Giam, Chou-Zen
2015-08-01
Human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, impacts a multitude of cellular processes, including I-κB kinase (IKK)/NF-κB signaling, DNA damage repair, and mitosis. These activities of Tax have been implicated in the development of adult T-cell leukemia (ATL) in HTLV-1-infected individuals, but the underlying mechanisms remain obscure. IKK and its upstream kinase, TGFβ-activated kinase 1 (TAK1), contain ubiquitin-binding subunits, NEMO and TAB2/3 respectively, which interact with K63-linked polyubiquitin (K63-pUb) chains. Recruitment to K63-pUb allows cross auto-phosphorylation and activation of TAK1 to occur, followed by TAK1-catalyzed IKK phosphorylation and activation. Using cytosolic extracts of HeLa and Jurkat T cells supplemented with purified proteins we have identified ubiquitin E3 ligase, ring finger protein 8 (RNF8), and E2 conjugating enzymes, Ubc13:Uev1A and Ubc13:Uev2, to be the cellular factors utilized by Tax for TAK1 and IKK activation. In vitro, the combination of Tax and RNF8 greatly stimulated TAK1, IKK, IκBα and JNK phosphorylation. In vivo, RNF8 over-expression augmented while RNF8 ablation drastically reduced canonical NF-κB activation by Tax. Activation of the non-canonical NF-κB pathway by Tax, however, is unaffected by the loss of RNF8. Using purified components, we further demonstrated biochemically that Tax greatly stimulated RNF8 and Ubc13:Uev1A/Uev2 to assemble long K63-pUb chains. Finally, co-transfection of Tax with increasing amounts of RNF8 greatly induced K63-pUb assembly in a dose-dependent manner. Thus, Tax targets RNF8 and Ubc13:Uev1A/Uev2 to promote the assembly of K63-pUb chains, which signal the activation of TAK1 and multiple downstream kinases including IKK and JNK. Because of the roles RNF8 and K63-pUb chains play in DNA damage repair and cytokinesis, this mechanism may also explain the genomic instability of HTLV-1-transformed T cells and ATL cells.
SCP4 Promotes Gluconeogenesis Through FoxO1/3a Dephosphorylation.
Cao, Jin; Yu, Yi; Zhang, Zhengmao; Chen, Xi; Hu, Zhaoyong; Tong, Qiang; Chang, Jiang; Feng, Xin-Hua; Lin, Xia
2018-01-01
FoxO1 and FoxO3a (collectively FoxO1/3a) proteins regulate a wide array of cellular processes, including hepatic gluconeogenesis. Phosphorylation of FoxO1/3a is a key event that determines its subcellular location and transcriptional activity. During glucose synthesis, the activity of FoxO1/3a is negatively regulated by Akt-mediated phosphorylation, which leads to the cytoplasmic retention of FoxO1/3a. However, the nuclear phosphatase that directly regulates FoxO1/3a remains to be identified. In this study, we discovered a nuclear phosphatase, SCP4/CTDSPL2 (SCP4), that dephosphorylated FoxO1/3a and promoted FoxO1/3a transcription activity. We found that SCP4 enhanced the transcription of FoxO1/3a target genes encoding PEPCK1 and G6PC, key enzymes in hepatic gluconeogenesis. Ectopic expression of SCP4 increased, while knockdown of SCP4 inhibited, glucose production. Moreover, we demonstrated that gene ablation of SCP4 led to hypoglycemia in neonatal mice. Consistent with the positive role of SCP4 in gluconeogenesis, expression of SCP4 was regulated under pathophysiological conditions. SCP4 expression was induced by glucose deprivation in vitro and in vivo and was elevated in obese mice caused by genetic (A vy ) and dietary (high-fat) changes. Thus, our findings provided experimental evidence that SCP4 regulates hepatic gluconeogenesis and could serve as a potential target for the prevention and treatment of diet-induced glucose intolerance and type 2 diabetes. © 2017 by the American Diabetes Association.
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Dongli Wan
Full Text Available Stipa grandis P. Smirn. is a dominant plant species in the typical steppe of the Xilingole Plateau of Inner Mongolia. Selection of suitable reference genes for the quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR is important for gene expression analysis and research into the molecular mechanisms underlying the stress responses of S. grandis. In the present study, 15 candidate reference genes (EF1 beta, ACT, GAPDH, SamDC, CUL4, CAP, SNF2, SKIP1, SKIP5, SKIP11, UBC2, UBC15, UBC17, UCH, and HERC2 were evaluated for their stability as potential reference genes for qRT-PCR under different stresses. Four algorithms were used: GeNorm, NormFinder, BestKeeper, and RefFinder. The results showed that the most stable reference genes were different under different stress conditions: EF1beta and UBC15 during drought and salt stresses; ACT and GAPDH under heat stress; SKIP5 and UBC17 under cold stress; UBC15 and HERC2 under high pH stress; UBC2 and UBC15 under wounding stress; EF1beta and UBC17 under jasmonic acid treatment; UBC15 and CUL4 under abscisic acid treatment; and HERC2 and UBC17 under salicylic acid treatment. EF1beta and HERC2 were the most suitable genes for the global analysis of all samples. Furthermore, six target genes, SgPOD, SgPAL, SgLEA, SgLOX, SgHSP90 and SgPR1, were selected to validate the most and least stable reference genes under different treatments. Our results provide guidelines for reference gene selection for more accurate qRT-PCR quantification and will promote studies of gene expression in S. grandis subjected to environmental stress.
Gα12/13 signaling promotes cervical cancer invasion through the RhoA/ROCK-JNK signaling axis
International Nuclear Information System (INIS)
Yuan, Bo; Cui, Jinquan; Wang, Wuliang; Deng, Kehong
2016-01-01
Several reports have indicated a role for the members of the G12 family of heterotrimeric G proteins (Gα12 and Gα13) in oncogenesis and tumor cell growth. The aims of the present study were to evaluate the role of G12 signaling in cervical cancer. We demonstrated that expression of the G12 proteins was highly upregulated in cervical cancer cells. Additionally, expression of the activated forms of Gα12/Gα13 but not expression of activated Gαq induced cell invasion through the activation of the RhoA family of G proteins, but had no effect on cell proliferation in the cervical cancer cells. Inhibition of G12 signaling by expression of the RGS domain of the p115-Rho-specific guanine nucleotide exchange factor (p115-RGS) blocked thrombin-stimulated cell invasion, but did not inhibit cell proliferation in cervical cells, whereas the inhibition of Gαq (RGS2) had no effect. Furthermore, G12 signaling was able to activate Rho proteins, and this stimulation was inhibited by p115-RGS, and Gα12-induced invasion was blocked by an inhibitor of RhoA/B/C (C3 toxin). Pharmacological inhibition of JNK remarkably decreased G12-induced JNK activation. Both a JNK inhibitor (SP600125) and a ROCK inhibitor (Y27632) reduced G12-induced JNK and c-Jun activation, and markedly inhibited G12-induced cellular invasion. Collectively, these findings demonstrate that stimulation of G12 proteins is capable of promoting invasion through RhoA/ROCK-JNK activation. -- Highlights: •Gα12/Gα13 is upregulated in cervical cancer cell lines. •Gα12/Gα13 is not involved in cervical cancer cell proliferation. •Gα12/Gα13 promotes cervical cancer cell invasion. •The role of Rho G proteins in G12-promoted cervical cancer cell invasion. •G12 promotes cell invasion through activation of the ROCK-JNK signaling axis.
CD13 Promotes Mesenchymal Stem Cell-mediated regeneration of ischemic muscle
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M. Mamunur eRahman
2014-01-01
Full Text Available Mesenchymal stem cells (MSCs are multipotent, tissue-resident cells that can facilitate tissue regeneration and thus show great promise as potential therapeutic agents. Functional MSCs have been isolated and characterized from a wide array of adult tissues and are universally identified by the shared expression of a core panel of MSCs markers. One of these markers is the multifunctional cell surface peptidase CD13 that has been shown to be expressed on human and murine MSCs from many tissues. To investigate whether this universal expression indicates a functional role for CD13 in MSC biology we isolated, expanded and characterized MSCs from bone marrow of wild type (WT and CD13KO mice. Characterization of these cells demonstrated that both WT and CD13KO MSCs expressed the full complement of MSC markers (CD29, CD44, CD49e, CD105, Sca1, showed comparable proliferation rates and were capable of differentiating toward the adipogenic and osteogenic lineages. However, MSCs lacking CD13 were unable to differentiate into vascular cells, consistent with our previous characterization of CD13 as an angiogenic regulator. Compared to WT MSCs, adhesion and migration on various extracellular matrices of CD13KO MSCs were significantly impaired, which correlated with decreased phospho-FAK levels and cytoskeletal alterations. Crosslinking human MSCs with activating CD13 antibodies increased cell adhesion to endothelial monolayers and induced FAK activation in a time dependent manner. In agreement with these in vitro data, intramuscular injection of CD13KO MSCs in a model of severe ischemic limb injury resulted in significantly poorer perfusion, decreased ambulation, increased necrosis and impaired vascularization compared to those receiving WT MSCs. This study suggests that CD13 regulates FAK activation to promote MSC adhesion and migration, thus contributing to MSC-mediated tissue repair. CD13 may present a viable target to enhance the efficacy of mesenchymal
Lai, Alex L.; Tamm, Lukas K.
2010-01-01
Our previous studies showed that an angled boomerang-shaped structure of the influenza hemagglutinin (HA) fusion domain is critical for virus entry into host cells by membrane fusion. Because the acute angle of ∼105° of the wild-type fusion domain promotes efficient non-leaky membrane fusion, we asked whether different angles would still support fusion and thus facilitate virus entry. Here, we show that the G13A fusion domain mutant produces a new leaky fusion phenotype. The mutant fusion domain structure was solved by NMR spectroscopy in a lipid environment at fusion pH. The mutant adopted a boomerang structure similar to that of wild type but with a shallower kink angle of ∼150°. G13A perturbed the structure of model membranes to a lesser degree than wild type but to a greater degree than non-fusogenic fusion domain mutants. The strength of G13A binding to lipid bilayers was also intermediate between that of wild type and non-fusogenic mutants. These membrane interactions provide a clear link between structure and function of influenza fusion domains: an acute angle is required to promote clean non-leaky fusion suitable for virus entry presumably by interaction of the fusion domain with the transmembrane domain deep in the lipid bilayer. A shallower angle perturbs the bilayer of the target membrane so that it becomes leaky and unable to form a clean fusion pore. Mutants with no fixed boomerang angle interacted with bilayers weakly and did not promote any fusion or membrane perturbation. PMID:20826788
Using social media to promote international student partnerships.
Garrett, Bernard M; Cutting, Roger
2012-11-01
This paper describes a project to establish and evaluate online study partnerships, using social networking applications, between final year Canadian nursing students at the University of British Columbia (UBC) and second year undergraduate science education students at the University of Plymouth (UoP) in the UK. The project took place between 2009 and 2010 and evaluated the use of social networking applications with international interdisciplinary partnerships between Canadian and UK students. A multi-method evaluation strategy incorporating questionnaires, online focus groups and web analytics was used to explore the value of social media to promote the exchange of ideas and discussion of scientific philosophy in different contexts, between students working in disciplines with differing philosophical perspectives principally modern/post-modern, quantitative/qualitative, empirical/theoretical. This project resulted in a very successful collaborative partnership between UK and Canadian students. Copyright © 2012 Elsevier Ltd. All rights reserved.
Case report: unicameral bone cysts in a young patient with acquired generalized lipodystrophy.
Gregory, James M; Arkader, Alexandre; Bokhari, Aqiba; Bothari, Aqiba; Dormans, John P
2010-05-01
We report the case of a 13-year-old boy with bilateral distal femoral unicameral bone cysts (UBCs) associated with acquired generalized lipodystrophy. As opposed to congenital generalized lipodystrophy, cystic bone lesions in acquired generalized lipodystrophy are rare. After radiographic and histologic confirmation of the UBCs, we performed percutaneous intramedullary decompression, curettage, and grafting. UBCs can be an important manifestation of acquired generalized lipodystrophy. Cystic bone lesions appear to be less common in acquired generalized lipodystrophy than in congenital generalized lipodystrophy, and intramedullary adipose tissue loss may be a predisposing factor for the development of bone lesions in patients with acquired generalized lipodystrophy. When evaluating a patient with lipodystrophy, doctors should recognize the clinical course may include the development of UBCs.
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Li Qingdi
2012-06-01
Full Text Available Abstract Background The selection of stable and suitable reference genes for real-time quantitative PCR (RT-qPCR is a crucial prerequisite for reliable gene expression analysis under different experimental conditions. The present study aimed to identify reference genes as internal controls for gene expression studies by RT-qPCR in azole-stimulated Candida glabrata. Results The expression stability of 16 reference genes under fluconazole stress was evaluated using fold change and standard deviation computations with the hkgFinder tool. Our data revealed that the mRNA expression levels of three ribosomal RNAs (RDN5.8, RDN18, and RDN25 remained stable in response to fluconazole, while PGK1, UBC7, and UBC13 mRNAs showed only approximately 2.9-, 3.0-, and 2.5-fold induction by azole, respectively. By contrast, mRNA levels of the other 10 reference genes (ACT1, EF1α, GAPDH, PPIA, RPL2A, RPL10, RPL13A, SDHA, TUB1, and UBC4 were dramatically increased in C. glabrata following antifungal treatment, exhibiting changes ranging from 4.5- to 32.7-fold. We also assessed the expression stability of these reference genes using the 2-ΔΔCT method and three other software packages. The stability rankings of the reference genes by geNorm and the 2-ΔΔCT method were identical to those by hkgFinder, whereas the stability rankings by BestKeeper and NormFinder were notably different. We then validated the suitability of six candidate reference genes (ACT1, PGK1, RDN5.8, RDN18, UBC7, and UBC13 as internal controls for ten target genes in this system using the comparative CT method. Our validation experiments passed for all six reference genes analyzed except RDN18, where the amplification efficiency of RDN18 was different from that of the ten target genes. Finally, we demonstrated that the relative quantification of target gene expression varied according to the endogenous control used, highlighting the importance of the choice of internal controls in such
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Choi Chan
2010-05-01
Full Text Available Abstract Background Androgen signaling plays a critical role in the development of prostate cancer and its progression. However, androgen-independent prostate cancer cells emerge after hormone ablation therapy, resulting in significant clinical problems. We have previously demonstrated that the HOXB13 homeodomain protein functions as a prostate cancer cell growth suppressor by inhibiting androgen-mediated signals. However, the role of the HOXB13 in androgen-independent growth of prostate cancer cells remains unexplained. Results In this report, we first demonstrated that HOXB13 was highly overexpressed in hormone-refractory tumors compared to tumors without prostate-specific antigen after initial treatment. Functionally, in an androgen-free environment minimal induction of HOXB13 in LNCaP prostate cancer cells, to the level of the normal prostate, markedly promoted cell proliferation while suppression inhibited cell proliferation. The HOXB13-mediated cell growth promotion in the absence of androgen, appears to be mainly accomplished through the activation of RB-E2F signaling by inhibiting the expression of the p21waf tumor suppressor. Indeed, forced expression of HOXB13 dramatically decreased expression of p21waf; this inhibition largely affected HOXB13-mediated promotion of E2F signaling. Conclusions Taken together, the results of this study demonstrated the presence of a novel pathway that helps understand androgen-independent survival of prostate cancer cells. These findings suggest that upregulation of HOXB13 is associated with an additive growth advantage of prostate cancer cells in the absence of or low androgen concentrations, by the regulation of p21-mediated E2F signaling.
International Nuclear Information System (INIS)
Heriyanto, Heri; Widya Ernayati, K.; Umam, Chairul; Margareta, Nita
2015-01-01
UBC (upgrading brown coal) is a method of improving the quality of coal by using oil as an additive. Through processing in the oil media, not just the calories that increase, but there is also water repellent properties and a decrease in the tendency of spontaneous combustion of coal products produced. The results showed a decrease in the water levels of natural coal bayah reached 69%, increase in calorific value reached 21.2%. Increased caloric value and reduced water content caused by the water molecules on replacing seal the pores of coal by oil and atoms C on the oil that is bound to increase the percentage of coal carbon. As a result of this experiment is, the produced coal has better calorific value, the increasing of this new calorific value up to 23.8% with the additive waste lubricant, and the moisture content reduced up to 69.45%
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Heriyanto, Heri [Chemical Engineering of University Sultan AgengTirtayasa, Indonesia Email: herfais@yahoo.com (Indonesia); Widya Ernayati, K.; Umam, Chairul; Margareta, Nita
2015-12-29
UBC (upgrading brown coal) is a method of improving the quality of coal by using oil as an additive. Through processing in the oil media, not just the calories that increase, but there is also water repellent properties and a decrease in the tendency of spontaneous combustion of coal products produced. The results showed a decrease in the water levels of natural coal bayah reached 69%, increase in calorific value reached 21.2%. Increased caloric value and reduced water content caused by the water molecules on replacing seal the pores of coal by oil and atoms C on the oil that is bound to increase the percentage of coal carbon. As a result of this experiment is, the produced coal has better calorific value, the increasing of this new calorific value up to 23.8% with the additive waste lubricant, and the moisture content reduced up to 69.45%.
Mural, Ravi V; Liu, Yao; Rosebrock, Tracy R; Brady, Jennifer J; Hamera, Sadia; Connor, Richard A; Martin, Gregory B; Zeng, Lirong
2013-09-01
The activation of an immune response in tomato (Solanum lycopersicum) against Pseudomonas syringae relies on the recognition of E3 ligase-deficient forms of AvrPtoB by the host protein kinase, Fen. To investigate the mechanisms by which Fen-mediated immunity is regulated, we characterize in this study a Fen-interacting protein, Fni3, and its cofactor, S. lycoperiscum Uev (Suv). Fni3 encodes a homolog of the Ubc13-type ubiquitin-conjugating enzyme that catalyzes exclusively Lys-63-linked ubiquitination, whereas Suv is a ubiquitin-conjugating enzyme variant. The C-terminal region of Fen was necessary for interaction with Fni3, and this interaction was required for cell death triggered by overexpression of Fen in Nicotiana benthamiana leaves. Fni3 was shown to be an active E2 enzyme, but Suv displayed no ubiquitin-conjugating activity; Fni3 and Suv together directed Lys-63-linked ubiquitination. Decreased expression of Fni3, another tomato Ubc13 homolog, Sl-Ubc13-2, or Suv in N. benthamiana leaves diminished cell death associated with Fen-mediated immunity and cell death elicited by several other resistance (R) proteins and their cognate effectors. We also discovered that coexpression of Fen and other R proteins/effectors with a Fni3 mutant that is compromised for ubiquitin-conjugating activity diminished the cell death. These results suggest that Fni3/Sl-Ubc13-2 and Suv regulate the immune response mediated by Fen and other R proteins through Lys-63-linked ubiquitination.
Long, Tran Khanh; Son, Phung Xuan; Giang, Kim Bao; Hai, Phan Thi; Huyen, Doan Thi Thu; Khue, Luong Ngoc; Nga, Pham Thi Quynh; Lam, Nguyen Tuan; Minh, Hoang Van; Huong, Le Thi Thanh
2016-01-01
Evidence shows that tobacco advertising and promotion activities may increase tobacco consumption and usage, especially in youth. Despite the regulation on prohibiting advertisement of any tobacco product, tobacco advertisement and promotion activities are still common in Vietnam. This article presents current exposure to tobacco advertising and promotion (TAP) among school children aged 13 to 15 years in Vietnam in 2014 and potential influencing factors. Data from the Global Youth Tobacco Survey 2014 in Vietnam covering 3,430 school aged children were used. Both descriptive and analytical statistics were carried out with Stata 13 statistical software. Binary logistic regression was applied to explain the exposure to TAP among youth and examine relationships with individual factors. A significance level of padvertising or promotion. Wearing or otherwise using products related to tobacco was the most exposure TAP type reported by students (22.3%). The internet (22.1), points of sales (19.2) and social events (11.5) were three places that students aged 13-15 frequently were exposed to TAP. Binary logistic results showed that gender (female vs male) (OR = 0.61, 95%CI: 0.52 - 0.71), susceptibility to smoking (OR = 2.12, 95%CI: 1.53 - 2.92), closest friends' smoked (OR = 1.43, 95%CI: 1.2 - 1.7) and parents smoking status (OR = 2.83, 95%CI: 1.6 - 5.01) were significantly associated with TAP exposure among school-aged children. The research findings should contribute to effective implementation of measures for preventing and controlling tobacco use among students aged 13-15 in Viet Nam.
Clinical factors affecting pathological fracture and healing of unicameral bone cysts.
Urakawa, Hiroshi; Tsukushi, Satoshi; Hosono, Kozo; Sugiura, Hideshi; Yamada, Kenji; Yamada, Yoshihisa; Kozawa, Eiji; Arai, Eisuke; Futamura, Naohisa; Ishiguro, Naoki; Nishida, Yoshihiro
2014-05-17
Unicameral bone cyst (UBC) is the most common benign lytic bone lesion seen in children. The aim of this study is to investigate clinical factors affecting pathological fracture and healing of UBC. We retrospectively reviewed 155 UBC patients who consulted Nagoya musculoskeletal oncology group hospitals in Japan. Sixty of the 155 patients had pathological fracture at presentation. Of 141 patients with follow-up periods exceeding 6 months, 77 were followed conservatively and 64 treated by surgery. The fracture risk was significantly higher in the humerus than other bones. In multivariate analysis, ballooning of bone, cyst in long bone, male sex, thin cortical thickness and multilocular cyst were significant adverse prognostic factors for pathological fractures at presentation. The healing rates were 30% and 83% with observation and surgery, respectively. Multivariate analysis revealed that fracture at presentation and history of biopsy were good prognostic factors for healing of UBC in patients under observation. The present results suggest that mechanical disruption of UBC such as fracture and biopsy promotes healing, and thus watchful waiting is indicated in these patients, whereas patients with poor prognostic factors for fractures should be considered for surgery.
Downregulation of SPINK13 Promotes Metastasis by Regulating uPA in Ovarian Cancer Cells
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Shengyun Cai
2018-02-01
Full Text Available Background/Aims: Ovarian cancer (OC is the fifth leading cause of cancer-related death in women, and it is difficult to diagnose at an early stage. The purpose of this study was to explore the prognostic biological markers of OC. Methods: Univariate Cox regression analysis was used to identify genes related to OC prognosis from the Cancer Genome Atlas(TCGA database. Immunohistochemistry was used to analyse the level of SPINK13 in OC and normal tissues. Cell proliferation, apoptosis and invasion were performed using MTT assay, flow cytometric analysis and Transwell assay, respectively. Results: We identified the Kazal-type serine protease inhibitor-13 (SPINK13 gene related to OC prognosis from the Cancer Genome Atlas (TCGA database by univariate Cox regression analysis. Overexpression of SPINK13 was associated with higher overall survival rate in OC patients. Immunohistochemistry showed that the level of SPINK13 protein was significantly lower in OC tissues than in normal tissues (P < 0.05.In vitro experiments showed that the overexpression of SPINK13 inhibited cellular proliferation and promoted apoptosis. Moreover, SPINK13 inhibited cell migration and epithelial to mesenchymal transition (EMT. SPINK13 was found to inhibit the expression of urokinase-type plasminogen activator (uPA, while recombinant uPA protein could reverse the inhibitory effect of SPINK13 on OC metastasis. Conclusion: These results indicate that SPINK13 functions as a tumour suppressor. The role of SPINK13 in cellular proliferation, apoptosis and migration is uPA dependent, and SPINK13 may be used as a potential biomarker for diagnosis and targeted therapy in OC.
MR imaging of simple bone cysts in children: not so simple
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Margau, R. [Faculty of Medicine, University of Toronto, Toronto, ON (Canada); Babyn, P. [Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, ON (Canada); Cole, W.; Lee, F. [Division of Orthopaedic Surgery, Department of Surgery, The Hospital for Sick Children and University of Toronto, Toronto, ON (Canada); Smith, C. [Department of Pathology, The Hospital for Sick Children and University of Toronto, Toronto, ON (Canada)
2000-08-01
Objective. The unicameral bone cyst (UBC) is a common cystic bone lesion seen in children. We review and summarize its MR findings, focusing on their appearance following contrast enhancement, and correlating them to known histologic features of UBC. Subjects and methods. A retrospective review of 20 cases (13 boys, 7 girls; age range, 1-17 years; mean age, 8.9) diagnosed as UBC was conducted. Clinical histories, radiographic and MR features, follow-up data, and available pathologic findings were noted. Results. At initial presentation 18 (90 %) of the patients with UBC had a history of acute or remote pathologic fracture. Cysts with history of fracture displayed heterogeneous fluid signals on T1- (n = 9, 50 %), and T2-weighted (n = 15, 83 %) MR images. Gadolinium-enhanced images were obtained in 15 of the 18 UBC cases with history of previous fracture. All showed enhancement with focal, thick peripheral, heterogeneous, or subcortical patterns. Focal nodules of homogeneous enhancement (diameter > 1 cm) within the UBC (n = 5) correlated with areas of ground-glass opacification on plain film. Other interesting MR features were fluid-fluid levels (n = 11), ''fallen-leaf'' sign (n = 1), soft-tissue changes (n = 2), and detection of septations not seen on plain film (n = 2). Conclusion. UBCs frequently appear complicated on MR imaging, with heterogeneous fluid signals and regions of nodular and thick peripheral enhancement related to previous pathologic fracture and early healing. (orig.)
MR imaging of simple bone cysts in children: not so simple
International Nuclear Information System (INIS)
Margau, R.; Babyn, P.; Cole, W.; Lee, F.; Smith, C.
2000-01-01
Objective. The unicameral bone cyst (UBC) is a common cystic bone lesion seen in children. We review and summarize its MR findings, focusing on their appearance following contrast enhancement, and correlating them to known histologic features of UBC. Subjects and methods. A retrospective review of 20 cases (13 boys, 7 girls; age range, 1-17 years; mean age, 8.9) diagnosed as UBC was conducted. Clinical histories, radiographic and MR features, follow-up data, and available pathologic findings were noted. Results. At initial presentation 18 (90 %) of the patients with UBC had a history of acute or remote pathologic fracture. Cysts with history of fracture displayed heterogeneous fluid signals on T1- (n = 9, 50 %), and T2-weighted (n = 15, 83 %) MR images. Gadolinium-enhanced images were obtained in 15 of the 18 UBC cases with history of previous fracture. All showed enhancement with focal, thick peripheral, heterogeneous, or subcortical patterns. Focal nodules of homogeneous enhancement (diameter > 1 cm) within the UBC (n = 5) correlated with areas of ground-glass opacification on plain film. Other interesting MR features were fluid-fluid levels (n = 11), ''fallen-leaf'' sign (n = 1), soft-tissue changes (n = 2), and detection of septations not seen on plain film (n = 2). Conclusion. UBCs frequently appear complicated on MR imaging, with heterogeneous fluid signals and regions of nodular and thick peripheral enhancement related to previous pathologic fracture and early healing. (orig.)
Mural, Ravi V.; Liu, Yao; Rosebrock, Tracy R.; Brady, Jennifer J.; Hamera, Sadia; Connor, Richard A.; Martin, Gregory B.; Zeng, Lirong
2013-01-01
The activation of an immune response in tomato (Solanum lycopersicum) against Pseudomonas syringae relies on the recognition of E3 ligase–deficient forms of AvrPtoB by the host protein kinase, Fen. To investigate the mechanisms by which Fen-mediated immunity is regulated, we characterize in this study a Fen-interacting protein, Fni3, and its cofactor, S. lycoperiscum Uev (Suv). Fni3 encodes a homolog of the Ubc13-type ubiquitin-conjugating enzyme that catalyzes exclusively Lys-63–linked ubiquitination, whereas Suv is a ubiquitin-conjugating enzyme variant. The C-terminal region of Fen was necessary for interaction with Fni3, and this interaction was required for cell death triggered by overexpression of Fen in Nicotiana benthamiana leaves. Fni3 was shown to be an active E2 enzyme, but Suv displayed no ubiquitin-conjugating activity; Fni3 and Suv together directed Lys-63–linked ubiquitination. Decreased expression of Fni3, another tomato Ubc13 homolog, Sl-Ubc13-2, or Suv in N. benthamiana leaves diminished cell death associated with Fen-mediated immunity and cell death elicited by several other resistance (R) proteins and their cognate effectors. We also discovered that coexpression of Fen and other R proteins/effectors with a Fni3 mutant that is compromised for ubiquitin-conjugating activity diminished the cell death. These results suggest that Fni3/Sl-Ubc13-2 and Suv regulate the immune response mediated by Fen and other R proteins through Lys-63–linked ubiquitination. PMID:24076975
Successful treatment of unicameral bone cyst by single percutaneous injection of alpha-BSM.
Thawrani, Dinesh; Thai, Chia Che; Welch, Robert D; Copley, Lawson; Johnston, Charles E
2009-01-01
Unicameral bone cyst (UBC) is a benign bone lesion, recognized for its high rate of recurrence and need for repeat procedures to achieve healing. We hypothesized that the osteoconductive material apatitic calcium phosphate (alpha-BSM) could be effective in filling and stimulating resolution of UBC. The purpose of this study was to evaluate clinical and radiographic outcomes of UBC treated by a single injection of alpha-BSM. Thirteen patients (6 male, 7 female) with a mean age of 10.5 years, underwent single percutaneous injection of alpha-BSM for presumed UBC. The aspiration of the cysts was followed by vigorous saline lavage using 2 wide bore needles to disrupt the cyst walls. alpha-BSM "paste" was then injected under fluoroscopic guidance. Radiographs were digitized to measure cystic area (millimeter squares) on 2 orthogonal views. Healing was rated according to a modified Neer outcome grading system. Nine of the 13 patients had had pathologic fractures in the past. Eleven of the 13 patients had had past unsuccessful treatment: multiple steroid injections in 6, curettage and bone grafting in 3, and bone marrow and demineralized bone matrix (Grafton) injection in 2. Five cysts were grade 1 (healed 100%), 6 grade 2 (healed >50%), 2 grade 3 (healed <50% with increased cortical thickness), and none grade 4 (recurrence/enlargement). The average resolution of cystic area in 11/13 cysts was 85.7% at final follow-up of 35.8 months (P=0.0001) with 2.8 mm of average gain in cortical thickness (P=0.0018). None of the 13 lesions required an additional procedure or repeat injection. All patients were clinically asymptomatic at latest follow-up. This is the first study quantifying cyst resolution objectively according to actual decrease in area (millimeter squares). A single injection of alpha-BSM is a safe, minimally invasive and efficacious method to treat UBC in the pediatric population.
Kawaguchi, Yuka; Nariki, Hiroaki; Kawamoto, Naoko; Kanehiro, Yuichi; Miyazaki, Satoshi; Suzuki, Mari; Magari, Masaki; Tokumitsu, Hiroshi; Kanayama, Naoki
2017-04-01
Activation-induced cytidine deaminase (AID) is essential for diversification of the Ig variable region (IgV). AID is excluded from the nucleus, where it normally functions. However, the molecular mechanisms responsible for regulating AID localization remain to be elucidated. The SR-protein splicing factor SRSF1 is a nucleocytoplasmic shuttling protein, a splicing isoform of which called SRSF1-3, has previously been shown to contribute to IgV diversification in chicken DT40 cells. In this study, we examined whether SRSF1-3 functions in IgV diversification by promoting nuclear localization of AID. AID expressed alone was localized predominantly in the cytoplasm. In contrast, co-expression of AID with SRSF1-3 led to the nuclear accumulation of both AID and SRSF1-3 and the formation of a protein complex that contained them both, although SRSF1-3 was dispensable for nuclear import of AID. Expression of either SRSF1-3 or a C-terminally-truncated AID mutant increased IgV diversification in DT40 cells. However, overexpression of exogenous SRSF1-3 was unable to further enhance IgV diversification in DT40 cells expressing the truncated AID mutant, although SRSF1-3 was able to form a protein complex with the AID mutant. These results suggest that SRSF1-3 promotes nuclear localization of AID probably by forming a nuclear protein complex, which might stabilize nuclear AID and induce IgV diversification in an AID C-terminus-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.
Zhao, Wei; Chang, Cunjie; Cui, Yangyan; Zhao, Xiaozhi; Yang, Jun; Shen, Lan; Zhou, Ji; Hou, Zhibo; Zhang, Zhen; Ye, Changxiao; Hasenmayer, Donald; Perkins, Robert; Huang, Xiaojing; Yao, Xin; Yu, Like; Huang, Ruimin; Zhang, Dianzheng; Guo, Hongqian; Yan, Jun
2014-04-18
Cancer cell proliferation is a metabolically demanding process, requiring high glycolysis, which is known as "Warburg effect," to support anabolic growth. Steroid receptor coactivator-3 (SRC-3), a steroid receptor coactivator, is overexpressed and/or amplified in multiple cancer types, including non-steroid targeted cancers, such as urinary bladder cancer (UBC). However, whether SRC-3 regulates the metabolic reprogramming for cancer cell growth is unknown. Here, we reported that overexpression of SRC-3 accelerated UBC cell growth, accompanied by the increased expression of genes involved in glycolysis. Knockdown of SRC-3 reduced the UBC cell glycolytic rate under hypoxia, decreased tumor growth in nude mice, with reduction of proliferating cell nuclear antigen and lactate dehydrogenase expression levels. We further revealed that SRC-3 could interact with hypoxia inducible factor 1α (HIF1α), which is a key transcription factor required for glycolysis, and coactivate its transcriptional activity. SRC-3 was recruited to the promoters of HIF1α-target genes, such as glut1 and pgk1. The positive correlation of expression levels between SRC-3 and Glut1 proteins was demonstrated in human UBC patient samples. Inhibition of glycolysis through targeting HK2 or LDHA decelerated SRC-3 overexpression-induced cell growth. In summary, overexpression of SRC-3 promoted glycolysis in bladder cancer cells through HIF1α to facilitate tumorigenesis, which may be an intriguing drug target for bladder cancer therapy.
Lisse, Thomas S; Middleton, Leah J; Pellegrini, Adriana D; Martin, Paige B; Spaulding, Emily L; Lopes, Olivia; Brochu, Elizabeth A; Carter, Erin V; Waldron, Ashley; Rieger, Sandra
2016-04-12
Paclitaxel is a microtubule-stabilizing chemotherapeutic agent that is widely used in cancer treatment and in a number of curative and palliative regimens. Despite its beneficial effects on cancer, paclitaxel also damages healthy tissues, most prominently the peripheral sensory nervous system. The mechanisms leading to paclitaxel-induced peripheral neuropathy remain elusive, and therapies that prevent or alleviate this condition are not available. We established a zebrafish in vivo model to study the underlying mechanisms and to identify pharmacological agents that may be developed into therapeutics. Both adult and larval zebrafish displayed signs of paclitaxel neurotoxicity, including sensory axon degeneration and the loss of touch response in the distal caudal fin. Intriguingly, studies in zebrafish larvae showed that paclitaxel rapidly promotes epithelial damage and decreased mechanical stress resistance of the skin before induction of axon degeneration. Moreover, injured paclitaxel-treated zebrafish skin and scratch-wounded human keratinocytes (HEK001) display reduced healing capacity. Epithelial damage correlated with rapid accumulation of fluorescein-conjugated paclitaxel in epidermal basal keratinocytes, but not axons, and up-regulation of matrix-metalloproteinase 13 (MMP-13, collagenase 3) in the skin. Pharmacological inhibition of MMP-13, in contrast, largely rescued paclitaxel-induced epithelial damage and neurotoxicity, whereas MMP-13 overexpression in zebrafish embryos rendered the skin vulnerable to injury under mechanical stress conditions. Thus, our studies provide evidence that the epidermis plays a critical role in this condition, and we provide a previously unidentified candidate for therapeutic interventions.
Risk of urinary bladder cancer: a case-control analysis of industry and occupation
Directory of Open Access Journals (Sweden)
Wu Xifeng
2009-12-01
Full Text Available Abstract Background Uncertainty remains about urinary bladder cancer (UBC risk for many occupations. Here, we investigate the association between occupation, industry and UBC. Methods Lifetime occupational history was collected by in-person interview for 604 newly diagnosed UBC patients and 604 cancer-free controls. Each job title was assigned a two-digit industry code and a three-digit occupation code. Odds ratios (ORs for UBC associated with ever being employed in an industry or occupation were calculated by unconditional logistic regression adjusting for age, gender and smoking status. We also examined UBC risk by duration of employment (>0 to Results Significantly increased risk of UBC was observed among waiters and bartenders (OR 2.87; 95% CI 1.05 to 7.72 and occupations related to medicine and health (OR 2.17; 95% CI 1.21 to 3.92, agricultural production, livestock and animal specialties (OR 1.90; 95% CI 1.03 to 3.49, electrical assembly, installation and repair (OR 1.69; 95% CI 1.07 to 2.65, communications (OR 1.74; 95% CI 1.00 to 3.01, and health services (OR 1.58; 95% CI 1.02 to 2.44. For these occupations we also observed a significant excess risk of UBC for long-term work (i.e. ≥10 years, with the exception of waiters and bartenders. Employment for 10 years or more was associated with increased risk of UBC in general farmers (OR 9.58; 95% CI 2.18 to 42.05, agricultural production of crops (OR 3.36; 95% CI 1.10 to 10.27, occupations related to bench working (OR 4.76; 95% CI 1.74 to 13.01, agricultural, fishery, forestry & related (OR 4.58; 95% CI 1.97 to 10.65, transportation equipment (OR 2.68; 95% CI 1.03 to 6.97, and structural work (OR 1.85; 95% CI 1.16 to 2.95. Conclusions This study provides evidence of increased risk of UBC for occupations that were previously reported as at-risk. Workers in several occupation and industry groups have a significantly higher risk of UBC, particularly when duration of employment is 10 years or
Silbermann, Katrin; Schneider, Grit; Grassmann, Ralph
2008-11-01
The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein transforms human lymphocytes and is critical for the pathogenesis of HTLV-1-induced adult T-cell leukaemia. In HTLV-transformed cells, Tax upregulates interleukin (IL)-13, a cytokine with proliferative and anti-apoptotic functions that is linked to leukaemogenesis. Tax-stimulated IL-13 is thought to result in autocrine stimulation of HTLV-infected cells and thus may be relevant to their growth. The causal transactivation of the IL-13 promoter by Tax is predominantly dependent on a nuclear factor of activated T cells (NFAT)-binding P element. Here, it was shown that the isolated IL-13 Tax-responsive element (IL13TaxRE) was sufficient to mediate IL-13 transactivation by Tax and NFAT1. However, cyclosporin A, a specific NFAT inhibitor, revealed that Tax transactivation of IL13TaxRE or wild-type IL-13 promoter was independent of NFAT and that NFAT did not contribute to IL-13 upregulation in HTLV-transformed cells. By contrast, Tax stimulation was repressible by an efficient nuclear factor (NF)-kappaB inhibitor (IkBaDN), indicating the requirement for NF-kappaB. The capacity of NF-kappaB to stimulate IL13TaxRE was demonstrated by a strong response to NF-kappaB in reporter assays and by direct binding of NF-kappaB to IL13TaxRE. Thus, IL13TaxRE in the IL-13 promoter represents a dually active promoter element responsive to NF-kappaB and NFAT. Together, these results indicate that Tax causes IL-13 upregulation in HTLV-1-infected cells via NF-kappaB.
Directory of Open Access Journals (Sweden)
Zhong Pei
2012-06-01
Full Text Available Cyclotripeptide X-13 is a core of novel marine compound xyloallenoide A isolated from mangrove fungus Xylaria sp. (no. 2508. We found that X-13 dose-dependently induced angiogenesis in zebrafish embryos and in human endothelial cells, which was accompanied by increased phosphorylation of eNOS and Akt and NO release. Inhibition of PI3K/Akt/eNOS by LY294002 or l-NAME suppressed X-13-induced angiogenesis. The present work demonstrates that X-13 promotes angiogenesis via PI3K/Akt/eNOS pathways.
Directory of Open Access Journals (Sweden)
Amir H Beiki
Full Text Available Various methods have been used to identify cultivares of olive trees; herein we used different bioinformatics algorithms to propose new tools to classify 10 cultivares of olive based on RAPD and ISSR genetic markers datasets generated from PCR reactions. Five RAPD markers (OPA0a21, OPD16a, OP01a1, OPD16a1 and OPA0a8 and five ISSR markers (UBC841a4, UBC868a7, UBC841a14, U12BC807a and UBC810a13 selected as the most important markers by all attribute weighting models. K-Medoids unsupervised clustering run on SVM dataset was fully able to cluster each olive cultivar to the right classes. All trees (176 induced by decision tree models generated meaningful trees and UBC841a4 attribute clearly distinguished between foreign and domestic olive cultivars with 100% accuracy. Predictive machine learning algorithms (SVM and Naïve Bayes were also able to predict the right class of olive cultivares with 100% accuracy. For the first time, our results showed data mining techniques can be effectively used to distinguish between plant cultivares and proposed machine learning based systems in this study can predict new olive cultivars with the best possible accuracy.
Poudrier, J; Graber, P; Herren, S; Gretener, D; Elson, G; Berney, C; Gauchat, J F; Kosco-Vilbois, M H
1999-08-01
A functional IL-13R involves at least two cell surface proteins, the IL-13R alpha 1 and IL-4R alpha. Using a soluble form of the murine IL-13R alpha 1 (sIL-13R), we reveal several novel features of this system. The sIL-13R promotes proliferation and augmentation of Ag-specific IgM, IgG2a, and IgG2b production by murine germinal center (GC) B cells in vitro. These effects were enhanced by CD40 signaling and were not inhibited by an anti-IL4R alpha mAb, a result suggesting other ligands. In GC cell cultures, sIL-13R also promoted IL-6 production, and interestingly, sIL-13R-induced IgG2a and IgG2b augmentation was absent in GC cells isolated from IL-6-deficient mice. Furthermore, the effects of the sIL-13R molecule were inhibited in the presence of an anti-IL-13 mAb, and preincubation of GC cells with IL-13 enhanced the sIL-13R-mediated effects. When sIL-13R was injected into mice, it served as an adjuvant-promoting production to varying degrees of IgM and IgG isotypes. We thus propose that IL-13R alpha 1 is a molecule involved in B cell differentiation, using a mechanism that may involve regulation of IL-6-responsive elements. Taken together, our data reveal previously unknown activities as well as suggest that the ligand for the sIL-13R might be a component of the IL-13R complex or a counterstructure yet to be defined.
Roy, Sarah H; Tobin, David V; Memar, Nadin; Beltz, Eleanor; Holmen, Jenna; Clayton, Joseph E; Chiu, Daniel J; Young, Laura D; Green, Travis H; Lubin, Isabella; Liu, Yuying; Conradt, Barbara; Saito, R Mako
2014-02-28
The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in Caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development. Copyright © 2014 Roy et al.
Yuspa, S H; Lichti, U; Ben, T
1980-01-01
The induction of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) activity in mouse epidermal cells in vivo and in vitro occurs rapidly after exposure to the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). This induction has characteristics of a cell surface receptor-mediated process. Local anesthetics modify a variety of cellular responses mediated by membrane receptors. When cultured mouse epidermal cells were exposed to the local anesthetics lidocaine, tetracaine...
Jue, Dengwei; Sang, Xuelian; Lu, Shengqiao; Dong, Chen; Zhao, Qiufang; Chen, Hongliang; Jia, Liqiang
2015-01-01
Background Ubiquitination is a post-translation modification where ubiquitin is attached to a substrate. Ubiquitin-conjugating enzymes (E2s) play a major role in the ubiquitin transfer pathway, as well as a variety of functions in plant biological processes. To date, no genome-wide characterization of this gene family has been conducted in maize (Zea mays). Methodology/Principal Findings In the present study, a total of 75 putative ZmUBC genes have been identified and located in the maize genome. Phylogenetic analysis revealed that ZmUBC proteins could be divided into 15 subfamilies, which include 13 ubiquitin-conjugating enzymes (ZmE2s) and two independent ubiquitin-conjugating enzyme variant (UEV) groups. The predicted ZmUBC genes were distributed across 10 chromosomes at different densities. In addition, analysis of exon-intron junctions and sequence motifs in each candidate gene has revealed high levels of conservation within and between phylogenetic groups. Tissue expression analysis indicated that most ZmUBC genes were expressed in at least one of the tissues, indicating that these are involved in various physiological and developmental processes in maize. Moreover, expression profile analyses of ZmUBC genes under different stress treatments (4°C, 20% PEG6000, and 200 mM NaCl) and various expression patterns indicated that these may play crucial roles in the response of plants to stress. Conclusions Genome-wide identification, chromosome organization, gene structure, evolutionary and expression analyses of ZmUBC genes have facilitated in the characterization of this gene family, as well as determined its potential involvement in growth, development, and stress responses. This study provides valuable information for better understanding the classification and putative functions of the UBC-encoding genes of maize. PMID:26606743
7 CFR 1219.13 - Hass Avocado Board.
2010-01-01
... 7 Agriculture 10 2010-01-01 2010-01-01 false Hass Avocado Board. 1219.13 Section 1219.13... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.13 Hass...
Queiroz, C B; Miranda, E C; Hanada, R E; Sousa, N R; Gasparotto, L; Soares, M A; Silva, G F
2013-02-08
The fungus Mycosphaerella fijiensis is the causative agent of black sigatoka, which is one of the most destructive diseases of banana plants. Infection with this pathogen results in underdeveloped fruit, with no commercial value. We analyzed the distribution of the M. fijiensis mating-type system and its genetic variability using M13 phage DNA markers. We found a 1:1 distribution of mating-type alleles, indicating MAT1-1 and MAT1-2 idiomorphs. A polymorphism analysis using three different primers for M13 markers showed that only the M13 minisatellite primers generated polymorphic products. We then utilized this polymorphism to characterize 40 isolates from various Brazilian states. The largest genetic distances were found between isolates from the same location and between isolates from different parts of the country. Therefore, there was no correlation between the genetic similarity and the geographic origin of the isolates. The M13 marker was used to generate genetic fingerprints for five isolates; these fingerprints were compared with the band profiles obtained from inter-simple sequence repeat (UBC861) and inter-retrotransposon amplified polymorphism analyses. We found that the M13 marker was more effective than the other two markers for differentiating these isolates.
Atomic structure of the APC/C and its mechanism of protein ubiquitination
Yang, Jing; McLaughlin, Stephen H.; Barford, David
2015-01-01
The anaphase-promoting complex (APC/C) is a multimeric RING E3 ubiquitin ligase that controls chromosome segregation and mitotic exit. Its regulation by coactivator subunits, phosphorylation, the mitotic checkpoint complex, and interphase inhibitor Emi1 ensures the correct order and timing of distinct cell cycle transitions. Here, we used cryo-electron microscopy to determine atomic structures of APC/C-coactivator complexes with either Emi1 or a UbcH10-ubiquitin conjugate. These structures define the architecture of all APC/C subunits, the position of the catalytic module, and explain how Emi1 mediates inhibition of the two E2s UbcH10 and Ube2S. Definition of Cdh1 interactions with the APC/C indicates how they are antagonized by Cdh1 phosphorylation. The structure of the APC/C with UbcH10-ubiquitin reveals insights into the initiating ubiquitination reaction. Our results provide a quantitative framework for the design of experiments to further investigate APC/C functions in vivo. PMID:26083744
The RNA-binding protein Spo5 promotes meiosis II by regulating cyclin Cdc13 in fission yeast.
Arata, Mayumi; Sato, Masamitsu; Yamashita, Akira; Yamamoto, Masayuki
2014-03-01
Meiosis comprises two consecutive nuclear divisions, meiosis I and II. Despite this unique progression through the cell cycle, little is known about the mechanisms controlling the sequential divisions. In this study, we carried out a genetic screen to identify factors that regulate the initiation of meiosis II in the fission yeast Schizosaccharomyces pombe. We identified mutants deficient in meiosis II progression and repeatedly isolated mutants defective in spo5, which encodes an RNA-binding protein. Using fluorescence microscopy to visualize YFP-tagged protein, we found that spo5 mutant cells precociously lost Cdc13, the major B-type cyclin in fission yeast, before meiosis II. Importantly, the defect in meiosis II was rescued by increasing CDK activity. In wild-type cells, cdc13 transcripts increased during meiosis II, but this increase in cdc13 expression was weaker in spo5 mutants. Thus, Spo5 is a novel regulator of meiosis II that controls the level of cdc13 expression and promotes de novo synthesis of Cdc13. We previously reported that inhibition of Cdc13 degradation is necessary to initiate meiosis II; together with the previous information, the current findings indicate that the dual control of Cdc13 by de novo synthesis and suppression of proteolysis ensures the progression of meiosis II. © 2014 The Authors Genes to Cells © 2014 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.
The role of osteoblast cells in the pathogenesis of unicameral bone cysts.
Aarvold, Alexander; Smith, James O; Tayton, Edward R; Edwards, Caroline J; Fowler, Darren J; Gent, Edward D; Oreffo, Richard O C
2012-08-01
The pathogenesis of unicameral bone cysts (UBCs) remains largely unknown. Osteoclasts have been implicated, but the role of osteoblastic cells has, to date, not been explored. This study investigated the pathophysiology of UBCs by examining the interactions between the cyst fluid and human bone marrow stromal cells (hBMSCs) and the effect of the fluid on osteogenesis. Fluid was aspirated from two UBCs and analysed for protein, electrolyte and cytokine levels. Graded concentrations of the fluid were used as culture media for hBMSCs to determine the effects of the fluid on hBMSC proliferation and osteogenic differentiation. The fibrocellular lining was analysed histologically and by electron microscopy. Alkaline phosphatase (ALP) staining of hBMSCs that were cultured in cyst fluid demonstrated increased cell proliferation and osteogenic differentiation compared to basal media controls. Biochemical analysis of these hBMSCs compared to basal controls confirmed a marked increase in DNA content (as a marker of proliferation) and ALP activity (as a marker of osteogenic differentiation) which was highly significant (p < 0.001). Osteoclasts were demonstrated in abundance in the cyst lining. The cyst fluid cytokine profile revealed levels of the pro-osteoclast cytokines IL-6, MIP-1α and MCP-1 that were 19×, 31× and 35× greater than those in reference serum. Cyst fluid promoted osteoblastic growth and differentiation. Despite appearing paradoxical that the cyst fluid promoted osteogenesis, osteoblastic cells are required for osteoclastogenesis through RANKL signalling. Three key cytokines in this pathway (IL-6, MIP-1α, MCP-1) were highly elevated in cyst fluid. These findings may hold the key to the pathogenesis of UBCs, with implications for treatment methods.
Treatment of Unicameral Bone Cysts of the Calcaneus: A Systematic Review.
Levy, David M; Gross, Christopher E; Garras, David N
2015-01-01
The calcaneus is the most common tarsal affected by unicameral bone cysts (UBCs); however, the treatment of calcaneal UBCs remains controversial. The purpose of the present systematic review was to evaluate the treatment modalities for calcaneal UBCs. A systematic review was performed using clinical studies of calcaneal UBCs with a minimum of 1 year of follow-up and level I to IV evidence. Ten studies with 171 patients (181 cysts) were selected. Heel pain and radiographic cyst consolidation were the primary outcomes. A series of Z tests were used to compare the outcomes in the nonoperative and operative groups, cannulated screw and bone augmentation groups, and autografting and allografting groups. All patients treated with open curettage and bone augmentation had significant improvements in heel pain (p < .001). Only 1.1% ± 1.0% of the cysts treated conservatively had healed on radiographs compared with 93.0% ± 13.0% of the cysts after surgery (p < .001). A greater percentage of patients treated with bone augmentation had preoperative heel pain and resolution of that pain than did patients treated with cannulated screws (p < .001). Autografting had a significantly greater percentage of radiographic cyst consolidation than did allografting (97.4% ± 11.1% versus 85.1% ± 15.8%, p < .001, Z = 3.5). Objective outcomes data on calcaneal UBCs are relatively sparse. The results of the present review suggest that open curettage with autograft bone augmentation is the most effective procedure. We would encourage future comparative clinical studies to elucidate differences in UBC treatment modalities. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.
Influence of metformin intake on the risk of bladder cancer in type 2 diabetes patients
DEFF Research Database (Denmark)
Goossens, Maria E; Buntinx, Frank; Zeegers, Maurice P
2015-01-01
, SUs, insulin or more than one combination), all metformin users (1 + 2) was compared with SU only users using Cox proportional hazards models. The estimates were adjusted for age, gender, smoking status, BMI and diabetes duration. RESULTS: The inception cohort included 165,398 participants of whom 132...... users, even after adjustment for diabetes duration (HR = 1.13, 95% CI 0.90, 1.40). We found a pattern of decreasing risk of UBC with increasing duration of metformin intake, which was statistically not significant. CONCLUSION: Metformin has no influence on the risk of UBC compared with SU in type 2...... Practice Research Datalink (CPRD) including all patients with at least one prescription of oral anti-diabetic drugs (ADD) and/or insulin. The risk of UBC in different groups of ADD users (metformin alone (one), metformin in combination (two) with other ADD medication (glinides, glitazones, DPP-4-inhibitors...
DEFF Research Database (Denmark)
Arenholt, D; Dabelsteen, Erik
1987-01-01
Cultures of rat palatal epithelium grown on collagen rafts were treated with different doses of the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Sections from biopsies taken 1, 6, 24, and 48 hr after the addition of TPA were examined for the localization of staining by blood ...
2010-01-01
... 7 Agriculture 10 2010-01-01 2010-01-01 false Process. 1215.13 Section 1215.13 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Definitions § 1215.13...
Biochemical function of typical and variant Arabidopsis thaliana U-box E3 ubiquitin-protein ligases
DEFF Research Database (Denmark)
Wiborg, Jakob; O'Shea, Charlotte; Skriver, Karen
2008-01-01
of the distant U-box protein, AtPUB49, representing a large family of eukaryotic proteins containing a U-box linked to a cyclophilin-like peptidyl-prolyl cis-trans isomerase domain, was characterized biochemically. AtPUB49 functioned both as a prolyl isomerase and a chaperone by catalysing cis......The variance of the U-box domain in 64 Arabidopsis thaliana (thale cress) E3s (ubiquitin-protein ligases) was used to examine the interactions between E3s and E2s (ubiquitin-conjugating enzymes). E2s and E3s are components of the ubiquitin protein degradation pathway. Seven U-box proteins were...... analysed for their ability to ubiquitinate proteins in vitro in co-operation with different E2s. All U-box domains exhibited ubiquitination activity and interacted productively with UBC4/5-type E2s. Three and four of the U-box domains mediated ubiquitin addition in the presence of UBC13 and UBC7 E2s...
Pavone, V; Caff, G; Di Silvestri, C; Avondo, S; Sessa, G
2014-05-01
Retrospective evaluation of long-term effectiveness of the steroid injections treatment in patients with unicameral bone cysts (UBC). From January 1993 to April 2005, 23 children affected by proximal humeral UBC were evaluated according to the Neer-Cole classification system and treated with serial methylprednisolone acetate's injections. The patients were followed up at 1, 3, 6 and 12 months and then every year until the adolescence. After treatment, in 15 out of 23 patients (65.2%), the humeral cysts were referred, respectively, as Grade 1 and in four as Grade 2. In 4 patients, a refracture occurred. Statistical analysis showed an overall good response in 82.6% of patients at the end of the follow-up. Minor complication including skin discoloration accounted for 13.04%. The steroid injections showed to be an alternative excellent treatment for UBC, with complete healing of the lesions in the majority of cases. This procedure is not expensive, mini-invasive, with low surgical risk and short hospitalization.
2010-01-01
... 7 Agriculture 10 2010-01-01 2010-01-01 false Market. 1230.13 Section 1230.13 Agriculture... CONSUMER INFORMATION Pork Promotion, Research, and Consumer Information Order Definitions § 1230.13 Market. Market means to sell, slaughter for sale, or otherwise dispose of a porcine animal in commerce. ...
International Nuclear Information System (INIS)
Forsyth, K.S.; Gensler, H.L.; Watson, R.R.
1989-01-01
In view of the clinical trials of retinoids as therapeutic agents for premalignant skin lesions, a radiographic study was undertaken to measure skeletal toxicities after chronic dietary administration of retinoids in mice exposed to tumor initiation and promotion. CD-1 mice were initiated with 0.15 moles of 7,12-dimethylbenz[a]anthracene and promoted twice daily with 8 nmoles of 12-O-tetradecanoylphorbol-13-acetate for 23 weeks. Diets were supplemented with 60 IU, 200 IU, or 700 IU or retinyl palmitate (RP) per g diet. After 5 weeks, the 700 IU of RP/g diet was lowered to 350 IU/g diet. Administration of these diets to mice during the 23 weeks of tumor promotion results in a 0-fold, 2-fold, or 10-fold increase in bone fractures, respectively. Osteoporotic bone lesions identified on radiographs rose 0-fold, 0-fold, and 10-fold at the respective doses, whereas metaphyseal flares increased O-fold, 1.4-fold, and 3.6-fold. Bone deformities was augmented O-fold, 1.8-fold and 2.9-fold at the respective doses. Addition of selenium did not alter the bone toxicity of RP. 13-cis-retionic acid (CRA) was less toxic at 700 IU/g diet than was RP at that dose, as evidence by the death of 12 of 70 mice by the 6th week of dietary RP and no deaths in the 35 mice fed 700 IU CRA/g diet for 23 weeks. CRA at 700 IU/g diet resulted in 3/4 as many osteoporotic bones, 1/3 as many bone fractures, 4/5 as many metaphyseal flares, and a similar number of bone deformities as mice fed 700/350 IU/g diet. At the dose of 200 IU/g food, osterotoxicities were similar in the mice fed diets supplemented with RP and CRA
The present and future burden of urinary bladder cancer in the world.
Ploeg, M.; Aben, K.K.H.; Kiemeney, L.A.L.M.
2009-01-01
Urinary bladder cancer (UBC) is a common disease worldwide. At any point in time 2.7 million people have a history of UBC. The incidence of UBC varies over the world with highest rates in developed communities. But the burden of UBC will increase in less developed areas of the world. These changes
Directory of Open Access Journals (Sweden)
K. Radkhah
2005-06-01
Full Text Available Cystoscopy and urinary cytology are currently the basis for diagnosis and follow-up of bladder tumors. Research to find a sensitive and specific tumor marker for diagnosis of bladder tumor is actively underway, however, due to low sensitivity and high cost of cytology. This cross-sectional study was performed in 65 patients to evaluate whether urinary bladder cancer (UBC antigen level can predict the presence of active bladder tumor. In patients with inactive tumor, UBC antigen level was determined in addition to standard cystoscopy and cytology for follow-up. Patients with active tumor were subjected to standard treatment and UBC antigen level determination. UBC antigen levels were measured by ELISA, using monoclonal antibodies specific for UBC antigen. As a control group, UBC antigen level was also determined in 65 persons who had been referred for urinalysis for other reasons. UBC antigen level more than 1 μg/L which was regarded as positive was found in 49.4% of the patients. In control group, 96.9% had UBC antigen < 1μg/L. Mean UBC antigen level in patients was 3.77 μg/L while it was 0.508 μg/L in controls (P < 0.0001. Sensitivity of UBC antigen was 53.3% and its specificity was 40%. Sensitivity and specificity of urinary cytology was 17.3% and 88.2%, respectively. This difference was statistically significant (P < 0.001. UBC antigen is more sensitive than urinary cytology, although cytology still retains its priority in specificity. It is not yet recommended to replace UBC antigen for cytology due to its low specificity and not favorable sensitivity.
DEFF Research Database (Denmark)
Helbo, Alexandra Søgaard; Treppendahl, Marianne; Aslan, Derya
2015-01-01
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders. MDS is frequently associated with deletions on chromosome 5q as well as aberrant DNA methylation patterns including hypermethylation of key tumor suppressors. We have previously shown that hypermethylation...... causes reactivation these genes. In normal hematopoiesis, we find that vault RNAs (vtRNAs) show differential methylation between various hematopoietic cell populations, indicating that allele-specific methylation events may occur during hematopoiesis. In addition, we show that VTRNA1-3 promoter...... hypermethylation is frequent in lower risk MDS patients and is associated with a decreased overall survival....
The UBCTM test may be useful for diagnosis of recurred urinary bladder cancer
International Nuclear Information System (INIS)
Kang, Do Young; Jung, Se Il; Hwang, Joon Seong; Gil, Myung Cheol; Yoon, Jin Han; Kim, Duk Kyu
2001-01-01
Previously we reported the usefulness of UBC TM test compared to urinary cytology for diagnosis of transitional cell carcinoma (TCC) of the bladder in patients with hematuria. Now we evaluated the usefulness of the UBC TM test for diagnosis of recurred urinary bladder cancer. 146 patients with hematuria were included in our study. UNC TM test (IDL Biotech, Sweden) were assayed in mid-stream urine according to the ordinary assay protocol. 33 patients were confirmed as TCC by cystoscopic examination and underwent transurethral resection (Group A). Other patients had various benign urinary tract conditions (Group B). Samples were considered positive as the UBC concentration was greater than 12 μ g/L. We compared UBC TM level with previous value 6 months later in patients whom diagnosed with TCC. UBC levels were significantly different between group A (95.9±166.4 μ g/L) and group B (19.2±85.6 μ g/L) (p TM test and 100% (97/97) in cytology. UBC TM test was significantly more sensitive in stage Ta. T 1 tumors (80 vs 20 %, p TM test showed tendency to be more sensitive as the stage and grade was higher (80% in Ta, 83.3% in T1 and 100% in T2, 80% in Grade I, 85.7% in Grade II and 100% in Grade III). We follow-up UBC TM test in 5 patients after 6 months. UBC TM levels and recurrence were correlated in 4 patient (80%). Follow-up levels of UBC TM were increased in two recurred patients and normalized in non-recurred patients. One patient showed increased level of UBC TM test but clinically no evidence of recurrence. Although Also our patients were small, UBC TM test may be useful method for detecting the recurrence of TCC and further follow-up is necessary
Ionizing radiation in tumor promotion and progression
International Nuclear Information System (INIS)
Mitchel, R.E.J.
1990-08-01
Chronic exposure to beta radiation has been tested as a tumor promoting or progressing agent. The dorsal skins of groups of 25 female SENCAR mice were chemically initiated with a single exposure to DMBA, and chronic exposure to strontium-90/yttrium-90 beta radiation was tested as a stage 1, stage 2 or complete skin tumor promoter. Exposure of initiated mice to 0.5 gray twice a week for 13 weeks produced no papillomas, indicating no action as a complete promoter. Another similar group of animals was chemically promoted through stage 1 (with TPA) followed by 0.5 gray of beta radiation twice a week for 13 weeks. Again no papillomas developed indicating no action of chronic radiation as a stage 2 tumor promoter. The same radiation exposure protocol in another DMBA initiated group receiving both stage 1 and 2 chemical promotion resulted in a decrease in papilloma frequency, compared to the control group receiving no beta irradiation, indicating a tumor preventing effect of radiation at stage 2 promotion, probably by killing initiated cells. Chronic beta radiation was tested three different ways as a stage 1 tumor promoter. When compared to the appropriate control, beta radiation given after initiation as a stage 1 promoter (0.5 gray twice a week for 13 weeks), after initiation and along with a known stage 1 chemical promoter (1.0 gray twice a week for 2 weeks), or prior to initiation as a stage 1 promoter (0.5 gray twice a week for 4 weeks), each time showed a weak (∼ 15% stimulation) but statistically significant (p<0.01) ability to act as a stage 1 promoter. When tested as a tumor progressing agent delivered to pre-existing papillomas, beta radiation (0.5 gray twice a week for 13 weeks) increased carcinoma frequency from 0.52 to 0.68 carcinoma/animal, but this increase was not statistically significant at the 95% confidence level. We conclude that in the addition to the known initiating, progressing and complete carcinogenic action of acute exposures to ionizing
International Nuclear Information System (INIS)
Lanteri, Marion; Ollier, Laurence; Giordanengo, Valérie; Lefebvre, Jean-Claude
2005-01-01
Our goal was to specifically render tumor cells susceptible to natural cytolytic anti-αGal antibodies by using a murine α1,3galactosyltransferase (mαGalT) transgene driven by a designed form of HER2/neu promoter (pNeu), the transcription of which is frequently observed to be above basal in breast tumors. Indeed, the αGalT activity that promotes Galα1,3Galβ1,4GlcNAc-R (αGal) epitope expression has been mutationally disrupted during the course of evolution, starting from Old World primates, and this has led to the counter-production of large amounts of cytotoxic anti-αGal antibodies in recent primates, including man. Expression of the endogenous c-erbB-2 gene was investigated in various cell lines by northern blotting. A mαGalT cDNA was constructed into pcDNA3 vector downstream of the original CMV promoter (pCMV/mαGalT) and various forms of pNeu were prepared by PCR amplification and inserted in the pCMV/mαGalT construct upstream of the mαGalT cDNA, in the place of the CMV promoter. These constructs were transferred into HEK-293 control and breast tumor cell lines. Stably transfected cells were analyzed by northern blotting for their expression of αGalT and c-erbB-2, and by flow cytometry for their binding with fluorescein isothiocyanate-conjugated Griffonia simplicifolia/isolectin B4. We show that expression of the mαGalT was up- or down-modulated according to the level of endogenous pNeu activity and the particular form of constructed pNeu. Among several constructs, two particular forms of the promoter, pNeu250 containing the CCAAT box and the PEA3 motif adjacent to the TATAA box, and pNeu664, which has three additional PEA3 motifs upstream of the CCAAT box, were found to promote differential αGalT expression. Our results strengthen current concepts about the crucial role played by the proximal PEA3 motif of pNeu, and may represent a novel therapeutic approach for the development of targeted transgene expression
Directory of Open Access Journals (Sweden)
Jennifer R Bailey
Full Text Available BACKGROUND: Fibrosis is a serious consequence of Crohn's disease (CD, often necessitating surgical resection. We examined the hypothesis that IL-13 may promote collagen accumulation within the CD muscle microenvironment. METHODS: Factors potentially modulating collagen deposition were examined in intestinal tissue samples from fibrotic (f CD and compared with cancer control (C, ulcerative colitis (UC and uninvolved (u CD. Mechanisms attributable to IL-13 were analysed using cell lines derived from uninvolved muscle tissue and tissue explants. RESULTS: In fCD muscle extracts, collagen synthesis was significantly increased compared to other groups, but MMP-2 was not co-ordinately increased. IL-13 transcripts were highest in fCD muscle compared to muscle from other groups. IL-13 receptor (R α1 was expressed by intestinal muscle smooth muscle, nerve and KIR(+ cells. Fibroblasts from intestinal muscle expressed Rα1, phosphorylated STAT6 in response to IL-13, and subsequently down-regulated MMP-2 and TNF-α-induced MMP-1 and MMP-9 synthesis. Cells with the phenotype KIR(+CD45(+CD56(+/-CD3(- were significantly increased in fCD muscle compared to all other groups, expressed Rα1 and membrane IL-13, and transcribed high levels of IL-13. In explanted CD muscle, these cells did not phosphorylate STAT6 in response to exogenous IL-13. CONCLUSIONS: The data indicate that in fibrotic intestinal muscle of Crohn's patients, the IL-13 pathway is stimulated, involving a novel population of infiltrating IL-13Rα1(+, KIR(+ innate lymphoid cells, producing IL-13 which inhibits fibroblast MMP synthesis. Consequently, matrix degradation is down-regulated and this leads to excessive collagen deposition.
Molecular Genetic Analysis of Somaclonal Lines Genotypes of Silver Birch and Hybrid Birch
Directory of Open Access Journals (Sweden)
A. V. Konstantinov
2014-08-01
Full Text Available Enrichment of genetic diversity by means of somaclonal variation can allow selection of individuals with increased adaptability to various unfavorable conditions. Twenty shoot cultures differing in organogenesis and morphological features were selected for two studied clones. Multilocus genetic passports of somaclonal lines were developed according to RAPD analysis. Among the samples derived from clone № 52-84/8 shoot cultures the changes in RAPD-spectra were detected over primers UBC-106 and UBC-254. In the case of clone № 6-161/3 the same changes were detected over primers UBC-268 and UBC-154. UBC-203 primer didn’t show any variation.
International Nuclear Information System (INIS)
Borek, C.; Troll, W.
1983-01-01
Using short-term cultures of hamster embryo cells, we have examined the effects of the free-radical scavenger superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and the enzyme catalase (hydrogen-peroxide:hydrogen-peroxide oxidoreductase, EC 1.11.1.6) on x-ray-and bleomycin-induced transformation and on the enhancement of radiogenic transformation by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). We find that superoxide dismutase inhibits (i) transformation induced by x-ray and bleomycin and (ii) promotional action of TPA in vitro. The results suggest that the oncogenic action of x-rays and bleomycin and the enhancement of oncogenic transformation by TPA are mediated in part by free radicals. The findings also suggest that superoxide dismutase can serve as an inhibitor of oncogenesis and that its actions, as seen in this in vitro system, are most predominantly on inhibiting late events in the progression of cellular transformation--those associated with promotion
Molecular basis of APC/C regulation by the spindle assembly checkpoint
Zhang, Ziguo; Yang, Jing; Maslen, Sarah; Skehel, Mark; Barford, David
2016-01-01
In the dividing eukaryotic cell the spindle assembly checkpoint (SAC) ensures each daughter cell inherits an identical set of chromosomes. The SAC coordinates the correct attachment of sister chromatid kinetochores to the mitotic spindle with activation of the anaphase-promoting complex/cyclosome (APC/C), the E3 ubiquitin ligase that initiates chromosome separation. In response to unattached kinetochores, the SAC generates the mitotic checkpoint complex (MCC), a multimeric assembly that inhibits the APC/C, delaying chromosome segregation. Here, using cryo-electron microscopy we determined the near-atomic resolution structure of an APC/C-MCC complex (APC/CMCC). We reveal how degron-like sequences of the MCC subunit BubR1 block degron recognition sites on Cdc20, the APC/C coactivator subunit (Cdc20APC/C) responsible for substrate interactions. BubR1 also obstructs binding of UbcH10 (APC/C’s initiating E2) to repress APC/C ubiquitination activity. Conformational variability of the complex allows for UbcH10 association, and we show from a structure of APC/CMCC in complex with UbcH10 how the Cdc20 subunit intrinsic to the MCC (Cdc20MCC) is ubiquitinated, a process that results in APC/C reactivation when the SAC is silenced. PMID:27509861
International Nuclear Information System (INIS)
Gil, Myung Cheol; Kang, Do Young; Seong, Youl Koon
2001-01-01
Urinary cytology and cystoscopic exam are effective methods for diagnosis of transitional cell carcinoma (TCC). But the former shows drawbacks such as the need for a well-trained examiner, and wide imprecision related to the variability of microscopic exam; the latter is a invasive method. UBC TM test detects the epitope on specific cytokeratin fragments released from epithelium of bladder cancer by immunoradiometric assay. We compared UBC TM test with urinary cytology for diagnosis of TCC to evaluate the utility of UBC TM test. Eighty-four patients with hematuria were included in our study, UBC TM tests (IDL Biotech, Sweden) were assayed in mid-stream urine according to the ordinary assay protocol. Nineteen patients were confirmed as TCC by cystoscopic examination and underwent transurethral resection (Group A). Other patients had various benign urinary tract conditions (Group B). Samples were considered positive as the UBC TM concentration was greater than 12 μg/L. UBC TM levels were significantly different between group A (95.9 ±166.4 μg/L) and group B (19.2 ± 85.6 μg/L)(p TM test and 100% (65/65) in cytology. UBC TM test was significantly more sensitive in stage Ta, T 1 tumors (84.6 vs 38.5%, p TM test showed a tendency to be more sensitive as the grade was higher (83.3% in Grade 1, 90% in Grade II and 100% in Grade III). UBC TM test could be a useful method in distinguishing TCC from other benign genitourinary diseases. Moreover, UBC TM test could be an especially valuable marker for diagnosis of TCC in patients with early TCC of low grade TCC compared to urinary cytology. Therefore, mbined use of UBC TM test in association with cytology is helpful to overcome the limited sensitivity of cytology
Lee, Sun Kyong; Sillitoe, Roy V; Silva, Coralie; Martina, Marco; Sekerkova, Gabriella
2015-10-01
α-Synuclein has a crucial role in synaptic vesicle release and synaptic membrane recycling. Although its general expression pattern has been described in the cerebellum, the precise cerebellar structures where α-synuclein is localized are poorly understood. To address this question, we used α-synuclein immunohistochemistry in adult mice cerebellar sections. We found that α-synuclein labels glutamatergic but not glycinergic and GABAergic synaptic terminals in the molecular and granule cell layers. α-Synuclein was preferentially expressed in parallel and mossy fiber synaptic terminals that also express vesicular glutamate transporter 1 (VGluT1), while it was not detected in VGluT2-positive climbing fibers. α-Synuclein was particularly enriched in lobules IX and X, a region known to contain a high density of unipolar brush cells (UBCs). To elucidate whether the α-synuclein-positive mossy fibers belong to UBCs, we double-labeled cerebellar sections with antibodies to α-synuclein and UBC-type-specific markers (calretinin for type I and metabotropic glutamate receptor 1α (mGluR1α) for type II UBCs) and took advantage of organotypic cerebellar cultures (in which all mossy fibers are UBC axons) and moonwalker mice (in which almost all UBCs are ablated) and found that both type I and type II UBCs express α-synuclein. In moonwalker mutant cerebella, the α-synuclein/VGluT1 immunolabeling showed a dramatic decrease in the vestibulocerebellum that correlated with the absence of UBC. α-Synuclein appears to be an excellent marker for intrinsic mossy fibers of the VGluT1 subset in conjunction with UBCs of both subtypes.
Asthma status is associated with decreased risk of aggressive urothelial bladder cancer.
Rava, Marta; Czachorowski, Maciej J; Silverman, Debra; Márquez, Mirari; Kishore, Sirish; Tardón, Adonina; Serra, Consol; García-Closas, Montse; Garcia-Closas, Reina; Carrato, Alfredo; Rothman, Nathaniel; Real, Francisco X; Kogevinas, Manolis; Malats, Núria
2018-02-01
Previous studies suggested an association between atopic conditions and specific cancers. The results on the association with urothelial bladder cancer (UBC) are scarce and inconsistent. To evaluate the association between asthma and risk of UBC, we considered 936 cases and 1,022 controls from the Spanish Bladder Cancer/EPICURO Study (86% males, mean age 65.4 years), a multicenter and hospital-based case-control study conducted during 1998-2001. Participants were asked whether they had asthma and detailed information about occupational exposures, smoking habits, dietary factors, medical conditions and history of medication was collected through face-to-face questionnaires performed by trained interviewers. Since asthma and UBC might share risk factors, association between patients' characteristics and asthma was studied in UBC controls. Association between UBC and asthma was assessed using logistic regression unadjusted and adjusted for potential confounders. The complex interrelationships, direct and mediating effect of asthma on UBC, were appraised using counterfactual mediation models. Asthma was associated with a reduced risk of UBC (odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.37, 0.79) after adjusting for a wide range of confounders. No mediating effect was identified. The reduced risk associated with asthma was restricted to patients with high-risk non-muscle invasive (OR = 0.25, 95%CI 0.10, 0.62) and muscle invasive UBC (OR = 0.32, 95%CI 0.15, 0.69). Our results support that asthma is associated with a decreased risk of UBC, especially among aggressive tumors. Further work on the relationship between asthma and other atopic conditions and cancer risk should shed light on the relationship between immune response mechanisms and bladder carcinogenesis. © 2017 UICC.
Degradation signals for ubiquitin system proteolysis in Saccharomyces cerevisiae.
Gilon, T; Chomsky, O; Kulka, R G
1998-01-01
Combinations of different ubiquitin-conjugating (Ubc) enzymes and other factors constitute subsidiary pathways of the ubiquitin system, each of which ubiquitinates a specific subset of proteins. There is evidence that certain sequence elements or structural motifs of target proteins are degradation signals which mark them for ubiquitination by a particular branch of the ubiquitin system and for subsequent degradation. Our aim was to devise a way of searching systematically for degradation signals and to determine to which ubiquitin system subpathways they direct the proteins. We have constructed two reporter gene libraries based on the lacZ or URA3 genes which, in Saccharomyces cerevisiae, express fusion proteins with a wide variety of C-terminal extensions. From these, we have isolated clones producing unstable fusion proteins which are stabilized in various ubc mutants. Among these are 10 clones whose products are stabilized in ubc6, ubc7 or ubc6ubc7 double mutants. The C-terminal extensions of these clones, which vary in length from 16 to 50 amino acid residues, are presumed to contain degradation signals channeling proteins for degradation via the UBC6 and/or UBC7 subpathways of the ubiquitin system. Some of these C-terminal tails share similar sequence motifs, and a feature common to almost all of these sequences is a highly hydrophobic region such as is usually located inside globular proteins or inserted into membranes. PMID:9582269
Directory of Open Access Journals (Sweden)
Hamutal Meiri
Full Text Available Hypertensive disorders affect about one third of all people aged 20 and above, and are treated with anti-hypertensive drugs. Preeclampsia (PE is one form of such disorders that only develops during pregnancy. It affects ten million pregnant women globally and additionally causes fetal loss and major newborn disabilities. The syndrome's origin is multifactorial, and anti-hypertensive drugs are ineffective in treating it. Biomarkers are helpful for predict its development. Generic drugs, such as low dose aspirin, were proven effective in preventing preterm PE. However, it does not cure the majority of cases and many studies are underway for fighting PE with extended use of additional generic drugs, or through new drug development programs.This review focuses on placental protein 13 (PP13. This protein is only expressed in the placenta. Impaired PP13 DNA structure and/or its reduced mRNA expression leads to lower blood PP13 level that predict a higher risk of developing PE. Two polymorphic PP13 variants have been identified: (1 The promoter PP13 variant with an “A/A” genotype in the -98 position (versus “A/C” or “C/C”. Having the “A/A” genotype is coupled to lower PP13 expression, mainly during placental syncytiotrophoblast differentiation and, if associated with obesity and history of previous preeclampsia, it accurately predicts higher risk for developing the disorder. (2 A thymidine deletion at position 221 causes a frame shift in the open reading frame, and the formation of an early stop codon resulting in the formation of DelT221, a truncated variant of PP13. In pregnant rodents, both short- and long- term replenishment of PP13 causes reversible hypotension and vasodilation of uterine vessels. Long-term exposure is also accompanied by the development of larger placentas and newborns. Also, only w/t PP13 is capable of inducing leukocyte apoptosis, providing maternal immune tolerance to pregnancy.Based on published data, we
p13 from group II baculoviruses is a killing-associated gene
Directory of Open Access Journals (Sweden)
Yipeng Qi
2012-12-01
Full Text Available p13 gene was first described in Leucania separata multinuclearpolyhedrosis virus (Ls-p13 several years ago, but the functionof P13 protein has not been experimentally investigated todate. In this article, we indicated that the expression of p13from Heliothis armigera single nucleocapsid nucleopolyhedrovirus(Ha-p13 was regulated by both early and late promoter.Luciferase assay demonstrated that the activity of Ha-p13promoter with hr4 enhancer was more than 100 times inheterologous Sf9 cells than that in nature host Hz-AM1 cells.Both Ls-P13 and Ha-P13 are transmembrane proteins. Confocalmicroscopic analysis showed that both mainly located in thecytoplasm membrane at 48 h. Results of RNA interferenceindicated that Ha-p13 was a killing-associated gene for hostinsects H. armigera. The AcMNPV acquired the mentionedkilling activity and markedly accelerate the killing rate whenexpressing Ls-p13. In conclusion, p13 is a killing associatedgene in both homologous and heterologous nucleopolyhedrovirus.
2010-01-01
... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.13 Order. Order means an order..., research, and information regarding agricultural commodities authorized under the Act. ...
Genetic and bibliographic information: UBE2N [GenLibi
Lifescience Database Archive (English)
Full Text Available UBE2N ubiquitin-conjugating enzyme E2N (UBC13 homolog, yeast) human Skin Neoplasms ...(MeSH) Neoplasms (C04) > Neoplasms by Site (C04.588) > Skin Neoplasms (C04.588.805) Skin and Connective Tissue Diseases (C17) > Skin... Diseases (C17.800) > Skin Neoplasms (C17.800.882) 03A0584544 ...
Risk of bladder cancer in patients with diabetes
DEFF Research Database (Denmark)
Goossens, Maria E; Zeegers, Maurice P; Bazelier, Marloes T
2015-01-01
Statistics (ONS). Patients diagnosed with diabetes mellitus type 1 or 2, or using antidiabetic drugs (ADDs), were compared to matched non-diabetic controls. Cox proportional hazards models were used to estimate the risk and mortality of UBC. We adjusted for age, sex, smoking status and body mass index....... RESULTS: The cohort included 329,168 patients using ADD, and 307,315 controls with 1295 and 1071 patients, respectively, diagnosed as having UBC during follow-up. The adjusted HRs of UBC were 0.77 (95% CI 0.57 to 1.05) and 1.04 (95% CI 0.96 to 1.14) for type 1 and 2 diabetes, respectively. These results...... haemoglobin. Mortality of UBC was not increased for patients with either type 1 (HR=0.95 (95% CI 0.39 to 2.34)) or type 2 diabetes (HR=1.16 (95% CI 0.91 to 1.46)). CONCLUSIONS: Neither the risk of UBC nor the mortality from UBC was increased in patients with type 1 and patients with type 2 diabetes...
MacDonald, Kevin M; Swanstrom, Morgan M; McCarthy, James J; Nemeth, Blaise A; Guliani, Teresa A; Noonan, Kenneth J
2010-03-01
Recurrent unicameral bone cysts (UBCs) can result in significant morbidity during a child's physical and emotional development. Multiple treatment options are available and a review of the literature fails to clearly define the optimal treatment for UBCs. Recombinant bone morphogenetic protein (BMP) has been used with success in other disorders of poor bone formation. This manuscript is the first to report on the use of recombinant BMP in the treatment of UBCs. Three patients with recurrent UBCs underwent revision surgery with recombinant BMP. Radiographic and medical review was performed and is reported here. In these patients, the use of BMP failed to fully resolve their UBC; 2 patients had complete recurrence that required further surgery. In addition to poor radiographic results, all patients developed exaggerated inflammatory responses in the acute postoperative period. Each child developed clinically significant limb swelling and pain that mimicked infection. On the basis of our poor radiographic results and a paradoxical clinical result, we no longer recommend the use of recombinant BMP in the manner reported here for the treatment of recurrent UBCs. Level IV, case series.
International Nuclear Information System (INIS)
Piette, J.; Decuyper-Debergh, D.; Gamper, H.
1985-01-01
Double-stranded M13 phage DNA (M13 mp10 replicative form) was photoreacted with 4'-hydroxymethyl-4,5',8-trimethylpsoralen, using light of wavelength greater than 320 nm or greater than 390 nm to generate predominantly crosslinks or monoadducts, respectively. The damaged DNAs were scored for inactivation and mutagenesis after transfection into Escherichia coli. The appearance of light-blue or colorless plaques on indicator medium showed that mutation had occurred in the lac insert of the viral DNA. A comparison of the consequences of the two phototreatments with psoralen supports the idea that crosslinks are both more lethal and more mutagenic than monoadducts. Numerous mutant clones partially or totally deficient in beta-galactosidase were plaque-purified and amplified. The viral DNA of each clone was sequenced by the dideoxy chain-terminating procedure. All of the observed base-pair changes were mapped to the lac promoter region and consisted of 3 transition, 14 transversion, and 6 single base-pair frame-shift mutations. The predominant mutation was a T.A----G.C transversion
International Nuclear Information System (INIS)
Bukhari, S.M.H.; Shahzad, S.Q.; Naeem, S.; Qureshi, G.R.; Naveed, I.A.
2002-01-01
Objective: To study the effects of chemical carcinogens on epithelial and mesenchymal tumorigenesis with tumor initiation-promotion protocol and the use of 13-cis retinoic acid as a chemo preventive agent. Design: It was an experimental study. Place and Duration of Study: The study was conducted at Postgraduate Medical Institute (PGML) Lahore for 20 weeks. Materials and Methods: Sixty albino rats were divided into six groups of ten of animals each. First group of animals (control) was not given carcinogens and 13-cis retinoic acid in second group DMBA was applied on the dorsal skin in repeated dos of 100 mu g/ml in acetone, twice a weak. In the third group DMBA was given 100 mu g/ml as single dose while TPA was given 10 mu g//ml in acetone, twice a weak after two weeks of DMBA applications. In fourth group only DMBA 100 mu g/ml in acetone was applied as a single dose. In fifth and sixth groups 13-cis retinoic acid was given topically before and after the application of DMBA and TPA. Results: First and fourth groups did not develop any tumor. In second groups 2 animals developed malignant fibrous histiocytoma, 4 squamous cell carcinoma while 1 dysphasia and 1 carcinoma in situ. Third group developed osteoma (3 animals), papilloma (3 animals, squamous cell carcinoma (01) and dysplasia (01). Conclusion: Our results showed that DMBA acts as tumor initiator while TPA as promoter. DMBA also produces tumors itself when given alone in repeated doses. The chemical carcinogens are not only a cause of epithelial carcinogenesis but also responsible for mesenchymal tumorigenesis. 13 cis retinoic acid was equally effective in both stages of tumorigenesis. It also prevents malignant conversion of chemically induced benign tumors. (author)
Synthesis of edatrexate (2-13C-glutamate)
International Nuclear Information System (INIS)
DeGraw, J.I.; Colwell, W.T.; Jue, Thomas
1997-01-01
The experimental antitumor drug Edatrexate, labeled with 99% 13 C at the 2-position of the glutamate acid group was required for 13 C-magnetic resonance spectroscopy studies in biological media. Coupling of 2,4-diamino-4-deoxy-10-ethyl-10-deazapteroic acid with diethyl L-2- 13 C-glutamate as promoted by BOP reagent afforded Edatrexate (2- 13 C-glu) diethyl ester in 60% yield following purification by column chromatography. Saponification by aqueous NaOH in 2-methoxyethanol gave the target molecule in 44% yield or 26% overall. (author)
VvWRKY13 enhances ABA biosynthesis in Vitis vinifera
Directory of Open Access Journals (Sweden)
JIe Hao
2017-06-01
Full Text Available Abscisic acid (ABA plays critical roles in plant growth and development as well as in plants’ responses to abiotic stresses. We previously isolated VvWRKY13, a novel transcription factor, from Vitis vinifera (grapevine, and here we present evidence that VvWRKY13 may regulate ABA biosynthesis in plants. When VvWRKY13 was ectopically expressed in Arabidopsis, the transgenic lines showed delayed seed germination, smaller stomatal aperture size, and several other phenotypic changes, indicating elevated ABA levels in these plants. Sequence analysis of several genes that are involved in grapevine ABA synthetic pathway identified WRKY-specific binding elements (W-box or W-like box in the promoter regions. Indeed, transient overexpression of VvWRKY13 in grapevine leaves significantly increased the transcript levels of ABA synthetic pathway genes. Taken together, we conclude that VvWRKY13 may promote ABA production by activating genes in the ABA synthetic pathway.
Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN
Energy Technology Data Exchange (ETDEWEB)
Stroschein, Shannon L.; Bonni, Shirin; Wrana, Jeffrey L.; Luo, Kunxin
2001-09-11
Smad proteins mediate transforming growth factor-b signaling to regulate cell growth and differentiation. SnoN is an important negative regulator of TGFb signaling that functions to maintain the repressed state of TGFb target genes in the absence of ligand. Upon TGFb stimulation, Smad3 and Smad2 translocate into the nucleus and induce a rapid degradation of SnoN, allowing activation of TGFb target genes. Here we show that Smad2- or Smad3-induced degradation of SnoN requires the ubiquitin-dependent proteasome and can be mediated by the anaphase promoting complex (APC) and the UbcH5 family of ubiquitin conjugating enzymes. Smad3 and to a lesser extent, Smad2, interact with both the APC and SnoN, resulting in the recruitment of the APC to SnoN and subsequent ubiquitination of SnoN in a destruction box-dependent manner. In addition to the destruction box, efficient degradation of SnoN also requires the Smad3 binding site in SnoN as well as key lysine residues necessary for ubiquitin attachment. Mutation of either the Smad3 binding site or lysine residues results in stabilization of SnoN and in enhanced antagonism of TGFb signaling. Our studies elucidate an important pathway for the degradation of SnoN and reveal a novel role of the APC in regulation of TGFb signaling.
Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN
International Nuclear Information System (INIS)
Stroschein, Shannon L.; Bonni, Shirin; Wrana, Jeffrey L.; Luo, Kunxin
2001-01-01
Smad proteins mediate transforming growth factor-b signaling to regulate cell growth and differentiation. SnoN is an important negative regulator of TGFb signaling that functions to maintain the repressed state of TGFb target genes in the absence of ligand. Upon TGFb stimulation, Smad3 and Smad2 translocate into the nucleus and induce a rapid degradation of SnoN, allowing activation of TGFb target genes. Here we show that Smad2- or Smad3-induced degradation of SnoN requires the ubiquitin-dependent proteasome and can be mediated by the anaphase promoting complex (APC) and the UbcH5 family of ubiquitin conjugating enzymes. Smad3 and to a lesser extent, Smad2, interact with both the APC and SnoN, resulting in the recruitment of the APC to SnoN and subsequent ubiquitination of SnoN in a destruction box-dependent manner. In addition to the destruction box, efficient degradation of SnoN also requires the Smad3 binding site in SnoN as well as key lysine residues necessary for ubiquitin attachment. Mutation of either the Smad3 binding site or lysine residues results in stabilization of SnoN and in enhanced antagonism of TGFb signaling. Our studies elucidate an important pathway for the degradation of SnoN and reveal a novel role of the APC in regulation of TGFb signaling
Directory of Open Access Journals (Sweden)
Erik van der Wal
2017-06-01
Full Text Available The most common variant causing Pompe disease is c.-32-13T>G (IVS1 in the acid α-glucosidase (GAA gene, which weakens the splice acceptor of GAA exon 2 and induces partial and complete exon 2 skipping. It also allows a low level of leaky wild-type splicing, leading to a childhood/adult phenotype. We hypothesized that cis-acting splicing motifs may exist that could be blocked using antisense oligonucleotides (AONs to promote exon inclusion. To test this, a screen was performed in patient-derived primary fibroblasts using a tiling array of U7 small nuclear RNA (snRNA-based AONs. This resulted in the identification of a splicing regulatory element in GAA intron 1. We designed phosphorodiamidate morpholino oligomer-based AONs to this element, and these promoted exon 2 inclusion and enhanced GAA enzyme activity to levels above the disease threshold. These results indicate that the common IVS1 GAA splicing variant in Pompe disease is subject to negative regulation, and inhibition of a splicing regulatory element using AONs is able to restore canonical GAA splicing and endogenous GAA enzyme activity.
Comparison of three surgical treatment options for unicameral bone cysts in humerus.
Mavčič, Blaž; Saraph, Vinay; Gilg, Magdalena M; Bergovec, Marko; Brecelj, Janez; Leithner, Andreas
2018-04-23
Treatment of unicameral bone cysts (UBC) in the humerus with drainage screws is scarcely reported in the literature. The aim of this retrospective study was to compare drainage screws and alternative treatment methods with respect to the number of required surgical procedures to achieve sufficient UBC healing, postoperative fractures/recurrences/complications, and radiological outcome. Medical archives of two tertiary orthopedic referral centers were screened for all patients who were treated surgically for humeral UBC in the period 1991-2015 with a histologically/cytologically confirmed diagnosis. Sex, age, all surgical procedures, fractures, complications, recurrences, and the final radiological outcome were compared between patients treated with drainage screws, elastic intramedullary nails, or curettage with optional grafting. The study included 106 operated patients with a mean age of 10.3 years, with a mean follow-up of 5.7 years. The average number of UBC-related surgical procedures in sex-matched and age-matched treatment groups was 2.7 with drainage screws, 2.8 with intramedullary nails, and 3.5 with curettage/grafting (P=0.54). Intramedullary nails (odds ratio 0.20) and older age (odds ratio for each year 0.83) predicted a lower risk of postoperative UBC recurrence. Patients with drainage screws had the highest UBC recurrence rates and the lowest rates of changed initial treatment method. There was no difference between the treatment groups in the postoperative fracture rate, complications, or the final radiological outcome. UBC treatment in the humerus therefore requires approximately three surgical procedures, irrespective of the treatment modality chosen. Adding an elastic intramedullary nail to a humeral UBC cyst may reduce recurrence risk and prevent further fractures. Level III - therapeutic retrospective comparative study.
DEFF Research Database (Denmark)
Hansen, Alexander B; Hoiland, Ryan L; Lewis, Nia C S
2018-01-01
the course of acclimatization to the hypoxia of terrestrial high altitude has not been examined. Thus, the purpose of the present study was to examine the influence of orally ingested antioxidants at clinically relevant doses (vitamins C and E and α-lipoic acid) on cerebrovascular regulation at sea level...... (344 m; n = 12; female n = 2 participants) and at high altitude (5050 m; n = 9; female n = 2) in a randomized, placebo-controlled and double-blinded crossover design. Hypercapnic and hypoxic cerebrovascular reactivity tests of the internal carotid artery (ICA) were conducted at sea level, and global...... that an oral antioxidant cocktail known to attenuate systemic oxidative stress failed to alter cerebrovascular function at sea level and CBF during acclimatization to high altitude....
Unicameral Bone Cysts in the Humerus: Treatment Outcomes.
Kadhim, Muayad; Sethi, Samir; Thacker, Mihir M
2016-06-01
Several treatment modalities have been described for the treatment of unicameral bone cysts (UBC). The aim of this study was to examine the outcome of various treatment modalities of UBC in a specific anatomic location, the humerus. This study is a retrospective case-only study of patients with humeral UBC with minimum follow-up of 1 year. Medical records and radiographs were assessed and UBC healing status was determined based on most recent follow-up radiographs and divided into 3 groups (healed, partially healed, and not healed). Descriptive statistics were utilized to summarize study outcome. Sixty-eight patients (54 boys and 14 girls) with humeral UBC comprised the study population. Sixty-four cases (94.1%) presented with a pathologic fracture. Fifty-one cases were in the proximal metaphysis and 17 were in the diaphysis. Mean age at diagnosis was 9.2±3.7 years, and mean follow-up was 4.0±2.6 years. Twenty-five patients were treated with observation, 38 by injection (27 with steroids and 11 with bone marrow), and 5 by open surgery. Patients who underwent open surgery had relatively larger cyst length, width, and cyst index, and all healed or partially healed at last follow-up. UBC persistence was observed in 29% of diaphyseal and 27.5% of metaphyseal cysts. Of the 19 patients with persistence, 8 were treated with observation, 9 with steroid injection, and 2 with bone marrow injection. Inner wall disruption before injection was performed in 17 patients (24% did not heal), whereas 21 patients did not have inner wall disruption (33% did not heal). Twenty patients received >1 injection. Eleven patients complained of pain at the last visit (8 had a persistent cyst, 2 were partially healed, and 1 had a healed UBC). Complete healing of humeral UBC is challenging to achieve irrespective of treatment modality. UBCs treated with open surgery tended to heal better. Unhealed cysts were more likely to be associated with pain. Level III-a retrospective comparative study.
The prognostic value of family history among patients with urinary bladder cancer.
Egbers, Lieke; Grotenhuis, Anne J; Aben, Katja K; Alfred Witjes, J; Kiemeney, Lambertus A; Vermeulen, Sita H
2015-03-01
A history of urinary bladder cancer (UBC) in first-degree relatives increases UBC risk by twofold. The influence of positive family history on UBC prognosis is unknown. Here, we investigated association of first-degree UBC family history with clinicopathological characteristics and prognosis of UBC patients. Detailed clinical data of 1,465 non-muscle-invasive bladder cancer (NMIBC) and 250 muscle-invasive or metastatic bladder cancer (MIBC) patients, diagnosed from 1995 to 2010, were collected through medical file review. Competing risk analyses were used to compare recurrence-free survival (RFS) and progression-free survival (PFS) of NMIBC patients according to self-reported UBC family history. Overall survival in MIBC patients was estimated using Kaplan-Meier analysis. The added value of family history in prediction of NMIBC prognosis was quantified with Harrell's concordance-index. Hundred (6.8%) NMIBC and 14 (5.6%) MIBC patients reported UBC in first-degree relatives. Positive family history was statistically significantly associated with smaller tumor size and non-significantly with more favorable distribution of other tumor characteristics. In univariable analyses, positive family history correlated with longer RFS (p = 0.11) and PFS (p = 0.04). Hazard ratios for positive vs. negative family history after adjustment for clinicopathological characteristics were 0.75 (95% CI = 0.53-1.07) and 0.45 (95% CI = 0.18-1.12) for RFS and PFS, respectively. Five familial and 48 sporadic MIBC patients (Kaplan-Meier 10-year risk: 41% and 25%) died within 10 years. Family history did not improve the c-index of prediction models. This study shows that a first-degree family history of UBC is not clearly associated with NMIBC prognosis. Family history does not aid in prediction of NMIBC recurrence or progression. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.
Water promoted allylic nucleophilic substitution reactions of (E)-1,3 diphenylallyl acetate
Ghorpade, Seema Arun; Sawant, Dinesh N; Makki, Arwa; Sekar, N; Eppinger, Jö rg
2017-01-01
Transition metal free, water based, greener protocol for allylic alkylation, allylic amination, O-allylation of (E)-1,3-diphenylallyl acetate is described. The developed methodology is applicable for a wide range of nucleophiles furnishing excellent yields of corresponding products up to 87% under mild reaction conditions. A Distinct effect of water and base is explored for allylic nucleophilic substitution reactions of (E)-1,3-diphenylallyl acetate.
Water promoted allylic nucleophilic substitution reactions of (E)-1,3 diphenylallyl acetate
Ghorpade, Seema Arun
2017-11-30
Transition metal free, water based, greener protocol for allylic alkylation, allylic amination, O-allylation of (E)-1,3-diphenylallyl acetate is described. The developed methodology is applicable for a wide range of nucleophiles furnishing excellent yields of corresponding products up to 87% under mild reaction conditions. A Distinct effect of water and base is explored for allylic nucleophilic substitution reactions of (E)-1,3-diphenylallyl acetate.
Nakajima, Jun'ichi; Nakae, Dai; Yasukawa, Ken
2013-08-01
Whether and how synthetic cannabinoids affect inflammation and carcinogenesis has not been well studied. The present study was thus conducted to assess effects of synthetic cannabinoids on inflammation and carcinogenesis in vivo in mice. Twenty-three analogues of synthetic cannabinoids were isolated from, and identified as adulterants in, illegal drugs distributed in the Tokyo metropolitan area, and were examined for their inhibitory effects on the induction of oedema in mouse ears by 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, selected cannabinoids, JWH-018, -122 and -210, were studied for their effects on carcinogenesis induced in mouse skin initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by TPA. Among cannabinoids, naphthoylindoles mostly exhibited superior inhibitory effects against TPA-induced ear oedema and, especially, JWH-018, -122 and -210 showed potent activity with 50% inhibitory dose (ID50) values of 168, 346 and 542 nm, respectively (an activity corresponding to that of indometacin (ID50 = 908 nm)). Furthermore these three compounds also markedly suppressed the tumour-promoting activity of TPA. This is the first report indicating the structure-activity relationships for the anti-inflammatory activity of synthetic cannabinoids on TPA-induced inflammation in mice. Naphthoylindoles, JWH-018, -122 and -210, had the most potent anti-inflammatory activity and also markedly inhibited tumour promotion by TPA in the two-stage mouse skin carcinogenesis model. The present results suggest that synthetic cannabinoids, such as JWH-018, -122 and -210, may be used as cancer chemopreventive agents in the future. © 2013 Royal Pharmaceutical Society.
Unicameral Bone Cyst in the Calcaneus of Mirror Image Twins.
Lenze, Ulrich; Stolberg-Stolberg, Josef; Pohlig, Florian; Lenze, Florian; von Eisenhart-Rothe, Rüdiger; Rechl, Hans; Toepfer, Andreas
2015-01-01
Unicameral bone cysts (UBCs) are benign tumor-like lesions that commonly occur in the diaphyseal or metaphyseal region of the long bones within the first 2 decades of life. Until today, the pathogenesis of UBC has been unclear, but mechanisms such as vascular occlusion or a response to trauma have been supposed. During the past decade, in particular, the genetic aspects of the development of this rare lesion have been discussed. We present the first case of mirror image monozygotic twins with a mirror image UBC of the calcaneus. Our findings reinforce the importance of additional studies to understand the significance of cytogenetic factors in the etiology of UBC. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.
A Highly Expressed High-Molecular-Weight S-Layer Complex of Pelosinus sp. Strain UFO1 Binds Uranium
Energy Technology Data Exchange (ETDEWEB)
Thorgersen, Michael P. [Univ. of Georgia, Athens, GA (United States). Dept. of Biochemistry and Molecular Biology; Lancaster, W. Andrew [Univ. of Georgia, Athens, GA (United States). Dept. of Biochemistry and Molecular Biology; Rajeev, Lara [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Ge, Xiaoxuan [Univ. of Georgia, Athens, GA (United States). Dept. of Biochemistry and Molecular Biology; Vaccaro, Brian J. [Univ. of Georgia, Athens, GA (United States). Dept. of Biochemistry and Molecular Biology; Poole, Farris L. [Univ. of Georgia, Athens, GA (United States). Dept. of Biochemistry and Molecular Biology; Arkin, Adam P. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Mukhopadhyay, Aindrila [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Adams, Michael W. W. [Univ. of Georgia, Athens, GA (United States). Dept. of Biochemistry and Molecular Biology
2016-12-02
Cell suspensions of Pelosinus sp. strain UFO1 were previously shown, using spectroscopic analysis, to sequester uranium as U(IV) complexed with carboxyl and phosphoryl group ligands on proteins. The goal of our present study was to characterize the proteins involved in uranium binding. Virtually all of the uranium in UFO1 cells was associated with a heterodimeric protein, which was termed the uranium-binding complex (UBC). The UBC was composed of two S-layer domain proteins encoded by UFO1_4202 and UFO1_4203. Samples of UBC purified from the membrane fraction contained 3.3 U atoms/heterodimer, but significant amounts of phosphate were not detected. The UBC had an estimated molecular mass by gel filtration chromatography of 15 MDa, and it was proposed to contain 150 heterodimers (UFO1_4203 and UFO1_4202) and about 500 uranium atoms. The UBC was also the dominant extracellular protein, but when purified from the growth medium, it contained only 0.3 U atoms/heterodimer. The two genes encoding the UBC were among the most highly expressed genes within the UFO1 genome, and their expressions were unchanged by the presence or absence of uranium. Therefore, the UBC appears to be constitutively expressed and is the first line of defense against uranium, including by secretion into the extracellular medium. Although S-layer proteins were previously shown to bind U(VI), here we showed that U(IV) binds to S-layer proteins, we identified the proteins involved, and we quantitated the amount of uranium bound. Widespread uranium contamination from industrial sources poses hazards to human health and to the environment. Here in this paper, we identified a highly abundant uranium-binding complex (UBC) from Pelosinus sp. strain UFO1. The complex makes up the primary protein component of the S-layer of strain UFO1 and binds 3.3 atoms of U(IV) per heterodimer. Finally, while other bacteria have been shown to bind U(VI) on their S-layer, we demonstrate here an example of U(IV) bound by
Placental Protein 13 (PP13 – a placental immunoregulatory galectin protecting pregnancy
Directory of Open Access Journals (Sweden)
Nandor Gabor Than
2014-08-01
Full Text Available Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13. It has a jelly-roll fold, carbohydrate-recognition domain and sugar-binding preference resembling to other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low first trimester maternal serum concentrations are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is an increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing
Bone marrow-derived CD13+ cells sustain tumor progression
Dondossola, Eleonora; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata
2014-01-01
Non-malignant cells found within neoplastic lesions express alanyl (membrane) aminopeptidase (ANPEP, best known as CD13), and CD13-null mice exhibit limited tumor growth and angiogenesis. We have recently demonstrated that a subset of bone marrow-derived CD11b+CD13+ myeloid cells accumulate within neoplastic lesions in several murine models of transplantable cancer to promote angiogenesis. If these findings were confirmed in clinical settings, CD11b+CD13+ myeloid cells could become a non-malignant target for the development of novel anticancer regimens. PMID:25339996
Treatment of unicameral bone cyst: systematic review and meta analysis.
Kadhim, Muayad; Thacker, Mihir; Kadhim, Amjed; Holmes, Laurens
2014-03-01
Different treatment modalities have been utilized to treat unicameral bone cyst (UBC), but evidence has not been fully described to support one treatment over another and the optimal treatment is controversial. The aim of this quantitative systematic review was to assess the effectiveness of different UBC treatment modalities. We utilized Pubmed to isolate retrospective studies on patients with UBC who received any kind of treatment. The included studies needed to have a minimum sample size of 15 patients, and have provided data on radiographic healing outcome. Sixty-two articles were selected for the meta-analysis from a total of 463 articles. The cumulative sample size was 3,211 patients with 3,217 UBC, and male to female ratio was 2.2:1. The summary or pool estimate of methylprednisolone acetate (MPA) injection resulted in a healing rate of (77.4 %) that was comparable to bone marrow injection (77.9 %). A higher healing rate was observed with MPA injection when inner wall disruption was performed. The pool estimate of bone marrow with demineralized bone matrix injection was high (98.7 %). UBC healing rate after surgical curettage was comparable whether autograft or allograft was utilized (90 %). UBC treatment with flexible intramedullary nails without curettage provided almost 100% healing rate, while continuous decompression with cannulated screws provided 89 % healing rate. Conservative treatment indicated a healing rate of 64.2, 95 % CI (26.7-101.8). Active treatment for UBC provided variable healing rates and the outcomes were favorable relative to conservative treatment. Due to the heterogeneity of the studies and reporting bias, the interpretation of these findings should be handled with caution.
Optimization of the trienzyme extraction for the microbiological assay of folate in vegetables.
Chen, Liwen; Eitenmiller, Ronald R
2007-05-16
Response surface methodology was applied to optimize the trienzyme digestion for the extraction of folate from vegetables. Trienzyme extraction is a combined enzymatic digestion by protease, alpha-amylase, and conjugase (gamma-glutamyl hydrolase) to liberate the carbohydrate and protein-bound folates from food matrices for total folate analysis. It is the extraction method used in AOAC Official Method 2004.05 for assay of total folate in cereal grain products. Certified reference material (CRM) 485 mixed vegetables was used to represent the matrix of vegetables. Regression and ridge analysis were performed by statistical analysis software. The predicted second-order polynomial model was adequate (R2 = 0.947), without significant lack of fit (p > 0.1). Both protease and alpha-amylase have significant effects on the extraction. Ridge analysis gave an optimum trienzyme digestion time: Pronase, 1.5 h; alpha-amylase, 1.5 h; and conjugase, 3 h. The experimental value for CRM 485 under this optimum digestion was close to the predicted value from the model, confirming the validity and adequacy of the model. The optimized trienzyme digestion condition was applied to five vegetables and yielded higher folate levels than the trienzyme digestion parameters employed in AOAC Official Method 2004.05.
CDM Project Opportunities in Thailand
DEFF Research Database (Denmark)
2009-01-01
Interview on Channel 2 UBC Thailand Fysisk medie: .dat mpeg video file Tidspunkt for udsendelse: 2003/06/28......Interview on Channel 2 UBC Thailand Fysisk medie: .dat mpeg video file Tidspunkt for udsendelse: 2003/06/28...
Li, Qiuhong; Chang, Leifu; Aibara, Shintaro; Yang, Jing; Zhang, Ziguo; Barford, David
2016-09-20
The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric cullin-RING E3 ubiquitin ligase that orchestrates cell-cycle progression by targeting cell-cycle regulatory proteins for destruction via the ubiquitin proteasome system. The APC/C assembly comprises two scaffolding subcomplexes: the platform and the TPR lobe that together coordinate the juxtaposition of the catalytic and substrate-recognition modules. The platform comprises APC/C subunits Apc1, Apc4, Apc5, and Apc15. Although the role of Apc1 as an APC/C scaffolding subunit has been characterized, its specific functions in contributing toward APC/C catalytic activity are not fully understood. Here, we report the crystal structure of the N-terminal domain of human Apc1 (Apc1N) determined at 2.2-Å resolution and provide an atomic-resolution description of the architecture of its WD40 (WD40 repeat) domain (Apc1(WD40)). To understand how Apc1(WD40) contributes to APC/C activity, a mutant form of the APC/C with Apc1(WD40) deleted was generated and evaluated biochemically and structurally. We found that the deletion of Apc1(WD40) abolished the UbcH10-dependent ubiquitination of APC/C substrates without impairing the Ube2S-dependent ubiquitin chain elongation activity. A cryo-EM structure of an APC/C-Cdh1 complex with Apc1(WD40) deleted showed that the mutant APC/C is locked into an inactive conformation in which the UbcH10-binding site of the catalytic module is inaccessible. Additionally, an EM density for Apc15 is not visible. Our data show that Apc1(WD40) is required to mediate the coactivator-induced conformational change of the APC/C that is responsible for stimulating APC/C catalytic activity by promoting UbcH10 binding. In contrast, Ube2S activity toward APC/C substrates is not dependent on the initiation-competent conformation of the APC/C.
Directory of Open Access Journals (Sweden)
Xin Long
Full Text Available The aim of this study was to determine whether two polymorphisms in the gene encoding IL13 previously associated with Schistosoma hematobium (S. hematobium and S. mansoni infection are associated with S. japonicum infection. Single nucleotide polymorphisms (SNPs rs1800925 (IL13/-1112C>T and rs20541 (IL13R130Q were genotyped in 947 unrelated individuals (307 chronically infected, 339 late-stage with liver fibrosis, 301 uninfected controls from a schistosomiasis-endemic area of Hubei province in China. Regression models were used to evaluate allelic and haplotypic associations with chronic and late-stage schistosomiasis adjusted for non-genetic covariates. Expression of IL-13 was measured in S. japonicun-infected liver fibrosis tissue and normal liver tissue from uninfected controls by immunohistochemistry (IHC. The role of rs1800925 in IL-13 transcription was further determined by Luciferase report assay using the recombinant PGL4.17-rs180092 plasmid. We found SNP rs1800925T was associated with late-stage schistosomiasis caused by S. japonicum but not chronic schistosomiasis (OR = 1.39, 95%CI = 1.02-1.91, p = 0.03 and uninfected controls (OR = 1.49, 95%CI = 1.03-2.13, p = 0.03. Moreover, the haplotype rs1800925T-rs20541C increased the risk of disease progression to late-stage schistosomiasis (OR = 1.46, p = 0.035, whereas haplotype rs1800925C-rs20541A showed a protective role against development of late-stage schistosomiasis (F = 0.188, OR = 0.61, p = 0.002. Furthermore, S. japonicum-induced fibrotic liver tissue had higher IL13 expression than normal liver tissue. Plasmid PGL4.17-rs1800925T showed a stronger relative luciferase activity than Plasmid PGL4.17-rs1800925C in 293FT, QSG-7701 and HL-7702 cell lines. In conclusion, the functional IL13 polymorphism, rs1800925T, previously associated with risk of schistosomiasis, also contributes to risk of late-stage schistosomiasis caused by S. japonicum.
Unicameral (simple) and aneurysmal bone cysts: the effect of insufficient curettage on recurrence.
Çelik, Suat; Uludağ, Abuzer; Tosun, Hacı Bayram; Serbest, Sancar; Gürger, Murat; Kılıç, Sabahattin
2016-01-01
Curettage of the cyst and bone grafting are the most common methods used in the treatment of unicameral bone cysts (UBC) and aneurysmal bone cysts (ABC). Recurrence of these cysts is often associated with insufficient curettage of the cyst during surgery. In this study, we aimed to evaluate the effect of insufficient curettage on recurrence in patients with UBC and ABC. The retrospective study included 18 patients with UBC and 14 patients with ABC that were surgically treated by curettage and bone grafting in our clinic between 2006-2013. Mean age was 19.80 (range, 4-50) years in the patients with UBC and 21.76 (range, 4-56) in the patients with ABC. The diagnosis of the cysts was established both clinically and radiologically. Mean follow-up period was 36 (range, 6-60) months both in the patients with UBC and ABC. The patients with recurrence underwent a second curettage and grafting procedure. Healing and recurrence were evaluated according to modified Neer's scale. Recurrence occurred in 8 patients. Of these, 5 patients underwent a second curettage and grafting procedure and 3 patients were lost to follow-up. Complete healing occurred in all the patients that underwent a second curettage and grafting procedure. The achievement of complete healing in the patients that underwent a second curettage and grafting procedure indicates that the recurrence of UBC and ABC is associated with insufficient curettage.
Controversial roles played by toll like receptor 4 in urinary bladder cancer; A systematic review.
Afsharimoghaddam, Amin; Soleimani, Mohammad; Lashay, Alireza; Dehghani, Mahdi; Sepehri, Zahra
2016-08-01
Urinary bladder cancer (UBC) is a prevalent human cancer. The main mechanisms which lead to eradication or progression the disease has yet to be clarified. Toll like receptor (TLR) 4 is a membrane receptor which is expressed either on immune cells or tumor cells. This review article was aimed to clear the main mechanisms played by TLR4 and its related intracellular pathways on outcome of UBC. PubMed, Scopus and Google scholar databases have been used for searching related research articles which have evaluated the roles played by TLR4 and its related intracellular pathways on outcome of UBC. Collected information from the related articles revealed that TLR4 either participates in induction of immune responses against UBC or development of the malignancy. There are limited investigations regarding the genetic variations of TLR4 in UBC. According to the results it seems that TLR4/ligands interaction outcome is dependent on several factors including TLR4 ligand doses, interaction of TLR4 with its ligands on immune cells or tumor cells, and other TLRs/ligand interaction simultaneously. Copyright © 2016 Elsevier Inc. All rights reserved.
2013-12-26
... carry out projects relating to research, consumer information, advertising, sales, promotion, producer... Service [Doc.No. AMS-LPS-13-0088] National Research, Promotion, and Consumer Information Programs; Request... of Softwood Lumber and National Processed Raspberry Promotion, Research, and Information Programs...
Meanings of care in health promotion.
Falcón, Gladys Carmela Santos; Erdmann, Alacoque Lorenzini; Backes, Dirce Stein
2008-01-01
The objective of the study is to understand the meaning built by students and professors on health promotion in the teaching and learning process of health care in Nursing. It is a qualitative study using ground theory as a methodological reference. Data was collected through interviews, with three samples groups, 13 students and four professors, by classroom observation, and through meetings with nursing professors. The central subject resulting from this analysis was: constructing teaching and learning in order, disorder and self organization for a new way of caring promoting health. The teaching/learning process directed at health promotion develops in a stage of crisis, going from a state of order to a state of disorder that is uncertain and contradictory regarding what society understands about health.
Biochemical function of typical and variant Arabidopsis thaliana U-box E3 ubiquitin-protein ligases.
Wiborg, Jakob; O'Shea, Charlotte; Skriver, Karen
2008-08-01
The variance of the U-box domain in 64 Arabidopsis thaliana (thale cress) E3s (ubiquitin-protein ligases) was used to examine the interactions between E3s and E2s (ubiquitin-conjugating enzymes). E2s and E3s are components of the ubiquitin protein degradation pathway. Seven U-box proteins were analysed for their ability to ubiquitinate proteins in vitro in co-operation with different E2s. All U-box domains exhibited ubiquitination activity and interacted productively with UBC4/5-type E2s. Three and four of the U-box domains mediated ubiquitin addition in the presence of UBC13 and UBC7 E2s respectively, but no productive interaction was observed with the UBC15 E2 tested. The activity of AtPUB54 [Arabidopsis thaliana (thale cress) plant U-box 54 protein] was dependent on Trp(266) in the E2-binding cleft, and the E2 selectivity was changed by substitution of this position. The function of the distant U-box protein, AtPUB49, representing a large family of eukaryotic proteins containing a U-box linked to a cyclophilin-like peptidyl-prolyl cis-trans isomerase domain, was characterized biochemically. AtPUB49 functioned both as a prolyl isomerase and a chaperone by catalysing cis-trans isomerization of peptidyl-prolyl bonds and dissolving protein aggregates. In conclusion, both typical and atypical Arabidopsis U-box proteins were active E3s. The overlap in the E3/E2 selectivity suggests that in vivo specificity is not determined only by the E3-E2 interactions, but also by other parameters, e.g. co-existence or interactions with additional domains. The biochemical functions of AtPUB49 suggest that the protein can be involved in folding or degradation of protein substrates. Similar functions can also be retained within a protein complex with separate chaperone and U-box proteins.
de Sanctis, Nando; Andreacchio, Antonio
2006-01-01
Since Virchow first described the unicameral bone cyst (UBC) in 1876, several methods for management were proposed. Currently performed surgical procedures include curettage combined with bone grafting, allografting with freeze-dried crushed cortical bone, use of homologous cancellous bone chips, the application of high-porosity hydroxyapatite, and cryosurgery. Decompression with multiple drill holes and intralesional injections of either steroids or bone marrow have also been used to treat UBC, with variable success rates. Elastic stable intramedullary nailing for the treatment of UBC in long bones has been rapidly gaining popularity. Elastic stable intramedullary nailing for the treatment of a UBC was performed in 56 patients between 1994 and 2003. The follow-up is between 2.1 and 11 years. Nine children were excluded because of short period of follow-up or were lost. The study population consisted of 47 children. The cyst was located in the humerus in 36 patients, in the femur in 11. The mean age of the patients at the time of surgery was 8.9 years. Results were evaluated on plain radiographs according to the classification system of Capanna et al. In our study population of 47 UBCs, 31 (65.9 %) were classified as completely healed, and 16 (34.1%) were healed with residual radiolucency. No recurrence or no response was observed. Each lesion responded to treatment after the nailing. This method can solve in time the pathology, and we feel that, with skilled hands, this method is the best one for UBC treatment in the long bones of the children.
Complete genome sequence of the plant-associated Serratia plymuthica strain AS13
Energy Technology Data Exchange (ETDEWEB)
Neupane, Saraswoti [Uppsala University, Uppsala, Sweden; Finlay, Roger D. [Uppsala University, Uppsala, Sweden; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Alstrom, Sadhna [Uppsala University, Uppsala, Sweden; Lucas, Susan [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Han, James [U.S. Department of Energy, Joint Genome Institute; Lapidus, Alla L. [U.S. Department of Energy, Joint Genome Institute; Cheng, Jan-Fang [U.S. Department of Energy, Joint Genome Institute; Bruce, David [Los Alamos National Laboratory (LANL); Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Peters, Lin [U.S. Department of Energy, Joint Genome Institute; Ovchinnikova, Galina [U.S. Department of Energy, Joint Genome Institute; Held, Brittany [Los Alamos National Laboratory (LANL); Han, Cliff [Los Alamos National Laboratory (LANL); Detter, J C [U.S. Department of Energy, Joint Genome Institute; Tapia, Roxanne [Los Alamos National Laboratory (LANL); Hauser, Loren John [ORNL; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Pagani, Ioanna [U.S. Department of Energy, Joint Genome Institute; Woyke, Tanja [U.S. Department of Energy, Joint Genome Institute; Klenk, Hans-Peter [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Hogberg, Nils [Uppsala University, Uppsala, Sweden
2012-01-01
Serratia plymuthica AS13 is a plant-associated Gammaproteobacteria, isolated from rapeseed roots. It is of special interest because of its ability to inhibit fungal pathogens of rapeseed and to promote plant growth. The complete genome of S. plymuthica AS13 consists of a 5,442,549 bp circular chromosome. The chromosome contains 4,951 protein-coding genes, 87 tRNA genes and 7 rRNA operons. This genome was sequenced as part of the project enti- tled Genomics of four rapeseed plant growth promoting bacteria with antagonistic effect on plant pathogens within the 2010 DOE-JGI Community Sequencing Program (CSP2010).
Considering University-Business Cooperation Modes from the Perspective of Enterprises
Pavlin, Samo
2016-01-01
This article analyses enterprises' engagement in university-business cooperation (UBC) activities: research and development, mobility of academics and students, curriculum development and lifelong learning. It first provides an introductory overview of university-business cooperation policy. It then presents a selection of UBC models, elements and…
Maine DOT Research Peer Exchange : June 13-15, 2017
2017-10-13
On June 13 15, 2017 the Maine Department of Transportation hosted a research peer exchange to promote the research program within the department, provide a mechanism for sharing research management ideas amongst the team members, identify opportun...
Aycan, Osman Emre; Çamurcu, İsmet Yalkın; Özer, Devrim; Arıkan, Yavuz; Kabukçuoğlu, Yavuz Selim
2015-06-01
Unicameral bone cysts (UBC) and aneurysmal bone cysts (ABC) are benign cystic lesions of bone which are easily diagnosed. However, unusual locations may lead to a false diagnosis. Therefore the aim of this retrospective study was to determine the frequency of unusual localizations. The authors studied 451 cases with histopathologically confirmed diagnosis of UBC or ABC, seen between 1981 and 2012. In the UBC group (352 cases) humerus, femur and calcaneus were found to be the most common sites, while acetabulum, scapula, scaphoid, lunatum, metacarpals, metatarsals, toe phalanges and ulna each accounted for less than 1%. In the ABC group (99 cases) the most common sites of involvement were femur, humerus and tibia, while finger phalanges, ilium, acetabulum, pubis, calcaneus, cuboid, and toe phalanges each accounted for only 1%. The differential diagnosis of cystic bone lesions should include both UBC and ABC. Pain complaints plead for the latter, except in case of fracture.
Bonanno, Laura; Costa, Carlota; Majem, Margarita; Sanchez, Jose Javier; Gimenez-Capitan, Ana; Rodriguez, Ignacio; Vergenegre, Alain; Massuti, Bartomeu; Favaretto, Adolfo; Rugge, Massimo; Pallares, Cinta; Taron, Miquel; Rosell, Rafael
2013-01-01
Platinum-based chemotherapy is the standard first-line treatment for non-oncogene-addicted non-small cell lung cancers (NSCLCs) and the analysis of multiple DNA repair genes could improve current models for predicting chemosensitivity. We investigated the potential predictive role of components of the 53BP1 pathway in conjunction with BRCA1. The mRNA expression of BRCA1, MDC1, CASPASE3, UBC13, RNF8, 53BP1, PIAS4, UBC9 and MMSET was analyzed by real-time PCR in 115 advanced NSCLC patients treated with first-line platinum-based chemotherapy. Patients expressing low levels of both BRCA1 and 53BP1 obtained a median progression-free survival of 10.3 months and overall survival of 19.3 months, while among those with low BRCA1 and high 53BP1 progression-free survival was 5.9 months (P <0.0001) and overall survival was 8.2 months (P=0.001). The expression of 53BP1 refines BRCA1-based predictive modeling to identify patients most likely to benefit from platinum-based chemotherapy. PMID:24197907
Transcriptional activation of Mina by Sp1/3 factors.
Lian, Shangli; Potula, Hari Hara S K; Pillai, Meenu R; Van Stry, Melanie; Koyanagi, Madoka; Chung, Linda; Watanabe, Makiko; Bix, Mark
2013-01-01
Mina is an epigenetic gene regulatory protein known to function in multiple physiological and pathological contexts, including pulmonary inflammation, cell proliferation, cancer and immunity. We showed previously that the level of Mina gene expression is subject to natural genetic variation linked to 21 SNPs occurring in the Mina 5' region. In order to explore the mechanisms regulating Mina gene expression, we set out to molecularly characterize the Mina promoter in the region encompassing these SNPs. We used three kinds of assays--reporter, gel shift and chromatin immunoprecipitation--to analyze a 2 kb genomic fragment spanning the upstream and intron 1 regions flanking exon 1. Here we discovered a pair of Mina promoters (P1 and P2) and a P1-specific enhancer element (E1). Pharmacologic inhibition and siRNA knockdown experiments suggested that Sp1/3 transcription factors trigger Mina expression through additive activity targeted to a cluster of four Sp1/3 binding sites forming the P1 promoter. These results set the stage for comprehensive analysis of Mina gene regulation from the context of tissue specificity, the impact of inherited genetic variation and the nature of upstream signaling pathways.
Alcohol promotions in Australian supermarket catalogues.
Johnston, Robyn; Stafford, Julia; Pierce, Hannah; Daube, Mike
2017-07-01
In Australia, most alcohol is sold as packaged liquor from off-premises retailers, a market increasingly dominated by supermarket chains. Competition between retailers may encourage marketing approaches, for example, discounting, that evidence indicates contribute to alcohol-related harms. This research documented the nature and variety of promotional methods used by two major supermarket retailers to promote alcohol products in their supermarket catalogues. Weekly catalogues from the two largest Australian supermarket chains were reviewed for alcohol-related content over 12 months. Alcohol promotions were assessed for promotion type, product type, number of standard drinks, purchase price and price/standard drink. Each store catalogue included, on average, 13 alcohol promotions/week, with price-based promotions most common. Forty-five percent of promotions required the purchase of multiple alcohol items. Wine was the most frequently promoted product (44%), followed by beer (24%) and spirits (18%). Most (99%) wine cask (2-5 L container) promotions required multiple (two to three) casks to be purchased. The average number of standard drinks required to be purchased to participate in catalogue promotions was 31.7 (SD = 24.9; median = 23.1). The median price per standard drink was $1.49 (range $0.19-$9.81). Cask wines had the lowest cost per standard drink across all product types. Supermarket catalogues' emphasis on low prices/high volumes of alcohol reflects that retailers are taking advantage of limited restrictions on off-premise sales and promotion, which allow them to approach market competition in ways that may increase alcohol-related harms in consumers. Regulation of alcohol marketing should address retailer catalogue promotions. [Johnston R, Stafford J, Pierce H, Daube M. Alcohol promotions in Australian supermarket catalogues. Drug Alcohol Rev 2017;36:456-463]. © 2016 Australasian Professional Society on Alcohol and other Drugs.
International Nuclear Information System (INIS)
Liu, B.Y.; Zhao, C.M.; Sun, X.M.; Jiang, H.B.
2015-01-01
In this study, DNA fingerprints were constructed by using ISSR markers for 20 clonal improved varieties developed by two breeding institutes in Yunnan province. Seven core ISSR primers were selected from 15 primers. A total of 110 bands were generated by PAGE with seven core primers, 93 of which were polymorphic bands, the percentage of polymorphic band (PPB) was 84.54%, and the mean value of polymorphism information content (PIC) reached 0.417; the genetic similarity coefficient of the cultivars was 0.574-0.854. The two primers, UBC835 and ISSR2, had high PIC values, and could be used to distinguish all cultivars, presenting the most efficient single primers. Among the all of primer combinations from the seven core primers, the three combinations, UBC835/UBC811, UBC835/ISSR2, and UBC835/ISSR3 showed lower similar coefficients, and more efficient in identifying the 20 improved varieties than the other primer combinations. Then these three primer combinations were further scored in 15 traditional cultivars. The results showed that UBC835/ISSR2 was the optimal primer combination, which could be used to distinguish each material among the 20 clonal improved varieties and 15 traditional cultivals. Finally, the DNA fingerprints of the 20 clonal improved varieties were constructed based on country and region code, breeding institute, core primer name and ISSR marker data. The established fingerprints could provide reliable scientific base for the protection of intellectual property right for these clonal improved varieties, and the important molecular information contained in these fingerprints would be useful for the authenticity identification and genetic relationship analysis of tea varieties. (author)
Is 3/4 of the Sales Promotion Bump Due to Brand Switching? No it is 1/3
van Heerde, H.J.; Gupta, S.; Wittink, D.R.
2003-01-01
Several researchers have decomposed sales promotion elasticities based on household scanner panel data.A key result is that the majority of the sales promotion elasticity, about 74 percent on average, is attributed to secondary demand effects (brand switching) and the remainder to primary demand
Plant growth promoters and methods of using them
Al-Babili, Salim
2017-01-01
New plant growth regulators, including compounds and compositions, and methods of use including for promoting root growth. The compounds are carotenoid oxidation products, and a preferred example is 3-OH--β-apo-13-Carotenone. A method comprising
Massard, Christophe; Gordon, Michael S.; Sharma, Sunil; Rafii, Saeed; Wainberg, Zev A.; Luke, Jason; Curiel, Tyler J.; Colon-Otero, Gerardo; Hamid, Omid; Sanborn, Rachel E.; O’Donnell, Peter H.; Drakaki, Alexandra; Tan, Winston; Kurland, John F.; Rebelatto, Marlon C.; Jin, Xiaoping; Blake-Haskins, John A.; Gupta, Ashok
2016-01-01
Purpose To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), and the role of PD-L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC). Methods A phase 1/2 multicenter, open-label study is being conducted in patients with inoperable or metastatic solid tumors. We report here the results from the UBC expansion cohort. Durvalumab (MEDI4736, 10 mg/kg every 2 weeks) was administered intravenously for up to 12 months. The primary end point was safety, and objective response rate (ORR, confirmed) was a key secondary end point. An exploratory analysis of pretreatment tumor biopsies led to defining PD-L1–positive as ≥ 25% of tumor cells or tumor-infiltrating immune cells expressing membrane PD-L1. Results A total of 61 patients (40 PD-L1–positive, 21 PD-L1–negative), 93.4% of whom received one or more prior therapies for advanced disease, were treated (median duration of follow-up, 4.3 months). The most common treatment-related adverse events (AEs) of any grade were fatigue (13.1%), diarrhea (9.8%), and decreased appetite (8.2%). Grade 3 treatment-related AEs occurred in three patients (4.9%); there were no treatment-related grade 4 or 5 AEs. One treatment-related AE (acute kidney injury) resulted in treatment discontinuation. The ORR was 31.0% (95% CI, 17.6 to 47.1) in 42 response-evaluable patients, 46.4% (95% CI, 27.5 to 66.1) in the PD-L1–positive subgroup, and 0% (95% CI, 0.0 to 23.2) in the PD-L1–negative subgroup. Responses are ongoing in 12 of 13 responding patients, with median duration of response not yet reached (range, 4.1+ to 49.3+ weeks). Conclusion Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1–positive patients with UBC, many of whom were heavily pretreated. PMID:27269937
Taguchi, Y-h
2015-01-01
Transgenerational epigenetics (TGE) are currently considered important in disease, but the mechanisms involved are not yet fully understood. TGE abnormalities expected to cause disease are likely to be initiated during development and to be mediated by aberrant gene expression associated with aberrant promoter methylation that is heritable between generations. However, because methylation is removed and then re-established during development, it is not easy to identify promoter methylation abnormalities by comparing normal lineages with those expected to exhibit TGE abnormalities. This study applied the recently proposed principal component analysis (PCA)-based unsupervised feature extraction to previously reported and publically available gene expression/promoter methylation profiles of rat primordial germ cells, between E13 and E16 of the F3 generation vinclozolin lineage that are expected to exhibit TGE abnormalities, to identify multiple genes that exhibited aberrant gene expression/promoter methylation during development. The biological feasibility of the identified genes were tested via enrichment analyses of various biological concepts including pathway analysis, gene ontology terms and protein-protein interactions. All validations suggested superiority of the proposed method over three conventional and popular supervised methods that employed t test, limma and significance analysis of microarrays, respectively. The identified genes were globally related to tumors, the prostate, kidney, testis and the immune system and were previously reported to be related to various diseases caused by TGE. Among the genes reported by PCA-based unsupervised feature extraction, we propose that chemokine signaling pathways and leucine rich repeat proteins are key factors that initiate transgenerational epigenetic-mediated diseases, because multiple genes included in these two categories were identified in this study.
Palytoxin: exploiting a novel skin tumor promoter to explore signal transduction and carcinogenesis.
Wattenberg, Elizabeth V
2007-01-01
Palytoxin is a novel skin tumor promoter, which has been used to help probe the role of different types of signaling mechanisms in carcinogenesis. The multistage mouse skin model indicates that tumor promotion is an early, prolonged, and reversible phase of carcinogenesis. Understanding the molecular mechanisms underlying tumor promotion is therefore important for developing strategies to prevent and treat cancer. Naturally occurring tumor promoters that bind to specific cellular receptors have proven to be useful tools for investigating important biochemical events in multistage carcinogenesis. For example, the identification of protein kinase C as the receptor for the prototypical skin tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) (also called phorbol 12-myristate 13-acetate, PMA) provided key evidence that tumor promotion involves the aberrant modulation of signaling cascades that govern cell fate and function. The subsequent discovery that palytoxin, a marine toxin isolated from zoanthids (genus Palythoa), is a potent skin tumor promoter yet does not activate protein kinase C indicated that investigating palytoxin action could help reveal new aspects of tumor promotion. Interestingly, the putative receptor for palytoxin is the Na(+),K(+)-ATPase. This review focuses on palytoxin-stimulated signaling and how palytoxin has been used to investigate alternate biochemical mechanisms by which important targets in carcinogenesis can be modulated.
BRISK--research-oriented storage kit for biology-related data.
Tan, Alan; Tripp, Ben; Daley, Denise
2011-09-01
In genetic science, large-scale international research collaborations represent a growing trend. These collaborations have demanding and challenging database, storage, retrieval and communication needs. These studies typically involve demographic and clinical data, in addition to the results from numerous genomic studies (omics studies) such as gene expression, eQTL, genome-wide association and methylation studies, which present numerous challenges, thus the need for data integration platforms that can handle these complex data structures. Inefficient methods of data transfer and access control still plague research collaboration. As science becomes more and more collaborative in nature, the need for a system that adequately manages data sharing becomes paramount. Biology-Related Information Storage Kit (BRISK) is a package of several web-based data management tools that provide a cohesive data integration and management platform. It was specifically designed to provide the architecture necessary to promote collaboration and expedite data sharing between scientists. The software, documentation, Java source code and demo are available at http://genapha.icapture.ubc.ca/brisk/index.jsp. BRISK was developed in Java, and tested on an Apache Tomcat 6 server with a MySQL database. denise.daley@hli.ubc.ca.
Barriers and Pathways to Creating Sustainability Education Programs: Policy, Rhetoric and Reality
Moore, Janet
2005-01-01
This article outlines an action-oriented research project regarding the University of British Columbia's engagement with sustainability. In 1997, the University of British Columbia (UBC) created a sustainability policy that suggests all UBC students should be educated about sustainability. Using data from a series of in-depth interviews the author…
Computational modeling predicts the ionic mechanism of late-onset responses in Unipolar Brush Cells
Directory of Open Access Journals (Sweden)
Sathyaa eSubramaniyam
2014-08-01
Full Text Available Unipolar Brush Cells (UBCs have been suggested to have a strong impact on cerebellar granular layer functioning, yet the corresponding cellular mechanisms remain poorly understood. UBCs have recently been reported to generate, in addition to early-onset glutamatergic synaptic responses, a late-onset response (LOR composed of a slow depolarizing ramp followed by a spike burst (Locatelli et al., 2013. The LOR activates as a consequence of synaptic activity and involves an intracellular cascade modulating H- and TRP-current gating. In order to assess the LOR mechanisms, we have developed a UBC multi-compartmental model (including soma, dendrite, initial segment and axon incorporating biologically realistic representations of ionic currents and a generic coupling mechanism regulating TRP and H channel gating. The model finely reproduced UBC responses to current injection, including a low-threshold spike sustained by CaLVA currents, a persistent discharge sustained by CaHVA currents, and a rebound burst following hyperpolarization sustained by H- and CaLVA-currents. Moreover, the model predicted that H- and TRP-current regulation was necessary and sufficient to generate the LOR and its dependence on the intensity and duration of mossy fiber activity. Therefore, the model showed that, using a basic set of ionic channels, UBCs generate a rich repertoire of delayed bursts, which could take part to the formation of tunable delay-lines in the local microcircuit.
Computational modeling predicts the ionic mechanism of late-onset responses in unipolar brush cells.
Subramaniyam, Sathyaa; Solinas, Sergio; Perin, Paola; Locatelli, Francesca; Masetto, Sergio; D'Angelo, Egidio
2014-01-01
Unipolar Brush Cells (UBCs) have been suggested to play a critical role in cerebellar functioning, yet the corresponding cellular mechanisms remain poorly understood. UBCs have recently been reported to generate, in addition to early-onset glutamate receptor-dependent synaptic responses, a late-onset response (LOR) composed of a slow depolarizing ramp followed by a spike burst (Locatelli et al., 2013). The LOR activates as a consequence of synaptic activity and involves an intracellular cascade modulating H- and TRP-current gating. In order to assess the LOR mechanisms, we have developed a UBC multi-compartmental model (including soma, dendrite, initial segment, and axon) incorporating biologically realistic representations of ionic currents and a cytoplasmic coupling mechanism regulating TRP and H channel gating. The model finely reproduced UBC responses to current injection, including a burst triggered by a low-threshold spike (LTS) sustained by CaLVA currents, a persistent discharge sustained by CaHVA currents, and a rebound burst following hyperpolarization sustained by H- and CaLVA-currents. Moreover, the model predicted that H- and TRP-current regulation was necessary and sufficient to generate the LOR and its dependence on the intensity and duration of mossy fiber activity. Therefore, the model showed that, using a basic set of ionic channels, UBCs generate a rich repertoire of bursts, which could effectively implement tunable delay-lines in the local microcircuit.
Efficacy of breast conservation therapy in early stage bilateral breast cancer
International Nuclear Information System (INIS)
Lee, Misa M.; Chen, Luci M.; Heimann, Ruth; Powers, Claire; Weichselbaum, Ralph R.
1996-01-01
PURPOSE: To evaluate outcome of patients with bilateral breast cancer as compared to unilateral breast cancer treated with breast conservation therapy. This is a complex issue, however, we address this by comparing (1) synchronous bilateral breast cancer patients, (2) metachronous bilateral breast cancer patients from the time of diagnosis of the second breast primary, and (3) unilateral breast cancer patients. The authors recognize that there are inherent biases in these comparisons. MATERIALS AND METHODS: A total of 60 bilateral patients and 1080 unilateral patients treated with breast conservation therapy from 1977-1994 were analyzed for outcome. Of the 60 bilateral patients, 44 were metachronous bilateral breast cancer patients (MBBC) and 16 were synchronous breast cancer patients (SBBC). Patients with bilateral breast cancer had local-regional disease with the following tumor stages: DCIS=8%, T1=80%, T2=12%, pathologic N0=90%, pathologic N+=10%. Unilateral patients had the following tumor stages: DCIS=10%, T1=66%, T2=20%, T3=1.2%, Tx=2%, pathological N0=80%, pathological N+=19%, and NX=1%. The majority of patients received lumpectomy and axillary node dissection followed by radiation therapy. The median size of the lesions were 1.4cm and 1.5cm for bilateral and unilateral patients, respectively. Median total dose to the primary tumor was 60Gy for both unilateral and bilateral patients. Of the 44 metachronous bilateral breast cancer patients, 14 patients received breast conservation for both the first and second lesions while 30 patients had breast conservation for only the second metachronous breast lesion. Thus 58 lesions in the 44 patients were treated with breast conservation therapy in the patients with metachronous bilateral breast cancer. Of the synchronous bilateral breast cancer patients, 13 out of 16 patients had breast conserving therapy for both breasts, and 3 patients received mastectomy for the second synchronous breast tumor. The median follow
Directory of Open Access Journals (Sweden)
Li Xianghua
2009-06-01
Full Text Available Abstract Background Rice transcription regulator OsWRKY13 influences the functioning of more than 500 genes in multiple signalling pathways, with roles in disease resistance, redox homeostasis, abiotic stress responses, and development. Results To determine the putative transcriptional regulation mechanism of OsWRKY13, the putative cis-acting elements of OsWRKY13-influenced genes were analyzed using the whole genome expression profiling of OsWRKY13-activated plants generated with the Affymetrix GeneChip Rice Genome Array. At least 39 transcription factor genes were influenced by OsWRKY13, and 30 of them were downregulated. The promoters of OsWRKY13-upregulated genes were overrepresented with W-boxes for WRKY protein binding, whereas the promoters of OsWRKY13-downregulated genes were enriched with cis-elements putatively for binding of MYB and AP2/EREBP types of transcription factors. Consistent with the distinctive distribution of these cis-elements in up- and downregulated genes, nine WRKY genes were influenced by OsWRKY13 and the promoters of five of them were bound by OsWRKY13 in vitro; all seven differentially expressed AP2/EREBP genes and six of the seven differentially expressed MYB genes were suppressed by in OsWRKY13-activated plants. A subset of OsWRKY13-influenced WRKY genes were involved in host-pathogen interactions. Conclusion These results suggest that OsWRKY13-mediated signalling pathways are partitioned by different transcription factors. WRKY proteins may play important roles in the monitoring of OsWRKY13-upregulated genes and genes involved in pathogen-induced defence responses, whereas MYB and AP2/EREBP proteins may contribute most to the control of OsWRKY13-downregulated genes.
International Nuclear Information System (INIS)
Zhang, Bin; Niu, Yun; Niu, Ruifang; Sun, Baocun; Hao, Xishan; Cao, Xuchen; Liu, Yanxue; Cao, Wenfeng; Zhang, Fei; Zhang, Shiwu; Li, Hongtao; Ning, Liansheng; Fu, Li
2008-01-01
Experimental evidence suggests that matrix metalloproteinase-13 (MMP-13) protein may promote breast tumor progression. However, its relevance to the progression of human breast cancer is yet to be established. Furthermore, it is not clear whether MMP-13 can be used as an independent breast cancer biomarker. This study was conducted to assess the expression profile of MMP-13 protein in invasive breast carcinomas to determine its diagnostic and prognostic significance, as well as its correlation with other biomarkers including estrogen receptor (ER), progesterone receptor (PR), Her-2/neu, MMP-2, MMP-9, tissue inhibitor of MMP-1 and -2 (TIMP-1 and TIMP-2). Immunohistochemistry (IHC) was performed on paraffin-embedded tissue microarray containing specimens from 263 breast carcinomas. The intensity and the extent of IHC were scored by pathologists in blind fashion. The correlation of the gene expression profiles with patients' clinicopathological features and clinical outcomes were analyzed for statistical significance. MMP-13 protein was detected in the cytoplasm of the malignant cells and the peritumoral stromal cells. MMP-13 expression by tumor cells (p < 0.001) and stromal fibroblasts (p <0.001) both correlated with carcinoma infiltration of lymph nodes. MMP-13 also correlated with the expression of Her-2/neu (p = 0.015) and TIMP-1 (p < 0.010), respectively in tumor cells. Tumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes. Moreover, high levels of MMP-13 expression were associated with decreased overall survival. In parallel, the prognostic value of MMP-13 expressed by peritumoral fibroblasts seems less significant. Our data suggest that lymph node status, tumor size, Her-2/neu expression, TIMP-1 and MMP-13 expression in cancer cells are independent prognostic factors. Tumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes, and inversely correlated with the
The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue
DEFF Research Database (Denmark)
Lynes, Matthew D; Leiria, Luiz O; Lundh, Morten
2017-01-01
and glucose tolerance; as a class, these lipids are referred to as 'lipokines'. Because BAT is a specialized metabolic tissue that takes up and burns lipids and is linked to systemic metabolic homeostasis, we hypothesized that there might be thermogenic lipokines that activate BAT in response to cold. Here we...... show that the lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) is a stimulator of BAT activity, and that its levels are negatively correlated with body-mass index and insulin sensitivity. Using a global lipidomic analysis, we found that 12,13-diHOME was increased in the circulation of humans...... and mice exposed to cold. Furthermore, we found that the enzymes that produce 12,13-diHOME were uniquely induced in BAT by cold stimulation. The injection of 12,13-diHOME acutely activated BAT fuel uptake and enhanced cold tolerance, which resulted in decreased levels of serum triglycerides...
Energy Technology Data Exchange (ETDEWEB)
Akiyama, Katsuya; Pak, Haeyang; Takubo, Yoji [Kobe Steel, Ltd, Kobe (Japan). Mechanical Engineering Research Lab.; Tada, Toshiya [Kobe Steel, Ltd, Takasago (Japan). Coal and Energy Technology Dept.; Ueki, Yasuaki [Nagoya Univ. (Japan). Energy Science Div.; Yoshiie, Ryo; Naruse, Ichiro [Nagoya Univ. (Japan). Dept. of Mechanical Science and Engineering
2013-07-01
The purpose of this study is to quantitatively evaluate behaviors of ash deposition during combustion of Upgraded Brown Coal (UBC) and bituminous coal in a 145 MW practical coal combustion boiler. A blended coal consisting 20 wt% of the UBC and 80 wt% of the bituminous coal was burned for the combustion tests. Before the actual ash deposition tests, the molten slag fractions of ash calculated by chemical equilibrium calculations under the combustion condition was adopted as one of the indices to estimate the tendency of ash deposition. The calculation results showed that the molten slag fraction for UBC ash reached approximately 90% at 1,523 K. However, that for the blended coal ash became about 50%. These calculation results mean that blending the UBC with a bituminous coal played a role in decreasing the molten slag fraction. Next, the ash deposition tests were conducted, using a practical pulverized coal combustion boiler. A water-cooled stainless-steel tube was inserted in locations at 1,523 K in the boiler to measure the amount of ash deposits. The results showed that the mass of deposited ash for the blended coal increased and shape of the deposited ash particles on the tube became large and spherical. This is because the molten slag fraction in ash for the blended coal at 1,523 K increased and the surface of deposited ash became sticky. However, the mass of the deposited ash for the blended coal did not greatly increase and no slagging problems occurred for 8 days of boiler operation under the present blending conditions. Therefore, appropriate blending of the UBC with a bituminous coal enables the UBC to be used with a low ash melting point without any ash deposition problems in a practical boiler.
Nagler, Rebekah H; Viswanath, Kasisomayajula
2013-04-01
Article 13 of the Framework Convention on Tobacco Control (FCTC) calls for a comprehensive ban on tobacco advertising, promotion, and sponsorship (TAPS), and Article 16 calls for prohibition of tobacco sales to and by minors. Although these mandates are based on sound science, many countries have found provision implementation to be rife with challenges. This paper reviews the history of tobacco marketing and minor access restrictions in high-, middle-, and low-income countries, identifying past challenges and successes. We consider current challenges to FCTC implementation, how these barriers can be addressed, and what research is necessary to support such efforts. Specifically, we identify implementation and research priorities for FCTC Articles 13 and 16. Although a solid evidence base underpins the FCTC's call for TAPS bans and minor access restrictions, we know substantially less about how best to implement these restrictions. Drawing on the regulatory experiences of high-, middle-, and low-income countries, we discern several implementation and research priorities, which are organized into 4 categories: policy enactment and enforcement, human capital expertise, the effects of FCTC marketing and youth access policies, and knowledge exchange and transfer among signatories. Future research should provide detailed case studies on implementation successes and failures, as well as insights into how knowledge of successful restrictions can be translated into tobacco control policy and practice and shared among different stakeholders. Tobacco marketing surveillance, sales-to-minors compliance checks, enforcement and evaluation of restriction policies, and capacity building and knowledge transfer are likely to prove central to effective implementation.
2013-01-01
Introduction: Article 13 of the Framework Convention on Tobacco Control (FCTC) calls for a comprehensive ban on tobacco advertising, promotion, and sponsorship (TAPS), and Article 16 calls for prohibition of tobacco sales to and by minors. Although these mandates are based on sound science, many countries have found provision implementation to be rife with challenges. Objective: This paper reviews the history of tobacco marketing and minor access restrictions in high-, middle-, and low-income countries, identifying past challenges and successes. We consider current challenges to FCTC implementation, how these barriers can be addressed, and what research is necessary to support such efforts. Specifically, we identify implementation and research priorities for FCTC Articles 13 and 16. Discussion: Although a solid evidence base underpins the FCTC’s call for TAPS bans and minor access restrictions, we know substantially less about how best to implement these restrictions. Drawing on the regulatory experiences of high-, middle-, and low-income countries, we discern several implementation and research priorities, which are organized into 4 categories: policy enactment and enforcement, human capital expertise, the effects of FCTC marketing and youth access policies, and knowledge exchange and transfer among signatories. Future research should provide detailed case studies on implementation successes and failures, as well as insights into how knowledge of successful restrictions can be translated into tobacco control policy and practice and shared among different stakeholders. Conclusion: Tobacco marketing surveillance, sales-to-minors compliance checks, enforcement and evaluation of restriction policies, and capacity building and knowledge transfer are likely to prove central to effective implementation. PMID:23291641
From Exam to Education: The Math Exam/Education Resources
Bruni, Carmen; Koch, Christina; Konrad, Bernhard; Lindstrom, Michael; Moyles, Iain; Thompson, Will
2016-01-01
The Math Exam/Education Resources (MER) is an open online learning resource hosted at The University of British Columbia (UBC), aimed at providing mathematics education resources for students and instructors at UBC. In this paper, there will be a discussion of the motivation for creating this resource on the MediaWiki platform, key features of the…
76 FR 25711 - Proposed Exemptions from Certain Prohibited Transaction Restrictions
2011-05-05
... the supervision of various governmental and self-regulatory bodies. Northern has a network of 79... Council is aligned with the UBC, as mentioned above, it is a separate and autonomous entity from UBC. As a.... Situated on the 19.25 acre tract are a car rental facility, which has a passenger terminal, a car wash, a...
Westhoff, Ellen; Maria de Oliveira-Neumayer, Julia; Aben, Katja K; Vrieling, Alina; Kiemeney, Lambertus A
2016-06-01
Data on urinary bladder cancer (UBC) patients' perceptions about causes of bladder cancer is limited, while this may be important knowledge for health prevention and education. We evaluated self-reported perceptions and beliefs about the causes of bladder cancer among UBC survivors in the Netherlands. UBC survivors identified through the Netherlands Cancer Registry from 2007 to 2012 were invited to participate. Patients who consented were asked to fill out a questionnaire, including questions on lifestyle characteristics, occupational and medical history, and family history of cancer. The final question was 'You have been diagnosed with bladder cancer. Do you have any idea what may have been the cause of your cancer?'. Of the 1793 UBC survivors included, 366 (20%) reported a possible cause for their bladder cancer. The most frequently reported suspected causes were smoking (10%), occupational exposure (5%), and heredity (2%). Smoking, occupational exposure and heredity were mentioned only slightly more frequently by participants with these risk factors (11%, 8%, and 5%, respectively) compared to the total population. Most UBC survivors did not suspect any cause that might have contributed to the development of their cancer. Even among participants with established risk factors for bladder cancer, these risk factors were not commonly perceived. This finding probably reflects the superficial knowledge of risk factors for bladder cancer in the population and highlights the importance of effective education on cancer prevention. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Effect of school eye health promotion on children's eye health literacy in Vietnam.
Paudel, Prakash; Yen, Phung Thi; Kovai, Vilas; Naduvilath, Thomas; Ho, Suit May; Giap, Nguyen Viet; Holden, Brien A
2017-10-06
Health promotion intervention in schools is a useful strategy to improve students' health awareness. The purpose of this study was to assess the effect of eye health promotion interventions on eye health literacy in school children in Vietnam. A piloted questionnaire was administered to 300 children from five secondary schools in Ba Ria-Vung Tau, Vietnam at baseline and re-administered after the eye health promotion interventions. McNemar chi-square and logistic regression were used for statistical analysis. A total of 300 children aged 12-15 years (mean, 13.3 ± 1.3 years; 60% female) participated in the baseline survey. The participation rate in the post-health promotion survey was 94.7%. After the health promotion interventions, number of children who had correct eye health knowledge increased by 10-20% (60-75% to 70-95%), more children reported having had an eye examination (63.3% to 84.7%; p promotion interventions significantly improve eye health knowledge, attitudes and practices of school children. Additionally, participation of parents and teachers as change agents may further improve children's health literacy. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Zhang, Zhiting; Guo, Qianqian; Zhang, Shufang; Xiang, Chenxi; Guo, Xinwei; Zhang, Feng; Gao, Lanlan; Ni, Haiwei; Xi, Tao; Zheng, Lufeng
2018-05-07
RNA binding proteins (RBPs) are pivotal post-transcriptional regulators. RNPC1, an RBP, acts as a tumor suppressor through binding and regulating the expression of target genes in cancer cells. This study disclosed that RNPC1 expression was positively correlated with breast cancer patients' relapse free and overall survival, and RNPC1suppressed breast cancer cells metastasis. Mechanistically, RNPC1 promoting a competing endogenous network (ceRNA) crosstalk between STARD13, CDH5, HOXD10, and HOXD1 (STARD13-correlated ceRNA network) that we previously confirmed in breast cancer cells through stabilizing the transcripts and thus facilitating the expression of these four genes in breast cancer cells. Furthermore, RNPC1 overexpression restrained the promotion of STARD13, CDH5, HOXD10, and HOXD1 knockdown on cell metastasis. Notably, RNPC1 expression was positively correlated with CDH5, HOXD1 and HOXD10 expression in breast cancer tissues, and attenuated adriamycin resistance. Taken together, these results identified that RNPC1 could inhibit breast cancer cells metastasis via promoting STARD13-correlated ceRNA network.
International Nuclear Information System (INIS)
Weinman, J.; Servaes, S.; Anupindi, S.A.
2013-01-01
Unicameral bone cysts (UBCs) are a common benign entity involving the metaphysis of growing bone, occurring within the first two decades of life. Assessment of these lesions, both before and after surgery, is performed routinely utilizing radiographs. We present a review of UBCs at various stages of treatment, including both successful and incomplete healing, and describe the imaging findings throughout their postoperative course
Characterization and functional analysis of the Paralichthys olivaceus prdm1 gene promoter.
Li, Peizhen; Wang, Bo; Cao, Dandan; Liu, Yuezhong; Zhang, Quanqi; Wang, Xubo
2017-10-01
PR domain containing protein 1 (Prdm1) is a transcriptional repressor identified in various species and plays multiple important roles in immune response and embryonic development. However, little is known about the transcriptional regulation of the prdm1 gene. This study aims to characterize the promoter of Paralichthys olivaceus prdm1 (Po-prdm1) gene and determine the regulatory mechanism of Po-prdm1 expression. A 2000bp-long 5'-flanking region (translation initiation site designated as +1) of the Po-prdm1 gene was isolated and characterized. The regulatory elements in this fragment were then investigated and many putative transcription factor (TF) binding sites involved in immunity and multiple tissue development were identified. A 5'-deletion analysis was then conducted, and the ability of the deletion mutants to promote luciferase and green fluorescent protein (GFP) expression in a flounder gill cell line was examined. The results revealed that the minimal promoter is located in the region between -446 and -13bp, and the region between -1415 and -13bp enhanced the promoter activity. Site-directed mutation analysis was subsequently performed on the putative regulatory elements sites, and the results indicated that FOXP1, MSX and BCL6 binding sites play negative functional roles in the regulation of the Po-prdm1 expression in FG cells. In vivo analysis demonstrated that a GFP reporter gene containing 1.4kb-long promoter fragment (-1415/-13) was expressed in the head and trunk muscle fibres of transient transgenic zebrafish embryos. Our study provided the basic information for the exploration of Po-prdm1 regulation and expression. Copyright © 2017 Elsevier Inc. All rights reserved.
Health promotion in Swedish schools: school managers' views.
Persson, Louise; Haraldsson, Katarina
2017-04-01
Schools are recognized worldwide as settings for health promotion, and leadership has a bearing on schools' ability to be health promoting. School managers have a great influence on what is prioritized in school, which in turn affects students' school performance and health. There is lack of research into school managers' views on health promotion, and what they consider to be central to health promotion. The aim was therefore to examine school managers' views about what health promotion in schools include. An explorative design, qualitative content analysis, was performed. In-depth interviews were conducted with all 13 school managers of a middle-sized municipality in central Sweden. The analysis had both manifest and latent content and three categories: 'Organization and Collaboration', 'Optimize the arena' and 'Strengthen the individual', and 10 subcategories emerged. The theme, 'Opportunities for learning and a good life', describes the latent content of these categories. Taking into account the views of school managers are important because these views help form a more complete picture of how school managers work with health promotion and what is needed to enhance health promotion to improve students' opportunities for learning and a good life. The Ottawa Charter for Health promotion is thereby transformed into practice. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Advancement & Promotion Review: 2003
2003-01-01
Advancement, exceptional advancement and promotion decisions were made at the end of June, following the procedures published in Weekly Bulletin No. 13/2003. These decisions were included, where applicable, in the salaries for the month of July 2003. The award of the periodic step was communicated to staff by the salary shown on the July salary slip. All other decisions are communicated by separate notification. The names of staff receiving exceptional advancements or promotions are now published on the HR Division website and are accessible for consultation only at the following address: http://cern.ch/hr-div/internal/personnel/advlist_2003.asp It is recalled that change of career path proposals submitted to the Technical Engineers and Administrative Careers Committee (TEACC) or to Human Resources Division are being examined with a view to preparing the latters' recommendations by the end of September 2003. Final decisions will be applied retroactively to 1 July 2003. Human Resources Division Tel:...
Active unicameral bone cysts in the upper limb are at greater risk of fracture.
Tey, Inn Kuang; Mahadev, Arjandas; Lim, Kevin Boon Leong; Lee, Eng Hin; Nathan, Saminathan Suresh
2009-08-01
To elucidate the natural history of unicameral bone cyst (UBC) and risk factors for pathological fracture. 14 males and 8 females (mean age, 9 years) diagnosed with UBC were reviewed. Cyst location, symptoms, and whether there was any fracture or surgery were recorded. Cyst parameters were measured on radiographs, and included (1) the cyst index, (2) the ratio of the widest cyst diameter to the growth plate diameter, and (3) the adjusted distance of the cyst border from the growth plate. There were 11 upper- and 11 lower-limb cysts. 13 patients had pathological fractures and 9 did not. 20 patients were treated conservatively with limb immobilisation; 2 underwent curettage and bone grafting (one resolved and one did not). Seven cysts resolved (5 had fractures and 2 did not). The risk of fracture was higher in the upper than lower limbs (100% vs 18%, pFractured cysts were larger than unfractured cysts (mean cyst index, 4.5 vs. 2.2, p=0.07). Active cysts were more likely to fracture. Conservative management had a 30% resolution rate. Surgery should be considered for large active cysts in the upper limbs in order to minimise the fracture risk.
Directory of Open Access Journals (Sweden)
Emanuela Chiarella
Full Text Available Lentiviral vectors are widely used to investigate the biological properties of regulatory proteins and/or of leukaemia-associated oncogenes by stably enforcing their expression in hematopoietic stem and progenitor cells. In these studies it is critical to be able to monitor and/or sort the infected cells, typically via fluorescent proteins encoded by the modified viral genome. The most popular strategy to ensure co-expression of transgene and reporter gene is to insert between these cDNAs an IRES element, thus generating bi-cistronic mRNAs whose transcription is driven by a single promoter. However, while the product of the gene located upstream of the IRES is generally abundantly expressed, the translation of the downstream cDNA (typically encoding the reporter protein is often inconsistent, which hinders the detection and the isolation of transduced cells. To overcome these limitations, we developed novel lentiviral dual-promoter vectors (named UMG-LV5 and -LV6 where transgene expression is driven by the potent UBC promoter and that of the reporter protein, EGFP, by the minimal regulatory element of the WASP gene. These vectors, harboring two distinct transgenes, were tested in a variety of human haematopoietic cell lines as well as in primary human CD34+ cells in comparison with the FUIGW vector that contains the expression cassette UBC-transgene-IRES-EGFP. In these experiments both UMG-LV5 and UMG-LV6 yielded moderately lower transgene expression than FUIGW, but dramatically higher levels of EGFP, thereby allowing the easy distinction between transduced and non-transduced cells. An additional construct was produced, in which the cDNA encoding the reporter protein is upstream, and the transgene downstream of the IRES sequence. This vector, named UMG-LV11, proved able to promote abundant expression of both transgene product and EGFP in all cells tested. The UMG-LVs represent therefore useful vectors for gene transfer-based studies in
Chiarella, Emanuela; Carrà, Giovanna; Scicchitano, Stefania; Codispoti, Bruna; Mega, Tiziana; Lupia, Michela; Pelaggi, Daniela; Marafioti, Maria G; Aloisio, Annamaria; Giordano, Marco; Nappo, Giovanna; Spoleti, Cristina B; Grillone, Teresa; Giovannone, Emilia D; Spina, Raffaella; Bernaudo, Francesca; Moore, Malcolm A S; Bond, Heather M; Mesuraca, Maria; Morrone, Giovanni
2014-01-01
Lentiviral vectors are widely used to investigate the biological properties of regulatory proteins and/or of leukaemia-associated oncogenes by stably enforcing their expression in hematopoietic stem and progenitor cells. In these studies it is critical to be able to monitor and/or sort the infected cells, typically via fluorescent proteins encoded by the modified viral genome. The most popular strategy to ensure co-expression of transgene and reporter gene is to insert between these cDNAs an IRES element, thus generating bi-cistronic mRNAs whose transcription is driven by a single promoter. However, while the product of the gene located upstream of the IRES is generally abundantly expressed, the translation of the downstream cDNA (typically encoding the reporter protein) is often inconsistent, which hinders the detection and the isolation of transduced cells. To overcome these limitations, we developed novel lentiviral dual-promoter vectors (named UMG-LV5 and -LV6) where transgene expression is driven by the potent UBC promoter and that of the reporter protein, EGFP, by the minimal regulatory element of the WASP gene. These vectors, harboring two distinct transgenes, were tested in a variety of human haematopoietic cell lines as well as in primary human CD34+ cells in comparison with the FUIGW vector that contains the expression cassette UBC-transgene-IRES-EGFP. In these experiments both UMG-LV5 and UMG-LV6 yielded moderately lower transgene expression than FUIGW, but dramatically higher levels of EGFP, thereby allowing the easy distinction between transduced and non-transduced cells. An additional construct was produced, in which the cDNA encoding the reporter protein is upstream, and the transgene downstream of the IRES sequence. This vector, named UMG-LV11, proved able to promote abundant expression of both transgene product and EGFP in all cells tested. The UMG-LVs represent therefore useful vectors for gene transfer-based studies in hematopoietic stem and
Wu, Deng-Chyang; Wang, Sophie S W; Liu, Chung-Jung; Wuputra, Kenly; Kato, Kohsuke; Lee, Yen-Liang; Lin, Ying-Chu; Tsai, Ming-Ho; Ku, Chia-Chen; Lin, Wen-Hsin; Wang, Shin-Wei; Kishikawa, Shotaro; Noguchi, Michiya; Wu, Chu-Chieh; Chen, Yi-Ting; Chai, Chee-Yin; Lin, Chen-Lung Steve; Kuo, Kung-Kai; Yang, Ya-Han; Miyoshi, Hiroyuki; Nakamura, Yukio; Saito, Shigeo; Nagata, Kyosuke; Lin, Chang-Shen; Yokoyama, Kazunari K
2017-10-01
Reprogramming of cancer cells into induced pluripotent stem cells (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP7 promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase, WD repeat-containing protein 5, and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells. By contrast, HOXA13 inhibited BMP7 expression in iPSLCs via the corecruitment of HOXA13, enhancer of zeste homolog 2, Jumonji and AT rich interactive domain 2, and lncRNA HoxA transcript antisense RNA (HOTAIR) to various cis-element of the BMP7 promoter. Knockdown experiments demonstrated that HOTTIP contributed positively, but HOTAIR regulated negatively to HOXA13-mediated BMP7 expression in cancer cells and iPSLCs, respectively. These findings indicate that the recruitment of HOXA13-HOTTIP and HOXA13-HOTAIR to different sites in the BMP7 promoter is crucial for the oncogenic fate of human gastric cells. Reprogramming with octamer-binding protein 4 and Jun dimerization protein 2 can inhibit tumorigenesis by switching off BMP7. Stem Cells 2017;35:2115-2128. © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.
Zhang, Huilan; Oak, Sameer R.; Coelho, Ana Lucia; Herath, Athula; Flaherty, Kevin R.; Lee, Joyce; Bell, Matt; Knight, Darryl A.; Martinez, Fernando J.; Sleeman, Matthew A.; Herzog, Erica L.; Hogaboam, Cory M.
2014-01-01
The aberrant fibrotic and repair responses in the lung are major hallmarks of idiopathic pulmonary fibrosis (IPF). Numerous antifibrotic strategies have been used in the clinic with limited success, raising the possibility that an effective therapeutic strategy in this disease must inhibit fibrosis and promote appropriate lung repair mechanisms. IL-13 represents an attractive target in IPF, but its disease association and mechanism of action remains unknown. In the present study, an overexpression of IL-13 and IL-13 pathway markers was associated with IPF, particularly a rapidly progressive form of this disease. Targeting IL-13 in a humanized experimental model of pulmonary fibrosis using tralokinumab (CAT354) was found to therapeutically block aberrant lung remodeling in this model. However, targeting IL-13 was also found to promote lung repair and to restore epithelial integrity. Thus, targeting IL-13 inhibits fibrotic processes and enhances repair processes in the lung. PMID:24325475
Directory of Open Access Journals (Sweden)
Chong Wang
2016-04-01
Full Text Available The HTLV-1 oncoprotein Tax plays a key role in CD4+ T cell transformation by promoting cell proliferation and survival, mainly through permanent activation of the NK-κB pathway and induction of many NF-κB target genes. Elucidating the underlying molecular mechanism is therefore critical in understanding HTLV-1-mediated transformation. Current studies have suggested multiple but controversial mechanisms regarding Tax-induced IKK activation mainly due to blending of primary Tax-induced IKK activation events and secondary IKK activation events induced by cytokines secreted by the primary Tax-induced IKK-NF-κB activation events. We reconstituted Tax-stimulated IKK activation in a cell-free system to dissect the essential cellular components for primary IKK activation by Tax and studied the underlying biochemical mechanism. We found that Tax is a putative E3 ubiquitin ligase, which, together with UbcH2, UhcH5c, or UbcH7, catalyzes the assembly of free mixed-linkage polyubiquitin chains. These free mixed-linkage polyubiquitin chains are then responsible for direct IKK activation by binding to the NEMO subunit of IKK. Our studies revealed the biochemical function of Tax in the process of IKK activation, which utilizes the minimal cellular ubiquitination components for NF-κB activation.
Wang, Chong; Long, Wenying; Peng, Chao; Hu, Lin; Zhang, Qiong; Wu, Ailing; Zhang, Xiaoqing; Duan, Xiaotao; Wong, Catherine C L; Tanaka, Yuetsu; Xia, Zongping
2016-04-01
The HTLV-1 oncoprotein Tax plays a key role in CD4+ T cell transformation by promoting cell proliferation and survival, mainly through permanent activation of the NK-κB pathway and induction of many NF-κB target genes. Elucidating the underlying molecular mechanism is therefore critical in understanding HTLV-1-mediated transformation. Current studies have suggested multiple but controversial mechanisms regarding Tax-induced IKK activation mainly due to blending of primary Tax-induced IKK activation events and secondary IKK activation events induced by cytokines secreted by the primary Tax-induced IKK-NF-κB activation events. We reconstituted Tax-stimulated IKK activation in a cell-free system to dissect the essential cellular components for primary IKK activation by Tax and studied the underlying biochemical mechanism. We found that Tax is a putative E3 ubiquitin ligase, which, together with UbcH2, UhcH5c, or UbcH7, catalyzes the assembly of free mixed-linkage polyubiquitin chains. These free mixed-linkage polyubiquitin chains are then responsible for direct IKK activation by binding to the NEMO subunit of IKK. Our studies revealed the biochemical function of Tax in the process of IKK activation, which utilizes the minimal cellular ubiquitination components for NF-κB activation.
In vivo RNAi screen reveals neddylation genes as novel regulators of Hedgehog signaling.
Directory of Open Access Journals (Sweden)
Juan Du
Full Text Available Hedgehog (Hh signaling is highly conserved in all metazoan animals and plays critical roles in many developmental processes. Dysregulation of the Hh signaling cascade has been implicated in many diseases, including cancer. Although key components of the Hh pathway have been identified, significant gaps remain in our understanding of the regulation of individual Hh signaling molecules. Here, we report the identification of novel regulators of the Hh pathway, obtained from an in vivo RNA interference (RNAi screen in Drosophila. By selectively targeting critical genes functioning in post-translational modification systems utilizing ubiquitin (Ub and Ub-like proteins, we identify two novel genes (dUba3 and dUbc12 that negatively regulate Hh signaling activity. We provide in vivo and in vitro evidence illustrating that dUba3 and dUbc12 are essential components of the neddylation pathway; they function in an enzyme cascade to conjugate the ubiquitin-like NEDD8 modifier to Cullin proteins. Neddylation activates the Cullin-containing ubiquitin ligase complex, which in turn promotes the degradation of Cubitus interruptus (Ci, the downstream transcription factor of the Hh pathway. Our study reveals a conserved molecular mechanism of the neddylation pathway in Drosophila and sheds light on the complex post-translational regulations in Hh signaling.
Shylesh, Sankaranarayanapillai; Gokhale, Amit A; Scown, Corinne D; Kim, Daeyoup; Ho, Christopher R; Bell, Alexis T
2016-06-22
1,3-Butadiene (1,3-BD) is a high-value chemical intermediate used mainly as a monomer for the production of synthetic rubbers. The ability to source 1,3-BD from biomass is of considerable current interest because it offers the potential to reduce the life-cycle greenhouse gas (GHG) impact associated with 1,3-BD production from petroleum-derived naphtha. Herein, we report the development and investigation of a new catalyst and process for the one-step conversion of ethanol to 1,3-BD. The catalyst is prepared by the incipient impregnation of magnesium oxide onto a silica support followed by the deposition of Au nanoparticles by deposition-precipitation. The resulting Au/MgO-SiO2 catalyst exhibits a high activity and selectivity to 1,3-BD and low selectivities to diethyl ether, ethylene, and butenes. Detailed characterization of the catalyst shows that the desirable activity and selectivity of Au/MgO-SiO2 are a consequence of a critical balance between the acidic-basic sites associated with a magnesium silicate hydrate phase and the redox properties of the Au nanoparticles. A process for the conversion of ethanol to 1,3-BD, which uses our catalyst, is proposed and analyzed to determine the life-cycle GHG impact of the production of this product from biomass-derived ethanol. We show that 1,3-BD produced by our process can reduce GHG emissions by as much as 155 % relative to the conventional petroleum-based production of 1,3-BD. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Biofluorescence as a survey tool for cryptic marine species.
De Brauwer, Maarten; Hobbs, Jean-Paul A; Ambo-Rappe, Rohani; Jompa, Jamaluddin; Harvey, Euan S; McIlwain, Jennifer L
2017-10-06
As ecosystems come under increasing anthropogenic pressure, rare species face the highest risk of extinction. Paradoxically, data necessary to evaluate the conservation status of rare species are often lacking because of the challenges of detecting species with low abundance. One group of fishes subject to this undersampling bias are those with cryptic body patterns. Twenty-one percent of cryptic fish species assessed for their extinction risk (International Union for Conservation of Nature [IUCN]) are data deficient. We developed a nondestructive method for surveying cryptically patterned marine fishes based on the presence of biofluorescence (underwater biofluorescence census, UBC). Blue LED torches were used to investigate how widespread biofluorescence was in cryptic reef fishes in the Coral Triangle region. The effectiveness of UBC to generate abundance data was tested on a data-deficient pygmy seahorse species (Hippocampus bargibanti) and compared with data obtained from standard underwater visual census (UVC) surveys. We recorded 95 reef fish species displaying biofluorescence, 73 of which had not been previously described as biofluorescent. Of those fish with cryptic patterns, 87% were biofluorescent compared with 9% for noncryptic fishes. The probability of species displaying biofluorescence was 70.9 times greater for cryptic species than for noncryptic species. Almost twice the number of H. bargibanti was counted using the UBC compared with UVC. For 2 triplefin species (Ucla xenogrammus, Enneapterygius tutuilae), the abundance detected with UBC was triple that detected with UVC. The UBC method was effective at finding cryptic species that would otherwise be difficult to detect and thus will reduce interobserver variability inherent to UVC surveys. Biofluorescence is ubiquitous in cryptic fishes, making this method applicable across a wide range of species. Data collected using UBC could be used with multiple IUCN criteria to assess the extinction risk of
Mid- and long-term clinical results of surgical therapy in unicameral bone cysts
Directory of Open Access Journals (Sweden)
Hagmann Sébastien
2011-12-01
Full Text Available Abstract Background Unicameral (or simple bone cysts (UBC are benign tumours most often located in long bones of children and adolescents. Pathological fractures are common, and due to high recurrence rates, these lesions remain a challenge to treat. Numerous surgical procedures have been proposed, but there is no general consensus of the ideal treatment. The aim of this investigation therefore was to study the long-term outcome after surgical treatment in UBC. Methods A retrospective analysis of 46 patients surgically treated for UBC was performed for short and mid-term outcome. Clinical and radiological outcome parameters were studied according to a modified Neer classification system. Long-term clinical information was retrieved via a questionnaire at a minimum follow-up of 10 years after surgery. Results Forty-six patients (17 female, 29 male with a mean age of 10.0 ± 4.8 years and with histopathologically confirmed diagnosis of UBC were included. Pathological fractures were observed in 21 cases (46%. All patients underwent surgery for UBC (35 patients underwent curettage and bone grafting as a primary therapy, 4 curettage alone, 3 received corticoid instillation and 4 decompression by cannulated screws. Overall recurrence rate after the first surgical treatment was 39% (18/46, second (17.4% of all patients and third recurrence (4.3% were frequently observed and were addressed by revision surgery. Recurrence was significantly higher in young and in male patients as well as in active cysts. After a mean of 52 months, 40 out of 46 cysts were considered healed. Prognosis was significantly better when recurrence was observed later than 30 months after therapy. After a mean follow-up of 15.5 ± 6.2 years, 40 patients acknowledged clinically excellent results, while five reported mild and casual pain. Only one patient reported a mild limitation of range of motion. Conclusions Our results suggest satisfactory overall long-term outcome for the
Mid- and long-term clinical results of surgical therapy in unicameral bone cysts.
Hagmann, Sébastien; Eichhorn, Florian; Moradi, Babak; Gotterbarm, Tobias; Dreher, Thomas; Lehner, Burkhard; Zeifang, Felix
2011-12-13
Unicameral (or simple) bone cysts (UBC) are benign tumours most often located in long bones of children and adolescents. Pathological fractures are common, and due to high recurrence rates, these lesions remain a challenge to treat. Numerous surgical procedures have been proposed, but there is no general consensus of the ideal treatment. The aim of this investigation therefore was to study the long-term outcome after surgical treatment in UBC. A retrospective analysis of 46 patients surgically treated for UBC was performed for short and mid-term outcome. Clinical and radiological outcome parameters were studied according to a modified Neer classification system. Long-term clinical information was retrieved via a questionnaire at a minimum follow-up of 10 years after surgery. Forty-six patients (17 female, 29 male) with a mean age of 10.0 ± 4.8 years and with histopathologically confirmed diagnosis of UBC were included. Pathological fractures were observed in 21 cases (46%). All patients underwent surgery for UBC (35 patients underwent curettage and bone grafting as a primary therapy, 4 curettage alone, 3 received corticoid instillation and 4 decompression by cannulated screws). Overall recurrence rate after the first surgical treatment was 39% (18/46), second (17.4% of all patients) and third recurrence (4.3%) were frequently observed and were addressed by revision surgery. Recurrence was significantly higher in young and in male patients as well as in active cysts. After a mean of 52 months, 40 out of 46 cysts were considered healed. Prognosis was significantly better when recurrence was observed later than 30 months after therapy. After a mean follow-up of 15.5 ± 6.2 years, 40 patients acknowledged clinically excellent results, while five reported mild and casual pain. Only one patient reported a mild limitation of range of motion. Our results suggest satisfactory overall long-term outcome for the surgical treatment of UBC, although short-and mid
Energy Technology Data Exchange (ETDEWEB)
Assis, Sergio Luiz de
2006-07-01
In this work, the in vitro corrosion resistance of the Ti-13Nb-13Zr alloy, manufactured at a national laboratory, and used for orthopedic applications, has been investigated in solutions that simulate the body fluids. The electrolytes used were 0.9 % (mass) NaCl, Hanks' solution, a culture medium (MEM), and the two last electrolytes, without and with addition of hydrogen peroxide. The aim of peroxide addition was to simulate the conditions found when inflammatory reactions occur due to surgical procedures. The corrosion resistance of alloys commercially in use as biomaterials, Ti-6Al-7Nb and Ti-6Al-4V, as well as of the pure titanium (Ti-cp), was also studied for comparison with the Ti-13Nb-13Zr alloy. The corrosion resistance characterization was carried out by electrochemical and surface analysis techniques. The electrochemical tests used were: open circuit potential measurements as a function of tim; potentiodynamic polarization; and electrochemical impedance spectroscopy (EIE). The impedance experimental diagrams were interpreted using equivalent electric circuits that simulate an oxide film with a duplex structure composed of an internal and compact, barrier type layer, and an external porous layer. The results showed that the corrosion resistance is due mainly to the barrier type layer. The titanium alloys and the Ti-cp showed high corrosion resistance in all electrolytes used. The oxides formed on the Ti-13Nb-13Zr, either naturally or during immersion in MEM ar Hank's solution was characterized by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (MEV). The results showed that the presence of hydrogen peroxide in MEM promotes the growth of the porous layer and incorporation of mineral ions, besides favouring hydroxyapatite formation. The cytotoxicity of the Ti-13Nb-13Zr alloy was also evaluated and it was shown to be non-toxic. (author)
Energy Technology Data Exchange (ETDEWEB)
Assis, Sergio Luiz de
2006-07-01
In this work, the in vitro corrosion resistance of the Ti-13Nb-13Zr alloy, manufactured at a national laboratory, and used for orthopedic applications, has been investigated in solutions that simulate the body fluids. The electrolytes used were 0.9 % (mass) NaCl, Hanks' solution, a culture medium (MEM), and the two last electrolytes, without and with addition of hydrogen peroxide. The aim of peroxide addition was to simulate the conditions found when inflammatory reactions occur due to surgical procedures. The corrosion resistance of alloys commercially in use as biomaterials, Ti-6Al-7Nb and Ti-6Al-4V, as well as of the pure titanium (Ti-cp), was also studied for comparison with the Ti-13Nb-13Zr alloy. The corrosion resistance characterization was carried out by electrochemical and surface analysis techniques. The electrochemical tests used were: open circuit potential measurements as a function of tim; potentiodynamic polarization; and electrochemical impedance spectroscopy (EIE). The impedance experimental diagrams were interpreted using equivalent electric circuits that simulate an oxide film with a duplex structure composed of an internal and compact, barrier type layer, and an external porous layer. The results showed that the corrosion resistance is due mainly to the barrier type layer. The titanium alloys and the Ti-cp showed high corrosion resistance in all electrolytes used. The oxides formed on the Ti-13Nb-13Zr, either naturally or during immersion in MEM ar Hank's solution was characterized by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (MEV). The results showed that the presence of hydrogen peroxide in MEM promotes the growth of the porous layer and incorporation of mineral ions, besides favouring hydroxyapatite formation. The cytotoxicity of the Ti-13Nb-13Zr alloy was also evaluated and it was shown to be non-toxic. (author)
The Effect of C-X-C Motif Chemokine 13 on Hepatocellular Carcinoma Associates with Wnt Signaling
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Chunyan Li
2015-01-01
Full Text Available Objects. To investigate the effect of CXCL13 (C-X-C motif chemokine 13 on hepatocellular carcinoma and clarify the potential mechanisms. Methods. 32 patients with hepatocellular carcinoma and 12 healthy controls were recruited for analyzing the expression of CXCL13 by RT-PCR (reverse transcription-polymerase chain reaction. ELISA (enzyme-linked immune-sorbent assay was used to test the concentration of serum CXCL13. The interaction between CXCL13 and Wnt signaling was analyzed by western blot. In vitro PBMCs cultured with HepG2 supernatant, the levels of IL-12, IL4, IL-6, and IL-17, and four IgG subclasses were detected by ELISA. Results. The rate of high expression CXCL13 was 63.4% in advanced HCC patients, and the serum CXCL13 was also at a high level in stage IV HCC patients. Meanwhile CXCL13 level was positively correlated with serum ALT (Alanine Transaminase and AST (Aspartate Aminotransferase. CXCL13 and Wnt/β-catenin signaling shared a positive feedback loop. Furthermore, CXCL13 could obviously promote the expressions of IL-12 and IL-17, and induce IgG4 secreted by B cells. Conclusions. The effect of CXCL13 on promoting liver cancer is related to the activation of Wnt/β-catenin pathway and the facilitation of IL-12, IL-17 and IgG4. CXCL13 plays an important role in the progression of HCC, and it may act as a potential target for the diagnosis and treatment of HCC.
Preparation and Reaction Chemistry of Novel Silicon-Substituted 1,3-Dienes
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Partha P. Choudhury
2015-09-01
Full Text Available 2-Silicon-substituted 1,3-dienes containing non transferrable groups known to promote transmetallation were prepared by Grignard chemistry and enyne metathesis. These dienes participated in one pot metathesis/Diels-Alder reactions in regio- and diastereoselective fashions. Electron-rich alkenes showed the fastest rates in metathesis reactions, and ethylene, a commonly used metathesis promoter slowed enyne metathesis. 2-Pyridyldimethylsilyl and 2-thienyldimethylsilyl substituted Diels-Alder cycloadducts participated in cross-coupling chemistry and the 2-thienyldimethylsilyl substituted cycloadducts underwent cross-coupling under very mild reaction conditions.
Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold.
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Roberta Noseda
2016-04-01
Full Text Available Microtubule-based kinesin motors have many cellular functions, including the transport of a variety of cargos. However, unconventional roles have recently emerged, and kinesins have also been reported to act as scaffolding proteins and signaling molecules. In this work, we further extend the notion of unconventional functions for kinesin motor proteins, and we propose that Kif13b kinesin acts as a signaling molecule regulating peripheral nervous system (PNS and central nervous system (CNS myelination. In this process, positive and negative signals must be tightly coordinated in time and space to orchestrate myelin biogenesis. Here, we report that in Schwann cells Kif13b positively regulates myelination by promoting p38γ mitogen-activated protein kinase (MAPK-mediated phosphorylation and ubiquitination of Discs large 1 (Dlg1, a known brake on myelination, which downregulates the phosphatidylinositol 3-kinase (PI3K/v-AKT murine thymoma viral oncogene homolog (AKT pathway. Interestingly, Kif13b also negatively regulates Dlg1 stability in oligodendrocytes, in which Dlg1, in contrast to Schwann cells, enhances AKT activation and promotes myelination. Thus, our data indicate that Kif13b is a negative regulator of CNS myelination. In summary, we propose a novel function for the Kif13b kinesin in glial cells as a key component of the PI3K/AKT signaling pathway, which controls myelination in both PNS and CNS.
Characterization of a Lactococcus lactis promoter for heterologous protein production
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Christian E. Ogaugwu
2018-03-01
Full Text Available Constitutively active promoter elements for heterologous protein production in Lactococcus lactis are scarce. Here, the promoter of the PTS-IIC gene cluster from L. lactis NZ3900 is described. This promoter was cloned upstream of an enhanced green fluorescent protein, GFPmut3a, and transformed into L. lactis. Transformants produced up to 13.5 μg of GFPmut3a per milliliter of log phase cells. Addition of cellobiose further increased the production of GFPmut3a by up to two-fold when compared to glucose. Analysis of mutations at two specific positions in the PTS-IIC promoter showed that a ‘T’ to ‘G’ mutation within the −35 element resulted in constitutive expression in glucose, while a ‘C’ at nucleotide 7 in the putative cre site enhanced promoter activity in cellobiose. Finally, this PTS-IIC promoter is capable of mediating protein expression in Bacillus subtilis and Escherichia coli Nissle 1917, suggesting the potential for future biotechnological applications of this element and its derivatives.
International Nuclear Information System (INIS)
Assis, Sergio Luiz de
2006-01-01
In this work, the in vitro corrosion resistance of the Ti-13Nb-13Zr alloy, manufactured at a national laboratory, and used for orthopedic applications, has been investigated in solutions that simulate the body fluids. The electrolytes used were 0.9 % (mass) NaCl, Hanks' solution, a culture medium (MEM), and the two last electrolytes, without and with addition of hydrogen peroxide. The aim of peroxide addition was to simulate the conditions found when inflammatory reactions occur due to surgical procedures. The corrosion resistance of alloys commercially in use as biomaterials, Ti-6Al-7Nb and Ti-6Al-4V, as well as of the pure titanium (Ti-cp), was also studied for comparison with the Ti-13Nb-13Zr alloy. The corrosion resistance characterization was carried out by electrochemical and surface analysis techniques. The electrochemical tests used were: open circuit potential measurements as a function of tim; potentiodynamic polarization; and electrochemical impedance spectroscopy (EIE). The impedance experimental diagrams were interpreted using equivalent electric circuits that simulate an oxide film with a duplex structure composed of an internal and compact, barrier type layer, and an external porous layer. The results showed that the corrosion resistance is due mainly to the barrier type layer. The titanium alloys and the Ti-cp showed high corrosion resistance in all electrolytes used. The oxides formed on the Ti-13Nb-13Zr, either naturally or during immersion in MEM ar Hank's solution was characterized by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (MEV). The results showed that the presence of hydrogen peroxide in MEM promotes the growth of the porous layer and incorporation of mineral ions, besides favouring hydroxyapatite formation. The cytotoxicity of the Ti-13Nb-13Zr alloy was also evaluated and it was shown to be non-toxic. (author)
Crabb, Simon; Caddy, Joshua; Dunkley, Denise; Rajaram, Jessica; Ellis, Deborah; Hill, Stephanie; Whitehead, Amy; Huddart, Robert; Griffiths, Gareth; Kalevras, Michail
2018-01-01
Background: urothelial bladder cancer (UBC) accounts for 10,000 new diagnoses and 5000 deaths annually in the UK (Cancer Research UK, http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer , Cancer Research UK, Accessed 26 Mar 2018). Cisplatin-based chemotherapy is standard of care therapy for UBC for both palliative first-line treatment of advanced/metastatic disease and radical neoadjuvant treatment of localised muscle invasive bladder...
[On motivations of adolescents to promote a healthy lifestyle].
Bal, L V; Mikhailov, A N; Gundarov, I A
2014-01-01
There was studied the motivation of modern adolescents to promote healthy lifestyle. There were observed two arrays, including adolescent-schoolchildren aged 16-17 and 13-14 years in Moscow. The results showed that health occupied one of the first places among the positive motivations, being stable dominant in the period of 13-17 years. The real motivation for a healthy lifestyle coincides with the perspective and informed choice coincides with the life goals. In this, almost all of the identified negative motivation are "manageable", available to be modified or eliminated.
International Nuclear Information System (INIS)
Kunz, B.A.; Hannan, M.A.; Haynes, R.H.
1980-01-01
Recently, it has been suggested that mitotic recombination is involved in tumor promotion. On this basis, one might expect tumor promoters to be recombinagenic. D7 is a diploid strain of yeast in which both mutation and mitotic recombination can be measured. We have used this strain to assay the known tumor promoters, iodacetate, anthralin, and 12-0-tetradecanoylphorbol-13-acetate, and the cocarcinogen, catechol, for mutagenicity, recombinagenicity, and the ability to enhance ultraviolet light (UV)-induced genetic events. In the absence of preirradiation with UV, iodoacetate was found to be recombinagenic whereas catechol was mutagenic; however, in both cases, the effects were small. Iodoacetate, anthralin, and catechol potentiated UV-induced mitotic crossing-over, aberrant colony formation, and mutation, while catechol also increased UV-induced gene conversion. We were unable to detect any mutagenic or recombinagenic effect of 12-0-tetradecanoyl-phorbol-13-acetate in either whole cells or spheroplasts. Our results do not indicate any consistent correlation between tumor-promoting activity and the ability of an agent to induce mitotic recombination in yeast. However, the ability to potentiate UV-induced mutation and mitotic recombination may reflect the cocarcinogenic activity of certain promoters
Clinical Experiences of Korean Medicine Treatment against Urinary Bladder Cancer in General Practice
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Taeyeol Park
2016-01-01
Full Text Available Urinary bladder cancer (UBC is one of the most common cancers, with 1 out of every 26 men and 1 out of every 80 women worldwide developing the disease during their lifetime. Moreover, it is a disease that predominantly affects the elderly and is becoming a major health problem as the elderly population continues to rapidly increase. In spite of the rapid development of medical science, the 5-year survival rate has remained around 75% since the 1990s, and the FDA has approved no new drugs for UBC over the last 10 years. In addition, most patients experience frequent recurrence and poor quality of life after diagnosis. Therefore, in order to solve unmet needs by alternative methods, we present our clinical cases of UBC where we observed outstanding results including regression and recurrence prevention exclusively through Traditional Korean Medicine such as (1 herbal therapy, (2 acupuncture, (3 pharmacopuncture and needle-embedding therapy, (4 moxibustion, and (5 cupping therapy. From our experience, it appears that multimodal strategies for synergistic efficiency are more effective than single Korean Medicine treatment. We hope this will encourage investigation of the efficacy of Korean Medicine treatment in clinical trials for UBC patients.
Wei, Fangyuan; Zhou, Jingming; Wei, Xiaochun; Zhang, Juntao; Fleming, Braden C.; Terek, Richard; Pei, Ming; Chen, Qian; Liu, Tao; Wei, Lei
2012-01-01
Objective The objectives of this study were to 1) determine the correlation between osteoarthritis (OA) and Ihh expression, and 2) establish the effects of Ihh on expression of markers of chondrocyte hypertrophy and MMP-13 in human OA cartilage. Design OA cartilage and synovial fluid samples were obtained during total knee arthroplasty. Normal cartilage samples were obtained from intra-articular tumor resections, and normal synovial fluid samples were obtained from healthy volunteers and the contralateral uninjured knee of patients undergoing anterior cruciate ligament reconstruction. OA was graded using the Mankin score. Expression of Ihh in synovial fluid was determined by western blot. Ihh, type X collagen and MMP-13 mRNA were determined by real time PCR. Protein expression of type X collagen and MMP-13 in cartilage samples were analyzed with immunohistochemistry. Chondrocyte size was measured using image analysis. Results Ihh expression was increased 2.6 fold in OA cartilage and 37% in OA synovial fluid when compared to normal control samples. Increased expression of Ihh was associated with the severity of OA and expression of markers of chondrocyte hypertrophy: type X collagen and MMP-13, and chondocyte size. Chondrocytes were more spherical with increasing severity of OA. There was a significant correlation between Mankin score and cell size (r2= 0.80) and Ihh intensity (r2 = 0.89). Exogenous Ihh induced a 6.8 fold increase of type X collagen and 2.8 fold increase of MMP-13 mRNA expression in cultured chondrocytes. Conversely, knockdown of Ihh by siRNA and Hh inhibitor Cyclopamine had the opposite effect. Conclusions Ihh expression correlates with OA progression and changes in chondrocyte morphology and gene expression consistent with chondrocyte hypertrophy and cartilage degradation seen in OA cartilage. Thus, Ihh may be a potential therapeutic target to prevent OA progression. PMID:22469853
Bailey, Michelle; Chauhan, Chitra; Liu, Canhui; Unnasch, Thomas R
2011-03-01
Previous studies of Brugia malayi promoters have suggested that they are unusual in that they lack the CAAT or TATAA boxes that are often emblematic of eucaryotic core promoter domains. Instead, the region surrounding the spliced leader (SL) addition site appears to function as the core promoter domain in B. malayi. To test the hypothesis that polymorphisms in this SL addition domain are important determinants of promoter activity, a series of domain swap mutants were prepared replacing the SL addition domain of the B. malayi 13kDa large subunit ribosomal protein (BmRPL13) with those of other ribosomal protein (RP) promoters exhibiting a wide range of activities. These constructs were then tested for promoter activity in a homologous transient transfection system. On average, polymorphisms in the SL addition domain were found to be responsible for 80% of the variation in promoter activity exhibited by the RP promoters tested. Essentially all of this effect could be attributable to polymorphisms in the 10nt located directly upstream of the SL addition site. A comparison of the sequence of this domain to the promoter activity exhibited by the domain swap mutants suggested that promoter activity was related to the number of T residues present in the coding strand of the upstream domain. Confirming this, mutation of the upstream domain of the promoter of the BmRPS4 gene to a homogeneous stretch of 10 T residues resulted in a significant increase in promoter activity. Copyright © 2010 Elsevier B.V. All rights reserved.
Marathon Month Promotes Healthful Lifestyles for Extension Employees
Donaldson, Joseph L.; Bell, Beth A.; Toman, John J.; Hastings, Shirley
2016-01-01
This article describes Marathon Month, a workplace wellness program for Extension employees. The program promoted physical activity by challenging employees to walk or run the length of a marathon (26.2 mi) or half marathon (13.1 mi) over the course of 1 month. Of the 317 participants, 90% achieved a self-set goal of completing a full or half…
Lavorgna, Alfonso; Harhaj, Edward William
2014-01-01
Human T-cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that infects CD4+ T cells and causes adult T-cell leukemia/lymphoma (ATLL) in 3%–5% of infected individuals after a long latent period. HTLV-1 Tax is a trans-activating protein that regulates viral gene expression and also modulates cellular signaling pathways to enhance T-cell proliferation and cell survival. The Tax oncoprotein promotes T-cell transformation, in part via constitutive activation of the NF-κB transcription factor; however, the underlying mechanisms remain unknown. Ubiquitination is a type of post-translational modification that occurs in a three-step enzymatic cascade mediated by E1, E2 and E3 enzymes and regulates protein stability as well as signal transduction, protein trafficking and the DNA damage response. Emerging studies indicate that Tax hijacks the ubiquitin machinery to activate ubiquitin-dependent kinases and downstream NF-κB signaling. Tax interacts with the E2 conjugating enzyme Ubc13 and is conjugated on C-terminal lysine residues with lysine 63-linked polyubiquitin chains. Tax K63-linked polyubiquitination may serve as a platform for signaling complexes since this modification is critical for interactions with NEMO and IKK. In addition to NF-κB signaling, mono- and polyubiquitination of Tax also regulate its subcellular trafficking and stability. Here, we review recent advances in the diverse roles of ubiquitin in Tax function and how Tax usurps the ubiquitin-proteasome pathway to promote oncogenesis. PMID:25341660
International Nuclear Information System (INIS)
Liao, W.-T.; Yu, H.-S.; Lin Pinpin; Chang, Louis W.
2010-01-01
Epidemiological evidence indicated that residents, especially cigarette smokers, in arseniasis areas had significantly higher lung cancer risk than those living in non-arseniasis areas. Thus an interaction between arsenite and cigarette smoking in lung carcinogenesis was suspected. In the present study, we investigated the interactions of a tobacco-specific carcinogen 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (nicotine-derived nitrosamine ketone, NNK) and arsenite on lung cell transformation. BEAS-2B, an immortalized human lung epithelial cell line, was selected to test the centrosomal abnormalities and colony formation by NNK and arsenite. We found that NNK, alone, could enhance BEAS-2B cell growth at 1-5 μM. Under NNK exposure, arsenite was able to increase centrosomal abnormality as compared with NNK or arsenite treatment alone. NNK treatment could also reduce arsenite-induced G2/M cell cycle arrest and apoptosis, these cellular effects were found to be correlated with p53 dysfunction. Increased anchorage-independent growth (colony formation) of BEAS-2B cells cotreated with NNK and arsenite was also observed in soft agar. Our present investigation demonstrated that NNK could provide a p53 compromised status. Arsenite would act specifically on this p53 compromised status to induce centrosomal abnormality and colony formation. These findings provided strong evidence on the carcinogenic promotional role of arsenite under tobacco-specific carcinogen co-exposure.
Health Promoting Lifestyles Among Primary School Teachers Working in Edirne
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Burcu Tokuc
2007-12-01
Full Text Available To determine some socio-demographic characteristics and to evaluate daily life behaviors of the teachers who are working in Primary Schools in Edirne with Health Promotion Life Style Profile (HPLSP, was aimed in this study. This is a cross-sectional, descriptive study. A questionnaire which was prepared by the investigators and HPLSP was sent to all teachers working in 33 primary schools in Edirne. 410 teachers accepted to participate and completed the questionnaire. Data were evaluated by SPSS v 13.0. It was found that teachers participated in the study were generally at medium level at health promoting behaviors, and the highest mean score was nutrition and the lowest was exercise. The total health promoting behaviors score and inter personel relations score was significantly higher in females but exercise score was significantly higher in males. It was also found that the total score of health promoting behaviors, increased with age. For increasing and supporting health promoting behaviors of the teachers, health promotion lectures should be included in occupational education and in-service training programs, and health professionals always must be in relation with teachers. [TAF Prev Med Bull. 2007; 6(6: 421-426
Health Promoting Lifestyles Among Primary School Teachers Working in Edirne
Directory of Open Access Journals (Sweden)
Burcu Tokuc
2007-12-01
Full Text Available To determine some socio-demographic characteristics and to evaluate daily life behaviors of the teachers who are working in Primary Schools in Edirne with Health Promotion Life Style Profile (HPLSP, was aimed in this study. This is a cross-sectional, descriptive study. A questionnaire which was prepared by the investigators and HPLSP was sent to all teachers working in 33 primary schools in Edirne. 410 teachers accepted to participate and completed the questionnaire. Data were evaluated by SPSS v 13.0. It was found that teachers participated in the study were generally at medium level at health promoting behaviors, and the highest mean score was nutrition and the lowest was exercise. The total health promoting behaviors score and inter personel relations score was significantly higher in females but exercise score was significantly higher in males. It was also found that the total score of health promoting behaviors, increased with age. For increasing and supporting health promoting behaviors of the teachers, health promotion lectures should be included in occupational education and in-service training programs, and health professionals always must be in relation with teachers. [TAF Prev Med Bull 2007; 6(6.000: 421-426
Directory of Open Access Journals (Sweden)
Rajeshree Pujari
2015-03-01
Full Text Available Persistent activation of NF-κB by the Human T-cell leukemia virus type 1 (HTLV-1 oncoprotein, Tax, is vital for the development and pathogenesis of adult T-cell leukemia (ATL and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. K63-linked polyubiquitinated Tax activates the IKK complex in the plasma membrane-associated lipid raft microdomain. Tax also interacts with TAX1BP1 to inactivate the NF-κB negative regulatory ubiquitin-editing A20 enzyme complex. However, the molecular mechanisms of Tax-mediated IKK activation and A20 protein complex inactivation are poorly understood. Here, we demonstrated that membrane associated CADM1 (Cell adhesion molecule1 recruits Ubc13 to Tax, causing K63-linked polyubiquitination of Tax, and IKK complex activation in the membrane lipid raft. The c-terminal cytoplasmic tail containing PDZ binding motif of CADM1 is critical for Tax to maintain persistent NF-κB activation. Finally, Tax failed to inactivate the NF-κB negative regulator ubiquitin-editing enzyme A20 complex, and activate the IKK complex in the lipid raft in absence of CADM1. Our results thus indicate that CADM1 functions as a critical scaffold molecule for Tax and Ubc13 to form a cellular complex with NEMO, TAX1BP1 and NRP, to activate the IKK complex in the plasma membrane-associated lipid rafts, to inactivate NF-κB negative regulators, and maintain persistent NF-κB activation in HTLV-1 infected cells.
Discovery of Ubiquitin Deamidases in the Pathogenic Arsenal of Legionella pneumophila
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Dylan Valleau
2018-04-01
Full Text Available Summary: Legionella pneumophila translocates the largest known arsenal of over 330 pathogenic factors, called “effectors,” into host cells during infection, enabling L. pneumophila to establish a replicative niche inside diverse amebas and human macrophages. Here, we reveal that the L. pneumophila effectors MavC (Lpg2147 and MvcA (Lpg2148 are structural homologs of cycle inhibiting factor (Cif effectors and that the adjacent gene, lpg2149, produces a protein that directly inhibits their activity. In contrast to canonical Cifs, both MavC and MvcA contain an insertion domain and deamidate the residue Gln40 of ubiquitin but not Gln40 of NEDD8. MavC and MvcA are functionally diverse, with only MavC interacting with the human E2-conjugating enzyme UBE2N (Ubc13. MavC deamidates the UBE2N∼Ub conjugate, disrupting Lys63 ubiquitination and dampening NF-κB signaling. Combined, our data reveal a molecular mechanism of host manipulation by pathogenic bacteria and highlight the complex regulatory mechanisms integral to L. pneumophila’s pathogenic strategy. : Legionella pneumophila, possessing the largest known arsenal of effectors, continues to reveal unique approaches to host cell control. Valleau et al. decrypt the functions of a trio of effectors, discovering a pair of ubiquitin-specific deamidases, their regulation by a neighboring dual-specificity protein inhibitor, and a mechanism of NF-κB suppression. Keywords: pathogen-host interaction, ubiquitination, Legionella, UBE2N/Ubc13, NF-κB signaling, Type IV secretion system, effectors, metaeffector, cycle inhibiting factor
Promotion of prescription drugs to consumers and providers, 2001-2010.
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Rachel Kornfield
Full Text Available Pharmaceutical firms heavily promote their products and may have changed marketing strategies in response to reductions in new product approvals, restrictions on some forms of promotion, and the expanding role of biologic therapies.We used descriptive analyses of annual cross-sectional data from 2001 through 2010 to examine direct-to-consumer advertising (DTCA (Kantar Media and provider-targeted promotion (IMS Health and SDI, including: (1 inflation-adjusted total promotion spending ($ and percent of sales; (2 distribution by channel (consumer v. provider; and (3 provider specialty both for the industry as a whole and for top-selling biologic and small molecule therapies.Total promotion peaked in 2004 at US$36.1 billion (13.4% of sales. By 2010 it had declined to $27.7B (9.0% of sales. Between 2006 and 2010, similar declines were seen for promotion to providers and DTCA (both by 25%. DTCA's share of total promotion increased from 12% in 2002 to 18% in 2006, but then declined to 16% and remains highly concentrated. Number of products promoted to providers peaked in 2004 at over 3000, and then declined 20% by 2010. In contrast to top-selling small molecule therapies having an average of $370 million (8.8% of sales spent on promotion, top biologics were promoted less, with only $33 million (1.4% of sales spent per product. Little change occurred in the composition of promotion between primary care physicians and specialists from 2001-2010.These findings suggest that pharmaceutical companies have reduced promotion following changes in the pharmaceutical pipeline and patent expiry for several blockbuster drugs. Promotional strategies for biologic drugs differ substantially from small molecule therapies.
Promotion of prescription drugs to consumers and providers, 2001-2010.
Kornfield, Rachel; Donohue, Julie; Berndt, Ernst R; Alexander, G Caleb
2013-01-01
Pharmaceutical firms heavily promote their products and may have changed marketing strategies in response to reductions in new product approvals, restrictions on some forms of promotion, and the expanding role of biologic therapies. We used descriptive analyses of annual cross-sectional data from 2001 through 2010 to examine direct-to-consumer advertising (DTCA) (Kantar Media) and provider-targeted promotion (IMS Health and SDI), including: (1) inflation-adjusted total promotion spending ($ and percent of sales); (2) distribution by channel (consumer v. provider); and (3) provider specialty both for the industry as a whole and for top-selling biologic and small molecule therapies. Total promotion peaked in 2004 at US$36.1 billion (13.4% of sales). By 2010 it had declined to $27.7B (9.0% of sales). Between 2006 and 2010, similar declines were seen for promotion to providers and DTCA (both by 25%). DTCA's share of total promotion increased from 12% in 2002 to 18% in 2006, but then declined to 16% and remains highly concentrated. Number of products promoted to providers peaked in 2004 at over 3000, and then declined 20% by 2010. In contrast to top-selling small molecule therapies having an average of $370 million (8.8% of sales) spent on promotion, top biologics were promoted less, with only $33 million (1.4% of sales) spent per product. Little change occurred in the composition of promotion between primary care physicians and specialists from 2001-2010. These findings suggest that pharmaceutical companies have reduced promotion following changes in the pharmaceutical pipeline and patent expiry for several blockbuster drugs. Promotional strategies for biologic drugs differ substantially from small molecule therapies.
Radiological mapping of functional transcription units of bacteriophage phiX174 and S13
International Nuclear Information System (INIS)
Pollock, T.J.; Tessman, I.; Tessman, E.S.
1978-01-01
It has been found that the nearest promoter is not always the primary promoter for making translatable message. The technique of ultraviolet mapping was used to determine the location of promoter sites for translated mRNA coded for by bacteriophages phiX174 and S13. The method is based on the theory that the 'target size' for u.v. inactivation of expression of a gene is proportional to the distance between the promoter and the 3' end of the gene. This method has revealed an expected and some unexpected locations for the promoters responsible for gene expression. Ultraviolet-survival curves for expression of phage genes were interpreted in the following way. The contiguous genes D, F, G and H are expressed as a unit under the control of a promoter located near gene D. However, gene B (and probably the adjacent genes K and C) are controlled by a promoter distant from gene B, possibly in the region of gene H, rather than from a promoter located just before gene B. Likewise, gene A is controlled by a promoter distant from gene A. (author)
Graber, P; Gretener, D; Herren, S; Aubry, J P; Elson, G; Poudrier, J; Lecoanet-Henchoz, S; Alouani, S; Losberger, C; Bonnefoy, J Y; Kosco-Vilbois, M H; Gauchat, J F
1998-12-01
To study the expression of IL-13 receptor alpha1 (IL-13Ralpha1), specific monoclonal antibodies (mAb) were generated. Surface expression of the IL-13Ralpha1 on B cells, monocytes and T cells was assessed by flow cytometry using these specific mAb. Among tonsillar B cells, the expression was the highest on the IgD+ CD38- B cell subpopulation which is believed to represent naive B cells. Expression was also detectable on a large fraction of the IgD-CD38- B cells but not on CD38+ B cells. Activation under conditions which promote B cell Ig class switching up-regulated the expression of the receptor. However, the same stimuli had an opposite effect for IL-13Ralpha1 expression levels on monocytes. While IL-13Ralpha1 mRNA was clearly detectable in T cell preparations, no surface expression was detected. However, permeabilization of the T cells showed a clear intracellular expression of the receptor. A soluble form of the receptor was immunoprecipitated from the supernatant of activated peripheral T cells, suggesting that T cell IL-13Ralpha1 might have functions unrelated to the capacity to form a type II IL-4/IL-13R with IL-4Ralpha.
Chronic tinnitus and unipolar brush cell alterations in the cerebellum and dorsal cochlear nucleus.
Brozoski, Thomas; Brozoski, Daniel; Wisner, Kurt; Bauer, Carol
2017-07-01
Animal model research has shown that the central features of tinnitus, the perception of sound without an acoustic correlate, include elevated spontaneous and stimulus-driven activity, enhanced burst-mode firing, decreased variance of inter-spike intervals, and distortion of tonotopic frequency representation. Less well documented are cell-specific correlates of tinnitus. Unipolar brush cell (UBC) alterations in animals with psychophysical evidence of tinnitus has recently been reported. UBCs are glutamatergic interneurons that appear to function as local-circuit signal amplifiers. UBCs are abundant in the dorsal cochlear nucleus (DCN) and very abundant in the flocculus (FL) and paraflocculus (PFL) of the cerebellum. In the present research, two indicators of UBC structure and function were examined: Doublecortin (DCX) and epidermal growth factor receptor substrate 8 (Eps8). DCX is a protein that binds to microtubules where it can modify their assembly and growth. Eps8 is a cell-surface tyrosine kinase receptor mediating the response to epidermal growth factor; it appears to have a role in actin polymerization as well as cytoskeletal protein interactions. Both functions could contribute to synaptic remodeling. In the present research UBC Eps8 and DCX immunoreactivity (IR) were determined in 4 groups of rats distinguished by their exposure to high-level sound and psychophysical performance: Unexposed, exposed to high-level sound with behavioral evidence of tinnitus, and two exposed groups without behavioral evidence of tinnitus. Compared to unexposed controls, exposed animals with tinnitus had Eps8 IR elevated in their PFL; other structures were not affected, nor was DCX IR affected. This was interpreted as UBC upregulation in animals with tinnitus. Exposure that failed to produce tinnitus did not increase either Eps8 or DCX IR. Rather Eps8 IR was decreased in the FL and DCN of one subgroup (Least-Tinnitus), while DCX IR decreased in the FL of the other subgroup (No
Nishino, H; Hayashi, T; Arisawa, M; Satomi, Y; Iwashima, A
1993-01-01
Scopadulcic acid B (SDB), a tetracyclic diterpenoid isolated from a medicinal plant, Scoparia dulcis L., inhibited the effects of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in vitro and in vivo; SDB inhibited TPA-enhanced phospholipid synthesis in cultured cells, and also suppressed the promoting effect of TPA on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene. The potency of SDB proved to be stronger than that of other natural antitumor-promoting terpenoids, such as glycyrrhetinic acid.
Treated unicameral bone cysts.
Weinman, J; Servaes, S; Anupindi, S A
2013-06-01
Unicameral bone cysts (UBCs) are a common benign entity involving the metaphysis of growing bone, occurring within the first two decades of life. Assessment of these lesions, both before and after surgery, is performed routinely utilizing radiographs. We present a review of UBCs at various stages of treatment, including both successful and incomplete healing, and describe the imaging findings throughout their postoperative course. Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
2017-06-01
a meta-analysis. Child development 73 (3), 916-934. Owen, J.M., 2011. Transdiagnostic cognitive processes in high trait anger. Clinical Psychology ...Award Number: W81XWH-13-2-0001 TITLE: : Development of Cognitive Bias Modification (CBM) Tools to Promote Adjustment during Reintegration...DATES COVERED 15-OCT-2012 TO 14-OCT-2016 4. TITLE AND SUBTITLE Development of Cognitive Bias Modification (CBM) Tools to Promote Adjustment during
Mercado, José A; Barceló, Marta; Pliego, Clara; Rey, Manuel; Caballero, José L; Muñoz-Blanco, Juan; Ruano-Rosa, David; López-Herrera, Carlos; de Los Santos, Berta; Romero-Muñoz, Fernando; Pliego-Alfaro, Fernando
2015-12-01
The expression of antifungal genes from Trichoderma harzianum, mainly chitinases, has been used to confer plant resistance to fungal diseases. However, the biotechnological potential of glucanase genes from Trichoderma has been scarcely assessed. In this research, transgenic strawberry plants expressing the β-1,3-glucanase gene bgn13.1 from T. harzianum, under the control of the CaMV35S promoter, have been generated. After acclimatization, five out of 12 independent lines analysed showed a stunted phenotype when growing in the greenhouse. Moreover, most of the lines displayed a reduced yield due to both a reduction in the number of fruit per plant and a lower fruit size. Several transgenic lines showing higher glucanase activity in leaves than control plants were selected for pathogenicity tests. When inoculated with Colletotrichum acutatum, one of the most important strawberry pathogens, transgenic lines showed lower anthracnose symptoms in leaf and crown than control. In the three lines selected, the percentage of plants showing anthracnose symptoms in crown decreased from 61 % to a mean value of 16.5 %, in control and transgenic lines, respectively. Some transgenic lines also showed an enhanced resistance to Rosellinia necatrix, a soil-borne pathogen causing root and crown rot in strawberry. These results indicate that bgn13.1 from T. harzianum can be used to increase strawberry tolerance to crown rot diseases, although its constitutive expression affects plant growth and fruit yield. Alternative strategies such as the use of tissue specific promoters might avoid the negative effects of bgn13.1 expression in plant performance.
Directory of Open Access Journals (Sweden)
Claudia Berrondo
Full Text Available Exosomes are 30-150nM membrane-bound secreted vesicles that are readily isolated from biological fluids such as urine (UEs. Exosomes contain proteins, micro RNA (miRNA, messenger RNA (mRNA, and long non-coding RNA (lncRNA from their cells of origin. Although miRNA, protein and lncRNA have been isolated from serum as potential biomarkers for benign and malignant disease, it is unknown if lncRNAs in UEs from urothelial bladder cancer (UBC patients can serve as biomarkers. lncRNAs are > 200 nucleotide long transcripts that do not encode protein and play critical roles in tumor biology. As the number of recognized tumor-associated lncRNAs continues to increase, there is a parallel need to include lncRNAs into biomarker discovery and therapeutic target algorithms. The lncRNA HOX transcript antisense RNA (HOTAIR has been shown to facilitate tumor initiation and progression and is associated with poor prognosis in several cancers. The importance of HOTAIR in cancer biology has sparked interest in using HOTAIR as a biomarker and potential therapeutic target. Here we show HOTAIR and several tumor-associated lncRNAs are enriched in UEs from UBC patients with high-grade muscle-invasive disease (HGMI pT2-pT4. Knockdown of HOTAIR in UBC cell lines reduces in vitro migration and invasion. Importantly, loss of HOTAIR expression in UBC cell lines alters expression of epithelial-to-mesenchyme transition (EMT genes including SNAI1, TWIST1, ZEB1, ZO1, MMP1 LAMB3, and LAMC2. Finally, we used RNA-sequencing to identify four additional lncRNAs enriched in UBC patient UEs. These data, suggest that UE-derived lncRNA may potentially serve as biomarkers and therapeutic targets.
Xu, Wen-Xiao; Liu, Sheng-Zhi; Wu, Di; Qiao, Guo-Fen; Yan, Jinglong
2015-01-01
Promyelocytic leukemia (PML) protein is a tumor suppressor that fuses with retinoic acid receptor-α (PML-RARα) to contribute to the initiation of acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) upregulates expression of TGF-β1, promoting collagen synthesis in osteoblasts, and ATO binds directly to PML to induce oligomerization, sumoylation, and ubiquitination. However, how ATO upregulates TGF-β1 expression is uncertain. Thus, we suggested that PML sumoylation is responsible for regulation of TGF-β1 protein expression. Kunming mice were treated with ATO, and osteoblasts were counted under scanning electron microscopy. Masson's staining was used to quantify collagen content. hFOB1.19 cells were transfected with siRNA against UBC9 or RNF4, and then treated with ATO or FBS. TGF-β1, PML expression, and sumoylation were quantified with Western blot, and collagen quantified via immunocytochemistry. ATO enhanced osteoblast accumulation, collagen synthesis, and PML-NB formation in vivo. Knocking down UBC9 in hFOB1.19 cells inhibited ATO- and FBS-induced PML sumoylation, TGF-β1 expression, and collagen synthesis. Conversely, knocking down RNF4 enhanced ATO- and FBS-induced PML sumoylation, TGF-β1 expression, and collagen synthesis. These data suggest that PML sumoylation is required for ATO-induced collagen synthesis in osteoblasts. © 2015 S. Karger AG, Basel.
Zarandi, Ashkan; Irani, Shiva; Savabkar, Sanaz; Chaleshi, Vahid; Ghavideldarestani, Maryam; Mirfakhraie, Reza; Khodadoostan, Mahsa; Nazemalhosseini-Mojarad, Ehsan; Asadzadeh Aghdaei, Hamid
2017-01-01
The aim of this study was to evaluate the methylation status of the promoter region of MLH1 gene in colorectal cancer (CRC) and its precursor lesions as well as elucidate its association with various clinicopathological characteristics among Iranian population. Epigenetic silencing of mismatch repair genes, such as MLH1 , by methylation of CpG islands of their promoter region has been proved to be an important mechanism in colorectal carcinogenesis. Fifty colorectal cancer and polyp tissue samples including 13 Primary colorectal tumor and 37 Adenoma polyp samples were enrolled in this study. Methylation-specific polymerase chain reaction (MSP) was performed to find the frequency of MLH1 Promoter Methylation. Promoter methylation of MLH1 gene was detected in 5 out of 13 tumor tissues and 4 out of 37 adenoma polyp. The frequency of MLH1 methylation in tumor samples was significantly higher compared to that in polyp tissues (P= 0.026). No significant association was observed between MLH1 promoter methylation and clinicopathological characteristics of the patients. The frequency of MLH1 promoter methylation in CRC and colon polyp was 18%. Our findings indicated that methylation of MLH1 promoter region alone cannot be considered as a biomarker for early detection of CRC.
Dondossola, Eleonora; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata
2014-01-01
Non-malignant cells found within neoplastic lesions express alanyl (membrane) aminopeptidase (ANPEP, best known as CD13), and CD13-null mice exhibit limited tumor growth and angiogenesis. We have recently demonstrated that a subset of bone marrow-derived CD11b + CD13 + myeloid cells accumulate within neoplastic lesions in several murine models of transplantable cancer to promote angiogenesis. If these findings were confirmed in clinical settings, CD11b + CD13 + myeloid cells could become a non-malignant target for the development of novel anticancer regimens.
13 CFR 124.403 - How is a business plan updated and modified?
2010-01-01
... incorporated into its business plan. The transition management strategy must describe: (1) How the Participant... business growth and promote profitable business operations after the expiration of its program term. (d... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false How is a business plan updated and...
2010-04-01
... 26 Internal Revenue 14 2010-04-01 2010-04-01 false [Reserved] 13.0-13.3 Section 13.0-13.3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) TEMPORARY INCOME TAX REGULATIONS UNDER THE TAX REFORM ACT OF 1969 §§ 13.0-13.3 [Reserved] ...
Feng, Ying; Wang, Zheng; Bao, Zhaoshi; Yan, Wei; You, Gan; Wang, Yinyan; Hu, Huimin; Zhang, Wei; Zhang, Quangeng; Jiang, Tao
2014-01-01
Hypermethylation of the suppressor of cytokine signaling 3(SOCS3) promoter has been reported to predict a poor prognosis in several cancers including glioblastoma multiforme (GBM). We explored the function of SOCS3 promoter hypermethylation in GBM cohorts, including analysis of the CpG island methylator phenotype (CIMP), when a large number of gene loci are simultaneously hypermethylated. A whole genome promoter methylation profile was performed in a cohort of 33 GBM samples, with 13 long-term survivors (LTS; overall survival ≥ 18 months) and 20 short-term survivors (STS; overall survival ≤ 9 months). The SOCS3 promoter methylation status was compared between the two groups. In addition, we investigated the relationship of SOCS3 promoter methylation and G-CIMP status. Interestingly, in our present study, we found that SOCS3 promoter methylation was statistically significantly higher in the 13 LTS than that in the 20 STS. Furthermore, high SOCS3 promoter methylation detected via pyro-sequencing predicted a better prognosis in an independent cohort containing 62 GBM patients. This correlation was validated by the dataset from the Cancer Genome Atlas(TCGA) and the Chinese Cancer Genome Atlas(CGGA). In addition, we found that hypermethylation of the SOCS3 promoter was tightly associated with the G-CIMP-positive GBM patients. Using a total of 359 clinical samples, we demonstrate that SOCS3 promoter hypermethylation status has a favorable prognostic value in GBM patients because of whole genome methylation status. Particularly, the hypermethylation of the SOCS3 promoter indicates positive G-CIMP status.
Directory of Open Access Journals (Sweden)
Ying Feng
Full Text Available Hypermethylation of the suppressor of cytokine signaling 3(SOCS3 promoter has been reported to predict a poor prognosis in several cancers including glioblastoma multiforme (GBM. We explored the function of SOCS3 promoter hypermethylation in GBM cohorts, including analysis of the CpG island methylator phenotype (CIMP, when a large number of gene loci are simultaneously hypermethylated.A whole genome promoter methylation profile was performed in a cohort of 33 GBM samples, with 13 long-term survivors (LTS; overall survival ≥ 18 months and 20 short-term survivors (STS; overall survival ≤ 9 months. The SOCS3 promoter methylation status was compared between the two groups. In addition, we investigated the relationship of SOCS3 promoter methylation and G-CIMP status.Interestingly, in our present study, we found that SOCS3 promoter methylation was statistically significantly higher in the 13 LTS than that in the 20 STS. Furthermore, high SOCS3 promoter methylation detected via pyro-sequencing predicted a better prognosis in an independent cohort containing 62 GBM patients. This correlation was validated by the dataset from the Cancer Genome Atlas(TCGA and the Chinese Cancer Genome Atlas(CGGA. In addition, we found that hypermethylation of the SOCS3 promoter was tightly associated with the G-CIMP-positive GBM patients.Using a total of 359 clinical samples, we demonstrate that SOCS3 promoter hypermethylation status has a favorable prognostic value in GBM patients because of whole genome methylation status. Particularly, the hypermethylation of the SOCS3 promoter indicates positive G-CIMP status.
[Simultaneous existence of unicameral bone cysts involving the femur and ischium].
Makris, Vassilios; Papavasiliou, Kyriakos A; Bobos, Mattheos; Hytiroglou, Prodromos; Kirkos, John M; Kapetanos, George A
2009-01-01
We report a 30-year-old male patient with two unicameral bone cysts (UBC) simultaneously located in the proximal third of the right femur and ipsilateral ischium ramus, respectively. Fine needle biopsies were attempted for both lesions. Biopsy of the femoral lesion under local anesthesia was unsuccessful, so an open biopsy was performed which confirmed the diagnosis of UBC. Biopsy of the ischial lesion was not sufficient for diagnosis. Cytological examination of both specimens showed no other benign or malignant pathology. The femoral lesion was treated with intralesional (due to its large size) excision-curettage, bone grafting, and the introduction of a long gamma locking intramedullary nail to prevent the occurrence of a pathological fracture. The ischial lesion was left untreated and followed conservatively. The patient was free of any symptoms and complications three years postoperatively. This is the first report of an adult patient with UBCs simultaneously located both in a long tubular bone (femur) and a flat bone (ischium ramus).
Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Hirose, Eiji; Yamaguchi, Yasuo
2015-06-01
Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes classically activated M1 macrophages. GM-CSF upregulates protease-activated receptor-2 (PAR-2) protein expression and activation of PAR-2 by human neutrophil elastase (HNE) regulates cytokine production. This study investigated the mechanism of PAR-2-mediated interleukin (IL)-13 production by GM-CSF-dependent macrophages stimulated with HNE. Adherent macrophages were obtained from primary cultures of human mononuclear cells. After stimulation with HNE to activate the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, IL-13 mRNA and protein levels were assessed by the reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. PAR-2 protein was detected in GM-CSF-dependent macrophages by Western blotting. Unexpectedly, PD98059 (an ERK1 inhibitor) increased IL-13 production, even at higher concentrations. Interestingly, U0126 (an ERK1/2 inhibitor) reduced IL-13 production in a concentration-dependent manner. Neither SB203580 (a p38alpha/p38beta inhibitor) nor BIRB796 (a p38gamma/p38delta inhibitor) affected IL-13 production, while TMB-8 (a calcium chelator) diminished IL-13 production. Stimulation with HNE promoted the production of IL-13 (a Th2 cytokine) by GM-CSF-dependent M1 macrophages. PAR-2-mediated IL-13 production may be dependent on the Ca(2+)/ERK2 signaling pathway. Copyright © 2015 Elsevier Inc. All rights reserved.
Munc13 controls the location and efficiency of dense-core vesicle release in neurons.
van de Bospoort, Rhea; Farina, Margherita; Schmitz, Sabine K; de Jong, Arthur; de Wit, Heidi; Verhage, Matthijs; Toonen, Ruud F
2012-12-10
Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent DCV release in hippocampal neurons at single vesicle resolution. DCVs fused preferentially at synaptic terminals. DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost. The remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in wild-type neurons. Conversely, Munc13-1 overexpression (M13OE) promoted extrasynaptic DCV release, also without prolonged stimulation. Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically.
Plant growth promoters and methods of using them
Al-Babili, Salim
2017-01-05
New plant growth regulators, including compounds and compositions, and methods of use including for promoting root growth. The compounds are carotenoid oxidation products, and a preferred example is 3-OH--β-apo-13-Carotenone. A method comprising promoting the growth of at least one plant with use of an effective amount of at least one composition comprising an effective amount of at least one compound which is represented by A-B-C, wherein B is a bivalent polyene moiety, A is a monovalent moiety linked to B by a six-membered carbon ring, wherein the ring has at least one substituent linked to the ring by an oxygen atom, and C is a monovalent moiety linked to B by a carbonyl group. Synergistic effects can be used with combinations of compounds.
Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter.
Directory of Open Access Journals (Sweden)
Jianqing Pan
Full Text Available Effective suicide gene delivery and expression are crucial to achieving successful effects in gene therapy. An ideal tumor-specific promoter expresses therapeutic genes in tumor cells with minimal normal tissue expression. We compared the activity of the FOS (FBJ murine osteosarcoma viral oncogene homolog promoter with five alternative tumor-specific promoters in glioma cells and non-malignant astrocytes. The FOS promoter caused significantly higher transcriptional activity in glioma cell lines than all alternative promoters with the exception of CMV. The FOS promoter showed 13.9%, 32.4%, and 70.8% of the transcriptional activity of CMV in three glioma cell lines (U87, U251, and U373. Importantly, however, the FOS promoter showed only 1.6% of the transcriptional activity of CMV in normal astrocytes. We also tested the biologic activity of recombinant adenovirus containing the suicide gene herpes simplex virus thymidine kinase (HSV-tk driven by the FOS promoter, including selective killing efficacy in vitro and tumor inhibition rate in vivo. Adenoviral-mediated delivery of the HSV-tk gene controlled by the FOS promoter conferred a cytotoxic effect on human glioma cells in vitro and in vivo. This study suggests that use of the FOS-tk adenovirus system is a promising strategy for glioma-specific gene therapy but still much left for improvement.
van Erpecum, K. J.; Portincasa, P.; Eckhardt, E.; Go, P. M.; vanBerge-Henegouwen, G. P.; Groen, A. K.
1996-01-01
Background & Aims: Ursodeoxycholic acid prevents gallstone formation in selected patients. The aim of this study was to examine whether decreased concentration and nucleation-promoting activity of various proteins contribute to this beneficial effect. Methods: Gallbladder bile of 13 patients with
Genes that cooperate with tumor promoters in transformation
International Nuclear Information System (INIS)
Colburn, N.H.; Smith, B.M.
1988-01-01
Tumor-promoting phorbol esters, like growth factors, elicit pleiotropic responses involving biochemical pathways that lead to different biological responses. Genetic variant cell lines that are resistant to mitogenic, differentiation, or transformation responses to tumor promoters have been valuable tools for understanding the molecular bases of these responses. Studies using the mouse epidermal JB6 cell lines that are sensitive or resistant to tumor promoter-induced transformation have yielded new understanding of genetic and signal transduction events involved in neoplastic transformation. The isolation and characterization of cloned mouse promotion sensitivity genes pro-1 and pro-2 is reviewed. A new activity of pro-1 has been identified: when transfected into human cancer prone basal cell nevus syndrome fibroblasts but not normal fibroblasts mouse pro-1 confers lifespan extension of these cells. Recently, we have found tat a pro-1 homolog from a library of nasopharyngeal carcinoma, but not the homolog from a normal human library, is activated for transferring promotion sensitivity. The many genetic variants for responses to tumor promoters have also proved valuable for signal transduction studies. JPB P- cells fail to show the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced syntheses of two proteins of 15 and 16 kD seen in P+ cells. P-, P+, and TPA transformed cells show a progressive decrease in both basal and TPA-inducible levels of a protein kinase C substrate of 80 kD. P- cells are relatively resistant both to anchorage-independent transformation and to a protein band shift induced by the calcium analog lanthanum. It appears that one or more calcium-binding proteins and one or more pro genes may be critical determinants of tumor promoter-induced neoplastic transformation
Promotion of Prescription Drugs to Consumers and Providers, 2001–2010
Kornfield, Rachel; Donohue, Julie; Berndt, Ernst R.; Alexander, G. Caleb
2013-01-01
Background Pharmaceutical firms heavily promote their products and may have changed marketing strategies in response to reductions in new product approvals, restrictions on some forms of promotion, and the expanding role of biologic therapies. Methods We used descriptive analyses of annual cross-sectional data from 2001 through 2010 to examine direct-to-consumer advertising (DTCA) (Kantar Media) and provider-targeted promotion (IMS Health and SDI), including: (1) inflation-adjusted total promotion spending ($ and percent of sales); (2) distribution by channel (consumer v. provider); and (3) provider specialty both for the industry as a whole and for top-selling biologic and small molecule therapies. Results Total promotion peaked in 2004 at US$36.1 billion (13.4% of sales). By 2010 it had declined to $27.7B (9.0% of sales). Between 2006 and 2010, similar declines were seen for promotion to providers and DTCA (both by 25%). DTCA’s share of total promotion increased from 12% in 2002 to 18% in 2006, but then declined to 16% and remains highly concentrated. Number of products promoted to providers peaked in 2004 at over 3000, and then declined 20% by 2010. In contrast to top-selling small molecule therapies having an average of $370 million (8.8% of sales) spent on promotion, top biologics were promoted less, with only $33 million (1.4% of sales) spent per product. Little change occurred in the composition of promotion between primary care physicians and specialists from 2001–2010. Conclusions These findings suggest that pharmaceutical companies have reduced promotion following changes in the pharmaceutical pipeline and patent expiry for several blockbuster drugs. Promotional strategies for biologic drugs differ substantially from small molecule therapies. PMID:23469165
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Mona H Fenstad
Full Text Available BACKGROUND: Preeclampsia is a serious pregnancy complication, demonstrating a complex pattern of inheritance. The elucidation of genetic liability to preeclampsia remains a major challenge in obstetric medicine. We have adopted a positional cloning approach to identify maternal genetic components, with linkages previously demonstrated to chromosomes 2q, 5q and 13q in an Australian/New Zealand familial cohort. The current study aimed to identify potential functional and structural variants in the positional candidate gene TNFSF13B under the 13q linkage peak and assess their association status with maternal preeclampsia genetic susceptibility. METHODOLOGY/PRINCIPAL FINDINGS: The proximal promoter and coding regions of the positional candidate gene TNFSF13B residing within the 13q linkage region was sequenced using 48 proband or founder individuals from Australian/New Zealand families. Ten sequence variants (nine SNPs and one single base insertion were identified and seven SNPs were successfully genotyped in the total Australian/New Zealand family cohort (74 families/480 individuals. Borderline association to preeclampsia (p = 0.0153 was observed for three rare SNPs (rs16972194, rs16972197 and rs56124946 in strong linkage disequilibrium with each other. Functional evaluation by electrophoretic mobility shift assays showed differential nuclear factor binding to the minor allele of the rs16972194 SNP, residing upstream of the translation start site, making this a putative functional variant. The observed genetic associations were not replicated in a Norwegian case/control cohort (The Nord-Trøndelag Health Study (HUNT2, 851 preeclamptic and 1,440 non-preeclamptic women. CONCLUSION/SIGNIFICANCE: TNFSF13B has previously been suggested to contribute to the normal immunological adaption crucial for a successful pregnancy. Our observations support TNFSF13B as a potential novel preeclampsia susceptibility gene. We discuss a possible role for TNFSF13B in
South Asia's health promotion kaleidoscope.
Mukhopadhyay, Alok
2007-01-01
South Asia has 22 percent of the world's population but only 1.3 percent of the global income. Consequently 40 percent of the population is living in absolute poverty. However the health transition in some of its countries including India and Sri Lanka is a testimony to the fact that there are proven solutions to the problems of health and development within the region. The countries of the region have much in common, including a democratic political system, four major religions, a vibrant and living tradition of voluntarism and an extensive health infrastructure which is operating well below par. Despite the underlying unity, South Asia enjoys enormous cultural, linguistic and ethnic diversity. In this large, complex and vibrant region, health promotion is a challenging task, but it also holds the key to a dramatic change in the global health situation. Many of these solutions lie in wider areas of socio-political action. There are much needed shifts in the health promotion and development efforts, particularly in the area of poverty and social justice; gender inequity; population stabilisation; health and environment; control of communicable and non-communicable diseases; and urban health strategies. The principle of cooperation, partnership and intersectoral collaboration for health will be explored. Developing an appropriate, sustainable and people centred health and development strategy in the coming decades is an enormous challenge. There has been an attempt to focus on the emerging needs of the region, which call for health promotion, and involvement of civil society, private sector and the governments bestowed with the increased responsibility of ensuring health security for people. Strengthening the existing health systems, allocating adequate resources for health development and ensuring community participation are all prerequisites to the success of health promotion in the region.
Jamshidi, Khodamorad; Mirkazemi, Masoud; Izanloo, Azra; Mirzaei, Alireza
2018-01-01
Several therapeutic strategies have been used for managing unicameral bone cyst (UBC) of the proximal femur. However, there is insufficient evidence to support one treatment over another, and the optimal treatment is controversial. This study aims at describing our experience with surgical reconstruction of paediatric UBCs of the proximal femur using a proximal locking plate and fibular strut allograft. In total, 14 consecutive paediatric patients with Dormans types IB (four cases) and IIB (10 cases) UBC were assessed. Mean patient age was 8.6 ± 2.3 years, and mean follow-up period was 41.7 ± 29.8 months. Six patients (42.8%) were referred with a pathologic fracture. Clinical/radiological outcome and complication rates were evaluated at the final follow-up session. No cysts were Capanna's class III (recurrence) or IV (no response). Complete healing (Capanna's class I) was seen in ten cysts, while four other cysts healed with residual radiolucent areas (Capanna's class II). Mean healing period was 14.1 ± 5.1 (9-24 months). One patient had superficial infection, one heterotopic ossification, and one mild coxa vara, and mean Musculoskeletal Tumor Society (MSTS) score was 99.5%. According to our results, locking plate and fibular strut graft in Dormans classification types IB and IIB results in a favorable outcome in managing UBC of the proximal femur in the paediatric population.
Energy Technology Data Exchange (ETDEWEB)
Larry G. Felix; P. Vann Bush; Stephen Niksa
2003-04-30
In full-scale boilers, the effect of biomass cofiring on NO{sub x} and unburned carbon (UBC) emissions has been found to be site-specific. Few sets of field data are comparable and no consistent database of information exists upon which cofiring fuel choice or injection system design can be based to assure that NOX emissions will be minimized and UBC be reduced. This report presents the results of a comprehensive project that generated an extensive set of pilot-scale test data that were used to validate a new predictive model for the cofiring of biomass and coal. All testing was performed at the 3.6 MMBtu/hr (1.75 MW{sub t}) Southern Company Services/Southern Research Institute Combustion Research Facility where a variety of burner configurations, coals, biomasses, and biomass injection schemes were utilized to generate a database of consistent, scalable, experimental results (422 separate test conditions). This database was then used to validate a new model for predicting NO{sub x} and UBC emissions from the cofiring of biomass and coal. This model is based on an Advanced Post-Processing (APP) technique that generates an equivalent network of idealized reactor elements from a conventional CFD simulation. The APP reactor network is a computational environment that allows for the incorporation of all relevant chemical reaction mechanisms and provides a new tool to quantify NOx and UBC emissions for any cofired combination of coal and biomass.
Directory of Open Access Journals (Sweden)
Molly Dragiewicz
2016-06-01
Full Text Available This special issue presents a series of papers by scholars who participated in a workshop entitled ‘Men's Groups: Challenging Feminism’, which was held at the University of British Columbia (UBC, Canada, 26-27 May 2014. The workshop was organised by Susan B Boyd, Professor of Law and Chair in Feminist Legal Studies at the UBC Faculty of Law, and was sponsored by the Peter Wall Institute for Advanced Studies at UBC, the Peter A Allard School of Law, the Centre for Feminist Legal Studies at UBC, and the Canadian Journal of Women and the Law. The aim of the workshop was to bring together feminist scholars from multiple disciplines and multiple national contexts to explore a source of resistance to feminism that has been largely overlooked in scholarly research: the growing number of nationally situated and globally linked organisations acting in the name of men's rights and interests which contend that men are discriminated against in law, education and government funding, and that feminism is to blame for this. This special edition presents eight papers inspired by the workshop, authored by scholars from Canada, New Zealand, Poland, Sweden and the United States. A second special issue comprised of eight other papers inspired by the workshop was published in the Canadian Journal of Women and the Law as volume 28(1 in 2016.To find out more about this special edition, download the PDF file from this page.
6 CFR 13.13 - Parties to the hearing.
2010-01-01
... 6 Domestic Security 1 2010-01-01 2010-01-01 false Parties to the hearing. 13.13 Section 13.13 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.13 Parties to the hearing. (a) The parties to the hearing will be the Defendant and the Authority...
What patients think about promotional activities of pharmaceutical companies in Turkey.
Semin, Semih; Güldal, Dilek; Ozçakar, Nilgün; Mevsim, Vildan
2006-08-01
Drugs, as commercial products, are subject to diverse marketing methods including promotional activities. Although the legal/ethical aspects of promotional activities have been discussed in a limited manner, the patient has remained the neglected variable of this equation. The goal of our study, therefore, is to investigate the patients' opinion on the promotional activities of pharmaceutical companies. A descriptive study was conducted at 44 primary health care centers in Turkey and 584 volunteers who applied to these centers were included. A questionnaire consisting of 42 questions was developed with demographic information in the first section, and drug ads and promotions included in the second section. Chi-square test and logistic regression analysis were used for statistical analysis. The awareness and ethical evaluation of patients of the promotional activities. Nearly 83% of the participants were aware of the promotion issue. Eighty percent found it unethical, 82% suggested that promotional activities should be forbidden, restricted or regulated. 1/3 of the participants believed that physicians made their drug choices based on the gifts and ads of pharmaceutical companies. Half of them had low confidence in the prescriptions of physicians who accepted gifts from the pharmaceutical companies. 54.5% of patients also considered promotional activities as a factor which increased drug prices. In our study, a considerable number of patients were aware of promotions and the effects of promotion on prescriptions. The findings of our study may contribute to the development of effective regulations on this issue. Very strict measures controlling drug companies' promotion activities must be formulated. Further, these regulations must incorporate and take into consideration the patients' opinion. Today, the basic need for the proper use of drugs does not rest in pharmaceutical promotion, but in providing adequate health services and effective education for both people
Point-of-sale tobacco promotion and youth smoking: a meta-analysis.
Robertson, Lindsay; Cameron, Claire; McGee, Rob; Marsh, Louise; Hoek, Janet
2016-12-01
Previous systematic reviews have found consistent evidence of a positive association between exposure to point-of-sale (POS) tobacco promotion and increased smoking and smoking susceptibility among children and adolescents. No meta-analysis has been conducted on these studies to date. Systematic literature searches were carried out to identify all quantitative observational studies that examined the relationship between POS tobacco promotion and individual-level smoking and smoking-related cognitions among children and adolescents, published between January 1990 and June 2014. Random-effects meta-analyses were used. Subgroup analyses were conducted according to extent of tobacco POS advertising environment in the study environment. Sensitivity analyses were performed according to study size and quality. 13 studies met the inclusion criteria; 11 reported data for behavioural outcomes, 6 for cognitive outcomes (each of these assessed smoking susceptibility). The studies were cross-sectional, with the exception of 2 cohort studies. For the behavioural outcomes, the pooled OR was 1.61 (95% CI 1.33 to 1.96) and for smoking susceptibility the pooled OR was 1.32 (95% CI 1.09 to 1.61). Children and adolescents more frequently exposed to POS tobacco promotion have around 1.6 times higher odds of having tried smoking and around 1.3 times higher odds of being susceptible to future smoking, compared with those less frequently exposed. Together with the available evaluations of POS display bans, the results strongly indicate that legislation banning tobacco POS promotion will effectively reduce smoking among young people. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Associations of RASSF1A, RARβ, and CDH1 promoter hypermethylation with oral cancer risk
Wen, Guohong; Wang, Huadong; Zhong, Zhaohui
2018-01-01
Abstract Background: Oral tumor is a heterogeneous group of tumors, in which it has several different histopathological and molecular features. Recently, genetic and epigenetic alterations are often detected in the development of oral cancer. Gene promoter hypermethylation leads to the silencing of cancer related genes without changes of genes sequence. To clarify the effect of RAS association domain family protein 1a (RASSF1A), retinoic acid receptor beta (RARβ), and E-cadherin (CDH1) promoter hypermethylation on the risk of oral cancer, we performed this meta-analysis. Methods: PubMed, Web of Science, Embase, and Chinese National Knowledge Infrastructure (CNKI) databases were retrieved to identify eligible articles. Stata 12.0 software was used to analyze extracted data of the included articles. Odds ratios (ORs) with the corresponding 95% confidence interval (95% CI) were calculated to evaluate the associations of RASSF1A, RARβ, and CDH1 promoter hypermethylation with oral cancer risk. Results: Around 23 literatures with 29 studies were included in the final meta-analysis, in which 12 studies were about RASSF1A promoter methylation, 4 studies were about RARβ promoter methylation, and 13 studies were about CDH1 promoter methylation. Overall, the results of this meta-analysis showed that there were significant associations between RASSF1A, RARβ, and CDH1 promoter hypermethylation and oral cancer risk (RASSF1A, OR = 11.8, 95% CI = 6.14–22.66; RARβ, OR = 20.35, 95% CI = 5.64–73.39; CDH1, OR = 13.46, 95% CI = 5.31–34.17). In addition, we found that RASSF1A promoter hypermethylation exerted higher frequency in the tongue tumor than other site tumor in mouth (RASSF1A, tongue tumor vs other site tumor in mouth, unmethylation vs methylation, OR = 0.65, 95%CI = 0.44–0.98). Conclusion: RASSF1A, RARβ, and CDH1 promoter hypermethylation might significantly increase the risk of oral cancer. PMID:29538221
Current topics in DNA double-strand break repair
International Nuclear Information System (INIS)
Kobayashi, Junya; Takata, Minoru; Iwabuchi, Kuniyoshi; Miyagawa, Kiyoshi; Sonoda, Eiichiro; Suzuki, Keiji; Tauchi, Hiroshi
2008-01-01
DNA double strand break (DSB) is one of the most critical types of damage which is induced by ionizing radiation. In this review, we summarize current progress in investigations on the function of DSB repair-related proteins. We focused on recent findings in the analysis of the function of proteins such as 53BP1, histone H2AX, Mus81-Eme1, Fanc complex, and UBC13, which are found to be related to homologous recombination repair or to non-homologous end joining. In addition to the function of these proteins in DSB repair, the biological function of nuclear foci formation following DSB induction is discussed. (author)
Histone H1 couples initiation and amplification of ubiquitin signalling after DNA damage
DEFF Research Database (Denmark)
Thorslund, Tina; Ripplinger, Anita; Hoffmann, Saskia
2015-01-01
DNA double-strand breaks (DSBs) are highly cytotoxic DNA lesions that trigger non-proteolytic ubiquitylation of adjacent chromatin areas to generate binding sites for DNA repair factors. This depends on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 (refs 1-6), and UBC13 (also...... known as UBE2N), an E2 ubiquitin-conjugating enzyme that specifically generates K63-linked ubiquitin chains. Whereas RNF168 is known to catalyse ubiquitylation of H2A-type histones, leading to the recruitment of repair factors such as 53BP1 (refs 8-10), the critical substrates of RNF8 and K63-linked...
DEFF Research Database (Denmark)
Lecomte, Julie; Masset, Anne; Blacher, Silvia
2012-01-01
producing cells were exclusively α-SMA(+) cells and derived from GFP(+) BM cells. To investigate their impact on tumor invasion, we isolated mesenchymal stem cells (MSCs) from the BM of wild-type and MMP13-deficient mice. Wild-type MSC promoted cancer cell invasion in a spheroid assay, whereas MSCs obtained......)-derived cells to generate different fibroblast subsets that putatively produce the matrix metalloproteinase 13 (MMP13) and affect cancer cell invasion. A murine model of skin carcinoma was applied to mice, irradiated, and engrafted with BM isolated from green fluorescent protein (GFP) transgenic mice. We...
Role for sumoylation in systemic inflammation and immune homeostasis in Drosophila larvae.
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Indira Paddibhatla
2010-12-01
Full Text Available To counter systemic risk of infection by parasitic wasps, Drosophila larvae activate humoral immunity in the fat body and mount a robust cellular response resulting in encapsulation of the wasp egg. Innate immune reactions are tightly regulated and are resolved within hours. To understand the mechanisms underlying activation and resolution of the egg encapsulation response and examine if failure of the latter develops into systemic inflammatory disease, we correlated parasitic wasp-induced changes in the Drosophila larva with systemic chronic conditions in sumoylation-deficient mutants. We have previously reported that loss of either Cactus, the Drosophila (IκB protein or Ubc9, the SUMO-conjugating enzyme, leads to constitutive activation of the humoral and cellular pathways, hematopoietic overproliferation and tumorogenesis. Here we report that parasite infection simultaneously activates NF-κB-dependent transcription of Spätzle processing enzyme (SPE and cactus. Endogenous Spätzle protein (the Toll ligand is expressed in immune cells and excessive SPE or Spätzle is pro-inflammatory. Consistent with this function, loss of Spz suppresses Ubc9⁻ defects. In contrast to the pro-inflammatory roles of SPE and Spätzle, Cactus and Ubc9 exert an anti-inflammatory effect. We show that Ubc9 maintains steady state levels of Cactus protein. In a series of immuno-genetic experiments, we demonstrate the existence of a robust bidirectional interaction between blood cells and the fat body and propose that wasp infection activates Toll signaling in both compartments via extracellular activation of Spätzle. Within each organ, the IκB/Ubc9-dependent inhibitory feedback resolves immune signaling and restores homeostasis. The loss of this feedback leads to chronic inflammation. Our studies not only provide an integrated framework for understanding the molecular basis of the evolutionary arms race between insect hosts and their parasites, but also offer
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Liu Wen-Sheng
2010-11-01
Full Text Available Abstract Background The dendritic cell-specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN is an important pathogen recognition receptor of the innate immune system. DC-SIGN promoter variants play important role in the susceptibility to various infectious diseases. Nasopharyngeal carcinoma (NPC is a malignancy that is common in southern China and whether DC-SIGN promoter variants have effects on susceptibility to NPC is still unknown. The aim of this study is to ascertain the potential involvement of DC-SIGN promoter single nucleotide polymorphisms (SNPs in NPC susceptibility. Methods We conducted a case control study based on Cantonese population including 444 NPC patients and 464 controls matched on age and sex. The 1041 bp of DC-SIGN promoter region was directly sequenced for all samples. Sequence alignment and SNP search were inspected using DNAStar analysis programs and haplotype frequencies were estimated in Haploview V 4.0. The associations between the SNPs and the risk of NPC were analyzed using chi-square test and non-conditional logistic regression analysis with SPSS 13.0 software. Results A total of six variants were observed in the DC-SIGN promoter region and DC-SIGN -139 GG and -939 AA were significantly associated with NPC risk with adjusted Odds Ratios (ORs of 2.10 (95% confidence interval [CI] = 1.23-3.59; P = 0.006 and 2.52 (1.29-4.93; P = 0.007 respectively and subjects carrying the risk allele DC-SIGN -871 G had 1.47-fold (95% CI = 1.14-1.90 increased risks of developing NPC (P = 0.003. Haplotype analysis revealed that h1 'AAAG' was significantly associated with protection against NPC (OR = 0.69; P = 0.0002 and the association was still significant when using 1000 permutation test runs (P = 0.001. Conclusions Our study indicated that DC-SIGN promoter variants appear to be involved in the susceptibility to NPC and the detailed mechanism of this effect need further studies.
Tobacco advertising/promotions and adolescents' smoking risk in Northern Africa.
Madkour, Aubrey Spriggs; Ledford, E Cannon; Andersen, Lori; Johnson, Carolyn C
2014-05-01
Comprehensive tobacco advertising/promotion bans are effective against adolescent smoking but many developing countries have implemented only partial bans. This study examines the association between advertising/promotions exposure and adolescent cigarette smoking risk in North Africa, and possible mediation of this association by parent and peer smoking. Adolescent data (n=12 329) from the Global Youth Tobacco Survey were analyzed (Libya, 2007; Egypt, 2005; Morocco, 2006; Tunisia 2007; and Sudan, 2005). Current smoking (any cigarette use in the past 30 days) and never-smokers' initiation susceptibility (composite of openness to accepting a cigarette from a friend and intention to start smoking in the next year) outcomes were examined. Advertising/promotion exposures included media and in-person contacts. Weighted univariate, bivariate and multivariable analyses were conducted. Current smoking prevalence ranged from 5.6% (Egypt) to 15.3% (Tunisia) among boys, and 1.1% (Libya and Egypt) to 2.0% (Morocco and Sudan) among girls. Initiation susceptibility ranged from 14.1% (Sudan) to 25.0% (Tunisia) among boys, and from 13.3% (Sudan) to 15.0% (Libya) among girls. Ninety-eight percent of adolescents reported exposure to at least one type of advertising/promotion. In multivariable analyses adjusting for demographics, each type of advertising/promotion was significantly and positively associated with boys' current smoking status; most advertising/promotion exposure types were also positively associated with initiation susceptibility among boys and girls. Peer smoking only partially mediated these associations. Tobacco advertising/promotion exposure was highly prevalent and associated with adolescents' smoking risk in these countries. The comprehensiveness and enforcement of advertising/promotion bans needs to be enhanced.
Velazquez, Cayley E; Black, Jennifer L; Ahmadi, Naseam
2015-01-01
The purpose of this study was to provide a descriptive profile of food-related advertising, messaging, and signage in Vancouver schools and to examine differences in the prevalence and characteristics of promotions between elementary and secondary schools. All food-related promotions were photographed in 23 diverse Vancouver public schools between November 2012 and April 2013. Key attributes, including the location, size, and main purpose of each promotion, as well as the type of food and/or beverage advertised and compliance with provincial school nutrition guidelines, were coded. Descriptive statistics assessed the prevalence and characteristics of promotions. Cross-tabulations examined whether the promotional landscape differed between elementary and secondary schools. All secondary and 80% of elementary schools contained food or beverage promotions (median = 17, range = 0-57 promotions per school). Of the 493 promotions documented, approximately 25% depicted "choose least" or "not recommended" items, prohibited for sale by provincial school nutrition guidelines. Nearly 1/3 of promotions advertised commercial items (e.g., brand name beverages such as Pepsi), in violation of the Board of Education's advertising policies and only 13% conveyed nutrition education messages. Close to half of all promotions were created by students for class projects, many of which marketed minimally nutritious items. In Vancouver schools, food-related promotions are common and are more prevalent in secondary than elementary schools. Students are regularly exposed to messaging for nutritionally poor items that are not in compliance with provincial school nutrition guidelines and which violate school board advertising policies. Stronger oversight of food-related promotional materials is needed to ensure that schools provide health promoting food environments.
Efficacy of tiamulin as a growth promotant for growing swine.
Cromwell, G L; Stahly, T S
1985-01-01
A study involving 244 pigs initially averaging 13 kg was conducted at two stations to evaluate tiamulin as a growth promotant for growing swine. In each experiment, four replicate pens of five (Exp. 1) or six (Exp. 2) pigs/pen were used to evaluate each treatment. In Exp. 1, pigs were fed 0, 11, 22 or 44 ppm tiamulin from 15 to 58 kg, then fed a nonmedicated control diet for the remainder of the experiment (to 95 kg). In Exp. 2, pigs were fed 0, 2.75, 5.5, 11 or 22 ppm tiamulin from 11 to 56 kg, followed by the nonmedicated control diet (to 95 kg). In each experiment, carbadox (55 ppm) was included as a positive control and was fed to an average weight of 35 kg, followed by the control diet. Averaged across all dietary levels, tiamulin resulted in a 14.1% improvement in gain and a 5.7% improvement in feed:gain ratio during the first 28 to 35 d of the experiment (to 30 kg). These improvements were slightly less than those resulting from the feeding of carbadox during the same period (21.5 and 6.9%, respectively). From 13 to 57 kg, pigs fed tiamulin gained 11.6% faster and 3.1% more efficiently than did controls. Over the entire experiment (13 to 95 kg), tiamulin-fed pigs gained 5.7% faster than did controls, even though the tiamulin was withdrawn at 57 kg body weight. Growth rate from 13 to 57 kg plateaued at the 11-ppm dietary level of tiamulin; whereas, feed:gain ratio plateaued at the 22-ppm level. The results indicate that tiamulin is an effective growth promotant for growing swine.
Assignment of sigma factors of RNA polymerase to promoters in Corynebacterium glutamicum
Czech Academy of Sciences Publication Activity Database
Dostálová, Hana; Holátko, Jiří; Busche, T.; Rucká, Lenka; Rapoport, Andrey; Halada, Petr; Nešvera, Jan; Kalinowski, J.; Pátek, Miroslav
2017-01-01
Roč. 7, JUN 23 (2017), s. 1-13, č. článku 133. ISSN 2191-0855 R&D Projects: GA ČR(CZ) GA17-06991S Institutional support: RVO:61388971 Keywords : Corynebacterium glutamicum * Promoter * Sigma factor Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 1.825, year: 2016
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Rachana Garg
2017-04-01
Full Text Available Summary: PKCε, an oncogenic member of the PKC family, is aberrantly overexpressed in epithelial cancers. To date, little is known about functional interactions of PKCε with other genetic alterations, as well as the effectors contributing to its tumorigenic and metastatic phenotype. Here, we demonstrate that PKCε cooperates with the loss of the tumor suppressor Pten for the development of prostate cancer in a mouse model. Mechanistic analysis revealed that PKCε overexpression and Pten loss individually and synergistically upregulate the production of the chemokine CXCL13, which involves the transcriptional activation of the CXCL13 gene via the non-canonical nuclear factor κB (NF-κB pathway. Notably, targeted disruption of CXCL13 or its receptor, CXCR5, in prostate cancer cells impaired their migratory and tumorigenic properties. In addition to providing evidence for an autonomous vicious cycle driven by PKCε, our studies identified a compelling rationale for targeting the CXCL13-CXCR5 axis for prostate cancer treatment. : Garg et al. find that PKCε overexpression cooperates with Pten loss to promote prostate cancer in mice. These two alterations together confer enhanced growth, tumorigenic, migratory and invasive capabilities to prostate epithelial cells, and promote the release of CXCL13, an effect that is mediated by the non-canonical NF-κB pathway. Keywords: PKCε, PTEN, CXCL13, NF-κB, prostate cancer, CXCR5, migration, proliferation, transgenic mice
ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling
Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.
2010-01-01
SUMMARY The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identified as substrates for ADAM13. ADAM13 upregulates canonical Wnt signaling and early expression of the transcription factor snail2, whereas EfnB1 inhibits the canonical Wnt pathway and snail2 expression. We propose that by cleaving class B Efns, ADAM13 promotes canonical Wnt signaling and early CNC induction. PMID:20708595
Fingerprinting for discriminating tea germplasm using inter-simple sequence repeat (ISSR) markers
International Nuclear Information System (INIS)
Liu, B.Y.; Li, Y.Y.; Wang, P.S.; Wang, L.Y.; Wang, P.S.
2012-01-01
For the discrimination of tea germplasm at the inter-specific level, 134 tea varieties preserved in the China National Germplasm Tea Repositories (CNGTR) were analyzed using inter simple sequence repeat (ISSR) markers. Eighteen primers were chosen from 60 screened for ISSR amplification, generating 99.4% polymorphic bands. The mean Nei's gene diversity (H) and the overall mean Shannon's Information index (I) were 0.396 and 0.578, respectively, indicating a wide gene pool. Using the presence, sometimes absence of unique ISSR markers, it was possible to discriminate 32 of the genotypes tested. No single primer could discriminate all the 134 genotypes. However, UBC811 provided rich band patterns and it can discriminate 35 genotypes. The combination of two and three primers could discriminate 99 and 121 genotypes, respectively. Furthermore, the combination of band patterns or the DNA fingerprinting based on specific ISSR markers generated by UBC811, UBC835, ISSR2 and ISSR3 could discriminate all 134 genotypes tested. ISSR markers also provide a powerful tool to discriminate tea germplasm at the inter-specific level. (author)
Interventions to promote cycling: systematic review.
Yang, Lin; Sahlqvist, Shannon; McMinn, Alison; Griffin, Simon J; Ogilvie, David
2010-10-18
To determine what interventions are effective in promoting cycling, the size of the effects of interventions, and evidence of any associated benefits on overall physical activity or anthropometric measures. Systematic review. Published and unpublished reports in any language identified by searching 13 electronic databases, websites, reference lists, and existing systematic reviews, and papers identified by experts in the field. Review methods Controlled "before and after" experimental or observational studies of the effect of any type of intervention on cycling behaviour measured at either individual or population level. Twenty five studies (of which two were randomised controlled trials) from seven countries were included. Six studies examined interventions aimed specifically at promoting cycling, of which four (an intensive individual intervention in obese women, high quality improvements to a cycle route network, and two multifaceted cycle promotion initiatives at town or city level) were found to be associated with increases in cycling. Those studies that evaluated interventions at population level reported net increases of up to 3.4 percentage points in the population prevalence of cycling or the proportion of trips made by bicycle. Sixteen studies assessing individualised marketing of "environmentally friendly" modes of transport to interested households reported modest but consistent net effects equating to an average of eight additional cycling trips per person per year in the local population. Other interventions that targeted travel behaviour in general were not associated with a clear increase in cycling. Only two studies assessed effects of interventions on physical activity; one reported a positive shift in the population distribution of overall physical activity during the intervention. Community-wide promotional activities and improving infrastructure for cycling have the potential to increase cycling by modest amounts, but further controlled
HEALTH PROMOTING BEHAVIOR AMONG COLLEGE STUDENTS IN CHANDIGARH, INDIA
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Suraj Senjam
2012-03-01
Full Text Available Background: India faces multiple threats of diseases. The increasing trend of lifestyle related health problems is becoming a serious issue in India. The best strategy to tackle this changing health concern is adoption of healthy lifestyle and health promotion activities. Objectives: To determine the level of involvement in health promoting behaviors of college students in Chandigarh. Material & Methods: This college based cross sectional study was conducted in four randomly selected colleges of Chandigarh during September 2007 to June 2008. Results: Two hundred students (F=100, M=100 were studied by using self administered health promoting lifestyle profile (HPLP questionnaires. Mean HPLP score was 138.69 (M=137.98, F=139.39. Female students were more likely to have better health promoting practices than their counterpart male students, but difference was not significant. Female students showed more sense of health responsibility than male students (p=0.00, whereas male students were significantly more involved in physical activities than female students (p=0.02. Overall, only few students (18.5% searched health related article from the internet; 26% went for normal health check up in the last year; 13.5% students practiced yoga regularly; 24.5% of them tried to choose diet with low fat content; 30% of them skipped meals regularly, and 25.5% of them ate processed food regularly. Conclusion: The study results showed that college students in Chandigarh had reasonably good orientation towards health promoting practices.
Arun, V.; Kuriakose, Boney; Sridhar, Vaniyambadi V.; Thomas, George
2011-01-01
T-urf13, a well-documented cms-associated gene from maize, has been shown to render methomyl sensitivity to heterologous systems like rice, yeast and bacteria when expressed constitutively. Since these transgenic plants were fertile, it was hypothesized that T-urf13 gene if expressed in anthers may result in male sterility that could be used for hybrid seed production. Hence, this work was aimed at analysing whether T-urf13 gene when expressed in anthers can result in male sterile plants or r...
International Nuclear Information System (INIS)
Roychoudhury, Paromita; Ghosh, Utpal; Bhattacharyya, Nitai P.; Chaudhuri, Keya
2006-01-01
The cellular response to ionizing radiation is mediated by a complex interaction of number of proteins involving different pathways. Previously, we have shown that up regulation of mitochondrial genes ND1, ND4, and COX1 transcribed from the heavy strand promoter (P H ) has been increased in a radio-resistant cell strain designated as M5 in comparison with the parental Chinese hamster V79 cells. These genes are also up regulated in Chinese hamster V79 cells VB13 that express exogenous human Bcl2. In the present study, the expression of the gene ND6 that is expressed from the light strand promoter (P L ) was found to be similar in both the cell lines, as determined by RT-PCR. To test the possibility that this differential expression of mitochondrial genes under these two promoters was mediated by differences in proteins' affinity to interact with these promoters, we have carried out electrophoretic mobility shift assay (EMSA) using mitochondrial cell extracts from these two cell lines. Our result of these experiments revealed that two different proteins formed complex with the synthetic promoters and higher amount of protein from M5 cell extracts interacted with the P H promoter in comparison to that observed with cell extracts from Chinese hamster V79 cells. The promoter-specific differential binding of proteins was also observed in VB13. These results showed that differential mitochondrial gene expression observed earlier in the radio-resistant M5 cells was due to enhanced interaction proteins with the promoters P H and mediated by the expression of Bcl2
What do health-promoting schools promote?
DEFF Research Database (Denmark)
Simovska, Venka
2012-01-01
-promotion interventions. Directly or indirectly the articles reiterate the idea that health promotion in schools needs to be linked with the core task of the school – education, and to the values inherent to education, such as inclusion, democracy, participation and influence, critical literacy and action competence......Purpose – The editorial aims to provide a brief overview of the individual contributions to the special issue, and a commentary positioning the contributions within research relating to the health-promoting schools initiative in Europe. Design/methodology/approach – The members of the Schools...... for Health in Europe Research Group were invited to submit their work addressing processes and outcomes in school health promotion to this special issue of Health Education. Additionally, an open call for papers was published on the Health Education web site. Following the traditional double blind peer...
Directory of Open Access Journals (Sweden)
Wei-Yi Ong
Full Text Available Atherosclerotic stenosis of cerebral arteries or intracranial large artery disease (ICLAD is a major cause of stroke especially in Asians, Hispanics and Africans, but relatively little is known about gene expression changes in vessels at risk. This study compares comprehensive gene expression profiles in the middle cerebral artery (MCA of New Zealand White rabbits exposed to two stroke risk factors i.e. hypertension and/or hypercholesterolemia, by the 2-Kidney-1-Clip method, or dietary supplementation with cholesterol. Microarray and Ingenuity Pathway Analyses of the MCA of the hypertensive rabbits showed up-regulated genes in networks containing the node molecules: UBC (ubiquitin, P38 MAPK, ERK, NFkB, SERPINB2, MMP1 and APP (amyloid precursor protein; and down-regulated genes related to MAPK, ERK 1/2, Akt, 26 s proteasome, histone H3 and UBC. The MCA of hypercholesterolemic rabbits showed differentially expressed genes that are surprisingly, linked to almost the same node molecules as the hypertensive rabbits, despite a relatively low percentage of 'common genes' (21 and 7% between the two conditions. Up-regulated common genes were related to: UBC, SERPINB2, TNF, HNF4A (hepatocyte nuclear factor 4A and APP, and down-regulated genes, related to UBC. Increased HNF4A message and protein were verified in the aorta. Together, these findings reveal similar nodal molecules and gene pathways in cerebral vessels affected by hypertension or hypercholesterolemia, which could be a basis for synergistic action of risk factors in the pathogenesis of ICLAD.
Bone cysts: unicameral and aneurysmal bone cyst.
Mascard, E; Gomez-Brouchet, A; Lambot, K
2015-02-01
Simple and aneurysmal bone cysts are benign lytic bone lesions, usually encountered in children and adolescents. Simple bone cyst is a cystic, fluid-filled lesion, which may be unicameral (UBC) or partially separated. UBC can involve all bones, but usually the long bone metaphysis and otherwise primarily the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC) is an expansive and hemorrhagic tumor, usually showing characteristic translocation. About 30% of ABCs are secondary, without translocation; they occur in reaction to another, usually benign, bone lesion. ABCs are metaphyseal, excentric, bulging, fluid-filled and multicameral, and may develop in all bones of the skeleton. On MRI, the fluid level is evocative. It is mandatory to distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve spontaneously between adolescence and adulthood; the main concern is the risk of pathologic fracture. Treatment in non-threatening forms consists in intracystic injection of methylprednisolone. When there is a risk of fracture, especially of the femoral neck, surgery with curettage, filling with bone substitute or graft and osteosynthesis may be required. ABCs are potentially more aggressive, with a risk of bone destruction. Diagnosis must systematically be confirmed by biopsy, identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra-lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and in aggressive lesions with a risk of fracture, surgical treatment should be preferred, possibly after preoperative embolization. The risk of malignant transformation is very low, except in case of radiation therapy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Ong, Wei-Yi; Ng, Mary Pei-Ern; Loke, Sau-Yeen; Jin, Shalai; Wu, Ya-Jun; Tanaka, Kazuhiro; Wong, Peter Tsun-Hon
2013-01-01
Atherosclerotic stenosis of cerebral arteries or intracranial large artery disease (ICLAD) is a major cause of stroke especially in Asians, Hispanics and Africans, but relatively little is known about gene expression changes in vessels at risk. This study compares comprehensive gene expression profiles in the middle cerebral artery (MCA) of New Zealand White rabbits exposed to two stroke risk factors i.e. hypertension and/or hypercholesterolemia, by the 2-Kidney-1-Clip method, or dietary supplementation with cholesterol. Microarray and Ingenuity Pathway Analyses of the MCA of the hypertensive rabbits showed up-regulated genes in networks containing the node molecules: UBC (ubiquitin), P38 MAPK, ERK, NFkB, SERPINB2, MMP1 and APP (amyloid precursor protein); and down-regulated genes related to MAPK, ERK 1/2, Akt, 26 s proteasome, histone H3 and UBC. The MCA of hypercholesterolemic rabbits showed differentially expressed genes that are surprisingly, linked to almost the same node molecules as the hypertensive rabbits, despite a relatively low percentage of ‘common genes’ (21 and 7%) between the two conditions. Up-regulated common genes were related to: UBC, SERPINB2, TNF, HNF4A (hepatocyte nuclear factor 4A) and APP, and down-regulated genes, related to UBC. Increased HNF4A message and protein were verified in the aorta. Together, these findings reveal similar nodal molecules and gene pathways in cerebral vessels affected by hypertension or hypercholesterolemia, which could be a basis for synergistic action of risk factors in the pathogenesis of ICLAD. PMID:23874591
Assessment of range of uric and serum biomarkers in determination of bladder cancer severity
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Popkov V.M.
2013-12-01
Full Text Available Purpose: to establish efficiency of a range of uric and serum biomarkers of bladder cancer for diagnostics and the prognosis of risk of development of disease recurrence. Material and methods: TPA and TPS, VEGF level research in blood serum, UBC in urine in 176 people, among which 135 patients with bladder cancer (RMP have been conducted. Group of comparison has included16 patients (patients with cystitis. The control group has been made of 25 almost healthy men. 75 patients had non-muscle invasive RMP (Ta-1N0M0. Results. It has been statistically determined that reliable growth of of TPA, TPS in blood serum and UBC in urine in patients with non-muscle invasive RMP in comparison with patients in groups of control and comparison has been established. The increase of UBC in urine of patients of this group with recurrence of tumoral growth within a year has been noted. In comparison with cytological research of urine sedimentation, molecular markers of RMP (the uric UBC and serum TPA, TPS possess diagnostic sensitivity, allow to confirm the presence of disease, to carry out diagnostics of stages of organ and extra invasion. RMP is possible to consider as an additional prognostic serum marker increase in the VEGF level in blood serum. Conclusion. Inclusion in diagnostic process in the clinical research of biomarkers showed that identification of NMIRMP increased from 18,1% in 2006 to 55,6% in 2011. The chosen volume of complex treatment allowed to reduce recurrence and lethality in the first two years from 32 to 15,5%.
CD147 and MCT1-potential partners in bladder cancer aggressiveness and cisplatin resistance.
Afonso, Julieta; Santos, Lúcio L; Miranda-Gonçalves, Vera; Morais, António; Amaro, Teresina; Longatto-Filho, Adhemar; Baltazar, Fátima
2015-11-01
The relapsing and progressive nature of bladder tumors, and the heterogeneity in the response to cisplatin-containing regimens, are the major concerns in the care of urothelial bladder carcinoma (UBC) patients. The metabolic adaptations that alter the tumor microenvironment and thus contribute to chemoresistance have been poorly explored in UBC setting. We found significant associations between the immunoexpressions of the microenvironment-related molecules CD147, monocarboxylate transporters (MCTs) 1 and 4, CD44 and CAIX in tumor tissue sections from 114 UBC patients. The presence of MCT1 and/or MCT4 expressions was significantly associated with unfavorable clinicopathological parameters. The incidence of CD147 positive staining significantly increased with advancing stage, grade and type of lesion, and occurrence of lymphovascular invasion. Similar associations were observed when considering the concurrent expression of CD147 and MCT1. This expression profile lowered significantly the 5-year disease-free and overall survival rates. Moreover, when selecting patients who received platinum-based chemotherapy, the prognosis was significantly worse for those with MCT1 and CD147 positive tumors. CD147 specific silencing by small interfering RNAs (siRNAs) in UBC cells was accompanied by a decrease in MCT1 and MCT4 expressions and, importantly, an increase in chemosensitivity to cisplatin. Our results provide novel insights for the involvement of CD147 and MCTs in bladder cancer progression and resistance to cisplatin-based chemotherapy. We consider that the possible cooperative role of CD147 and MCT1 in determining cisplatin resistance should be further explored as a potential theranostics biomarker. © 2014 Wiley Periodicals, Inc.
Promoter Hypermethylation of the EMP3 Gene in a Series of 229 Human Gliomas
Directory of Open Access Journals (Sweden)
Marta Mellai
2013-01-01
Full Text Available The epithelial membrane protein 3 (EMP3 is a candidate tumor suppressor gene in the critical region 19q13.3 for several solid tumors, including tumors of the nervous systems. The aim of this study was to investigate the EMP3 promoter hypermethylation status in a series of 229 astrocytic and oligodendroglial tumors and in 16 GBM cell lines. The analysis was performed by methylation-specific PCR and capillary electrophoresis. Furthermore, the EMP3 expression at protein level was evaluated by immunohistochemistry and Western blotting analysis. Associations of EMP3 hypermethylation with total 1p/19q codeletion, MGMT promoter hypermethylation, IDH1/IDH2 and TP53 mutations, and EGFR amplification were studied, as well as its prognostic significance. The EMP3 promoter hypermethylation has been found in 39.5% of gliomas. It prevailed in low-grade tumors, especially in gliomas with an oligodendroglial component, and in sGBMs upon pGBMs. In oligodendroglial tumors, it was strongly associated with both IDH1/IDH2 mutations and total 1p/19q codeletion and inversely with EGFR gene amplification. No association was found with MGMT hypermethylation and TP53 mutations. In the whole series, the EMP3 hypermethylation status correlated with 19q13.3 loss and lack of EMP3 expression at protein level. A favorable prognostic significance on overall survival of the EMP3 promoter hypermethylation was found in patients with oligodendroglial tumors.
Selective AR Modulators that Distinguish Proliferative from Differentiative Gene Promoters
2016-08-01
levels, and in some cases be useful in early stage disease or watchful waiting, and in other cases castration resistant prostate cancer (CRPC...dependent kinase inhibitor p21 gene through an androgen response element in the proximal promoter. Molecular endocrinology 13, 376 (Mar, 1999). 9...analyses and in mouse xenograft experiments, as planned. We will also continue to probe the molecular mechanism by which dox elicits these differential
13 CFR 305.13 - Contract change orders.
2010-01-01
... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Contract change orders. 305.13 Section 305.13 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE... all such work will be at the Recipient's risk until EDA completes its review. ...
Aminopeptidase N/CD13 as a Potential Therapeutic Target in Malignant Pleural Mesothelioma.
Otsuki, Takahiko; Nakashima, Taku; Hamada, Hironobu; Takayama, Yusuke; Akita, Shin; Masuda, Takeshi; Horimasu, Yasushi; Miyamoto, Shintaro; Iwamoto, Hiroshi; Fujitaka, Kazunori; Miyata, Yoshihiro; Miyake, Masayuki; Kohno, Nobuoki; Okada, Morihito; Hattori, Noboru
2018-03-08
Angiogenesis is a crucial factor in the progression of malignant pleural mesothelioma (MPM), and antiangiogenic strategies might be effective against MPM. Aminopeptidase N/CD13 (APN/CD13) promotes tumour angiogenesis and is associated with poor prognosis; however, its clinical significance in MPM remains unclear.In 37 consecutive patients with surgically resected MPM, we evaluated the association between immunohistochemical APN/CD13 expression in resected tumours and survival. Additionally, the antitumour and antiangiogenic effects of MT95-4, a fully humanized anti-APN/CD13 monoclonal antibody, were evaluated in mice orthotopically implanted with EHMES-10 (abundantly expressing APN/CD13) and MSTO-211H (scarcely expressing APN/CD13) MPM cells.High tumour APN/CD13 expression was associated with poor prognosis in MPM patients ( P =0.04), and MT95-4 treatment reduced tumour growth and angiogenesis in mice harbouring EHMES-10, but not MSTO-211H, cells. Furthermore, in mice harbouring EHMES-10 cells, MT95-4 combined with cisplatin more effectively suppressed tumour progression than cisplatin alone.Taken together these results suggested that APN/CD13 is implicated in the aggressiveness of MPM. Here, MT95-4 treatment reduced tumour progression likely by inhibiting angiogenesis, suggesting APN/CD13 as a potential molecular target for MPM treatment. Additionally, combination treatment with MT95-4 and cisplatin could represent a promising approach to treating MPM exhibiting high APN/CD13 expression. Copyright ©ERS 2018.
13 CFR 315.13 - Audit and examination.
2010-01-01
... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Audit and examination. 315.13 Section 315.13 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE... books, documents, papers, and records of a Firm, TAAC or other recipient of Adjustment Assistance...
Synthesis of 1,3-diaminated stereotriads via rearrangement of 1,4-diazaspiro[2.2]pentanes.
Weatherly, Cale D; Rigoli, Jared W; Schomaker, Jennifer M
2012-04-06
The synthesis of 1,3-diaminated stereotriads via the bis-aziridination of allenes is reported. The reactive 1,4-diazaspiro[2.2]pentane intermediates undergo a mild Brønsted acid-promoted rearrangement to yield 1,3-diaminated ketones in good yields with excellent stereocontrol. Directed reduction of the ketone can be achieved to yield a C-N/C-O/C-N stereotriad in high dr. The ability to transfer the axial chirality of the substrates to the products allows for the facile preparation of enantioenriched stereotriads from allenes in two simple steps.
Sp1/3 and NF-1 mediate basal transcription of the human P2X1 gene in megakaryoblastic MEG-01 cells
Directory of Open Access Journals (Sweden)
Ennion Steven J
2006-03-01
Full Text Available Abstract Background P2X1 receptors play an important role in platelet function as they can induce shape change, granule centralization and are also involved in thrombus formation. As platelets have no nuclei, the level of P2X1 expression depends on transcriptional regulation in megakaryocytes, the platelet precursor cell. Since nothing is known about the molecular mechanisms regulating megakaryocytic P2X1 expression, this study aimed to identify and functionally characterize the P2X1 core promoter utilized in the human megakaryoblastic cell line MEG-01. Results In order to identify cis-acting elements involved in the transcriptional regulation of P2X1 expression, the ability of 4.7 kb P2X1 upstream sequence to drive luciferase reporter gene expression was tested. Low promoter activity was detected in proliferating MEG-01 cells. This activity increased 20-fold after phorbol-12-myristate-13-acetate (PMA induced differentiation. A transcription start site was detected 365 bp upstream of the start codon by primer extension. Deletion analysis of reporter constructs indicated a core promoter located within the region -68 to +149 bp that contained two Sp1 sites (named Sp1a and Sp1b and an NF-1 site. Individual mutations of Sp1b or NF-1 binding sites severely reduced promoter activity whereas triple mutation of Sp1a, Sp1b and NF-1 sites completely abolished promoter activity in both untreated and PMA treated cells. Sp1/3 and NF-1 proteins were shown to bind their respective sites by EMSA and interaction of Sp1/3, NF-1 and TFIIB with the endogenous P2X1 core promoter in MEG-01 cells was demonstrated by chromatin immunoprecipitation. Alignment of P2X1 genes from human, chimp, rat, mouse and dog revealed consensus Sp1a, Sp1b and NF-1 binding sites in equivalent positions thereby demonstrating evolutionary conservation of these functionally important sites. Conclusion This study has identified and characterized the P2X1 promoter utilized in MEG-01 cells and
Ambient gold-catalyzed O-vinylation of cyclic 1,3-diketone: A vinyl ether synthesis
Directory of Open Access Journals (Sweden)
Yumeng Xi
2013-11-01
Full Text Available Gold-catalyzed O-vinylation of cyclic 1,3-diketones has been achieved for the first time, which provides direct access to various vinyl ethers. A catalytic amount of copper triflate was identified as the significant additive in promoting this transformation. Both aromatic and aliphatic alkynes are suitable substrates with good to excellent yields.
LLW Forum meeting report, February 13--16, 1996
International Nuclear Information System (INIS)
1996-01-01
The Low-Level Radioactive Waste Forum (LLW Forum) is an association of state and compact representatives, appointed by governors and compact commissions, established to facilitate state and compact implementation of the Low-Level Radioactive Waste Policy Act of 1980 and the Low-Level Radioactive Waste Policy Amendments Act of 1985 and to promote the objectives of low-level radioactive waste regional compacts. The LLW forum provides an opportunity for state and compact officials to share information with one another and to exchange views with officials of federal agencies and other interested parties. This report details activities at the meeting held February 13-16, 1996
International Nuclear Information System (INIS)
Kido, H.; Fukusen, N.; Katunuma, N.
1987-01-01
In adrenalectomized rats, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) markedly enhanced the inductions of tyrosine aminotransferase (TAT) and ornithine decarboxylase by glucocorticoids, even with sufficient concentration of glucocorticoids to have a maximal effect, whereas it had no effect on TAT activity and increased ornithine decarboxylase activity only slightly in the absence of glucocorticoids. Phorbol derivatives and components of TPA such as 4β-phorbol, phorbol 12-tetradecanoate, phorbol 13-acetate, and 4-O-methylphorbol 12-tetradecanoate 13-acetate, which have no tumor-promoting activity or ability to activate protein kinase C, did not have any effect on TAT induction by glucocorticoid. TPA enhanced the induction of TAT by various glucocorticoids but had no effect on induction of TAT by glucagon or insulin and did not enhance the induction of glucose-6-phosphate dehydrogenase by 17β-estradiol. These results suggest that TPA specifically enhances the induction of TAT and ornithine decarboxylase by glucocorticoids. Similar effects of TPA on TAT induction by glucocorticoid were observed in primary cultures of adult rat hepatocytes. Another activator of protein kinase C, rac-1,2-dioctanoylglycerol, was also found to have similar effects on the cells
Climate change impact on river flows in Chitral watershed
International Nuclear Information System (INIS)
Shakir, A.S.; Rehman, H.U.; Ehsan, S.
2010-01-01
The impact of climate change has always been very important for water resources in the world. In countries like Pakistan where different weather conditions exist, the effects of climate change can be more crucial. Generally, the climate changes are considered in terms of global warming i.e. increase in the average temperature of earth's near surface air. The global warming can have a strong impact on river flows in Pakistan. This may be due to the melting of snow and glaciers at a higher rate and changes in precipitation patterns. Glaciers in Pakistan cover about 13,680 km/sup 2/, which is 13% of the mountainous regions of the Upper Indus Basin. Glacier and Snow melt water from these glaciers contributes significantly to the river flows in Pakistan. Due to climate change, the changes in temperature and the amount of precipitation could have diversified effects on river flows of arid and semi-arid regions of Pakistan. This paper reviews the existing research studies on climate change impact on water resources of Pakistan. The past trend of river flows in Pakistan has been discussed with respect to the available data. Further, different projections about future climate changes in terms of glacier melting and changes in temperature and precipitation have also been taken into consideration in order to qualitatively assess the future trend of river flows in Pakistan. As a case study, the flows were generated for the Chitral watershed using UBC Watershed Model. Model was calibrated for the year 2002, which is an average flow year. Model results show good agreement between simulated and observed flows. UBC watershed model was applied to a climate change scenario of 1 deg. C increase in temperature and 15% decrease in glaciated area. Results of the study reveal that the flows were decreased by about 4.2 %. (author)
Energy Technology Data Exchange (ETDEWEB)
Hagiwara, N.; Irie, K.; Tokuda, H.; Koshimizu, K.
1987-07-01
Metabolic activation and/or deactivation of indole alkaloid tumor promoter, (-)-indolactam V (ILV), was examined using rat liver microsomes. Reaction of ILV with the microsomes supplemented with NADPH and MgCl/sub 2/ gave three major metabolites, which were identified as (-)-N13-desmethylindolactam V and two diastereomers of (-)-2-oxyindolactam V at C-3. The tumor-promoting activities of these metabolites were evaluated by induction of Epstein-Barr virus early antigen and inhibition of specific binding of (/sup 3/H)-12-O-tetradecanoylphorbol-13-acetate to a mouse epidermal particulate fraction, and proved to be conspicuously lower than that of ILV. These results demonstrate that the metabolism of ILV results in detoxification, and that it itself is the tumor-promoting entity. Studies on the enzymes concerned with this metabolism suggested the involvement of cytochrome P-450-containing mixed-function oxidases. Similar deactivation seems to be possible by skin, where the mixed-function oxidases are known to exist.
Promoting a Hand Hygiene Program Using Social Media: An Observational Study.
Pan, Sung-Ching; Sheng, Wang-Huei; Tien, Kuei-Lien; Chien, Kuang-Tse; Chen, Yee-Chun; Chang, Shawn-Chwen
2016-01-01
Hand hygiene is an important component in infection control to protect patient safety and reduce health care-associated infection. Our aim was to evaluate the efficacy of different social media on the promotion of a hand hygiene (HH) program. The observational study was conducted from May 5 to December 31, 2014, at a 2600-bed tertiary care hospital. A 3-minute video of an HH campaign in 8 languages was posted to YouTube. The Chinese version was promoted through three platforms: the hospital website, the hospital group email, and the Facebook site of a well-known Internet illustrator. The video traffic was analyzed via Google Analytics. HH compliance was measured in November 2013 and 2014. There were 5252 views of the video, mainly of the Chinese-language version (3509/5252, 66.81%). The NTUH website had 24,000 subscribers, and 151 of them viewed the video (connection rate was 151/24,000, 0.63%). There were 9967 users of the hospital email group and the connection rate was 0.91% (91/9967). The connection rate was 6.17% (807/13,080) from Facebook, significantly higher than the other 2 venues (both P<.001). HH compliance sustained from 83.7% (473/565) in 2013 to 86.7% (589/679) in 2014 (P=.13) among all HCWs. Facebook had the highest connection rate in the HH video campaign. The use of novel social media such as Facebook should be considered for future programs that promote hand hygiene and other healthy behaviors.
Effect of organic school meals to promote healthy diet in 11–13 year old children
DEFF Research Database (Denmark)
He, Chen; Breiting, Søren; Perez-Cuetoa, Federico J.A.
2012-01-01
The aim of this study was to investigate whether organic school meals can be an effective strategy to pro- vide healthy food to children and promote their healthy eating habits. Furthermore, the study aimed to examine pupils’ attitudes predicting intention and behaviours in relation to organic food...... to consume organic food but not on their behaviour. In addition, all participants were willing to adopt healthier eating habits in the future both at school and in the home. These findings suggest that children attending schools where meals include organic ingredients might be more aware of healthy foods......, organic foods and healthy eating habits....
Directory of Open Access Journals (Sweden)
Puri Raj K
2011-04-01
Full Text Available Abstract Background Interleukin-13 Receptor α2 (IL-13Rα2 is a tumor-associated antigen and target for cancer therapy. Since IL-13Rα2 is heterogeneously overexpressed in a variety of human cancers, it would be highly desirable to uniformly upregulate IL-13Rα2 expression in tumors for optimal targeting. Methods We examined epigenetic regulation of IL-13Rα2 in a murine model of human pancreatic cancer by Bisulfite-PCR, sequencing for DNA methylation and chromatin immunoprecipitation for histone modification. Reverse transcription-PCR was performed for examining changes in IL-13Rα2 mRNA expression after treatment with histone deacetylase (HDAC and c-jun inhibitors. In vitro cytotoxicity assays and in vivo testing in animal tumor models were performed to determine whether HDAC inhibitors could enhance anti-tumor effects of IL-13-PE in pancreatic cancer. Mice harboring subcutaneous tumors were treated with HDAC inhibitors systemically and IL-13-PE intratumorally. Results We found that CpG sites in IL-13Rα2 promoter region were not methylated in all pancreatic cancer cell lines studied including IL-13Rα2-positive and IL-13Rα2-negative cell lines and normal cells. On the other hand, histones at IL-13Rα2 promoter region were highly-acetylated in IL-13Rα2-positive but much less in receptor-negative pancreatic cancer cell lines. When cells were treated with HDAC inhibitors, not only histone acetylation but also IL-13Rα2 expression was dramatically enhanced in receptor-negative pancreatic cancer cells. In contrast, HDAC inhibition did not increase IL-13Rα2 in normal cell lines. In addition, c-jun in IL-13Rα2-positive cells was expressed at higher level than in negative cells. Two types of c-jun inhibitors prevented increase of IL-13Rα2 by HDAC inhibitors. HDAC inhibitors dramatically sensitized cancer cells to immunotoxin in the cytotoxicity assay in vitro and increased IL-13Rα2 in the tumors subcutaneously implanted in the immunodeficient
TMEM129 is a Derlin-1 associated ERAD E3 ligase essential for virus-induced degradation of MHC-I.
van den Boomen, Dick J H; Timms, Richard T; Grice, Guinevere L; Stagg, Helen R; Skødt, Karsten; Dougan, Gordon; Nathan, James A; Lehner, Paul J
2014-08-05
The US11 gene product of human cytomegalovirus promotes viral immune evasion by hijacking the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. US11 initiates dislocation of newly translocated MHC I from the ER to the cytosol for proteasome-mediated degradation. Despite the critical role for ubiquitin in this degradation pathway, the responsible E3 ligase is unknown. In a forward genetic screen for host ERAD components hijacked by US11 in near-haploid KBM7 cells, we identified TMEM129, an uncharacterized polytopic membrane protein. TMEM129 is essential and rate-limiting for US11-mediated MHC-I degradation and acts as a novel ER resident E3 ubiquitin ligase. TMEM129 contains an unusual cysteine-only RING with intrinsic E3 ligase activity and is recruited to US11 via Derlin-1. Together with its E2 conjugase Ube2J2, TMEM129 is responsible for the ubiquitination, dislocation, and subsequent degradation of US11-associated MHC-I. US11 engages two degradation pathways: a Derlin-1/TMEM129-dependent pathway required for MHC-I degradation and a SEL1L/HRD1-dependent pathway required for "free" US11 degradation. Our data show that TMEM129 is a novel ERAD E3 ligase and the central component of a novel mammalian ERAD complex.
International Nuclear Information System (INIS)
Jeffrey, A.M.; Liskamp, R.M.J.
1986-01-01
In the two-stage model of skin carcinogenesis, it is believed that initiators bind to DNA and that tumor promoters such as phorbol 12-tetradecanoate 13-acetate (TPA) bind noncovalently to membrane-associated high-affinity receptors, probably protein kinase C. Two other types of potent tumor-promoting substances, aplysiatoxin and teleocidin, appear to act also by binding to and activating protein kinase C, even though their chemical structures are quite different. Therefore, the authors have undertaken computer modeling of the special relationship of various functional groups in these three chemical classes of tumor promoters in an attempt to explain how these diverse structures bind to the same receptor molecule. They propose a stereochemical model in which the oxygens in TPA at C-3, C-4, C-9, and C-20 (O-3, O-4, O-9, and O-20) correspond to the O-11, N-13, N-1, and O-24 positions in teleocidin and the O-27, O-3, O-11, and O-30 oxygens in aplysiatoxin, respectively. In this model all distances with respect to overlap of the corresponding atoms are <1 A. In addition, all three types of molecules have their hydrophobic moieties oriented in the similar position. This model is further discussed with respect to other compounds showing various degrees of activity as tumor promoters, including mezerein, ingenol, and 4α-TPA. The model explains how chemically diverse structures can have similar biological activity as tumor promoters and provides a basis for designing both agonists and antagonists of tumor promoters
How music may promote healthy behaviour.
Batt-Rawden, Kari; Tellnes, Gunnar
2011-03-01
Using music to promote healthy behaviour may enhance coping mechanisms in spite of illness. 1) To explore the role and significance of music and musicking in the life of men and women with long-term illnesses in or through different life phases, situations, events, issues and contexts. 2) To increase knowledge on how participants, through exposure to and exchange of new musical materials and practices, may learn to use music as a ''technology of self '' in relation to health promotion and rehabilitation. This exploratory study sought to instigate narratives about music's role in supporting health through a pragmatic synthesis of elements of action-research, ethnography and grounded theory. Music CDs were conceived as an interactive and dialectical tool. This longitudinal study involved eight in-depth ethnographic interviews per participant, involving nine men and 13 women, aged between 35 and 65 with long-term illnesses. Music is a motivational device for moving our bodies, releasing anger or aggression and even transcending pain. Personal preferences in music seemed to be important for these participants while exercising, substantiated in the importance of well-being and pleasure in everyday activities and situations. This study has contributed to an increase in self-awareness and consciousness, well-being and health for the majority of the participants in the study. It has brought to the level of consciousness forms of ''expert'' practice that may otherwise have occurred tacitly. Implementation of future health promotion and rehabilitation programmes ought to strengthen their focus on musical, cultural and physical activity both at an individual level and within local communities.
DEFF Research Database (Denmark)
Lehn-Christiansen, Sine
The paper discusses the implications of health promotion in education. The paper is based on my PhD project entitled “Health promotion education seen through a power/knowledge and subjectification perspective” (in prep). The PhD project explores how professional health promotion skills are concei......The paper discusses the implications of health promotion in education. The paper is based on my PhD project entitled “Health promotion education seen through a power/knowledge and subjectification perspective” (in prep). The PhD project explores how professional health promotion skills...
TPR and TPD studies of effects of Cu and Ca promotion on Fe–Zn ...
Indian Academy of Sciences (India)
promoted with Cu and Ca showed even much lower reduction temperature for Fe2O3 → Fe3O4. Ca promo- ... the FTS section in the scheme are: low cost, low CO2 and CH4 selectivity. ..... 77 43. 13. Klerk A D 2009 Energy Fuel 23 4593. 14.
Promoting social behavior with oxytocin in high-functioning autism spectrum disorders
Andari, Elissar; Duhamel, Jean-René; Zalla, Tiziana; Herbrecht, Evelyn; Leboyer, Marion; Sirigu, Angela
2010-01-01
Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participan...
Immobilization of Cu2 + and Cd2 + by earthworm manure derived biochar in acidic circumstance
Institute of Scientific and Technical Information of China (English)
Zhanghong Wang; Fei Shen; Dekui Shen; Yahui Jiang; Rui Xiao
2017-01-01
Earthworm manure,the by-product obtained from the disposing of biowastes by earthworm breeding,is largely produced and employed as a feedstock for biochar preparation through pyrolysis.For repairing acidic soil or acidic electroplating effluent,biochar physicochemical properties would suffer from some changes like an acidic washing process,which hence affected its application functions.Pristine biochar (UBC)from pyrolysis of earthworm manure at 700℃ and biochar treated by HCl (WBC) were comparatively investigated regarding their physicochemical properties,adsorption capability and adsorption mechanism of Cu2+ and Cd2+ from aqueous solution to explore the immobilization characteristics ofbiochar in acidic environment.After HCl treatment,the soluble ash content and phenolic-OH in the WBC sample was notably decreased against the increase of the carboxyl C==O,aromatic C=C and Si-O-Si,compared to that of UBC.All adsorption processes can be well described by Langmuir isotherm model.The calculated maximum adsorption capacity of Cu2+ and Cd2+ adsorption on UBC were 36.56and 29.31 mg/g,respectively,which were higher than that of WBC (8.64 and 12.81 mg/g,respectively),indicating that HCl treatment significantly decreased biochar adsorption ability.Mechanism analysis revealed that alkali and alkaline earth metallic,salts (carbonates,phosphates and silicates),and surface functional groups were responsible for UBC adsorption,corresponding to ion exchange,precipitation and complexation,respectively.However,ion exchange made little contributions to WBC adsorption due to the great loss of soluble ash content.WBC adsorption was mainly attributed to the abundant exposure of silicates and surface functional groups (carboxyl C==O and aromatic C=C).
Directory of Open Access Journals (Sweden)
Izabela Ruduś
Full Text Available Molecular studies of primary and secondary dormancy in Avena fatua L., a serious weed of cereal and other crops, are intended to reveal the species-specific details of underlying molecular mechanisms which in turn may be useable in weed management. Among others, quantitative real-time PCR (RT-qPCR data of comparative gene expression analysis may give some insight into the involvement of particular wild oat genes in dormancy release, maintenance or induction by unfavorable conditions. To assure obtaining biologically significant results using this method, the expression stability of selected candidate reference genes in different data subsets was evaluated using four statistical algorithms i.e. geNorm, NormFinder, Best Keeper and ΔCt method. Although some discrepancies in their ranking outputs were noticed, evidently two ubiquitin-conjugating enzyme homologs, AfUBC1 and AfUBC2, as well as one homolog of glyceraldehyde 3-phosphate dehydrogenase AfGAPDH1 and TATA-binding protein AfTBP2 appeared as more stably expressed than AfEF1a (translation elongation factor 1α, AfGAPDH2 or the least stable α-tubulin homolog AfTUA1 in caryopses and seedlings of A. fatua. Gene expression analysis of a dormancy-related wild oat transcription factor VIVIPAROUS1 (AfVP1 allowed for a validation of candidate reference genes performance. Based on the obtained results it can be recommended that the normalization factor calculated as a geometric mean of Cq values of AfUBC1, AfUBC2 and AfGAPDH1 would be optimal for RT-qPCR results normalization in the experiments comprising A. fatua caryopses of different dormancy status.
Ruduś, Izabela; Kępczyński, Jan
2018-01-01
Molecular studies of primary and secondary dormancy in Avena fatua L., a serious weed of cereal and other crops, are intended to reveal the species-specific details of underlying molecular mechanisms which in turn may be useable in weed management. Among others, quantitative real-time PCR (RT-qPCR) data of comparative gene expression analysis may give some insight into the involvement of particular wild oat genes in dormancy release, maintenance or induction by unfavorable conditions. To assure obtaining biologically significant results using this method, the expression stability of selected candidate reference genes in different data subsets was evaluated using four statistical algorithms i.e. geNorm, NormFinder, Best Keeper and ΔCt method. Although some discrepancies in their ranking outputs were noticed, evidently two ubiquitin-conjugating enzyme homologs, AfUBC1 and AfUBC2, as well as one homolog of glyceraldehyde 3-phosphate dehydrogenase AfGAPDH1 and TATA-binding protein AfTBP2 appeared as more stably expressed than AfEF1a (translation elongation factor 1α), AfGAPDH2 or the least stable α-tubulin homolog AfTUA1 in caryopses and seedlings of A. fatua. Gene expression analysis of a dormancy-related wild oat transcription factor VIVIPAROUS1 (AfVP1) allowed for a validation of candidate reference genes performance. Based on the obtained results it can be recommended that the normalization factor calculated as a geometric mean of Cq values of AfUBC1, AfUBC2 and AfGAPDH1 would be optimal for RT-qPCR results normalization in the experiments comprising A. fatua caryopses of different dormancy status.
Study on de-coating used beverage cans with thick sulfuric acid for recycle
International Nuclear Information System (INIS)
Wang, Minghua; Woo, Kee-Do; Kim, Dong-Keon; Ma, Lirong
2007-01-01
More than 1800 hundreds of millions of beverage cans are manufactured yearly over the world, which will pollute the globe environment without recycle. The recycle and regeneration estates of used beverage cans are highly profitable enterprises. Vacuum technologies are mature on a large scale today, and therefore, the re-melting process of used beverage cans (UBCs) does not have to use flux. Furthermore, the coating on UBCs becomes the key factor causing poor product quality. The present paper concerns removing the coating of UBCs and compares two different kinds of methods to remove the coating: a thermal method and a chemical reagent method. A new kind of reagent, thick sulfuric acid, was employed in the chemical reagent de-coating process. The de-coating ratio in the thermal method reached 93% at most, but the de-coating ratio reached 100% within 30 min in the chemical reagent method by using thick sulfuric acid. Recycling the used thick sulfuric acid was also supplied. A titanium yellow product can be simultaneously obtained. The experiments show that the chemical reagent method is more available than the thermal method, which will enhance the purity of the regeneration product enormously
Canavese, Federico; Wright, James G; Cole, William G; Hopyan, Sevan
2011-01-01
The purpose of this study was to compare the outcome of percutaneous curettage with intralesional injection of methylprednisolone and bone marrow for unicameral bone cysts (UBCs). This was a retrospective review of 46 children and adolescents with UBC treated with autologous bone marrow injection, methylprednisolone acetate injection or percutaneous curettage alone. Inclusion criteria were a radiological diagnosis of UBC and at least 24 months follow-up from the last procedure. Healing was determined using Neer/Cole 4-grades rating scale. The 3 treatment groups were comparable with regard to age, sex, location of the cyst, and the number of procedures undertaken. At 2 years follow-up, the proportion of patients with satisfactory healing (Neer/Cole grades I and II) was greatest among those who underwent percutaneous curettage (70%) compared with bone marrow injection (21%) and methylprednisolone acetate injection (41%) (P = 0.03). We found no association between healing and age (P = 0.80) nor between healing and sex (P = 0.61). These results suggest that mechanical disruption of the cyst membrane may be helpful in healing of cysts and that this technique may be preferred to simple intralesional injections. Level III.
Li, Y; Chen, J; Zhao, M; Yang, Z; Yue, L; Zhang, X
2017-02-01
To demonstrate the resuscitation-promoting activities of recombinant YeaZ from Vibrio harveyi SF-1. The gene of resuscitation-promoting factor YeaZ was cloned from genomic DNA of V. harveyi SF-1. The gene was expressed in Escherichia coli, and the expressed protein was purified by Ni 2+ -affinity chromatography. A yeaZ mutant was constructed by using the suicide plasmid pNQ705 with homologous recombination. Disruption of yeaZ did not affect cell growth significantly in 2216 E broth at 28°C. The wild-type and mutant viable but nonculturable (VBNC) cells could be resuscitated by temperature upshift method. In addition, the recombinant YeaZ increased the culturable counts from 1·27 × 10 4 CFU per ml and 1·99 × 10 4 CFU per ml to 2·88 × 10 5 CFU per ml and 4·59 × 10 5 CFU per ml, respectively. After the VBNC cells of wild-type and mutant cells were maintained at 4°C for 120 days, no resuscitation was obtained by temperature upshift method, but addition of the recombinant YeaZ promoted the resuscitation of the wild-type and mutant cells, with the culturable cell counts of 1·13 × 10 3 and 1·44 × 10 3 CFU per ml, respectively. Disruption of yeaZ decreased the virulence of V. harveyi in zebrafish. The lethal dose 50% of the yeaZ null mutant was more than 10-fold higher than that of the wild-type cells. The recombinant YeaZ could efficiently promote resuscitation of the wild-type and mutant cells of V. harveyi from VBNC to culturable state. The protein also promoted resuscitation of the VBNC wild-type and mutant cells, which were maintained at 4°C for 120 days and not recovered by temperature upshift method. Disruption of yeaZ decreased the virulence of V. harveyi in zebrafish. Here, we show clear evidence of a resuscitation-promoting factor YeaZ of V. harveyi and the roles in resuscitation of the VBNC cells and its pathogenicity. © 2016 The Society for Applied Microbiology.
Lifescience Database Archive (English)
Full Text Available Molecule: Ubiquitin Conjugating Enzyme; Chain: Null; Synonym: Ubc1; Engineered: Yes Ubiquitin Conjugation 6....TPARKRLMRDFKRLQQDPPAGISGAPQDNNIMLWNAVIFGPDDTPWDGGTFKLSLQFSEDYPNKPPTVRFVSRMFHPNIYADGSICLDILQNQWSPIYDVAAILTSIQSLLCDPNPNSPANSEAARMYSESKREYNRRVRDVVEQSWTAD arabi_2AAK.jpg ...
NRC/UBC fuelling station with intelligent compression
International Nuclear Information System (INIS)
Dada, A.; Boyd, B.; Law, L.; Semczyszyn, D.
2004-01-01
BOC Canada Ltd. will design, integrate and construct the second fueling station on the Hydrogen Highway. This station will be located at the National Research Council's Institute for Fuel Cell Innovation on the campus of the University of British Columbia. BOC's design will bring together an existing alkaline electrolyser, new compression, storage and dispensing. The station will be designed to serve fuel cell passenger vehicles using 350-bar storage. However, the flexible design concept will allow for many other user needs including the potential for servicing larger vehicles, as well as filling portable storage systems for use at satellite stations. The novel station design also offers the potential to fuel from multiple hydrogen sources. Together with NRC, this fueling station will be used to increase public, consumer and investor awareness of hydrogen technologies. Design and construction of this facility will assist in the development of industry codes and standards and familiarize authorities having jurisdiction with hydrogen fueling. The system concept offers the utmost attention to safety, novelty and flexibility. (author)
Cukras, Anthony R; Southworth, Daniel R; Brunelle, Julie L; Culver, Gloria M; Green, Rachel
2003-08-01
Translocation of the mRNA:tRNA complex through the ribosome is promoted by elongation factor G (EF-G) during the translation cycle. Previous studies established that modification of ribosomal proteins with thiol-specific reagents promotes this event in the absence of EF-G. Here we identify two small subunit interface proteins S12 and S13 that are essential for maintenance of a pretranslocation state. Omission of these proteins using in vitro reconstitution procedures yields ribosomal particles that translate in the absence of enzymatic factors. Conversely, replacement of cysteine residues in these two proteins yields ribosomal particles that are refractive to stimulation with thiol-modifying reagents. These data support a model where S12 and S13 function as control elements for the more ancient rRNA- and tRNA-driven movements of translocation.
Purification of SUMO conjugating enzymes and kinetic analysis of substrate conjugation
Yunus, Ali A.; Lima, Christopher D.
2009-01-01
SUMO conjugation to protein substrates requires the concerted action of a dedicated E2 ubiquitin conjugation enzyme (Ubc9) and associated E3 ligases. Although Ubc9 can directly recognize and modify substrate lysine residues that occur within a consensus site for SUMO modification, E3 ligases can redirect specificity and enhance conjugation rates during SUMO conjugation in vitro and in vivo. In this chapter, we will describe methods utilized to purify SUMO conjugating enzymes and model substrates which can be used for analysis of SUMO conjugation in vitro. We will also describe methods to extract kinetic parameters during E3-dependent or E3-independent substrate conjugation. PMID:19107417
Perceptions of health promoters about health promotion ...
African Journals Online (AJOL)
2013-02-11
Feb 11, 2013 ... regarding a health promotion programme for families with ... to contribute to high rates of not going to school (ibid. ... sector in order, amongst other objectives, to prevent health ... exercise and mental health promotion must be incorporated ..... (2009:141) identified ignorance and misconception about the.
Kim, Sang Yoon; Song, Hajin; Sang, Mee Kyung; Weon, Hang-Yeon; Song, Jaekyeong
2017-10-10
The bacterial strain Bacillus velezensis GH1-13, isolated from rice paddy soil in Korea, has been shown to promote plant growth and have strong antagonistic activities against pathogens. Here, we report the complete genome sequence of GH1-13, revealing that it possesses a single 4,071,980-bp circular chromosome with 46.2% GC-content. The chromosome encodes 3,930 genes, and we have also identified a unique plasmid in the strain that encodes a further 104 genes (71,628bp and 31.7% GC-content). The genome was found to contain various enzyme-encoding operons, including indole-3-acetic acid (IAA) biosynthesis proteins, 2,3-butanediol dehydrogenase, various non-ribosomal peptide synthetases, and several polyketide synthases. These properties are responsible for the promotion of plant growth and the biosynthesis of secondary metabolites. They therefore have multiple beneficial effects that could be applied to agriculture. Through curing, we found that the unique plasmid of GH1-13 has important roles in the production of phytohormones, such as IAA, and in shaping phenotypic and physiological characteristics. The plasmid therefore likely influences the biological activities of GH1-13. The complete genome sequence of B. velezensis GH1-13 contributes to our understanding of this beneficial strain and will encourage research into its development for agricultural or biotechnological applications, enhancing productivity and crop quality. Copyright © 2017 Elsevier B.V. All rights reserved.
Porritoxins, metabolites of Alternaria porri, as anti-tumor-promoting active compounds.
Horiuchi, Masayuki; Tokuda, Harukuni; Ohnishi, Keiichiro; Yamashita, Masakazu; Nishino, Hoyoku; Maoka, Takashi
2006-02-01
To search for possible cancer chemopreventive agents from natural sources, we performed primary screening of metabolites of Alternaria porri by examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. The ethyl acetate extract of A. porri showed the inhibitory effect on EBV-EA activation. Three porritoxins (1-3) were obtained as inhibitory active compounds for EBV-EA from ethyl acetate extract. 6-(3',3'-Dimethylallyloxy)-4-methoxy-5-methylphthalide (2) showed the strongest activity among them. Inhibitory effect of porritoxin (1) and (2) was superior to that of beta-carotene, a well-known anti-tumor promoter. Furthermore, the structure-activity correlation of porritoxins and their related compounds were discussed.
DEFF Research Database (Denmark)
Povlsen, Lene; Borup, I.
2015-01-01
and Adolescent Health Promotion', Salutogenesis - from theory to practice' and Health, Stress and Coping'. More than half of all doctoral theses undertaken at NHV during these years had health promotion as their theme. As a derivative, the Nordic Health Promotion Research Network (NHPRN) was established in 2007......In 1953 when the Nordic School of Public Health was founded, the aim of public health programmes was disease prevention more than health promotion. This was not unusual, since at this time health usually was seen as the opposite of disease and illness. However, with the Ottawa Charter of 1986......, the World Health Organization made a crucial change to view health not as a goal in itself but as the means to a full life. In this way, health promotion became a first priority and fundamental action for the modern society. This insight eventually reached NHV and in 2002 - 50 years after the foundation...
Active gas adsorption-promoted evaporation of tungsten and niobium in strong electric fields
International Nuclear Information System (INIS)
Ksenofontov, V.A.; Kul'ko, V.B.; Mikhajlovskij, I.M.
1980-01-01
Field-ion methods and pulsed mass-spectrometeric analysis are used to study field evaporation of tungsten and niobium affected by nitrogen and hydrogen. Active gas-promoted evaporation is found to take place at field intensities high enough for the field ionization of active gases. The evaporating field intensity is established to increase from 1.45x10 8 to 5.5x10 8 V/cm while passing from continuous to pulsed conditions of evaporation, this testifies to the change of the mechanism of the promoted evaporation. Under the effect of active gases, the evaporation rate essentially depends on the surface state. It is shown that in the microcrystals irradiated with 1-3 kV helium ions, the dependence of the evaporation rate of Nb in hydrogen on the field intensity gets monotonous. The obtained results are in fair agreement with the recombination model of a promoted evaporation [ru
Kocken, P.L.; Eeuwijk, J.; Kesten, N.M.C. van; Dusseldorp, E.; Buijs, G.; Bassa-Dafesh, Z.; Snel, J.
2012-01-01
BACKGROUND: Vending machines account for food sales and revenue in schools. We examined 3 strategies for promoting the sale of lower-calorie food products from vending machines in high schools in the Netherlands. METHODS: A school-based randomized controlled trial was conducted in 13 experimental
The Effects of Amphiregulin Induced MMP-13 Production in Human Osteoarthritis Synovial Fibroblast
Directory of Open Access Journals (Sweden)
Yi-Te Chen
2014-01-01
Full Text Available Osteoarthritis (OA belongs to a group of degenerative diseases. Synovial inflammation, cartilage abrasion, and subchondral sclerosis are characteristics of OA. Researchers do not fully understand the exact etiology of OA. However, matrix metalloproteinases (MMPs, which are responsible for cartilage matrix degradation, play a pivotal role in the progression of OA. Amphiregulin (AREG binds to the EGF receptor (EGFR and activates downstream proteins. AREG is involved in a variety of pathological processes, such as the development of tumors, inflammatory diseases, and rheumatoid arthritis. However, the relationship between AREG and MMP-13 in OA synovial fibroblasts (SFs remains unclear. We investigated the signaling pathway involved in AREG-induced MMP-13 production in SFs. AREG caused MMP-13 production in a concentration- and time-dependent manner. The results of using pharmacological inhibitors and EGFR siRNA to block EGFR revealed that the EGFR receptor was involved in the AREG-mediated upregulation of MMP-13. AREG-mediated MMP-13 production was attenuated by PI3K and Akt inhibitors. The stimulation of cells by using AREG activated p65 phosphorylation and p65 translocation from the cytosol to the nucleus. Our results provide evidence that AREG acts through the EGFR and activates PI3K, Akt, and finally NF-kappaB on the MMP-13 promoter, thus contributing to cartilage destruction during osteoarthritis.
Promoting physical activity among youth through community-based prevention marketing.
Bryant, Carol A; Courtney, Anita H; McDermott, Robert J; Alfonso, Moya L; Baldwin, Julie A; Nickelson, Jen; McCormack Brown, Kelli R; Debate, Rita D; Phillips, Leah M; Thompson, Zachary; Zhu, Yiliang
2010-05-01
Community-based prevention marketing (CBPM) is a program planning framework that blends community-organizing principles with a social marketing mind-set to design, implement, and evaluate public health interventions. A community coalition used CBPM to create a physical activity promotion program for tweens (youth 9-13 years of age) called VERB Summer Scorecard. Based on the national VERB media campaign, the program offered opportunities for tweens to try new types of physical activity during the summer months. The VERB Summer Scorecard was implemented and monitored between 2004 and 2007 using the 9-step CBPM framework. Program performance was assessed through in-depth interviews and a school-based survey of youth. The CBPM process and principles used by school and community personnel to promote physical activity among tweens are presented. Observed declines may become less steep if school officials adopt a marketing mind-set to encourage youth physical activity: deemphasizing health benefits but promoting activity as something fun that fosters spending time with friends while trying and mastering new skills. Community-based programs can augment and provide continuity to school-based prevention programs to increase physical activity among tweens.
The 1.3GeV electron synchrotron INS-ES
International Nuclear Information System (INIS)
Yoshida, Katsuhide
2006-01-01
The 1.3GeV electron synchrotron at Institute for Nuclear Study, University of Tokyo (INS-ES) is the first high energy accelerator in Japan. It was constructed during 1956-1961 and shut down in 1999. It had played key roles in originating high energy physics in Japan. Based upon accelerator technologies developed in the construction and the operation of INS-ES, a 12 GeV proton synchrotron was built at KEK. INS-ES was also the base to promote synchrotron radiation science in Japan and to establish Photon Factory at KEK. After 1980, it was operated mainly to deliver tagged photon beam for high energy nuclear physics. (K.Y.)
Directory of Open Access Journals (Sweden)
Vasu Punj
Full Text Available Infection with Kaposi's sarcoma associated herpesvirus (KSHV has been linked to the development of primary effusion lymphoma (PEL, a rare lymphoproliferative disorder that is characterized by loss of expression of most B cell markers and effusions in the body cavities. This unique clinical presentation of PEL has been attributed to their distinctive plasmablastic gene expression profile that shows overexpression of genes involved in inflammation, adhesion and invasion. KSHV-encoded latent protein vFLIP K13 has been previously shown to promote the survival and proliferation of PEL cells. In this study, we employed gene array analysis to characterize the effect of K13 on global gene expression in PEL-derived BCBL1 cells, which express negligible K13 endogenously. We demonstrate that K13 upregulates the expression of a number of NF-κB responsive genes involved in cytokine signaling, cell death, adhesion, inflammation and immune response, including two NF-κB subunits involved in the alternate NF-κB pathway, RELB and NFKB2. In contrast, CD19, a B cell marker, was one of the genes downregulated by K13. A comparison with K13-induced genes in human vascular endothelial cells revealed that although there was a considerable overlap among the genes induced by K13 in the two cell types, chemokines genes were preferentially induced in HUVEC with few exceptions, such as RANTES/CCL5, which was induced in both cell types. Functional studies confirmed that K13 activated the RANTES/CCL5 promoter through the NF-κB pathway. Taken collectively, our results suggest that K13 may contribute to the unique gene expression profile, immunophenotype and clinical presentation that are characteristics of KSHV-associated PEL.
Guzman-Rojas, Liliana; Rangel, Roberto; Salameh, Ahmad; Edwards, Julianna K; Dondossola, Eleonora; Kim, Yun-Gon; Saghatelian, Alan; Giordano, Ricardo J; Kolonin, Mikhail G; Staquicini, Fernanda I; Koivunen, Erkki; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata
2012-01-31
Processes that promote cancer progression such as angiogenesis require a functional interplay between malignant and nonmalignant cells in the tumor microenvironment. The metalloprotease aminopeptidase N (APN; CD13) is often overexpressed in tumor cells and has been implicated in angiogenesis and cancer progression. Our previous studies of APN-null mice revealed impaired neoangiogenesis in model systems without cancer cells and suggested the hypothesis that APN expressed by nonmalignant cells might promote tumor growth. We tested this hypothesis by comparing the effects of APN deficiency in allografted malignant (tumor) and nonmalignant (host) cells on tumor growth and metastasis in APN-null mice. In two independent tumor graft models, APN activity in both the tumors and the host cells cooperate to promote tumor vascularization and growth. Loss of APN expression by the host and/or the malignant cells also impaired lung metastasis in experimental mouse models. Thus, cooperation in APN expression by both cancer cells and nonmalignant stromal cells within the tumor microenvironment promotes angiogenesis, tumor growth, and metastasis.
Directory of Open Access Journals (Sweden)
Alexandru Lucian MIHAI
2013-10-01
Full Text Available In sport marketing, the word promotion covers a range of interrelated activities. All of these activities are designed to attract attention, stimulate the interest and awareness of consumers, and of course, encourage them to purchase a sport product. Promotion is about communicating with and educating consumers. The purpose of a sport promotional strategy is to build brand loyalty and product credibility, develop image, and position the brand. A promotional strategy is similar to a marketing strategy, but the promotional strategy seeks short-term objectives, both direct and indirect. Promotional objectives usually include increased sales, stimulate impulse buying, raise customer traffic, and present and reinforce image. It also provides information about products and services, publicizes new stores or websites, and creates and enhances customer satisfaction.
High-yielding Wheat Varieties Harbour Superior Plant Growth Promoting-Bacterial Endophytes
Directory of Open Access Journals (Sweden)
Mehwish Yousaf
2017-06-01
Full Text Available Background and Objective: The purpose of this study was to compare the endophytic microbial flora of different wheat varieties to check whether a better yielding variety also harbours superior plant growth promoting bacteria. Such bacteria are helpful in food biotechnology as their application can enhance the yield of the crop.Material and Methods: Three wheat varieties (Seher, Faisalabad and Lasani were selected, Seher being the most superior variety. endophytic bacteria were isolated from the histosphere of the leaves and roots at different growth phases of the plants. The isolates were analyzed for plant growth promoting activities. Isolates giving best results were identified through 16S rRNA gene sequencing. Statistical analysis was done using Microsoft Excel 2013. All the experiments were conducted in triplicates.Results and Conclusion: The endophytes of Seher variety showed maximum plant growth promoting abilities. Among the shoot endophytes, the highest auxin production was shown by Seher isolate SHHP1-3 up to 51.9μg ml-1, whereas in the case of root endophytes, the highest auxin was produced by SHHR1-5 up to 36 μg ml-1. The bacteria showing significant plant growth promoting abilities were identified by 16S rRNA sequencing. Bacillus, Proteobacteria and Actinobacteria species were the dominant bacteria showing all the traits of plant growth promotion. It can be concluded that Seher variety harbours superior plant growth promoting endophytes that must be one of the reasons for its better growth and yield as compared to the other two varieties. The investigated results support possible utilization of the selected isolates in wheat growth promotion with respect to increase in agro-productivity. The application of such bacteria could be useful to enhance wheat yield and can help in food biotechnology.Conflict of interest: The authors declare no conflict of interest.
Yang, Yan; Wu, Xi; Li, Qiang; Jiao, Shu-fang; Li, Xun; Li, Xin-jian; Zhu, Guo-ping; Du, Lin; Zhao, Jian-hua; Jiang, Yuan; Feng, Guo-ze
2009-04-01
To know the situation of tobacco advertisement, promotions and related factors in six cities in China. 4815 adults (above 18 years), selected form Beijing, Shanghai, Shenyang, Changsha, Guangzhou and Yinchuan through probability proportionate sampling and simple random sampling, were investigated through questionnaires. The most commonly reported channels that smokers noticed tobacco advertisements were billboards (35.6%) and television (34.4%). The most commonly reported tobacco promotional activities that were noticed by smokers were free gifts when buying cigarettes (23.1%) and free samples of cigarettes (13.9%). Smokers in Changsha were more likely to report noticing tobacco advertisement on billboards (chi2 = 562.474, P advertisement and promotion. It was universal to see tobacco advertisement and promotions in cities in China but the laws and regulations about tobacco-control were not uniformly executed in different cities. It is necessary to perfect and uniform related laws and regulations.
PREFACE: 13th International Conference on Muon Spin Rotation, Relaxation and Resonance
2014-12-01
submitted 227 contributions, which were intensively discussed during day and evening sessions. The scientific program was centered around invited talks from speakers outside the μSR community, who presented lectures on topics where μSR is giving or expected to give significant contributions. The invited speakers, covering various fields of interest, included Radu Coldea (Oxford, Quantum Magnetism), Claude- Henri Delmas (Bordeaux, Electro- and Solid State Chemistry), Dirk Johrendt (Munich, Iron Based Materials), Marc-Henri Julien (Grenoble, Cuprate Superconductors), Manfred Fiebig (Zürich, Multiferroics), Allan MacDonald (Austin, Topological Electronic States), Hidenori Takagi (Stuttgart and Tokyo, Transition Metal Oxides), and Jean-Marc Triscone (Geneva, Oxide Heterostructures). In addition to an overview about status and progress of the existing facilities in Europe, Canada and Japan, future projects and new ideas for μSR facilities in South Korea, China and the USA were presented. A special evening session was held to discuss about muon site and muon states calculations by DFT and other techniques. Several talks and posters can be found on the conference web page www.psi.ch/muSR2014. In a ceremony at the beginning of the conference, Roberto De Renzi from the University of Parma was awarded the 2014 Yamazaki Prize for muon science by the International Society for Muon Spin Spectroscopy (ISMS) for his sustained and exceptional contributions to the development of the muon spin relaxation technique to investigate magnetism and superconductivity and for promoting synergies between μSR and NMR. In the closing session Rob Kie (UBC Vancouver and TRIUMF) very effectively summarized the five days of meeting, while giving an enlightening personal impression. In the same session five best poster prizes were awarded and ISMS gave two prizes to young researchers presenting outstanding work at the conference. The conference organizers also on behalf of the entire μSR community are
The study on Egr-1 promoter which is radioactive promoter
International Nuclear Information System (INIS)
Zhang Chunzhi; Guo Yang; Lv Zhonghong
2006-01-01
Radiogenetic therapy is a heated reaseach on oncotherapy. Early growth response gene-1 (Egr-1) gene promoter is a probably means in radiogenetic therapy. The article review studying on Egr-1 gene promoter and constructing regulating gene expressing system by radiation-inducible Egr-1 gene promoter. (authors)
Koerts, T.; Santen, van R.A.
1992-01-01
The rate of CO insertion into surface CHx species was investigated on silica-supported rhodium and rhodium-vanadium catalysts. Isotopically labelled 13CO was used in a transient kinetic experiment under steady-state conditions. A main conclusion is that vanadium promotion does not affect the rate of
Inverse correlation between promoter strength and excision activity in class 1 integrons.
Directory of Open Access Journals (Sweden)
Thomas Jové
2010-01-01
Full Text Available Class 1 integrons are widespread genetic elements that allow bacteria to capture and express gene cassettes that are usually promoterless. These integrons play a major role in the dissemination of antibiotic resistance among Gram-negative bacteria. They typically consist of a gene (intI encoding an integrase (that catalyzes the gene cassette movement by site-specific recombination, a recombination site (attI1, and a promoter (Pc responsible for the expression of inserted gene cassettes. The Pc promoter can occasionally be combined with a second promoter designated P2, and several Pc variants with different strengths have been described, although their relative distribution is not known. The Pc promoter in class 1 integrons is located within the intI1 coding sequence. The Pc polymorphism affects the amino acid sequence of IntI1 and the effect of this feature on the integrase recombination activity has not previously been investigated. We therefore conducted an extensive in silico study of class 1 integron sequences in order to assess the distribution of Pc variants. We also measured these promoters' strength by means of transcriptional reporter gene fusion experiments and estimated the excision and integration activities of the different IntI1 variants. We found that there are currently 13 Pc variants, leading to 10 IntI1 variants, that have a highly uneven distribution. There are five main Pc-P2 combinations, corresponding to five promoter strengths, and three main integrases displaying similar integration activity but very different excision efficiency. Promoter strength correlates with integrase excision activity: the weaker the promoter, the stronger the integrase. The tight relationship between the aptitude of class 1 integrons to recombine cassettes and express gene cassettes may be a key to understanding the short-term evolution of integrons. Dissemination of integron-driven drug resistance is therefore more complex than previously thought.
International Nuclear Information System (INIS)
Shebaita, M.K.
1975-01-01
The concept of radiation promotion was proposed in this study. The proposal of this concept was dependent upon stimulation in growth weight of survived chicks when fertile eggs were exposed to 60 Co gamma radiation. It was found that female chick (Promotive Sex) responded to this proposal concept rather than the male. Moreover, the dose level of 640 rads was found to be the Promotive Dose. It is important before applying ionizing radiation as a growth promotive to take into consideration whether you want increasing egg or meat production, as meat promotion in layers breed is bound to decrease egg production. (orig.) [de
Directory of Open Access Journals (Sweden)
Ansaya Thonpho
Full Text Available Pyruvate carboxylase (PC is an enzyme that plays a crucial role in many biosynthetic pathways in various tissues including glucose-stimulated insulin secretion. In the present study, we identify promoter usage of the human PC gene in pancreatic beta cells. The data show that in the human, two alternative promoters, proximal and distal, are responsible for the production of multiple mRNA isoforms as in the rat and mouse. RT-PCR analysis performed with cDNA prepared from human liver and islets showed that the distal promoter, but not the proximal promoter, of the human PC gene is active in pancreatic beta cells. A 1108 bp fragment of the human PC distal promoter was cloned and analyzed. It contains no TATA box but possesses two CCAAT boxes, and other putative transcription factor binding sites, similar to those of the distal promoter of rat PC gene. To localize the positive regulatory region in the human PC distal promoter, 5'-truncated and the 25-bp and 15-bp internal deletion mutants of the human PC distal promoter were generated and used in transient transfections in INS-1 832/13 insulinoma and HEK293T (kidney cell lines. The results indicated that positions -340 to -315 of the human PC distal promoter serve as (an activator element(s for cell-specific transcription factor, while the CCAAT box at -71/-67, a binding site for nuclear factor Y (NF-Y, as well as a GC box at -54/-39 of the human PC distal promoter act as activator sequences for basal transcription.
Promoting Health in Early Childhood Environments: A Health-Promotion Approach
Minniss, Fiona Rowe; Wardrope, Cheryl; Johnston, Donni; Kendall, Elizabeth
2013-01-01
This paper investigates the mechanisms by which a health-promotion intervention might influence the health-promoting behaviours of staff members working in early childhood centres. The intervention was an ecological health-promotion initiative that was implemented within four early childhood centres in South-East Queensland, Australia. In-depth,…
Using Paid Radio Advertisements to Promote Physical Activity Among Arkansas Tweens
Rath, David; Balamurugan, Appathurai; Oakleaf, Ernest J
2005-01-01
Introduction The level of physical activity among children is a growing concern. Evidence shows that many children aged 9 to 13 years (tweens) do not participate in any organized physical activity during their nonschool hours, and some do not engage in any free-time physical activity. Physical inactivity is associated with a host of chronic diseases such as diabetes and cardiovascular disease. Paid media advertisements have been an effective method of promoting physical activity. Methods Fro...
International Nuclear Information System (INIS)
Fujiwara, Y.; Kano, Y.; Tatsumi, M.; Paul, P.
1980-01-01
The effects of a tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and/or an anti-promoter antipain (protease inhibitor) on spontaneous and ultraviolet-induced sister-chromatid exchanges (SCEs) and 6-thioguanine-resistant (6TGsup(r)) recessive mutations were examined in V79 Chinese hamster cells in culture. TPA and/or antipain neither significantly altered base-line and UV-induced immediate SCE frequencies, nor decreased the level of delayed SCEs which persisted 6-7 days after irradiation. TPA and/or antipain appeared to enhance the recovery of UV-induced 6TGsup(r) colonies at the plateau expression phase despite non-mutagenicity by themselves and unaltered metabolic cooperation. Thus, the results conceivably imply that the 6TGsup(r)-recessive mutation expression, but not fixation, can be modulated at the cell level by TPA and/or antipain. Our results, together with the recent results of Loveday and Latt, may argue against the notion that TPA enhances the antipain-suppressible SCEs as an index of mitotic recombination in relevance with a tumor-promotion mechanism. (orig.)
Letting Students Take the Lead: A User-Centred Approach to Evaluating Subject Guides
Directory of Open Access Journals (Sweden)
Kimberley Hintz
2010-12-01
Full Text Available Objective – What do students need and want from library subject guides? Options such as Web 2.0 enhancement are now available to librarians creating subject-specific web pages. Librarians may be eager to implement these new tools, but are such add-ons a priority forstudents? This paper aims to start a dialogue on this issue by presenting the findings of the University of British Columbia (UBC Library’s Subject Guides Working Group (SGWG, which was tasked with assessing current library subject guides in order to make recommendations for the update and future development of UBC Library subject guides.Methods – The working group solicited feedback through a questionnaire that was distributed to undergraduate and graduate students from a variety of disciplines at UBC. The questionnaire included an evaluation of UBC subject guides, as well as guides from other academic libraries that used various platforms such as LibGuides and SubjectsPlus.Results – Respondents to the student questionnaire indicated that a simple and clean layout was of primary importance. Students also desired succinct annotations to resources and limited page scrolling. Meanwhile, few students identified Web 2.0 features such as rating systems and discussion forums as being important for their needs. The working group used the questionnaire data to create a “Top Ten” list of student recommendations.Conclusions – The “Top Ten” list of student recommendations was combined with stakeholder feedback from faculty, liaison librarians and Library Systems and Information Technology representatives to create the SGWG’s final recommendation for subject guide revision and enhancement. For the SGWG these findings called into question the necessity of Web 2.0 technologies within subject guide pages and highlighted the need for further research on the topic of subject guide usability and effectiveness.
Gentile, John V; Weinert, Carl R; Schlechter, John A
2013-01-01
Multiple treatment modalities exist for unicameral bone cysts (UBC), including steroid injection, autologous bone marrow injection, mechanical decompression, intramedullary fixation, curettage, and bone grafting. All have their own potential limitations such as high recurrence rates, cyst persistence, need for multiple procedures, and prolonged immobilization. A minimally invasive regimen consisting of curettage, decompression, and injection of a calcium sulfate-calcium phosphate (CaSO4-CaPO4) composite has been utilized at our institution in an attempt to obtain optimal results for the treatment of UBCs in the pediatric population. We retrospectively evaluated 16 patients with pathologically confirmed UBC who were treated with curettage, decompression, and injection of a calcium sulfate-calcium phosphate composite between April 2006 and August 2010 at a single institution. The average age of the patients at time of surgical intervention was 9.4 years of age (range, 3 to 16 y). Average follow-up was 16 months (range, 6 to 36 mo). Radiographic healing, clinical outcomes, and complications were evaluated. Final follow-up radiographs demonstrated healing in 93.7% (15 of 16) of patients after a single procedure. Complete healing was observed in 14 of 16 patients and partially healed with a defect in 1 of 16 patients. One patient had a persistent cyst but did not wish to receive further treatment. All patients returned to full activities including sports on average at 3.1 months (range, 1 to 6 mo) and were asymptomatic on most recent follow-up. No postoperative complications, including refracture, were observed. Curettage, decompression, and injection of a calcium sulfate-calcium phosphate composite for UBC in the pediatric population demonstrates encouraging results with low recurrence rates and complications compared with conventional methods. Case series, Level of Evidence IV.
Ramos-Pascua, Luis R; Sánchez-Herraéz, Sergio; Casas-Ramos, Paula; Molnar Fuentes, Sebastián; Santos Sánchez, José Ángel
2014-10-01
There is no consensus on when and how to treat unicameral bone cysts (UBCs), partly because of a lack of knowledge of the aetiology. To review the different treatment techniques for UBCs and to describe our results with a single injection of autogenous bone marrow (BM) mixed with demineralised bone matrix (DBM) in very young children. We reviewed five patients under the age of 8 years with UBCs treated by percutaneous aspiration and a single injection of BM associated with DBM. The cyst was located in the proximal humerus in four patients and in the proximal femur in one patient. Assessment of the need for surgery was based on the clinical and radiographic suspicion of new pathological fractures. The administration of a second injection, when necessary, was based on the surgeon's judgement regarding the risk of fracture. The mean follow-up after first injection was 41 months. There were no complications related to the procedure, except a non-displaced fracture, which healed without problems. All patients were pain free and progressively resumed their activities without restriction until a new fracture occurred in two cases. According to Capanna's classification, only one case healed completely (grade 1), one lesion was classified as grade 2, and there were three recurrences at 11, 12 and 27 months after initial treatment (grade 3). The final outcome was treatment failure for three out of the five patients. Two patients were treated with a second injection and one patient is waiting for surgery. A single injection of aspirated autogenous BM mixed with DBM in very young children with active UBCs at risk of fracture is very simple, comfortable and safe. Nevertheless, the results seem to be unpredictable and are probably more dependent on the natural evolution of the cyst than on the treatment. Further comparative studies with larger sample numbers are needed.
Dormans, John P; Sankar, Wudbhav N; Moroz, Leslie; Erol, Bülent
2005-01-01
Several treatment options exist for unicameral bone cysts (UBCs), including observation, steroid injection, bone marrow injection, and curettage and bone grafting. These are all associated with high recurrence rates, persistence, and occasional complications. Newer techniques have been described, most with variable success and only short follow-up reported. Because of these factors, a new minimally invasive percutaneous technique was developed for the treatment of UBCs in children. Twenty-eight children with UBCs who underwent percutaneous intramedullary decompression, curettage, and grafting with medical-grade calcium sulfate (MGCS) pellets by the senior author (J.P.D.) between April 2000 and April 2003 were analyzed as part of a pediatric musculoskeletal tumor registry at a large tertiary children's hospital. Four patients were lost to follow-up, and the remaining 24 patients had an average follow-up of 21.9 months (range 4-48 months). Twelve patients were followed for at least 24 months. Six of the 24 children had received previous treatment of their UBC, most often at an outside institution. Follow-up was performed through clinical evaluation and radiographic review. Postoperative radiographs at most recent follow-up showed complete healing, defined as more than 95% opacification, in 22 of 24 patients (91.7%). One patient (4.2%) demonstrated partial healing, defined as 80% to 95% opacification. One patient had less than 80% radiographic healing (4.2%). All 24 patients returned to full activities and were asymptomatic at most recent follow-up. The only complication noted was a superficial suture abscess that occurred in one patient; this resolved with local treatment measures. The new minimally invasive technique of percutaneous intramedullary decompression, curettage, and grafting with MGCS pellets demonstrates favorable results with low complication and recurrence rates compared with conventional techniques. The role of intramedullary decompression as a part
Energy Technology Data Exchange (ETDEWEB)
Benedito, E.; Takeda, A.M., E-mail: eva@nupelia.uem.br [Universidade Estadual de Maringa (UEM), PR (Brazil). Nucleo de Pesquisas em Limnologia, Ictiologia e Aquicultura; Figueroa, L. [Universidade Estadual de Maringa (UEM), PR (Brazil). Pos-Graduacao em Ecologia de Ambientes Aquaticos Continentais; Manetta, GI. [Universidade Estadual de Maringa (UEM), PR (Brazil). Pos-Graduacao em Biologia Comparada
2013-11-15
The objective of this study was to evaluate the effect of Oreochromis niloticus cage culture promoted variations in the δ{sup 13}C and δ{sup 15}N in Corbicula fluminea (Mollusca; Bivalvia) and in the sediment of an aquatic food web. Samples were taken before and after net cage installation in the Rosana Reservoir (Paranapanema River, PR-SP). Samples of specimens of the bivalve filter C. fluminea and samples of sediment were collected using a modified Petersen grab. All samples were dried in an oven (60 °C) for 72 hours, macerated to obtain homogenous fine powders and sent for carbon (δ{sup 13}C) and nitrogen (δ{sup 15}N) isotopic value analysis in a mass spectrometer. There were significant differences in the δ{sup 13}C and δ{sup 15}N values of the invertebrate C. fluminea between the beginning and the end of the experiment. There were no differences between the δ{sup 13}C and δ{sup 15}N values of sediment. These results indicate that the installation of fish cage culture promoted impacts in the isotopic composition of the aquatic food web organisms, which could exert influence over the native species and the ecosystem. (author)
Istenič, Vesna
2013-01-01
The thesis titled Promoting preschool reading consists of a theoretiral and an empirical part. In the theoretical part I wrote about reading, the importance of reading, types of reading, about reading motivation, promoting reading motivation, internal and external motivation, influence of reading motivation on the child's reading activity, reading and familial literacy, the role of adults in promotion reading literacy, reading to a child and promoting reading in pre-school years, where I ...
48 CFR 13.104 - Promoting competition.
2010-10-01
... cost of the purchase. (a) The contracting officer must not— (1) Solicit quotations based on personal... practicable competition ordinarily can be obtained by soliciting quotations or offers from sources within the... the maximum extent practicable. Whenever practicable, request quotations or offers from two sources...
Ginesta, Mireia M; Diaz-Riascos, Zamira Vanessa; Busquets, Juli; Pelaez, Núria; Serrano, Teresa; Peinado, Miquel Àngel; Jorba, Rosa; García-Borobia, Francisco Javier; Capella, Gabriel; Fabregat, Joan
2016-09-01
Early detection of pancreatic and periampullary neoplasms is critical to improve their clinical outcome. The present authors previously demonstrated that DNA hypermethylation of adenomatous polyposis coli (APC), histamine receptor H2 (HRH2), cadherin 13 (CDH13), secreted protein acidic and cysteine rich (SPARC) and engrailed-1 (EN-1) promoters is frequently detected in pancreatic tumor cells. The aim of the present study was to assess their prevalence in pancreatic juice of carcinomas of the pancreas and periampullary area. A total of 135 pancreatic juices obtained from 85 pancreatic cancer (PC), 26 ampullary carcinoma (AC), 10 intraductal papillary mucinous neoplasm (IPMN) and 14 chronic pancreatitis (CP) patients were analyzed. The methylation status of the APC, HRH2, CDH13, SPARC and EN-1 promoters was analyzed using methylation specific-melting curve analysis (MS-MCA). Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were also tested with allele-specific quantitative polymerase chain reaction amplification. Out of the 5 promoters analyzed, APC (71%) and HRH2 (65%) were the most frequently methylated in PC juice. APC methylation was also detected at a high frequency in AC (76%) and IPMN (80%), but only occasionally observed in CP (7%). APC methylation had a high sensitivity (71-80%) for all types of cancer analyzed. The panel (where a sample scored as positive when ≥2 markers were methylated) did not outperform APC as a single marker. Finally, KRAS detection in pancreatic juice offered a lower sensitivity (50%) and specificity (71%) for detection of any cancer. APC hypermethylation in pancreatic juice, as assessed by MS-MCA, is a frequent event of potential clinical usefulness in the diagnosis of pancreatic and periampullary neoplasms.
Gender differences in promotions and scholarly productivity in academic urology.
Awad, Mohannad A; Gaither, Thomas W; Osterberg, E Charles; Yang, Glen; Greene, Kirsten L; Weiss, Dana A; Anger, Jennifer T; Breyer, Benjamin N
2017-10-01
The gender demographics within urology are changing as more women are entering the workforce. Since research productivity strongly influence career advancement, we aim to characterize gender differences in scholarly productivity and promotions in a cohort of graduated academic urologists. Urologists who graduated between 2002 and 2008 from 34 residency programs affiliated with the top 50 urology hospitals as ranked in 2009 by U.S. News & World Report were followed longitudinally. Only urologists affiliated with an academic teaching hospital were included for analysis. A total of 543 residents graduated, 459 (84.5%) males and 84 (15.5%) females. Of these, 173 entered academia, 137 (79.2%) males and 36 (20.8%) females. Women had fewer publications compared to men (mean 19.3 versus 61.7, p = 0.001). Fewer women compared to men were promoted from assistant professor 11 (30.6%) versus 83 (60.6%), p = 0.005. Fewer women achieved associate professor 10 (27.8%) versus 67 (48.9%), p = 0.005 or professor ranks 1 (2.8%) versus 16 (11.7%), p = 0.005 respectively compared to men. In a multivariate logistic regression analysis, after controlling for the number of total publications and number of years since graduation, gender was not predictive of achieving promotion, OR = 0.81 (95% CI 0.31-2.13), p = 0.673. Women are underrepresented in senior faculty roles in urology. Scholarly productivity seems to play a major role in academic promotion within urology. With increasing women in academic urology, further studies are needed to explore predictors of promotion and how women can achieve higher leadership roles in the field.
Price promotions for food and beverage products in a nationwide sample of food stores.
Powell, Lisa M; Kumanyika, Shiriki K; Isgor, Zeynep; Rimkus, Leah; Zenk, Shannon N; Chaloupka, Frank J
2016-05-01
Food and beverage price promotions may be potential targets for public health initiatives but have not been well documented. We assessed prevalence and patterns of price promotions for food and beverage products in a nationwide sample of food stores by store type, product package size, and product healthfulness. We also assessed associations of price promotions with community characteristics and product prices. In-store data collected in 2010-2012 from 8959 food stores in 468 communities spanning 46 U.S. states were used. Differences in the prevalence of price promotions were tested across stores types, product varieties, and product package sizes. Multivariable regression analyses examined associations of presence of price promotions with community racial/ethnic and socioeconomic characteristics and with product prices. The prevalence of price promotions across all 44 products sampled was, on average, 13.4% in supermarkets (ranging from 9.1% for fresh fruits and vegetables to 18.2% for sugar-sweetened beverages), 4.5% in grocery stores (ranging from 2.5% for milk to 6.6% for breads and cereals), and 2.6% in limited service stores (ranging from 1.2% for fresh fruits and vegetables to 4.1% for breads and cereals). No differences were observed by community characteristics. Less-healthy versus more-healthy product varieties and larger versus smaller product package sizes generally had a higher prevalence of price promotion, particularly in supermarkets. On average, in supermarkets, price promotions were associated with 15.2% lower prices. The observed patterns of price promotions warrant more attention in public health food environment research and intervention. Copyright © 2016 Elsevier Inc. All rights reserved.
International Nuclear Information System (INIS)
Nishino, H.; Fujiki, H.; Terada, M.; Sato, S.
1983-01-01
Teleocidin, a new tumor promoter, increased incorporation of radioactive inorganic phosphate ( 32 P/sub i/) into phospholipids in HeLa cells. This effect was detected within 1 h on incubation of the cells in medium containing teleocidin. The half-maximum effective dose of teleocidin was approximately 10 ng/ml. The main effect of teleocidin was on the incorporation of 32 P/sub i/ into the phosphatidylcholine fraction, with a lesser effect on 32 P/sub i/ incorporation into other phospholipid fractions. Increased incorporation of 32 P/sub i/ into phospholipids was also observed on incubation of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), dihydroteleocidin B, or lyngbyatoxin A, which are all complete tumor promoters, and also with mezerein, which is an incomplete and second stage promoter. On the other hand, at concentrations of up to 1 microgram/ml, 4-O-methyl TPA and C/sub a/ 2 + ionophore A23187, which are incomplete and first stage promoters, and phorbol, which has no promoting activity in skin carcinogenesis, did not cause any increased incorporation of 32 P/sub i/ into phospholipid fractions of HeLa cells
Community-based health and schools of nursing: supporting health promotion and research.
Shannon, Crystal
2014-01-01
This article examines the role of community-based schools of nursing in the promotion of public health and research in poverty-stricken areas. This was a three-phase study (questionnaire and key-informants' interviews) that surveyed representatives of prelicensure associate and baccalaureate nursing schools (n=17), nursing-school key informants (n=6) and community leaders (n=10). A 13-question web-based survey and semi-structured interview of key informants elicited data on demographics, nursing program design, exposure of faculty and students to various research and health promotion methods, and beliefs about student involvement. Nursing schools participated minimally in community-based health promotion (CBHP) and community-based participatory research saw reduced need for student involvement in such activities, cited multiple barriers to active community collaboration, and reported restricted community partnerships. CBHP was recognized to be a valuable element of health care and student education, but is obstructed by many barriers. This study suggests that nursing schools are not taking full advantage of relationships with community leaders. Recommendations for action are given. © 2013 Wiley Periodicals, Inc.
Sreevidya, M.; Gopalakrishnan, S.; Kudapa, H.; Varshney, R.K.
2016-01-01
The main objective of the present study was to isolate and characterize actinomycetes for their plant growth-promotion in chickpea. A total of 89 actinomycetes were screened for their antagonism against fungal pathogens of chickpea by dual culture and metabolite production assays. Four most promising actinomycetes were evaluated for their physiological and plant growth-promotion properties under in vitro and in vivo conditions. All the isolates exhibited good growth at temperatures from 20 °C to 40 °C, pH range of 7–11 and NaCl concentrations up to 8%. These were also found highly tolerant to Bavistin, slightly tolerant to Thiram and Captan (except VAI-7 and VAI-40) but susceptible to Benlate and Ridomil at field application levels and were found to produce siderophore, cellulase, lipase, protease, chitinase (except VAI-40), hydrocyanic acid (except VAI-7 and VAI-40), indole acetic acid and β-1,3-glucanase. When the four actinomycetes were evaluated for their plant growth-promotion properties under field conditions on chickpea, all exhibited increase in nodule number, shoot weight and yield. The actinomycetes treated plots enhanced total N, available P and organic C over the un-inoculated control. The scanning electron microscope studies exhibited extensive colonization by actinomycetes on the root surface of chickpea. The expression profiles for indole acetic acid, siderophore and β-1,3-glucanase genes exhibited up-regulation for all three traits and in all four isolates. The actinomycetes were identified as Streptomyces but different species in the 16S rDNA analysis. It was concluded that the selected actinomycetes have good plant growth-promotion and biocontrol potentials on chickpea. PMID:26887230
Directory of Open Access Journals (Sweden)
M. Sreevidya
2016-03-01
Full Text Available Abstract The main objective of the present study was to isolate and characterize actinomycetes for their plant growth-promotion in chickpea. A total of 89 actinomycetes were screened for their antagonism against fungal pathogens of chickpea by dual culture and metabolite production assays. Four most promising actinomycetes were evaluated for their physiological and plant growth-promotion properties under in vitro and in vivo conditions. All the isolates exhibited good growth at temperatures from 20 °C to 40 °C, pH range of 7–11 and NaCl concentrations up to 8%. These were also found highly tolerant to Bavistin, slightly tolerant to Thiram and Captan (except VAI-7 and VAI-40 but susceptible to Benlate and Ridomil at field application levels and were found to produce siderophore, cellulase, lipase, protease, chitinase (except VAI-40, hydrocyanic acid (except VAI-7 and VAI-40, indole acetic acid and β-1,3-glucanase. When the four actinomycetes were evaluated for their plant growth-promotion properties under field conditions on chickpea, all exhibited increase in nodule number, shoot weight and yield. The actinomycetes treated plots enhanced total N, available P and organic C over the un-inoculated control. The scanning electron microscope studies exhibited extensive colonization by actinomycetes on the root surface of chickpea. The expression profiles for indole acetic acid, siderophore and β-1,3-glucanase genes exhibited up-regulation for all three traits and in all four isolates. The actinomycetes were identified as Streptomyces but different species in the 16S rDNA analysis. It was concluded that the selected actinomycetes have good plant growth-promotion and biocontrol potentials on chickpea.
Gundle, Kenneth R; Bhatt, Etasha M; Punt, Stephanie E; Bompadre, Viviana; Conrad, Ernest U
2017-01-01
Many treatment options exist for unicameral bone cysts (UBC), without clear evidence of superiority. Meta-analyses have been limited by small numbers of patients in specific anatomic and treatment subgroups. The purpose of this study was to report the outcomes of injecting bone marrow aspirate and demineralized bone matrix (BMA/DBM) for the treatment of proximal humerus UBC. Fifty-one patients with proximal humerus lesions treated by BMA/DBM injection were retrospectively reviewed from a single academic medical center. The mean number of injections performed per patient was 2.14 (range 1-5). Eleven patients underwent only one injection (22%), an additional 19 patients completed treatment after two injections (37%), four patients healed after three injections (8%), and one patient healed after four injections (2%). The cumulative success rate of serial BMA/DBM injections was 22% (11/51), 58% (30/51), 67% (34/51), and 69% (35/51). Eleven patients (22%) ultimately underwent open curettage and bone grafting, and five patients (10%) were treated with injection of calcium phosphate bone substitute. A BMA/DBM injection strategy avoided an open procedure in 78% of patients with a proximal humerus UBC. The majority of patients underwent at least 2 injection treatments. Level IV retrospective cohort study.
Vernick, Jon S; Alcorn, Ted; Horwitz, Joshua
2017-03-01
There were more than 36,000 firearm-related deaths in the U.S. in 2015. Under federal law, a background check is required only for gun purchases from licensed dealers. Research suggests that some persons prohibited from owning a gun turn to private sellers, including those identified online, to attempt to obtain a firearm. State-level approaches to make it more difficult for high-risk persons to purchase or possess firearms include universal background check (UBC) and gun violence restraining order (GVRO) laws. UBC laws, on the books in 18 states as of the end of 2016, can reduce both homicide and suicide rates. After Colorado adopted a UBC law in 2013, the number of background checks conducted by private sellers for sales occurring at places other than gun shows steadily increased. GVRO laws give law enforcement and families the authority to petition a court to temporarily remove firearms from an individual who presents a danger to himself or others during times of crisis, regardless of whether that person has been diagnosed with a mental illness. California enacted a GVRO law in 2014. Data are emerging to suggest the effectiveness of GVRO-type laws at averting suicides and providing an entryway to services.
Cavallo, Delia; Casadio, Valentina; Bravaccini, Sara; Iavicoli, Sergio; Pira, Enrico; Romano, Canzio; Fresegna, Anna Maria; Maiello, Raffaele; Ciervo, Aureliano; Buresti, Giuliana; Zoli, Wainer; Calistri, Daniele
2014-01-01
The aim of the present study was to identify sensitive and noninvasive biomarkers of early carcinogenic effect at target organ to use in biomonitoring studies of workers at risk for previous occupational exposure to potential carcinogens. Standard urine cytology (Papanicolaou staining test), comet assay, and quantitative telomerase repeat amplification protocol (TRAP) assay were performed in 159 ex-rubber workers employed in tyres production and 97 unexposed subjects. In TRAP positive cases, a second level analysis using FISH (Urovysion) was done. Cystoscopy results were available for 11 individuals whose 6 FISH/TRAP/comet positive showed in 3 cases a dysplastic condition confirmed by biopsy, 1 comet positive resulted in infiltrating UBC to the biopsy and with hyperplasia and slight dysplasia to the urinary cytology, 1 comet positive resulted in papillary superficial UBC to the biopsy, 1 FISH/TRAP positive showed a normal condition, and 2 TRAP positive showed in one case a phlogosis condition. The results evidenced good concordance of TRAP, comet, and FISH assays as early biomarkers of procarcinogenic effect confirmed by the dysplastic condition and UBC found by cystoscopy-biopsy analysis. The analysis of these markers in urine cells could be potentially more accurate than conventional cytology in monitoring workers exposed to mixture of bladder potential carcinogens.
Directory of Open Access Journals (Sweden)
Delia Cavallo
2014-01-01
Full Text Available The aim of the present study was to identify sensitive and noninvasive biomarkers of early carcinogenic effect at target organ to use in biomonitoring studies of workers at risk for previous occupational exposure to potential carcinogens. Standard urine cytology (Papanicolaou staining test, comet assay, and quantitative telomerase repeat amplification protocol (TRAP assay were performed in 159 ex-rubber workers employed in tyres production and 97 unexposed subjects. In TRAP positive cases, a second level analysis using FISH (Urovysion was done. Cystoscopy results were available for 11 individuals whose 6 FISH/TRAP/comet positive showed in 3 cases a dysplastic condition confirmed by biopsy, 1 comet positive resulted in infiltrating UBC to the biopsy and with hyperplasia and slight dysplasia to the urinary cytology, 1 comet positive resulted in papillary superficial UBC to the biopsy, 1 FISH/TRAP positive showed a normal condition, and 2 TRAP positive showed in one case a phlogosis condition. The results evidenced good concordance of TRAP, comet, and FISH assays as early biomarkers of procarcinogenic effect confirmed by the dysplastic condition and UBC found by cystoscopy-biopsy analysis. The analysis of these markers in urine cells could be potentially more accurate than conventional cytology in monitoring workers exposed to mixture of bladder potential carcinogens.
Whitehead, Dean
2008-04-01
To arrive at an expert consensus in relation to health promotion and health education constructs as they apply to nursing practice, education and policy. Nursing has often been maligned and criticized, both inside and outside of the profession, for its ability to understand and conduct effective health promotion and health education-related activities. In the absence of an expert-based consensus, nurses may find it difficult to progress beyond the current situation. In the absence of any previously published nursing-related consensus research, this study seeks to fill that knowledge-gap. A two-round Delphi technique via email correspondence. A first-round qualitative questionnaire used open-ended questions for defining health promotion and health education. This was both in general terms and as participants believed these concepts related to the clinical, theoretical (academic/educational) and the policy (political) setting in nursing. Line-by-line qualitative content and thematic analysis of the first-round data generated 13 specific categories. These categories contained 134 statement items. The second-round questionnaire comprised the identified 134 statements. Using a five-point Likert scale (ranging from 1 = strongly disagree to 5 = strongly agree) participants scored and rated their level of agreement/disagreement against the listed items. Data from the second-round was descriptively analysed according to distribution and central tendency measures. An expert consensus was reached on 65 of the original 134 statements. While some minor contradiction was demonstrated, strong consensus emerged around the issues of defining health promotion and health education and the emergence of a wider health promotion and health education role for nursing. No consensus was reached on only one of the 13 identified topic categories - that of 'nurses working with other disciplines and agencies in a health education and health promotion role.' This study provides a hitherto
Wang, Bing; Wu, Chao; Kang, Liangguo; Huang, Lang; Pan, Wei
2018-03-20
In recent years, the Chinese government has attached great importance to occupational health under the guidance of people-oriented concept. This paper introduces the current status and future development of occupational health in China's Thirteenth Five-Year Plan (13th FYP) period (2016-2020) to promote the cooperation and exchange on occupational health between China and other countries. We collected statistical data about occupational diseases and information addressing occupational diseases. We included all types of official reports, guidelines, policies, and relevant laws published by the Chinese government. China has carried out a series of strategies and measures to reduce the incidence of occupational diseases, and has made progress in occupational health protection. However, occupational health in China still faces severe conditions and challenges for occupational diseases that have not been prevented and controlled effectively. To actively promote the future development of occupational health during the 13th FYP period, China has issued a series of important policy documents (such as the Plan for a Healthy China 2030, the 13th FYP for Occupational Disease Prevention and Control, and the 13th FYP for Occupational Health Hazard Prevention and Control) in the last two years. The overall situation condition of occupational health in China is still serious. Occupational health in China's 13th FYP period faces a series of challenges, future tasks include plans to add the employer and regulatory levels of occupational health management, and occupational health education and publicity to the current technology-dominated approaches.
Streamlining Appointment, Promotion, and Tenure Procedures to Promote Early-Career Faculty Success.
Smith, Shannon B; Hollerbach, Ann; Donato, Annemarie Sipkes; Edlund, Barbara J; Atz, Teresa; Kelechi, Teresa J
2016-01-01
A critical component of the progression of a successful academic career is being promoted in rank. Early-career faculty are required to have an understanding of appointment, promotion, and tenure (APT) guidelines, but many factors often impede this understanding, thwarting a smooth and planned promotion pathway for professional advancement. This article outlines the steps taken by an APT committee to improve the promotion process from instructor to assistant professor. Six sigma's DMAIC improvement model was selected as the guiding operational framework to remove variation in the promotion process. After faculty handbook revisions were made, several checklists developed, and a process review rubric was implemented; recently promoted faculty were surveyed on satisfaction with the process. Faculty opinions captured in the survey suggest increased transparency in the process and perceived support offered by the APT committee. Positive outcomes include a strengthened faculty support framework, streamlined promotion processes, and improved faculty satisfaction. Changes to the APT processes resulted in an unambiguous and standardized pathway for successful promotion. Copyright © 2016 Elsevier Inc. All rights reserved.
PKC and Rab13 mediate Ca2+ signal-regulated GLUT4 traffic.
Deng, Bangli; Zhu, Xiaocui; Zhao, Yihe; Zhang, Da; Pannu, Alisha; Chen, Liming; Niu, Wenyan
2018-01-08
Exercise/muscle contraction increases cell surface glucose transporter 4 (GLUT4), leading to glucose uptake to regulate blood glucose level. Elevating cytosolic Ca 2+ mediates this effect, but the detailed mechanism is not clear yet. We used calcium ionophore ionomycin to raise intracellular cytosolic Ca 2+ level to explore the underlying mechanism. We showed that in L6 myoblast muscle cells stably expressing GLUT4myc, ionomycin increased cell surface GLUT4myc levels and the phosphorylation of AS160, TBC1D1. siPKCα and siPKCθ but not siPKCδ and siPKCε inhibited the ionomycin-increased cell surface GLUT4myc level. siPKCα, siPKCθ inhibited the phosphorylation of AS160 and TBC1D1 induced by ionomycin. siPKCα and siPKCθ prevented ionomycin-inhibited endocytosis of GLUT4myc. siPKCθ, but not siPKCα inhibited ionomycin-stimulated exocytosis of GLUT4myc. siRab13 but not siRab8a, siRab10 and siRab14 inhibited the exocytosis of GLUT4myc promoted by ionomycin. In summary, ionomycin-promoted exocytosis of GLUT4 is partly reversed by siPKCθ, whereas ionomycin-inhibited endocytosis of GLUT4 requires both siPKCα and siPKCθ. PKCα and PKCθ contribute to ionomycin-induced phosphorylation of AS160 and TBC1D1. Rab13 is required for ionomycin-regulated GLUT4 exocytosis. Copyright © 2017 Elsevier Inc. All rights reserved.
Fujikura, Ushio; Elsaesser, Lore; Breuninger, Holger; Sánchez-Rodríguez, Clara; Ivakov, Alexander; Laux, Thomas; Findlay, Kim; Persson, Staffan; Lenhard, Michael
2014-01-01
Growth of plant organs relies on cell proliferation and expansion. While an increasingly detailed picture about the control of cell proliferation is emerging, our knowledge about the control of cell expansion remains more limited. We demonstrate here that the internal-motor kinesin AtKINESIN-13A (AtKIN13A) limits cell expansion and cell size in Arabidopsis thaliana, with loss-of-function atkin13a mutants forming larger petals with larger cells. The homolog, AtKINESIN-13B, also affects cell expansion and double mutants display growth, gametophytic and early embryonic defects, indicating a redundant role of the two genes. AtKIN13A is known to depolymerize microtubules and influence Golgi motility and distribution. Consistent with this function, AtKIN13A interacts genetically with ANGUSTIFOLIA, encoding a regulator of Golgi dynamics. Reduced AtKIN13A activity alters cell wall structure as assessed by Fourier-transformed infrared-spectroscopy and triggers signalling via the THESEUS1-dependent cell-wall integrity pathway, which in turn promotes the excess cell expansion in the atkin13a mutant. Thus, our results indicate that the intracellular activity of AtKIN13A regulates cell expansion and wall architecture via THESEUS1, providing a compelling case of interplay between cell wall integrity sensing and expansion. PMID:25232944
Davis, Elizabeth L.
2016-01-01
Emotion regulation predicts positive academic outcomes like learning, but little is known about "why". Effective emotion regulation likely promotes learning by broadening the scope of what may be attended to after an emotional event. One hundred twenty-six 6- to 13-year-olds' (54% boys) regulation of sadness was examined for changes in…
Kocken, Paul L.; Eeuwijk, Jennifer; van Kesteren, Nicole M.C.; Dusseldorp, Elise; Buijs, Goof; Bassa-Dafesh, Zeina; Snel, Jeltje
2012-01-01
Background: Vending machines account for food sales and revenue in schools. We examined 3 strategies for promoting the sale of lower-calorie food products from vending machines in high schools in the Netherlands. Methods: A school-based randomized controlled trial was conducted in 13 experimental schools and 15 control schools. Three strategies…
Promoter2.0: for the recognition of PolII promoter sequences
DEFF Research Database (Denmark)
Knudsen, Steen; Knudsen, Steen
1999-01-01
transcription start sites. On standardized test setsconsisting of human genomic DNA, the performance of Promoter2.0 compares well with other softwaredeveloped for the same purpose. Availability : Promoter2.0 is available as a Web server at http://www.cbs.dtu.dk/services/promoter/ Contact : steen@cbs.dtu.dk...
Geng, Y; Tsai-Morris, C H; Zhang, Y; Dufau, M L
1999-09-24
To understand the transcriptional mechanism(s) of human LH receptor (LHR) gene expression, we have identified the dominant functional cis-elements that regulate the activity of the promoter domain (-1 to -176 bp from ATG). Mutagenesis demonstrated that the promoter activity was dependent on two Sp1 domains (-79 bp, -120 bp) in a transformed normal placental cell (PLC) and the choriocarcinoma JAR cell. Both elements interacted with endogenous Sp1 and Sp3 factors but not with Sp2 or Sp4. In Drosophila SL2 cells, the promoter was activated by either Sp1 or Sp3. An ERE half-site (EREhs) at -174 bp was inhibitory (by 100%), but was unresponsive to estradiol and did not bind the estrogen receptor or orphan receptors ERR1 and SF-1. The 5' upstream sequence (-177 to -2056 bp) inhibited promoter activity in PLC by 60%, but only minimally in JAR cells. Activation of the human LHR promoter through Sp1/3 factors is negatively regulated through EREhs and upstream sequences to exert control of gene expression. Copyright 1999 Academic Press.
DEFF Research Database (Denmark)
Kwan, Stella Y L; Petersen, Poul Erik; Pine, Cynthia M
2005-01-01
Schools provide an important setting for promoting health, as they reach over 1 billion children worldwide and, through them, the school staff, families and the community as a whole. Health promotion messages can be reinforced throughout the most influential stages of children's lives, enabling...... them to develop lifelong sustainable attitudes and skills. Poor oral health can have a detrimental effect on children's quality of life, their performance at school and their success in later life. This paper examines the global need for promoting oral health through schools. The WHO Global School...... Health Initiative and the potential for setting up oral health programmes in schools using the health-promoting school framework are discussed. The challenges faced in promoting oral health in schools in both developed and developing countries are highlighted. The importance of using a validated...
Huong, Le Thi Thanh; Long, Tran Khanh; Van Anh, Tran Thi; Tuyet-Hanh, Tran Thi; Giang, Kim Bao; Hai, Phan Thi; Huyen, Doan Thu; Khue, Luong Ngoc; Lam, Nguyen Tuan; Nga, Pham Quynh; Quan, Nguyen The; Linh, Tran Nu Quy; Ha, Nguyen Thanh; Van Minh, Hoang
2017-10-01
The Law on Tobacco Control and the Law on Advertisement prohibit the advertising of any tobacco product in Vietnam. Tobacco promotion and marketing are alsostrictly prohibited. However, the violation of tobacco adverting and promotion is still common in Vietnam. This article aims at describing the exposure to tobacco advertising and promotion among the population aged 15+ years in Vietnam based on the data from the Global Adult Tobacco Survey 2015 from the view of the community, identifying any possible associations between the exposure to tobacco advertising and promotion and other individual factors, and discussing its possible public health implications. A cross-sectional study with the nationwide scale. Secondary data from the Global Adult Tobacco Survey 2015 was explored and analyzed. Chi-square test and multivariate logistic regressions were applied in the data analysis. The most common type of adults' exposure to tobacco advertising and promotion was points of sale (8.6%); 9.8% adults exposure to one source of tobacco advertising and 4.0% of them exposed to one source of tobacco promotion. Around 13.3% of Vietnamese adults were exposed to tobacco advertisement, while 2.0% were exposed to tobacco promotion, 5.3% were exposed to both tobacco advertising and promotion, and 16.6% were exposed to tobacco advertising or promotion. Gender, educational level, age, occupation, marital status, socioeconomic status, location (urban, rural), and current smoking status were associated with the exposure to tobacco advertising, tobacco promotion, tobacco advertising and promotion, and tobacco advertising or promotion. Although there are comprehensive bans on tobacco advertising and promotion in Vietnam, adults aged 15+ years still reported their exposure to tobacco advertising and promotion. There should be a strict enforcement of the ban on tobacco advertising and promotion in Vietnam.
Pergamit, Michael R.; Veum, Jonathan R.
1999-01-01
For a sample of young workers, "promotion" involved no change in position or duties; promotion was more likely for males than females and Whites than Blacks or Hispanics. Company training and prior promotions were important predictors. Promotion did not appear to have a direct impact on job satisfaction. (SK)
Ju, Chengting; Ji, Ming; Lan, Jijun; You, Xuqun
2017-12-01
Optimism bias is a crucial feature of risk perception that leads to increased risk-taking behaviour, which is a particularly salient issue among pilots in aviation settings due to the high-stakes nature of flight. The current study sought to address the roles of narcissism and promotion focus on optimism bias in risk perception in aviation context. Participants were 239 male flight cadets from the Civil Aviation Flight University of China who completed the Narcissistic Personality Inventory-13, the Work Regulatory Focus Scale, and an indirect measure of unrealistic optimism in risk perception, which measured risk perception for the individual and the risk assumed by other individuals performing the same task. Higher narcissism increased the likelihood of underestimating personal risks, an effect that was mediated by high promotion focus motivation, such that high narcissism led to high promotion focus motivation. The findings have important implications for improving the accuracy of risk perception in aviation risks among aviators. © 2016 International Union of Psychological Science.
Directory of Open Access Journals (Sweden)
Nina Milutin Gašperov
Full Text Available Change in the host and/or human papillomavirus (HPV DNA methylation profile is probably one of the main factors responsible for the malignant progression of cervical lesions to cancer. To investigate those changes we studied 173 cervical samples with different grades of cervical lesion, from normal to cervical cancer. The methylation status of nine cellular gene promoters, CCNA1, CDH1, C13ORF18, DAPK1, HIC1, RARβ2, hTERT1, hTERT2 and TWIST1, was investigated by Methylation Specific Polymerase Chain Reaction (MSP. The methylation of HPV18 L1-gene was also investigated by MSP, while the methylated cytosines within four regions, L1, 5'LCR, enhancer, and promoter of the HPV16 genome covering 19 CpG sites were evaluated by bisulfite sequencing. Statistically significant methylation biomarkers distinguishing between cervical precursor lesions from normal cervix were primarily C13ORF18 and secondly CCNA1, and those distinguishing cervical cancer from normal or cervical precursor lesions were CCNA1, C13ORF18, hTERT1, hTERT2 and TWIST1. In addition, the methylation analysis of individual CpG sites of the HPV16 genome in different sample groups, notably the 7455 and 7694 sites, proved to be more important than the overall methylation frequency. The majority of HPV18 positive samples contained both methylated and unmethylated L1 gene, and samples with L1-gene methylated forms alone had better prognosis when correlated with the host cell gene promoters' methylation profiles. In conclusion, both cellular and viral methylation biomarkers should be used for monitoring cervical lesion progression to prevent invasive cervical cancer.
Promoter2.0: for the recognition of PolII promoter sequences
DEFF Research Database (Denmark)
Knudsen, Steen; Knudsen, Steen
1999-01-01
Motivation : A new approach to the prediction of eukaryotic PolII promoters from DNA sequence takesadvantage of a combination of elements similar to neural networks and genetic algorithms to recognize a set ofdiscrete subpatterns with variable separation as one pattern: a promoter. The neural...... of optimization, the algorithm was able todiscriminate between vertebrate promoter and non-promoter sequences in a test set with a correlationcoefficient of 0.63. In addition, all five known transcription start sites on the plus strand of the completeadenovirus genome were within 161 bp of 35 predicted...
Molecular characterization of accessions of Cratylia argentea (Camaratuba) using ISSR markers.
Luz, G A; Gomes, S O; Araujo Neto, R B; Nascimento, M S C B; Lima, P S C
2015-11-27
Cratylia argentea (Desv.) Kuntze (Fabaceae) is a drought-tolerant, perennial legume found primarily in Brazil, Bolivia, and Peru. The shrub is well adapted to acid soils and exhibits high productivity and nutritional value, characteristics that would favor its use as a dry season animal forage supplement in semiarid regions. In plant improvement programs, the production of elite hybrids with superior traits is generally achieved by crossing parents that exhibit the highest level of genetic divergence. Therefore, the aim of the present study was to assess genetic diversity among 13 accessions of C. argentea from the same population maintained in the active germplasm bank of Embrapa Meio-Norte using inter-simple sequence repeat (ISSR) markers. Genetic similarities between C. argentea accessions were estimated from Jaccard coefficients, and a dendrogram was constructed using the unweighted pair group method with arithmetic average (UPGMA). The set of 15 primers selected for ISSR analysis generated a total of 313 loci of which 79.23% were polymorphic. The mean number of bands per primer was 20.87, and the amplicons ranged from 280 to 3000 bp in size. Primers UBC834 and UBC827 generated the largest number of polymorphic loci and exhibited 90.91 and 100% polymorphism, respectively. The coefficients of genetic similarity among accessions varied between 0.49 and 0.73. UPGMA cluster analysis allowed the identification of four genotypic groups and demonstrated the existence of considerable variability within the collection. Potential progenitors were selected that would offer good possibilities of obtaining unusual and favorable combinations of genes in a plant breeding program.
Energy Technology Data Exchange (ETDEWEB)
Esteves, Vinicius Teixeira; Lima, Marco Aurelio Oliveira [Det Norske Veritas Ltda. (DNV), Rio de Janeiro, RJ (Brazil)
2012-07-01
In Brazil, the Regulatory Standard n. 13 (NR 13) establishes requirements for the inspection of boilers and pressure vessels which has main objective of preventing accidents with these types of equipment. Additionally, it has the Risk-Based Inspection (RBI) technique as an effective way to manage the mechanical integrity of various types of static mechanical equipment by through an inspection planning based on the risk factor. In this study, it is being proposed to include the RBI technique, in the NR 13, for the planning and definition of periods for the safety inspection of boilers and pressure vessels in order to promote an increase in the operational safety in process industries in Brazil. In this study it was carried out a critical analysis of NR 13 and RBI, and beyond that a bibliographic research of various international documents that relate the operational safety of pressurized equipment with the inspection activity, and the acceptability of RBI by governments, agencies and organizations around the world. It is considered that the inclusion and formal acceptance of RBI technique in the NR 13 must be accompanied by a rigorous control to avoid the 'trivialization' of its use and ensure the implementation rational, efficient and reliable. Finally, it was developed and suggested basic elements and minimum requirements to be inserted in the NR 13, to be attended, in order mandatory, by the companies that choose the implementation and use of the RBI technique as a tool for the planning of safety inspection of boilers and pressure vessels. It is concluded that the formal acceptance of the RBI technique in the NR 13 could aggregate much value to this standard, with regard to the prevention of accidents involving boilers or pressure vessels, and provide a technological jump to the companies that make use of RBI technique in Brazil. (author)
Kwon, Yun; Park, Sunghyouk; Shin, Jongheon; Oh, Dong-Chan
2014-08-01
The elucidation of the structures of complex natural products bearing many quaternary carbons remains challenging, even in this advanced spectroscopic era. (13)C-(13)C COSY NMR spectroscopy shows direct couplings between (13)C and (13)C, which comprise the backbone of a natural product. Thus, this type of experiment is particularly useful for natural products bearing consecutive quaternary carbons. However, the low sensitivity of (13)C-based NMR experiments, due to the low natural abundance of the (13)C nucleus, is problematic when applying these techniques. Our efforts in the (13)C labeling of a microbial natural product, cyclopiazonic acid (1), by feeding (13)C-labeled glucose to the fungal culture, enabled us to acquire (13)C-(13)C COSY NMR spectra on a milligram scale that clearly show the carbon backbone of the compound. This is the first application of (13)C-(13)C COSY NMR experiments for a natural product. The results suggest that (13)C-(13)C COSY NMR spectroscopy can be routinely used for the structure determination of microbial natural products by (13)C-enrichment of a compound with (13)C-glucose.
Piotrowski, Maurício J; Piquini, Paulo; Cândido, Ladir; Da Silva, Juarez L F
2011-10-14
The crystalline structure of transition-metals (TM) has been widely known for several decades, however, our knowledge on the atomic structure of TM clusters is still far from satisfactory, which compromises an atomistic understanding of the reactivity of TM clusters. For example, almost all density functional theory (DFT) calculations for TM clusters have been based on local (local density approximation--LDA) and semilocal (generalized gradient approximation--GGA) exchange-correlation functionals, however, it is well known that plain DFT fails to correct the self-interaction error, which affects the properties of several systems. To improve our basic understanding of the atomic and electronic properties of TM clusters, we report a DFT study within two nonlocal functionals, namely, the hybrid HSE (Heyd, Scuseria, and Ernzerhof) and GGA+U functionals, of the structural and electronic properties of the Co(13), Rh(13), and Hf(13) clusters. For Co(13) and Rh(13), we found that improved exchange-correlation functionals decrease the stability of open structures such as the hexagonal bilayer (HBL) and double simple-cubic (DSC) compared with the compact icosahedron (ICO) structure, however, DFT-GGA, DFT-GGA+U, and DFT-HSE yield very similar results for Hf(13). Thus, our results suggest that the DSC structure obtained by several plain DFT calculations for Rh(13) can be improved by the use of improved functionals. Using the sd hybridization analysis, we found that a strong hybridization favors compact structures, and hence, a correct description of the sd hybridization is crucial for the relative energy stability. For example, the sd hybridization decreases for HBL and DSC and increases for ICO in the case of Co(13) and Rh(13), while for Hf(13), the sd hybridization decreases for all configurations, and hence, it does not affect the relative stability among open and compact configurations.
Correlation between the 12C+12C, 12C+13C, and 13C+13C fusion cross sections
Notani, M.; Esbensen, H.; Fang, X.; Bucher, B.; Davies, P.; Jiang, C. L.; Lamm, L.; Lin, C. J.; Ma, C.; Martin, E.; Rehm, K. E.; Tan, W. P.; Thomas, S.; Tang, X. D.; Brown, E.
2012-01-01
The fusion cross section for 12C+13C has been measured down to Ec.m.=2.6 MeV, at which the cross section is of the order of 20 nb. By comparing the cross sections for the three carbon isotope systems, 12C+12C, 12C+13C, and 13C+13C, it is found that the cross sections for 12C+13C and 13C+13C provide an upper limit for the fusion cross section of 12C+12C over a wide energy range. After calibrating the effective nuclear potential for 12C+12C using the 12C+13C and 13C+13C fusion cross sections, it is found that a coupled-channels calculation with the ingoing wave boundary condition (IWBC) is capable of predicting the major peak cross sections in 12C+12C. A qualitative explanation for this upper limit is provided by the Nogami-Imanishi model and by level density differences among the compound nuclei. It is found that the strong resonance found at 2.14 MeV in 12C+12C exceeds this upper limit by a factor of more than 20. The preliminary result from the most recent measurement shows a much smaller cross section at this energy, which agrees with our predicted upper limit.
Prognostic significance of CDH13 hypermethylation and mRNA in NSCLC
Directory of Open Access Journals (Sweden)
Xue R
2014-10-01
Full Text Available Ruilin Xue,1 Cuili Yang,1 Fang Zhao,2 Dejia Li1 1Global Health Institute, School of Public Health, 2Zhongnan Hospital, Wuhan University, Wuhan, People's Republic of ChinaAbstract: Aberrant methylation of CpG dinucleotides is a commonly observed epigenetic modification in human cancer. Thus, detection of aberrant gene promoter methylation as a tool for diagnosis of tumors or as a prognostic marker has been widely described for many types of cancers, including nonsmall cell lung cancer (NSCLC. Emerging evidence indicates that CDH13 is a candidate tumor suppressor in several types of human tumors, including NSCLC. However, the correlation between CDH13 hypermethylation and clinicopathological characteristics of NSCLC remains unclear. In the current study, we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of CDH13 hypermethylation on the incidence of NSCLC and clinicopathological characteristics. Final analysis of 803 NSCLC patients from eleven eligible studies was performed. CDH13 hypermethylation was observed to be significantly higher in NSCLC than in normal lung tissue, with the pooled odds ratio (OR from seven studies including 448 NSCLC and 345 normal lung tissue (OR, 7.85; 95% confidence interval, 5.12–12.03; P<0.00001. CDH13 hypermethylation was also associated with pathological types. The pooled OR was obtained from four studies, including 111 squamous cell carcinoma and 106 adenocarcinoma (OR, 0.35; 95% confidence interval, 0.19–0.66; P=0.001, which indicated that CDH13 hypermethylation plays a more important role in the pathogenesis of adenocarcinoma. NSCLC with CDH13 hypermethylation was found more frequently in poorly differentiated NSCLC patients. NSCLC patients with CDH13 hypermethylation had a lower survival rate than those without CDH13 hypermethylation. In addition, CDH13 mRNA high expression was found to correlate with better overall survival for all NSCLC patients followed for 20 years
Promoting mental health as an essential aspect of health promotion.
Sturgeon, Shona
2006-12-01
This paper advocates that mental health promotion receive appropriate attention within health promotion. It is of great concern that, in practice, mental health promotion is frequently overlooked in health promotion programmes although the WHO definitions of health and the Ottawa Charter describe mental health as an integral part of health. It is suggested that more attention be given to addressing the determinants of mental health in terms of protective and risk factors for both physical and mental conditions, particularly in developing countries. Examples of evidence-based mental health programmes operating in widely diverse settings are presented to demonstrate that well designed interventions can contribute to the well-being of populations. It is advocated that particular attention be given to the intersectorial cooperation needed for this work.
Data describing the effect of DRD4 promoter polymorphisms on promoter activity
Directory of Open Access Journals (Sweden)
Shoin Tei
2016-06-01
Full Text Available This data article tested whether polymorphisms within the dopamine D4 receptor (DRD4 gene promoter can lead to differences in the promoter activity. The variants, a 120-bp variable number tandem repeat (VNTR, −906 T/C, −809 G/A, −616G/C, and −521C/T, were introduced into the DRD4 promoter and the promoter activity was measured in a neural cell line using the luciferase assay. However, no differences were detected among the haplotypes investigated, and the in vitro data obtained from our protocol could not support the involvement of DRD4 promoter polymorphisms in heritable human traits.
Directory of Open Access Journals (Sweden)
Yang Yu
2017-07-01
Full Text Available Seed setting rate is one of the most important components of rice grain yield. To date, only several genes regulating setting rate have been identified in plant. In this study, we showed that laccase-13 (OsLAC13, a member of laccase family genes which are known for their roles in modulating phenylpropanoid pathway and secondary lignification in cell wall, exerts a regulatory function in rice seed setting rate. OsLAC13 expressed in anthers and promotes hydrogen peroxide production both in vitro and in the filaments and anther connectives. Knock-out of OsLAC13 showed significantly increased seed setting rate, while overexpression of this gene exhibited induced mitochondrial damage and suppressed sugar transportation in anthers, which in turn affected seed setting rate. OsLAC13 also induced H2O2 production and mitochondrial damage in the root tip cells which caused the lethal phenotype. We also showed that high abundant of OsmiR397, the suppressor of OsLAC13 mRNA, increased the seed setting rate of rice plants, and restrains H2O2 accumulation in roots during oxidative stress. Our results suggested a novel regulatory role of OsLAC13 gene in regulating seed setting rate by affecting H2O2 dynamics and mitochondrial integrity in rice.
Promotion primer. Foerderfibel
Energy Technology Data Exchange (ETDEWEB)
1981-01-01
This revised edition of the promotion primer is to serve as a topical orientation aid for industrial firms, unions, boards and other bodies interested where the actions of governmental R and D and innovation policy are compiled and clearly arranged. It is important for the success of governmental aids that the institutions concerned are informed about all possibilities of the promotion, financing and advisory programme. Beyond the presentation of the research promotion sectors, the fiscal measures and the contractual as well as the joint research this revised edition focussess on the fields of consultative services for innovation and information. For many firms the access to qualified information and guidance is of particular importance. That is why this brochure points out the ways towards governmental research promotion. The BMFT has provided a remarkable contribution to research promotion by establishing information and consultative services for trade and industry.
Identification of the Drosophila skpA gene as a novel target of the transcription factor DREF
International Nuclear Information System (INIS)
Dang Thi Phuong Thao; Ida, Hiroyuki; Yoshida, Hideki; Yamaguchi, Masamitsu
2006-01-01
SKPa is component of a Drosophila SCF complex that functions in combination with the ubiquitin-conjugating enzyme UbcD1. skpA null mutation results in centrosome overduplication, unusual chromatin condensation, defective endoreduplication and cell-cycle progression. While the molecular mechanisms that regulate expression of the skpA gene are poorly understood, the DNA replication-related element (DRE) and the DRE-binding factor (DREF) play important roles in regulating proliferation-related genes in Drosophila and DRE (5'-TATCGATA) and DRE-like (5'-CATCGATT) sequences were here found to be involved in skpA promoter activity. Thus both luciferase transient expression assays in cultured Drosophila S2 cells using skpA promoter-luciferase fusion plasmids and anti-lacZ immunostaining of various tissues from transgenic third instar larvae carrying the skpA promoter-lacZ fusion genes provided supportive evidence. Furthermore, anti-SKPa immunostaining of eye imaginal discs from flies overexpressing DREF showed ectopic expression of protein in the region posterior to the morphogenetic furrow where DREF is overexpressed. Knockdown of DREF in some tissues where SKPa distribution is well known almost completely abrogated the skpA gene expression. These findings, taken together, indicate that the Drosophila skpA gene is a novel target of the transcription factor DREF
Promoting high efficiency residential HVAC equipment: Lessons learned from leading utility programs
Energy Technology Data Exchange (ETDEWEB)
Neme, C.; Peters, J.; Rouleau, D.
1998-07-01
The Consortium for Energy Efficiency recently sponsored a study of leading electric utility efforts to promote high efficiency residential HVAC equipment. Given growing concerns from some utilities about the level of expenditures associated with rebate programs, special emphasis was placed on assessing the success of financing and other non-rebate options for promoting efficiency. Emphasis was also placed on review of efforts--rebate or otherwise--to push the market to very high levels of efficiency (i.e., SEER 13). This paper presents the results of the study. It includes discussion of key lessons from the utility programs analyzed. It also examines program participation rates and other potential indicators of market impacts. One notable conclusion is that several utility programs have pushed market shares for SEER 12 equipment to about 50% (the national average is less than 20%). At least one utility program has achieved a 50% market share for SEER 13 equipment (the national average is less than 3%). In general, financing does not appear to have as broad an appeal as consumer rebates. However, one unique utility program which combines the other of customer financing with modest incentives to contractors--in the form of frequent seller points that can be redeemed for advertising, technician training, travel and other merchandise--offers some promise that high participation rates can be achieved without customer rebates.
[13N]ammonia in organic solvents; a potent synthetic precursor for 13N-labeling
International Nuclear Information System (INIS)
Tominaga, Toshiyoshi; Hirobe, Masaaki
1987-01-01
13 NH 3 in an organic solvent was prepared and its utility as a labeling precursor was studied. [ 13 N]adenine ([ 13 N]ADN), [ 13 N]nicotinamide ([ 13 N]NAM), [ 13 N]p-nitrophenyl carbamate ([ 13 N]NPC), and [ 13 N]L-glutamine ([ 13 N]Gln) were labeled utilizing this precursor. [ 13 N]ADN and [ 13 N]NAM were labeled in much better yields than from an aqueous solution of 13 NH 3 . [ 13 N]NPC and [ 13 N]Gln, which could not be labeled in an aqueous solution, were labeled in high radiochemical yields. Thus, the advantages of this precursor are the improvement of the labeling yield and the feasibility of labeling compounds unstable in aqueous conditions. (author)
Tumor-promoting phorbol esters effect alkalinization of canine renal proximal tubular cells
International Nuclear Information System (INIS)
Mellas, J.; Hammerman, M.R.
1986-01-01
We have demonstrated the presence of specific receptors for tumor-promoting phorbol esters in the plasma membrane of the canine renal proximal tubular cell. These compounds affect proximal tubular metabolism in vitro. For example, we have shown that they inhibit gluconeogenesis in canine renal proximal tubular segments. Tumor-promoting phorbol esters have been shown to effect alkalinization of non-renal cells, by enhancing Na + -H + exchange across the plasma membrane. To determine whether the actions of tumor-promoting phorbol esters in proximal tubular segments might be mediated by a similar process, we incubated suspensions of segments from dog kidney with these compounds and measured changes in intracellular pH using [ 14 C]-5,5-dimethoxazoladine-2-4-dione (DMO) and flow dialysis. Incubation of segments with phorbol 12,13 dibutyrate, but not inactive phorbol ester, 4 γ phorbol, effected alkalinization of cells within the segments in a concentration-dependent manner. Alkalinization was dependent upon the presence of extracellular [Na + ] > intracellular [Na + ], was prevented by amiloride and was demonstrable in the presence of SITS. Our findings suggest that tumor-promoting esters stimulate the Na + -H + exchanger known to be present in the brush border membrane of the renal proximal tubular cell. It is possible that the stimulation reflects a mechanism by which phorbol esters affect metabolic processes in these cells
2010-01-01
... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1210.312 Section 1210.312 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any...
2010-01-01
... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1216.23 Section 1216.23 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.23 Promotion. Promotion...
TMEM16A mediates the hypersecretion of mucus induced by Interleukin-13
Energy Technology Data Exchange (ETDEWEB)
Lin, Jiachen; Jiang, Youfan; Li, Li; Liu, Yanan; Tang, Hui; Jiang, Depeng, E-mail: depengjiang@163.com
2015-06-10
Previous studies showed that the Ca{sup 2+}-activated Cl{sup −} channel (CaCC) was involved in the pathogenesis of mucus hypersecretion induced by Interleukin-13 (IL-13). However, the mechanisms underlying the process were unknown. Recently, transmembrane protein 16A (TMEM16A) was identified as the channel underlying the CaCC current. The aim of the current study was to investigate whether the TMEM16A channel is part of the mechanism underlying IL-13-induced mucus hypersecretion. We observed that both TMEM16A mRNA and protein expression were significantly up-regulated after treatment with IL-13 in human bronchial epithelial 16 (HBE 16) cells, which correlated with an increase in mucus production. Additionally, mucus hypersecretion in rat airways was induced by intratracheal instillation of IL-13 and similar increases were observed in the expression of TMEM16A mRNA and protein in the bronchial epithelium. Niflumic acid (NA), a selective antagonist of CaCC, markedly blocked IL-13-induced mucin (MUC) 5AC mRNA and protein production in vivo and in vitro. Further investigation with HBE16 cells revealed that TMEM16A overexpression clearly promoted mucus production, IκBα phosphorylation, and p65 accumulation in the nucleus. The loss of TMEM16A resulted in inhibition of mucus production, and the TMEM16A-mediated production of MUC5AC was significantly blocked by a nuclear factor-kappa B (NF-κB) inhibitor. Therefore, the TMEM16A channel acts upstream of NF-κB in the regulation of mucus production. This is the first demonstration that the TMEM16A-NF-κB pathway is positively involved in IL-13-induced mucus production, which provides novel insight into the molecular mechanism of mucin overproduction. - Highlights: • TMEM16A acts as downstream events of IL-13 signaling pathway. • Established the link between TMEM16A and mucus hypersecretion. • NF-κB activation might be responsible for TMEM16A mediated mucus secretion.
2010-01-01
... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1250.310 Section 1250.310 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE EGG RESEARCH AND PROMOTION Egg Research and Promotion Order Definitions § 1250.310 Promotion. Promotion means any action, including paid...
2010-01-01
... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1260.122 Section 1260.122 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BEEF PROMOTION AND RESEARCH Beef Promotion and Research Order Definitions § 1260.122 Promotion. Promotion means any action, including paid...
2010-01-01
... and Orders; Milk), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Dairy Promotion and Research Order Definitions § 1150.114 Promotion. Promotion means actions such as paid advertising, sales... 7 Agriculture 9 2010-01-01 2009-01-01 true Promotion. 1150.114 Section 1150.114 Agriculture...
Local atomic characterization of LiCo1/3Ni1/3Mn1/3O2 cathode material
International Nuclear Information System (INIS)
Nedoseykina, Tatiana; Kim, Sung-Soo; Nitta, Yoshiaki
2006-01-01
Co, Ni and Mn K-edge XAFS investigation of LiCo 1/3 Ni 1/3 Mn 1/3 O 2 as alternative cathode material to commercially used LiCoO 2 in lithium rechargeable battery has been performed. Parameters of a local atomic structure such as radii of metal-oxygen and metal-metal coordination shells and disorder in those shells have been determined. It has been found that the radius of the first coordination shell (metal-oxygen) as well as a local disorder in the second shell (metal-metal) around each of the 3d-metals are in a good agreement with obtained for superlattice model of √3 x √3] R30 o type in triangular lattice of sites by first principle calculation. Other parameters of the local atomic structure around Co, Ni and Mn atoms do not provide evidence for presence of superstructure in LiCo 1/3 Ni 1/3 Mn 1/3 O 2
GITT studies on oxide cathode LiNi1/3Co1/3Mn1/3O2 synthesized ...
Indian Academy of Sciences (India)
Li diffusion; LiNi1/3Co1/3Mn1/3O2; lithium ion batteries; layered structure. 1. Introduction ... The coin-type cell CR2012 consisting of a metallic- lithium foil anode ... and the polyvinylidenefluoride (PVDF) binder with a mass ratio of 4:1:1 in NMP ...
Deletion analysis of susy-sl promoter for the identification of optimal promoter sequence
International Nuclear Information System (INIS)
Bacha, S.; Khatoon, A.; Asif, M.; Bshir, A.
2015-01-01
The promoter region of sucrose synthase (susy-Sl) was identified and isolated from tomato. The 5? deletion analysis was carried out for the identification of minimum optimal promoter. Transgenic lines of Arabidopsis thaliana were developed by floral dip method incorporating various promoter deletion cassettes controlling GUS reporter gene. GUS assay of transgenic tissues indicated that full length susy-Sl promoter and its deletion mutants were constitutively expressed in vegetative and floral tissues of A. thaliana. The expression was observed in roots, shoots and flowers of A. thaliana. Analysis of 5? deletion series of susy-Sl promoter showed that a minimum of 679 bp fragment of the promoter was sufficient to drive expression of GUS reporter gene in the major tissues of transgenic A. thaliana. (author)
Cederquist, Carly T; Lentucci, Claudia; Martinez-Calejman, Camila; Hayashi, Vanessa; Orofino, Joseph; Guertin, David; Fried, Susan K; Lee, Mi-Jeong; Cardamone, M Dafne; Perissi, Valentina
2017-01-01
Insulin signaling plays a unique role in the regulation of energy homeostasis and the impairment of insulin action is associated with altered lipid metabolism, obesity, and Type 2 Diabetes. The main aim of this study was to provide further insight into the regulatory mechanisms governing the insulin signaling pathway by investigating the role of non-proteolytic ubiquitination in insulin-mediated activation of AKT. The molecular mechanism of AKT regulation through ubiquitination is first dissected in vitro in 3T3-L1 preadipocytes and then validated in vivo using mice with adipo-specific deletion of GPS2, an endogenous inhibitor of Ubc13 activity (GPS2-AKO mice). Our results indicate that K63 ubiquitination is a critical component of AKT activation in the insulin signaling pathway and that counter-regulation of this step is provided by GPS2 preventing AKT ubiquitination through inhibition of Ubc13 enzymatic activity. Removal of this negative checkpoint, through GPS2 downregulation or genetic deletion, results in sustained activation of insulin signaling both in vitro and in vivo . As a result, the balance between lipid accumulation and utilization is shifted toward storage in the adipose tissue and GPS2-AKO mice become obese under normal laboratory chow diet. However, the adipose tissue of GPS2-AKO mice is not inflamed, the levels of circulating adiponectin are elevated, and systemic insulin sensitivity is overall improved. Our findings characterize a novel layer of regulation of the insulin signaling pathway based on non-proteolytic ubiquitination of AKT and define GPS2 as a previously unrecognized component of the insulin signaling cascade. In accordance with this role, we have shown that GPS2 presence in adipocytes modulates systemic metabolism by restricting the activation of insulin signaling during the fasted state, whereas in absence of GPS2, the adipose tissue is more efficient at lipid storage, and obesity becomes uncoupled from inflammation and insulin
Directory of Open Access Journals (Sweden)
Yaju Wang
Full Text Available Stra13, a basic helix-loop-helix (bHLH transcription factor is involved in myriad biological functions including cellular growth arrest, differentiation and senescence. However, the mechanisms by which its transcriptional activity and function are regulated remain unclear. In this study, we provide evidence that post-translational modification of Stra13 by Small Ubiquitin-like Modifier (SUMO dramatically potentiates its ability to transcriptionally repress cyclin D1 and mediate G(1 cell cycle arrest in fibroblast cells. Mutation of SUMO acceptor lysines 159 and 279 located in the C-terminal repression domain has no impact on nuclear localization; however, it abrogates association with the co-repressor histone deacetylase 1 (HDAC1, attenuates repression of cyclin D1, and prevents Stra13-mediated growth suppression. HDAC1, which promotes cellular proliferation and cell cycle progression, antagonizes Stra13 sumoylation-dependent growth arrest. Our results uncover an unidentified regulatory axis between Stra13 and HDAC1 in progression through the G(1/S phase of the cell cycle, and provide new mechanistic insights into regulation of Stra13-mediated transcriptional repression by sumoylation.
Mechanistic studies of copper(I)-catalyzed 1,3-halogen migration.
Van Hoveln, Ryan; Hudson, Brandi M; Wedler, Henry B; Bates, Desiree M; Le Gros, Gabriel; Tantillo, Dean J; Schomaker, Jennifer M
2015-04-29
An ongoing challenge in modern catalysis is to identify and understand new modes of reactivity promoted by earth-abundant and inexpensive first-row transition metals. Herein, we report a mechanistic study of an unusual copper(I)-catalyzed 1,3-migration of 2-bromostyrenes that reincorporates the bromine activating group into the final product with concomitant borylation of the aryl halide bond. A combination of experimental and computational studies indicated this reaction does not involve any oxidation state changes at copper; rather, migration occurs through a series of formal sigmatropic shifts. Insight provided from these studies will be used to expand the utility of aryl copper species in synthesis and develop new ligands for enantioselective copper-catalyzed halogenation.
Tissue-specific interactions between nuclear proteins and the aminopeptidase N promoter
DEFF Research Database (Denmark)
Kärnström, U; Sjöström, H; Norén, O
1991-01-01
Aminopeptidase N/CD13 is a metallopeptidase found in many tissues. Aminopeptidase N activity is high in the small intestinal mucosa, moderate in the liver, and low in the spleen. Using DNase I footprinting and electrophoretic mobility shift assays with nuclear extracts from these tissues, three cis...... elements (DF, LF-B1, UF) were identified in the aminopeptidase N promoter. The DF region (-53 to -30) interacts with the ubiquitously expressed transcription factor Sp1. The LF-B1 region (-85 to -58) interacts with the liver transcription factor LF-B1 (HNF-1) which was detected as well in nuclei from small...... intestinal mucosa. The UF region (-112 to -90) interacts with nuclear factors which seem to be expressed differentially in the liver and the small intestine. Transfection of promoter deletions into HepG2 cells showed that the LF-B1 region is necessary for high expression of the aminopeptidase N gene in liver...
Processing of water-based LiNi1/3Mn1/3Co1/3O2 pastes for ...
Indian Academy of Sciences (India)
Results show that a substitution of the conventional organic solvent-based manufacturing route for LiNi1/3Mn1/3Co1/3O2 cathodes by water-based processing exhibits a promising way to realise Li-ion batteries with comparable electrochemical behaviour, while avoiding toxic processing aids and reducing overall ...
Promoters of Escherichia coli versus promoter islands: function and structure comparison.
Directory of Open Access Journals (Sweden)
Valeriy V Panyukov
Full Text Available Expression of bacterial genes takes place under the control of RNA polymerase with exchangeable σ-subunits and multiple transcription factors. A typical promoter region contains one or several overlapping promoters. In the latter case promoters have the same or different σ-specificity and are often subjected to different regulatory stimuli. Genes, transcribed from multiple promoters, have on average higher expression levels. However, recently in the genome of Escherichia coli we found 78 regions with an extremely large number of potential transcription start points (promoter islands, PIs. It was shown that all PIs interact with RNA polymerase in vivo and are able to form transcriptionally competent open complexes both in vitro and in vivo but their transcriptional activity measured by oligonucleotide microarrays was very low, if any. Here we confirmed transcriptional defectiveness of PIs by analyzing the 5'-end specific RNA-seq data, but showed their ability to produce short oligos (9-14 bases. This combination of functional properties indicated a deliberate suppression of transcriptional activity within PIs. According to our data this suppression may be due to a specific conformation of the DNA double helix, which provides an ideal platform for interaction with both RNA polymerase and the histone-like nucleoid protein H-NS. The genomic DNA of E.coli contains therefore several dozen sites optimized by evolution for staying in a heterochromatin-like state. Since almost all promoter islands are associated with horizontally acquired genes, we offer them as specific components of bacterial evolution involved in acquisition of foreign genetic material by turning off the expression of toxic or useless aliens or by providing optimal promoter for beneficial genes. The putative molecular mechanism underlying the appearance of promoter islands within recipient genomes is discussed.
(Wormwood capillary) by random amplified polymorphic DNA (RAPD)
African Journals Online (AJOL)
STORAGESEVER
2009-05-04
May 4, 2009 ... Faculty of Agrotechnology and Food Science, Universiti Malaysia Terengganu, .... Operon and UBC (University of British Columbia, Canada) 10mers .... a visual representation of the relationship of difference population of.
Health promotion in globalization
Directory of Open Access Journals (Sweden)
Álvaro Franco-Giraldo
2012-10-01
Full Text Available Objective: to unravel some theoretical and factual elements required to implement more effective health promotion strategies and practices in the field of health services whilst following the great challenges that globalization has imposed on the health systems, which are inevitably expressed in the local context (glocalization. Methodology: a narrative review taking into account the concepts of globalization and health promotion in relation to health determinants. The authors approach some courses of action and strategies for health promotion based on the social principles and universal values that guide health promotion, health service reorientation and primary healthcare, empowerment, social participation, and inter-sectoral and social mobilization. Discussion: the discussion focuses on the redirection of health promotion services in relation to the wave of health reforms that has spread throughout the world under the neoliberal rule. The author also discusses health promotion, its ineffectiveness, and the quest for renewal. Likewise, the author sets priorities for health promotion in relation to social determinants. Conclusion: the current global order, in terms of international relations, is not consistent with the ethical principles of health promotion. In this paper, the author advocates for the implementation of actions to change the social and physical life conditions of people based on changes in the use of power in society and the appropriate practice of politics in the context of globalization in order to achieve the effectiveness of the actions of health promotion.
Studies on the tumor initiation/promotion potential of six middle distillates (MDs) in mouse skin.
Jungen, H; Mellert, W; Wenzel-Hartung, R
1995-08-01
Six middle distillates (MDs) were tested for tumor initiating/promoting activity after application to the skin of 30 male CD-1 (ICR) BR mice per group. As the control, 7,12-dimethylbenz[a]-anthracene (DMBA) was used for initiation followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) for promotion. For assessing the tumor-initiating activity, 50 microliters of neat MDs was administered for 5 days with subsequent TPA promotion. In the promotion bioassay, after DMBA initiation 50 microliters of the neat MDs was administered twice weekly until Week 28. For the examination of complete carcinogenic activity, one MD was given without DMBA initiation. Hyperkeratosis, hyperplasia, and dermal inflammation, occurring during the initiation with the MDs, were completely reversible during the 2-week treatment-free period after initiation. Similar skin findings were observed during promotion with the MDs. Regarding the number of affected animals and the severity of the response, TPA was more irritating than the MDs. The initiation study revealed skin tumors for the DMBA/TPA control (30/30), MD 57,389 (14/30), MD 57,396 (5/30), MD 57,383 (4/30) and MD 57,324 (2/30). The promotion study revealed tumor induction by MDs 57,389 (9/30), 57,324 (1/30), 57,393 (1/30), and 57,396 (1/30). Two of 30 animals treated with MD 57,389 developed tumors without DMBA initiation thus indicating that it also is a complete carcinogen. MD 57,399 caused neither initiating nor promoting effects. The tumors observed were diagnosed histopathologically predominantly as squamous cell papillomas.(ABSTRACT TRUNCATED AT 250 WORDS)
Kooiker, Maarten; Drenth, Janneke; Glassop, Donna; McIntyre, C. Lynne; Xue, Gang-Ping
2013-01-01
Fructans are the major component of temporary carbon reserve in the stem of temperate cereals, which is used for grain filling. Three families of fructosyltransferases are directly involved in fructan synthesis in the vacuole of Triticum aestivum. The regulatory network of the fructan synthetic pathway is largely unknown. Recently, a sucrose-upregulated wheat MYB transcription factor (TaMYB13-1) was shown to be capable of activating the promoter activities of sucrose:sucrose 1-fructosyltransferase (1-SST) and sucrose:fructan 6-fructosyltransferase (6-SFT) in transient transactivation assays. This work investigated TaMYB13-1 target genes and their influence on fructan synthesis in transgenic wheat. TaMYB13-1 overexpression resulted in upregulation of all three families of fructosyltransferases including fructan:fructan 1-fructosyltransferase (1-FFT). A γ-vacuolar processing enzyme (γ-VPE1), potentially involved in processing the maturation of fructosyltransferases in the vacuole, was also upregulated by TaMYB13-1 overexpression. Multiple TaMYB13 DNA-binding motifs were identified in the Ta1-FFT1 and Taγ-VPE1 promoters and were bound strongly by TaMYB13-1. The expression profiles of these target genes and TaMYB13-1 were highly correlated in recombinant inbred lines and during stem development as well as the transgenic and non-transgenic wheat dataset, further supporting a direct regulation of these genes by TaMYB13-1. TaMYB13-1 overexpression in wheat led to enhanced fructan accumulation in the leaves and stems and also increased spike weight and grain weight per spike in transgenic plants under water-limited conditions. These data suggest that TaMYB13-1 plays an important role in coordinated upregulation of genes necessary for fructan synthesis and can be used as a molecular tool to improve the high fructan trait. PMID:23873993
Preparation of layered oxide Li(Co1/3Ni1/3Mn1/3)O2 via the sol-gel process
Institute of Scientific and Technical Information of China (English)
ZHANG Wen; LIU Hanxing; HU Chen; ZHU Xianjun; LI Yanxi
2008-01-01
To obtain homogenous layered oxide Li(Co1/3Ni1/3Ni1/3Mn1/3)O2 as a lithium insertion positive electrode material,the sol-gel process using citric acid as a chelating agent was applied.The material Li(Co1/3,Ni1/3Mn1/3)O2 was synthesized at different calcination temperatures.XRD experiment indicated that the hyered Li(Co1/3Ni1/3Mn1/3)O2material could he synthesized at a lower temperature of 800℃,and the oxidation state of Co,Ni,and Mn in the cathode confirmed by XPS were +3,+2,and +4,respectively.SEM observations showed that the synthesized material could form homogenous particle morphology with the particle size of about 200nm In spite of different calcination temperatures,the charge-discharge curves of all the samples for the initial cycle were similar,and the cathode synthesized at 900℃ showed a small irreversible capacity loss of 11.24% and a high discharge capacity of 212.2 mAh.g-1 in the voltage range of 2.9-4.6 V.
A novel cell growth-promoting factor identified in a B cell leukemia cell line, BALL-1
International Nuclear Information System (INIS)
Dao, T.; Holan, V.; Minowada, J.
1993-01-01
A novel leukemia cell growth-promoting activity has been identified in the culture supernatant from a human B cell leukemia cell line, BALL-1. The supernatant from unstimulated cultures of the BALL-1 cells significantly promoted the growth of 16 out of 24 leukemia/lymphoma cell lines of different lineages (T, B and non-lymphoid) in a minimal concentration of fetal bovine serum (FBS), and 5 out of 12 cases of fresh leukemia cells in FBS-free medium. The growth-promoting sieve filtration and dialysis. The MW of the factor was less than 10 kDa. The growth-promoting activity was heat and acid stable and resistant to trypsin treatment. The factor isolated from the BALL-1 supernatant was distinct from known polypeptide growth factors with MW below 10 kDa, such as epidermal growth factor, transforming growth factor α, insulin-like growth factor I (IGF-I), IGF-II and insulin, as determine by specific antibodies and by cell-growth-promoting tests. The factor is the BALL-1 supernatant did not promote the proliferation of normal human fresh peripheral blood lymphocytes or mouse fibroblast cell line, BALB/C 3T3. In addition to the BALL-1 supernatant, a similar growth-promoting activity was found in the culture supernatant from 13 of 17 leukemia/lymphoma cell lines tested. The activity in these culture supernatant promoted the growth of leukemia/lymphoma cell lines in autocrine and/or paracrine fashions. These observations suggest that the low MW cell growth-promoting activity found in the BALL-1 culture supernatant is mediated by a novel factor which may be responsible for the clonal expansion of particular leukemic clones. (author)
Syntheses of protoporphyrin-IX regioselectivity carbon-13 labelled at the alpha-vinyl carbons
International Nuclear Information System (INIS)
Smith, K.M.; Fujinari, E.M.
1986-01-01
A method for transformation of readily available beta-vinyl 99% carbon-13 enriched derivatives of protoporphyrin-IX dimethyl ester into the less accessible alpha-vinyl labelled isomers is described. The procedure involves thallium(III) promoted vinyl carbon rearrangement, and proceeds through 2,2-dimethoxyethyl, formylmethyl, 2-hydroxyethyl and 2-chloroethyl porphyrins; the rearranged vinyl groups are regenerated from 2-chloroethyl in the last step by treatment with base. No evidence of vinyl carbon scrambling in the sequence is observed, and spectroscopic data of the products are given. (author)
Institute of Scientific and Technical Information of China (English)
Feng XIE; Di WU; Shi-fang HUANG; Jian-gang CAO; He-ning LI; Lu HE; Mei-qing LIU; Lan-fang LI; Lin-xi CHEN
2017-01-01
Apelin is the endogenous ligand for the G protein-coupled receptor APJ,and plays important roles in the cardiovascular system.Our previous studies showed that apelin-13 promotes the hypertrophy of H9c2 rat cardiomyocytes through the PI3K-autophagy pathway.The aim of this study was to explore what roles ER stress and autophagy played in apelin-13-induced hypertrophy of cardiomyocytes in vitro.Treatment of H9c2 cells with apelin-13 (0.001-2 μJmol/L) dose-dependently increased the production of ROS and the expression levels of NADPH oxidase 4 (NOX4).Knockdown of Nox4 with siRNAs effectively prevented the reduction of GSH/GSSG ratio in apelin-13-treated cells.Furthermore,apelin-13 treatment dose-dependently increased the expression of Bip and CHOP,two ER stress markers,in the cells.Knockdown of APJ or Nox4 with the corresponding siRNAs,or application of NADPH inhibitor DPI blocked apelin-13-induced increases in Bip and CHOP expression.Moreover,apelin-13 treatment increased the formation of autophagosome and ER fragments and the LC3 puncta in the ER of the cells.Knockdown of APJ,Nox4,Bip or CHOP with the corresponding siRNAs,or application of DPI or salubrinal attenuated apelin-13-induced overexpression of LC3-Ⅱ/Ⅰ and beclin 1.Finally,knockdown of Nox4,Bip or CHOP with the corresponding siRNAs,or application of salubrinal significantly suppressed apelin-13-induced increases in the cell diameter,volume and protein contents.Our results demonstrate that ER stress-autophagy is involved in apelin-13-induced H9c2 cell hypertrophy.
Aspects of Hydrological Modelling In The Punjab Himalayan and Karakoram Ranges, Pakistan
Loukas, A.; Khan, M. I.; Quick, M. C.
Various aspects of hydrologic modelling of high mountainous basins in the Punjab Hi- malayan and Karakoram ranges of Northern Pakistan were studied. The runoff from three basins in this region was simulated using the U.B.C. watershed model, which re- quires limited meteorological data of minimum and maximum daily temperature and precipitation. The structure of the model is based on the concept that the hydrolog- ical behavior is a function of elevation and thus, a watershed is conceptualized as a number of elevational zones. A simplified energy budget approach, which is based on daily maximum and minimum temperature and can account for forested and open areas, and aspect and latitude, is used in the U.B.C. model for the estimation of the snowmelt and glacier melt. The studied basins have different hydrological responses and limited data. The runoff from the first basin, the Astore basin, is mainly gener- ated by snowmelt. In the second basin, the Kunhar basin, the runoff is generated by snowmelt but significant redistribution of snow, caused by snow avalanches, affect the runoff generation. The third basin, the Hunza basin, is a highly glacierized basin and its runoff is mainly generated by glacier melt. The application of the U.B.C. watershed model to these three basins showed that the model could estimate reasonably well the runoff generated by the different components.
GITT studies on oxide cathode LiNi1/3Co1/3Mn1/3O2 synthesized ...
Indian Academy of Sciences (India)
2016-08-26
Aug 26, 2016 ... GITT studies on oxide cathode LiNi1/3Co1/3Mn1/3O2 synthesized by citric acid assisted high-energy ball milling ... The State Key Laboratory Base of Novel Functional Materials and Preparation Science; The Faculty of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, P. R. ...
Genomic organization and promoter cloning of the human X11α gene APBA1.
LENUS (Irish Health Repository)
Chai, Ka-Ho
2012-05-01
X11α is a brain specific multi-modular protein that interacts with the Alzheimer\\'s disease amyloid precursor protein (APP). Aggregation of amyloid-β peptide (Aβ), an APP cleavage product, is believed to be central to the pathogenesis of Alzheimer\\'s disease. Recently, overexpression of X11α has been shown to reduce Aβ generation and to ameliorate memory deficit in a transgenic mouse model of Alzheimer\\'s disease. Therefore, manipulating the expression level of X11α may provide a novel route for the treatment of Alzheimer\\'s disease. Human X11α is encoded by the gene APBA1. As evidence suggests that X11α expression can be regulated at transcription level, we have determined the gene structure and cloned the promoter of APBA1. APBA1 spans over 244 kb on chromosome 9 and is composed of 13 exons and has multiple transcription start sites. A putative APBA1 promoter has been identified upstream of exon 1 and functional analysis revealed that this is highly active in neurons. By deletion analysis, the minimal promoter was found to be located between -224 and +14, a GC-rich region that contains a functional Sp3 binding site. In neurons, overexpression of Sp3 stimulates the APBA1 promoter while an Sp3 inhibitor suppresses the promoter activity. Moreover, inhibition of Sp3 reduces endogenous X11α expression and promotes the generation of Aβ. Our findings reveal that Sp3 play an essential role in APBA1 transcription.
Biotechnological application and taxonomical distribution of plant growth promoting actinobacteria.
Hamedi, Javad; Mohammadipanah, Fatemeh
2015-02-01
Plant growth promoting (PGP) bacteria are involved in various interactions known to affect plant fitness and soil quality, thereby increasing the productivity of agriculture and stability of soil. Although the potential of actinobacteria in antibiotic production is well-investigated, their capacity to enhance plant growth is not fully surveyed. Due to the following justifications, PGP actinobacteria (PGPA) can be considered as a more promising taxonomical group of PGP bacteria: (1) high numbers of actinobacteria per gram of soil and their filamentous nature, (2) genome dedicated to the secondary metabolite production (~5 to 10 %) is distinctively more than that of other bacteria and (3) number of plant growth promoter genera reported from actinobacteria is 1.3 times higher than that of other bacteria. Mechanisms by which PGPA contribute to the plant growth by association are: (a) enhancing nutrients availability, (b) regulation of plant metabolism, (c) decreasing environmental stress, (d) control of phytopathogens and (e) improvement of soil texture. Taxonomical and chemical diversity of PGPA and their biotechnological application along with their associated challenges are summarized in this paper.
Towards a more adaptive co - management of natural resources ...
African Journals Online (AJOL)
2014-06-01
Jun 1, 2014 ... being channelled into Madagascar's environmental sector since the mid-1980s, the ...... firmly embedded in Malagasy environmental legislation, there is little potential to ..... UBC Press, British Colombia. Norris, S. 2006.
Cimmino, Alessio; Fernández-Aparicio, Mónica; Avolio, Fabiana; Yoneyama, Koichi; Rubiales, Diego; Evidente, Antonio
2015-01-01
Orobanche and Phelipanche species (the broomrapes) are root parasitic plants, some of which represent serious weed problems causing heavy yield losses on important crops. Current control relies on the use of certain agronomic practices, resistant crop varieties, and herbicides, albeit success has been marginal. Agronomic practices such as the use of allelopathic species in intercropping or cover crops, or the use of direct seedling over residues of allelopathic species incorporate the principle of allelopathy exerted by molecules exuded from roots or released by crop residues to control broomrapes. In addition, the isolation of natural substances from root exudates of plants with potential to inhibit broomrape development opens the door to the design of new herbicides based on natural and benign sources. Ryecyanatines A and B and ryecarbonitrilines A and B, the first new substituted cyanatophenol, substituted cyanatobenzo[1,3]dioxole, and the latter two new substituted benzo[1,3]dioxolecarbonitriles were isolated from rye (Secale cereale L.) root exudates. They were characterized as 4-cyanato-2-methoxyphenol, 2-cyanato-benzo[1,3]dioxole, 2-methoxybenzo[1,3]dioxole-5-carbonitrile and benzo[1,3]dioxole-2-carbonitrile by spectroscopic (essentially NMR and HRESI MS spectra) methods. These compounds were investigated for allelopathic activity on Orobanche germination and development. Ryecarbonitriline A induced germination of Orobanche cumana seeds, and this germination can be considered as suicidal because O. cumana does not parasite rye roots and cannot survive without host resources beyond germination stage. In addition, ryecyanatine A promotes a rapid cessation of O. cumana, Orobanche crenata and Orobanche minor radicle growth with the promotion of a layer of papillae at the radicle tip in O. cumana and O. crenata hampering the contact of the parasite to the host. Ryecarbonitriline B also displayed the same activity although being less active than ryecyanatine A and
DEFF Research Database (Denmark)
Brandt, C A; Hertz, Jens Michael; Petersen, M B
1992-01-01
A stillborn male child with anencephaly and multiple malformations was found to have the karyotype 46,XY,r(13) (p11q21.1). The breakpoint at 13q21.1, determined by high resolution banding, is the most proximal breakpoint ever reported in patients with ring chromosome 13. In situ hybridisation...
Directory of Open Access Journals (Sweden)
Julie Lecomte
2012-10-01
Full Text Available Carcinoma-associated fibroblasts are key contributors of the tumor microenvironment that regulates carcinoma progression. They consist of a heterogeneous cell population with diverse origins, phenotypes, and functions. In the present report, we have explored the contribution of bone marrow (BM-derived cells to generate different fibroblast subsets that putatively produce the matrix metalloproteinase 13 (MMP13 and affect cancer cell invasion. A murine model of skin carcinoma was applied to mice, irradiated, and engrafted with BM isolated from green fluorescent protein (GFP transgenic mice. We provide evidence that one third of BM-derived GFP+ cells infiltrating the tumor expressed the chondroitin sulfate proteoglycan NG2 (pericytic marker or α-smooth muscle actin (α-SMA, myofibroblast marker, whereas almost 90% of Thy1+ fibroblasts were originating from resident GFP-negative cells. MMP13producing cells were exclusively α-SMA+ cells and derived from GFP+ BM cells. To investigate their impact on tumor invasion, we isolated mesenchymal stem cells (MSCs from the BM of wild-type and MMP13-deficient mice. Wild-type MSC promoted cancer cell invasion in a spheroid assay, whereas MSCs obtained from MMP13-deficient mice failed to. Our data support the concept of fibroblast subset specialization with BM-derived α-SMA+ cells being the main source of MMP13, a stromal mediator of cancer cell invasion.
Agrawal, Swati; Townley, Robert G
2014-02-01
Asthma markedly diminishes quality of life due to limited activity, absences from work or school and hospitalizations. Patients with severe asthma which are not controlled despite taking effective therapy are most in need of new treatment approaches. IL-13 was demonstrated as 'central mediator of allergic asthma'. IL-13 has been implicated in the pathogenesis of asthma, idiopathic pulmonary fibrosis and COPD. IL-13 levels in the sputum and bronchial biopsy samples remain elevated in severe asthma despite the use of inhaled and systemic corticosteroids. Thus, IL-13 is a mediator involved in corticosteroid resistance. Periostin enhances profibrotic TGF-β signaling in subepithelial fibrosis associated with asthma. IL-13 induces bronchial epithelial cells to secrete periostin. Periostin may be a biomarker for Th2 induced airway inflammation. Lebrikizumab is a monoclonal antibody against IL-13. Lebrikizumab improved lung function in asthmatics who were symptomatic despite treatment with long acting beta agonist and inhaled corticosteroids and provided benefit in the treatment of severe uncontrolled asthma. Lebrikizumab block IL-13 signaling through the IL-13Rα1/IL-4Rα receptor. There was a larger reduction in FENO in the high periostin subgroup than in the low periostin subgroup (34.4 vs 4.3%). Serum CCL17, CCL13 and total IgE levels decreased in the lebrikizumab group.
Heck, Nicholas C
2015-09-01
This article describes the results of a pilot study to determine the feasibility and acceptability of a mental health promotion program that was developed to address minority stressors and promote coping skills among lesbian, gay, bisexual, transgender, and queer (LGBTQ) youth. It was hypothesized that the program would be feasible to implement within the context of a gay-straight alliance (GSA) and that GSA members would find the program acceptable (e.g., educational, enjoyable, helpful, and relevant). Participants included ten members of a high school GSA in the northeastern United States. The program sessions were delivered during GSA meetings. The first session emphasized the identification of minority and general stressors, which was followed by a discussion of coping strategies. The remaining sessions emphasized the development of cognitive coping, affect regulation, and problem-solving skills. After each session, participants completed a 13-item feedback form. Ten items assessed acceptability and three open-ended items allowed participants to provide constructive feedback. Although the program was feasible to implement within the GSA setting, attendance at the sessions was variable. Those who attended the sessions reported them to be enjoyable, informative, relevant to their lives, and potentially helpful for other LGBTQ students. After revising the program, future research is needed to investigate its dissemination potential and determine whether the program can disrupt the minority stress-psychiatric distress relationship.
Characterization of the promoter of human CRTh2, a prostaglandin D{sub 2} receptor
Energy Technology Data Exchange (ETDEWEB)
Quapp, Russell; Madsen, Norman [Department of Medicine, Division of Pulmonary Medicine, Pulmonary Research Group, 574B Heritage Medical Research Centre, University of Alberta, Edmonton, AB, T6G 2S2 (Canada); Cameron, Lisa [Department of Medicine, Division of Pulmonary Medicine, Pulmonary Research Group, 574B Heritage Medical Research Centre, University of Alberta, Edmonton, AB, T6G 2S2 (Canada)
2007-11-30
Chemoattractant-receptor homologous molecule expressed on Th2 cells (CRTh2) is a receptor for prostaglandin (PG)D{sub 2}, a lipid mediator involved in allergic inflammation. CRTh2 is expressed by Th2 cells, eosinophils and basophils and PDG{sub 2}-CRTh2 signaling induces calcium mobilization, cell migration and expression of the Th2 cytokines IL-4, IL-5, and IL-13. Despite the role of CRTh2 in allergic inflammation, transcriptional regulation of this gene has not been studied. Here, we demonstrated that a reporter construct of the CRTh2 promoter was induced following T cell stimulation. This activity could be further enhanced by over-expression of GATA-3, but not NFAT2 or STAT6. Electromobility shift assay demonstrated GATA-3 binding to a probe from the CRTh2 promoter. This study provides the first detailed analysis of transcriptional regulation of the human CRTh2 promoter. These findings may help identify strategies to attenuate expression of this gene and influence the maintenance and proliferation of Th2 cells in allergic inflammation.
Li, Shuang; Li, Tao; Li, Jian-guo; Chen, Li; Ren, Jun; Li, Chao-lin
2012-02-01
To evaluate the comprehensive workplace health promotion intervention effect in a pharmaceutical company. The evaluation was conducted by using questionnaires, access to information, on-site surveys, satisfaction surveys and interviews. After the intervention, the awareness rate of the staff on "Occupational Disease Prevention Law", occupational disease prevention measures, the definition of hypertension, HIV transmission and high blood pressure, coronary heart disease preventive measures, have been raised from 72.4%, 13.8%, 67.5%, 45.8%, 51.7% to 97.8%, 19.9%, 82.3%, 94.7%, 53.1% respectively. The lifestyle of the staff has been improved, the improvement rate of smoking, drinking, having breakfast 4 times a week and above are 98.5%, 70.2% and 30.6% separately. Out of the 47 evaluation indicators, 41 meet the requirements, 5 basically meet the requirements. After implementing workplace health promotion activities, the level of occupational safety and health management of the pharmaceutical company has been enhanced, the physical and mental health of the staff have been promoted. The WHP comprehensive interventions are feasible and effective.
2010-01-01
... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1218.17 Section 1218.17 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.17 Promotion...
2010-01-01
... in the United States, including paid advertising, sales promotion, and publicity. Promotion... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1219.22 Section 1219.22 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH...
2010-07-01
... 29 Labor 3 2010-07-01 2010-07-01 false Livestock auction employees exempt from overtime pay....13 Livestock auction employees exempt from overtime pay requirements under section 13(b)(13) of the... employee is employed both in agriculture and in connection with livestock auction operations: (a) The total...
Littman, Marissa A; Sonne, James W; Smith, Gerald V
2017-01-01
Little information exists on the research productivity of successfully promoted tenure-track Doctor of Physical Therapy (DPT) faculty. To determine the research productivity that typically results in successful promotion. We collected publicly available curriculum vitae (CVs) from faculty currently in accredited DPT programs and who had been successfully promoted from an institution in the southeastern USA from 2000 through 2016. Total publication count, journal impact factor, funding, citations, and other metrics were analysed from 45 subjects of 22 of the 64 CAPTE-accredited DPT programs in the southeast. None of the studied metrics were normally distributed with time to promotion as determined by a Shapiro-Wilk test. These faculty exhibited a median publication count of 4, range 0 to 43; median of average citation count of 12.4, range 0 to 87.25; median of average journal impact factor of 2.866, range 0 to 6.280; median external funding received of $9910, range $0.00 to $19 543 198; and median author h-index of 3, range 0 to 17. The median number of years before promotion was 6, ranging from 3 to 13 years. Linear regression analysis indicates a poor fit with no significant correlation between years before promotion and any of the studied metrics. No correlation between journal impact factor and number of citations was observed (m = -0.22, p = 0.728, R 2 = 0.0003). Prior to promotion 31% (14 of 45) did not receive external funding and 24% (11 of 45) had a 0 h-index. The Carnegie Classification of the institution did not significantly correlate with research productivity metrics in this dataset (p = 0.213). While faculty unsuccessful in promotion were not identifiable using this method, this research can be used by faculty and committees to evaluate research productivity against regional data and promote competitive standards with peer institutions. CAPTE: Commission on Accreditation in Physical Therapist Education; DPT: Doctor of Physical Therapy.
2010-01-01
... Promotion. Promotion means any action, including paid advertising, to enhance the image or desirability of... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1215.16 Section 1215.16 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND...
2010-01-01
... demand for fluid milk products. (b) Advertising, which means any advertising or promotion program... 7 Agriculture 9 2010-01-01 2009-01-01 true Promotion. 1160.111 Section 1160.111 Agriculture... and Orders; Milk), DEPARTMENT OF AGRICULTURE FLUID MILK PROMOTION PROGRAM Fluid Milk Promotion Order...
2010-01-01
... Promotion. Promotion means any action, including but not limited to paid advertising and retail or food... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1230.22 Section 1230.22 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND...
Wang, Yuesheng; Feng, Zimin; Yang, Shi-Ze; Gagnon, Catherine; Gariépy, Vincent; Laul, Dharminder; Zhu, Wen; Veillette, René; Trudeau, Michel L.; Guerfi, Abdelbast; Zaghib, Karim
2018-02-01
High-performance and long-cycling rechargeable lithium-ion batteries have been in steadily increasing demand for the past decades. Nevertheless, the two dominant anodes at the moment, graphite and L4T5O12, suffer from a safety issue of lithium plating (operating voltage at ∼ 0.1 V vs. Li+/Li) and low capacity (175 mAh/g), respectively. Here, we report LiNi1/3Co1/3Mn1/3O2 as an alternative anode material which has a working voltage of ∼1.1 V and a capacity as high as 330 mAh/g at the current rate of C/15. Symmetric cells with both electrodes containing LiNi1/3Co1/3Mn1/3O2 can deliver average discharge voltage of 2.2 V. In-situ XRD, HRTEM and first principles calculations indicate that the reaction mechanism of a LiNi1/3Co1/3Mn1/3O2 anode is comprised mainly of conversion. Both the fundamental understanding and practical demonstrations suggest that LiNi1/3Co1/3Mn1/3O2 is a promising negative electrode material for lithium-ion batteries.
Safety, Dosimetry, and Tumor Detection Ability of 68Ga-NOTA-AE105
DEFF Research Database (Denmark)
Skovgaard Lund, Dorthe; Persson, Morten; Brandt-Larsen, Malene
2017-01-01
The overexpression of urokinase-type plasminogen activator receptors (uPARs) represents an established biomarker for aggressiveness in most common malignant diseases, including breast cancer (BC), prostate cancer (PC), and urinary bladder cancer (UBC), and is therefore an important target for new...... cancer therapeutic and diagnostic strategies. In this study, uPAR PET imaging using a68Ga-labeled version of the uPAR-targeting peptide (AE105) was investigated in a group of patients with BC, PC, and UBC. The aim of this first-in-human, phase I clinical trial was to investigate the safety.......Conclusion:This first-in-human, phase I clinical trial demonstrates the safe use and clinical potential of68Ga-NOTA-AE105 as a new radioligand for uPAR PET imaging in cancer patients....
Directory of Open Access Journals (Sweden)
O. S. Streltsova
2014-07-01
Full Text Available The investigation examined the feasibility of cross-polarization optical cohe-rence tomography (CP OCT to detect early urinary bladder cancer (UBC. Studies were performed in 376 patients; 5290 images were obtained using an OCT 133-U optical coherence tomograph. To acquire and compare intrared-light scattering images in baseline and orthogonal polarizations is the basis of CP OCT; their analysis makes it possible to judge from the state of the epithelium/connective tissue system and to obtain information on changes in tissue depolarizing components, collagen in particular. The authors elaborated criteria as determinants of the nature of CP OCT changes in direct and orthogonal polarizations in health, inflammatory changes, and UBC at its early stage - urothelial dysplasia and carcinoma in situ in flat suspected areas.
Fujiki, H; Suganuma, M; Yoshizawa, S; Kanazawa, H; Sugimura, T; Manam, S; Kahn, S M; Jiang, W; Hoshina, S; Weinstein, I B
1989-01-01
Three okadaic acid class tumor promoters, okadaic acid, dinophysistoxin-1, and calyculin A, have potent tumor-promoting activity in two-stage carcinogenesis experiments on mouse skin. DNA isolated from tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) and each of these tumor promoters revealed the same mutation at the second nucleotide of codon 61 (CAA----CTA) in the c-Ha-ras gene, determined by the polymerase chain reaction procedure and DNA sequencing. Three potent 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters, TPA, teleocidin, and aplysiatoxin, showed the same effects. These results provide strong evidence that this mutation in the c-Ha-ras gene is due to a direct effect of DMBA rather than a selective effect of specific tumor promoters.
Directory of Open Access Journals (Sweden)
Xia Li
Full Text Available To describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC; to explore the associations between MLH1 promoter methylation and clinicopathological and molecular factors using a systematic review and meta-analysis.A literature search of the PubMed and Embase databases was conducted to identify relevant articles published up to September 7, 2012 that described the frequency of MLH1 promoter methylation or its associations with clinicopathological and molecular factors in CRC. The pooled frequency, odds ratio (OR and 95% confidence intervals (95% CI were calculated.The pooled frequency of MLH1 promoter methylation in unselected CRC was 20.3% (95% CI: 16.8-24.1%. They were 18.7% (95% CI: 14.7-23.6% and 16.4% (95% CI: 11.9-22.0% in sporadic and Lynch syndrome (LS CRC, respectively. Significant associations were observed between MLH1 promoter methylation and gender (pooled OR = 1.641, 95% CI: 1.215-2.215; P = 0.001, tumor location (pooled OR = 3.804, 95% CI: 2.715-5.329; P<0.001, tumor differentiation (pooled OR = 2.131, 95% CI: 1.464-3.102; P<0.001, MSI (OR: 27.096, 95% CI: 13.717-53.526; P<0.001. Significant associations were also observed between MLH1 promoter methylation and MLH1 protein expression, BRAF mutation (OR = 14.919 (95% CI: 6.427-34.631; P<0.001 and 9.419 (95% CI: 2.613-33.953; P = 0.001, respectively.The frequency of MLH1 promoter methylation in unselected CRC was 20.3%. They were 18.7% in sporadic CRC and 16.4% in LS CRC, respectively. MLH1 promoter methylation may be significantly associated with gender, tumor location, tumor differentiation, MSI, MLH1 protein expression, and BRAF mutation.
The impact of the distance-dependent promotional effect on the promotion cost sharing decision
Sheen, Gwo-Ji; Wang, Shih-Yen; Yeh, Yingchieh
2016-02-01
This paper considers the promotion cost sharing decision between a supplier and a retailer. The customer demand is affected by both national and local promotional effects while the local promotional effect on a customer is dependent on the distance between the retailer and this customer. We propose a continuous approximation approach to modelling the sum of the customer demand in the whole market area served by the retailer. A model is provided to help managers decide on the retail price, the local advertising expenditure, the national advertising expenditure, and the supplier participation rate, with consideration of the influence of distance on the promotional effect. We also find that the supplier's promotion cost sharing rate increases as the market size increases or the influence of distance on the promotional effect decreases. A numerical example is given to show that the nature of distance-dependent promotional effect has a significant impact on the decisions and profits.
Challenges of Parental Involvement Within a Health Promoting School Framework in New Zealand
Directory of Open Access Journals (Sweden)
Tracy Clelland
2013-01-01
Full Text Available The study sought to identify key issues regarding parental involvement within a health promoting school (HPS approach directed at addressing children’s nutrition and physical activity. A case study research design was used, involving six primary schools in Auckland, New Zealand. Data were collected via six individual interviews with principals, six group interviews with a total of 26 teachers, 13 focus groups with a total of 92 children, and a survey of 229 parents. The study found that while schools agreed on the importance of schools and parents promoting the same healthy behaviours, there was a lack of agreement on the role of school staff in educating parents. School principals identified issues around managing the food brought from home and the extent to which they should regulate types of food. Parents stressed the importance of modelling healthy food and exercise practices in the home environment but identified factors that often made this difficult, a scenario that did not go unnoticed by their children. It is recommended that parental involvement be encouraged and supported so that schools and families can achieve consistency in health promotion practices across both school and home environments.
Directory of Open Access Journals (Sweden)
Yih Yih Kok
2012-04-01
Full Text Available Girinimbine, a carbazole alkaloid isolated from the stem bark of Murraya koenigii was tested for the in vitro anti-tumour promoting and antioxidant activities. Anti-tumour promoting activity was determined by assaying the capability of this compound to inhibit the expression of early antigen of Epstein-Barr virus (EA-EBV in Raji cells that was induced by the tumour promoter, phorbol 12-myristate 13-acetate. The concentration of this compound that gave an inhibition rate at fifty percent was 6.0 µg/mL and was not cytotoxic to the cells. Immunoblotting analysis of the expression of EA-EBV showed that girinimbine was able to suppress restricted early antigen (EA-R. However, diffused early antigen (EA-D was partially suppressed when used at 32.0 µg/mL. Girinimbine exhibited a very strong antioxidant activity as compared to a-tocopherol and was able to inhibit superoxide generation in the 12-O-tetradecanoylphorbol-13-acetate (TPA-induced differentiated premyelocytic HL-60 cells more than 95%, when treated with the compound at 5.3 and 26.3 µg/mL, respectively. However girinimbine failed to scavenge the stable diphenyl picryl hydrazyl (DPPH-free radical.
Dohn, Anita L; Chávez, Andrea; Dohn, Michael N; Saturria, Luis; Pimentel, Carlos
2004-03-01
To assess the impact of health promotion programs and microcredit programs on three communities in the Dominican Republic. One community had only the health promotion program, one community had only the microcredit program, and one community had both a health promotion program and a microcredit program. This pilot project examined the hypothesis that the largest changes in 11 health indicators that were studied would be in the community with both a health promotion program and a microcredit program, that there would be intermediate changes in the community with only a health promotion program, and that the smallest changes would be in the community with only a microcredit program. The health promotion programs used community volunteers to address two major concerns: (1) the prevalent causes of mortality among children under 5 years of age and (2) women's health (specifically breast and cervical cancer screening). The microcredit program made small loans to individuals to start or expand small businesses. Outcome measures were based on comparisons for 11 health indicators from baseline community surveys (27 households surveyed in each of the three communities, done in December 2000 and January 2001) and from follow-up surveys (also 27 households surveyed in each of the three communities, in June and July 2002, after the health promotion program had been operating for about 13 months). Households were randomly chosen during both the baseline and follow-up surveys, without regard to their involvement in the microcredit or health promotion programs. The health indicators improved in all three communities. However, the degree of change was different among the communities (P microcredit and health promotion programs had the largest changes for 10 of the 11 health indicators. Multisector development is known to be important on a macroeconomic scale. The results of this pilot project support the view that multisector development is also important on a microeconomic level
Horng, Yu-Tze; Chang, Kai-Chih; Chou, Ta-Chung; Yu, Chung-Jen; Chien, Chih-Ching; Wei, Yu-Hong; Soo, Po-Chi
2010-07-01
1,3-Propanediol (1,3-PD) can be used for the industrial synthesis of a variety of compounds, including polyesters, polyethers, and polyurethanes. 1,3-PD is generated from petrochemical and microbial sources. 1,3-Propanediol is a typical product of glycerol fermentation, while acetate, lactate, 2,3-butanediol, and ethanol also accumulate during the process. Substrate and product inhibition limit the final concentration of 1,3-propanediol in the fermentation broth. It is impossible to increase the yield of 1,3-propanediol by using the traditional whole-cell fermentation process. In this study, dhaD and dhaK, the genes for glycerol dehydrogenase and dihydroxyacetone kinase, respectively, were inactivated by homologous recombination in Klebsiella pneumoniae. The dhaD/dhaK double mutant (designated TC100), selected from 5,000 single or double cross homologous recombination mutants, was confirmed as a double cross by using polymerase chain reaction. Analysis of the cell-free supernatant with high-performance liquid chromatography revealed elimination of lactate and 2,3-butanediol, as well as ethanol accumulation in TC100, compared with the wild-type strain. Furthermore, 1,3-propanediol productivity was increased in the TC100 strain expressing glycerol dehydratase and 1,3-PDO dehydrogenase regulated by the arabinose P(BAD) promoter. The genetic engineering and medium formulation approaches used here should aid in the separation of 1,3-propanediol from lactate, 2,3-butanediol, and ethanol and lead to increased production of 1,3-propanediol in Klebsiella pneumoniae.
Spin freezing phenomenon and transport properties in La{sub 1/3}Nd{sub 1/3}Ba{sub 1/3}MnO{sub 3}
Energy Technology Data Exchange (ETDEWEB)
Li Guoqing E-mail: gqli@mail.sy.ln.cn; Ze Xianyu; Kim, C.-O.; Kim, H.-J.; Lee, Y.-W
2002-02-01
The magnetic and transport properties of La{sub 1/3}Nd{sub 1/3}Ba{sub 1/3}MnO{sub 3} with the colossal magnetoresistant (CMR) effect were studied by using SQUID. The irreversible curve for magnetizing intensity vs. temperature in an applied magnetic field of 13 Oe indicates that the spins of electrons are frozen, and therefore spin-glass state is probably formed below the Curie temperature. This fact implied that La{sub 1/3}Nd{sub 1/3}Ba{sub 1/3}MnO{sub 3} is mictomagnetic, that is, ferromagnetism and antiferromagnetism co-exist in this kind of material.
Promoter And Duties And Responsibilities Of Promoters In English Company Law
Neval Okan
2003-01-01
Any person who does an act with reference to the formation of a company or in aid of its organization whether he has the intention to be a partners or not is a promoter. No statuory definition of promoter is given in English company law; definition is given in case law. Promoters stand in a fiduciary relation to the proposed company. Apromoter is not an agent for the company which he is forming because a company cannot have an agent before it comes into existence. The fiduciary duty is owed t...
Directory of Open Access Journals (Sweden)
Dorcas J Orengo
Full Text Available The insulin/TOR signal transduction pathway plays a critical role in determining such important traits as body and organ size, metabolic homeostasis and life span. Although this pathway is highly conserved across the animal kingdom, the affected traits can exhibit important differences even between closely related species. Evolutionary studies of regulatory regions require the reliable identification of transcription factor binding sites. Here we have focused on the Insulin Receptor (InR expression from its P2 promoter in the Drosophila genus, which in D. melanogaster is up-regulated by hypophosphorylated Drosophila FOXO (dFOXO. We have finely characterized this transcription factor binding sites in vitro along the 1.3 kb region upstream of the InR P2 promoter in five Drosophila species. Moreover, we have tested the effect of mutations in the characterized dFOXO sites of D. melanogaster in transgenic flies. The number of experimentally established binding sites varies across the 1.3 kb region of any particular species, and their distribution also differs among species. In D. melanogaster, InR expression from P2 is differentially affected by dFOXO binding sites at the proximal and distal halves of the species 1.3 kb fragment. The observed uneven distribution of binding sites across this fragment might underlie their differential contribution to regulate InR transcription.
Self-tracking as Health promotion
DEFF Research Database (Denmark)
Jelsøe, Erling
Self-tracking has become widespread in many parts of the world and is understood by many of its proponents as a way to obtain bodily control and through that to improve healthy living. As such self-tracking can be understood as a particular approach to practicing individual health promotion (even...... though this is not the only incentive for self-tracking). Even though health promotion is often seen as an activity, which resonates with a focus on individual responsibility, such a conception of health promotion contrasts with a broader critical concept of health promotion that emphasize social...... an analysis of social and community oriented dimensions of self-tracking as a form of health promotion compared to the above mentioned broad critical approach to health promotion in order to identify the contradictions as well as common traits and discuss implications for health promoting initiatives...
Moral issues in workplace health promotion.
Robroek, Suzan J W; van de Vathorst, Suzanne; Hilhorst, Medard T; Burdorf, Alex
2012-04-01
There is debate to what extent employers are entitled to interfere with the lifestyle and health of their workers. In this context, little information is available on the opinion of employees. Within the framework of a workplace health promotion (WHP) program, moral considerations among workers were investigated. Employees from five companies were invited to participate in a WHP program. Both participants (n = 513) and non-participants (n = 205) in the program filled in a questionnaire on individual characteristics, lifestyle, health, and opinions regarding WHP. Nineteen percent of the non-participants did not participate in the WHP program because they prefer to arrange it themselves, and 13% (also) preferred to keep private life and work separate. More participants (87%) than non-participants (77%) agreed with the statement that it is good that employers try to improve employees' health (χ(2) = 12.78, p = 0.002), and 26% of the non-participants and 21% of the participants think employer interference with their health is a violation of their privacy. Employees aged 50 year and older were more likely to agree with the latter statement than younger workers (OR = 1.56, 95% CI 1.02-2.39). This study showed that most employees support the importance of WHP, but in a modest group of employees, moral considerations may play a role in their decision whether or not to participate in WHP. Older workers were more likely to resist employer interference with their health. Therefore, special attention on such moral considerations may be needed in the communication, design, and implementation of workplace health promotion programs.
Blockade of lysophosphatidic acid receptors LPAR1/3 ameliorates lung fibrosis induced by irradiation
International Nuclear Information System (INIS)
Gan, Lu; Xue, Jian-Xin; Li, Xin; Liu, De-Song; Ge, Yan; Ni, Pei-Yan; Deng, Lin; Lu, You; Jiang, Wei
2011-01-01
development of RLF through promoting fibroblast proliferation in a CTGF-dependent manner. The LPA-LPAR1/3-CTGF pathway may be a potential target for RLF therapy.
Blockade of lysophosphatidic acid receptors LPAR1/3 ameliorates lung fibrosis induced by irradiation
Energy Technology Data Exchange (ETDEWEB)
Gan, Lu [State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu (China); Xue, Jian-Xin [Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu (China); Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, Chengdu (China); Li, Xin [Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu (China); Liu, De-Song [Department of Pediatrics, Sichuan Provincial Hospital of Women and Children, Chengdu (China); Ge, Yan; Ni, Pei-Yan; Deng, Lin [State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu (China); Lu, You, E-mail: radyoulu@hotmail.com [State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu (China); Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu (China); Jiang, Wei, E-mail: wcumsjw72@hotmail.com [State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu (China); Molecular Medicine Research Center, West China Hospital, Sichuan University, Chengdu (China)
2011-05-27
signaling system is involved in the development of RLF through promoting fibroblast proliferation in a CTGF-dependent manner. The LPA-LPAR1/3-CTGF pathway may be a potential target for RLF therapy.
Gossip Versus Punishment: The Efficiency of Reputation to Promote and Maintain Cooperation
Wu, Junhui; Balliet, Daniel; Van Lange, Paul A. M.
2016-01-01
Prior theory suggests that reputation spreading (e.g., gossip) and punishment are two key mechanisms to promote cooperation in groups, but no behavioral research has yet examined their relative effectiveness and efficiency in promoting and maintaining cooperation. To examine these issues, we observed participants interacting in a four-round public goods game (PGG) with or without gossip and punishment options, and a subsequent two-round trust game (TG). We manipulated gossip as the option to send notes about other group members to these members’ future partners, and punishment as the option to assign deduction points to reduce other group members’ outcomes with a fee-to-fine ratio of 1:3. Findings revealed that in the four-round PGG, the option to gossip increased both cooperation and individual earnings, whereas the option to punish had no overall effect on cooperation (but a positive effect on cooperation in the last two rounds of the PGG) and significantly decreased individual earnings. Importantly, the initial option to gossip made people more trusting and trustworthy in the subsequent TG when gossip was no longer possible, compared to the no-gossip condition. Thus, we provide some initial evidence that gossip may be more effective and efficient than punishment to promote and maintain cooperation. PMID:27039896
Gossip Versus Punishment: The Efficiency of Reputation to Promote and Maintain Cooperation.
Wu, Junhui; Balliet, Daniel; Van Lange, Paul A M
2016-04-04
Prior theory suggests that reputation spreading (e.g., gossip) and punishment are two key mechanisms to promote cooperation in groups, but no behavioral research has yet examined their relative effectiveness and efficiency in promoting and maintaining cooperation. To examine these issues, we observed participants interacting in a four-round public goods game (PGG) with or without gossip and punishment options, and a subsequent two-round trust game (TG). We manipulated gossip as the option to send notes about other group members to these members' future partners, and punishment as the option to assign deduction points to reduce other group members' outcomes with a fee-to-fine ratio of 1:3. Findings revealed that in the four-round PGG, the option to gossip increased both cooperation and individual earnings, whereas the option to punish had no overall effect on cooperation (but a positive effect on cooperation in the last two rounds of the PGG) and significantly decreased individual earnings. Importantly, the initial option to gossip made people more trusting and trustworthy in the subsequent TG when gossip was no longer possible, compared to the no-gossip condition. Thus, we provide some initial evidence that gossip may be more effective and efficient than punishment to promote and maintain cooperation.
International Nuclear Information System (INIS)
Guo, Xin; Cong, Li-Na; Zhao, Qin; Tai, Ling-Hua; Wu, Xing-Long; Zhang, Jing-Ping; Wang, Rong-Shun; Xie, Hai-Ming; Sun, Li-Qun
2015-01-01
LiNi_1_/_3Co_1_/_3Mn_1_/_3O_2 is successfully coated with MnO_2 by a chemical deposition method. The X-ray diffraction (XRD), scanning electron microscope (SEM) and high resolution transmission electron microscope (HRTEM) results demonstrate that MnO_2 forms a thin layer on the surface of LiNi_1_/_3Co_1_/_3Mn_1_/_3O_2 without destroying the crystal structure of the core material. Compared with pristine LiNi_1_/_3Co_1_/_3Mn_1_/_3O_2, the MnO_2-coated sample shows enhanced electrochemical performance especially the rate capability. Even at a current density of 750 mA g"−"1, the discharge capacity of MnO_2-coated LiNi_1_/_3Co_1_/_3Mn_1_/_3O_2 is 155.15 mAh g"−"1, while that of the pristine electrode is only 132.84 mAh g"−"1 in the range of 2.5–4.5 V. The cyclic voltammetry (CV) and X-ray photoelectron spectroscopy (XPS) curves show that the MnO_2 coating layer reacts with Li"+ during cycling, which is responsible for the higher discharge capacity of MnO_2-coated LiNi_1_/_3Co_1_/_3Mn_1_/_3O_2. Electrochemical impedance spectroscopy (EIS) results confirmed that the MnO_2 coating layer plays an important role in reducing the charge transfer resistance on the electrolyte–electrode interfaces. - Highlights: • MnO_2 coated LiNi_1_/_3Co_1_/_3Mn_1_/_3O_2 cathode material is synthesized for the first time. • MnO_2 offers available sites for insertion of extracted lithium. • The preserved surface and crystal structures results in the improved kinetics.
Effect of parity on healthy promotion lifestyle behavior in women.
Nazik, Hakan; Nazik, Evşen; Özdemir, Funda; Gül, Şule; Tezel, Ayfer; Narin, Raziye
2015-01-01
Health-promoting lifestyle behaviors are not only for the prevention of a disease or discomfort, but are also behaviors that aim to improve the individual's general health and well-being. Nurses have an important position in the development of healthy lifestyle behaviors in women. The aim of this study was to assess the effect of parity on health-promoting lifestyle behaviors in women. This descriptive and cross-sectional survey was performed in Adana, Turkey. This study was conducted with 352 women. The questionnaire consisted of two parts; the first part consisted of questions that assessed the socio-demographic and obstetric characteristics, and the second part employed the "Health Promotion Lifestyle Profile Scale" (HPLP). Data analysis included percentage, arithmetic average, and ANOVA tests. The results revealed that 24.1% of the women had no parity, 13.6% had one parity, 30.7% had two parities, 14.6% had three parities, and 17% had four and above parities. The mean total HPLP was 126.66±18.12 (interpersonal support subscale, 24.46±4.02; nutrition subscale, 21.59±3.92; self-actualization subscale, 24.42±4.30; stress management subscale, 18.73±3.81; health responsibility subscale, 21.75±4.31; and exercise subscale, 15.71±4.22). The health behavior of women was moderate. A statistically significant correlation was found between the number of parities and the Health Responsibility, Nutrition, Interpersonal Support, which is the subscale of the HPLP Scale.
2010-01-01
... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Promotion. 532.407 Section 532.407... Administration § 532.407 Promotion. (a) An employee who is promoted is entitled to be paid at the lowest.... (c) If the promotion is to a position in a different wage area, the agency shall determine the...
Promoción deportiva: “Disfruta con el balonmano” [Sport promotion: "Enjoys with the handball"
Directory of Open Access Journals (Sweden)
Juan Francisco Nogales González
2009-12-01
Full Text Available Resumen “Disfruta con el Balonmano” es el eslogan de una iniciativa desarrollada por el Club Balonmano Badajoz dirigida a los Centros Escolares de la ciudad de Badajoz (13.243 niños. El objetivo para el club es la creación de Afición y el fomento de la identificación Emocional. Este proyecto cuenta con leal apoyo de una serie de empresas colaboradoras y patrocinadoras. Para estas entidades (siete “partners” y dos entidades colaboradoras el objetivo es utilizar la campaña como un gran escaparate para promover sus marcas, productos o servicios. Palabras clave: Club Balonmano Badajoz, Identificación Emocional, patrocinador, Grass-Root, Partnership, Eduselling. Abstract “Enjoy with handball” is the slogan of a initiativa developed by the C.B.Badajoz directed to schools of Badajoz city (13.243 childs. The sport organization´s objetive is create fans and promote emotional identification. This project has got the support and sponsorship of several companies and firms. For these firms (seven partners and two contributors the aim is to use the campaign to promote their brands, products and services. Key word: C. B. Badajoz, emotional identification, sponsor, Grass-Root, Partnership, Eduselling.
Castresana, C; de Carvalho, F; Gheysen, G; Habets, M; Inzé, D; Van Montagu, M
1990-01-01
The Nicotiana plumbaginifolia gn1 gene encoding a beta-1,3-glucanase isoform has been characterized. The gn1 product represents an isoform distinct from the previously identified tobacco beta-1,3-glucanases. By expressing gn1 in Escherichia coli, we have determined directly that the encoded protein does, indeed, correspond to a beta-1,3-glucanase. In N. plumbaginifolia, gn1 was found to be expressed in roots and older leaves. Transgenic tobacco plants containing the 5'-noncoding region of gn1 fused to the beta-glucuronidase (GUS) reporter gene also showed maximum levels of GUS activity in roots and older leaves. No detectable activity was present in the upper part of the transgenic plants with the exception of stem cells at the bases of emerging shoots. The expression conferred by the gn1 promoter was differentially induced in response to specific plant stress treatments. Studies of three plant-bacteria interactions showed high levels of GUS activity when infection resulted in a hypersensitive reaction. Increased gene expression was confined to cells surrounding the necrotic lesions. The observed expression pattern suggests that the characterized beta-1,3-glucanase plays a role both in plant development and in the defense response against pathogen infection. PMID:2152158
He, Yan-Bing; Ning, Feng; Yang, Quan-Hong; Song, Quan-Sheng; Li, Baohua; Su, Fangyuan; Du, Hongda; Tang, Zhi-Yuan; Kang, Feiyu
The structural and thermal stabilities of the layered Li(Ni 1/3Co 1/3Mn 1/3)O 2 cathode materials under high rate cycling and abusive conditions are investigated using the commercial 18650 Li(Ni 1/3Co 1/3Mn 1/3)O 2/graphite high power batteries. The Li(Ni 1/3Co 1/3Mn 1/3)O 2 materials maintain their layered structure even when the power batteries are subjected to 200 cycles with 10 C discharge rate at temperatures of 25 and 50 °C, whereas their microstructure undergoes obvious distortion, which leads to the relatively poor cycling performance of power batteries at high charge/discharge rates and working temperature. Under abusive conditions, the increase in the battery temperature during overcharge is attributed to both the reactions of electrolyte solvents with overcharged graphite anode and Li(Ni 1/3Co 1/3Mn 1/3)O 2 cathode and the Joule heat that results from the great increase in the total resistance (R cell) of batteries. The reactions of fully charged Li(Ni 1/3Co 1/3Mn 1/3)O 2 cathodes and graphite anodes with electrolyte cannot be activated during short current test in the fully charged batteries. However, these reactions occur at around 140 °C in the fully charged batteries during oven test, which is much lower than the temperature of about 240 °C required for the reactions outside batteries.
Yuan, Y; Zhang, G Q; Chai, W; Ni, M; Xu, C; Chen, J Y
2016-10-01
Osteoarthritis (OA) is characterised by articular cartilage degradation. MicroRNAs (miRNAs) have been identified in the development of OA. The purpose of our study was to explore the functional role and underlying mechanism of miR-138-5p in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage. Human articular cartilage was obtained from patients with and without OA, and chondrocytes were isolated and stimulated by IL-1β. The expression levels of miR-138-5p in cartilage and chondrocytes were both determined. After transfection with miR-138-5p mimics, allele-specific oligonucleotide (ASO)-miR-138-5p, or their negative controls, the messenger RNA (mRNA) levels of aggrecan (ACAN), collagen type II and alpha 1 (COL2A1), the protein levels of glycosaminoglycans (GAGs), and both the mRNA and protein levels of matrix metalloproteinase (MMP)-13 were evaluated. Luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot were performed to explore whether Forkhead Box C1 (FOCX1) was a target of miR-138-5p. Further, we co-transfected OA chondrocytes with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 and then stimulated with IL-1β to determine whether miR-138-5p-mediated IL-1β-induced cartilage matrix degradation resulted from targeting FOXC1. MiR-138-5p was significantly increased in OA cartilage and in chondrocytes in response to IL-1β-stimulation. Overexpression of miR-138-5p significantly increased the IL-1β-induced downregulation of COL2A1, ACAN, and GAGs, and increased the IL-1β-induced over expression of MMP-13.We found that FOXC1 is directly regulated by miR-138-5p. Additionally, co-transfection with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 resulted in higher levels of COL2A1, ACAN, and GAGs, but lower levels of MMP-13. miR-138-5p promotes IL-1β-induced cartilage degradation in human chondrocytes, possibly by targeting FOXC1.Cite this article: Y. Yuan, G. Q. Zhang, W. Chai,M. Ni, C. Xu, J
Popovic, B; Breed, J; Rees, D G; Gardener, M J; Vinall, L M K; Kemp, B; Spooner, J; Keen, J; Minter, R; Uddin, F; Colice, G; Wilkinson, T; Vaughan, T; May, R D
2017-01-20
Interleukin (IL)-13 is a pleiotropic T helper type 2 cytokine frequently associated with asthma and atopic dermatitis. IL-13-mediated signalling is initiated by binding to IL-13Rα1, which then recruits IL-4Rα to form a heterodimeric receptor complex. IL-13 also binds to IL-13Rα2, considered as either a decoy or a key mediator of fibrosis. IL-13-neutralising antibodies act by preventing IL-13 binding to IL-13Rα1, IL-4Rα and/or IL-13Rα2. Tralokinumab (CAT-354) is an IL-13-neutralising human IgG4 monoclonal antibody that has shown clinical benefit in patients with asthma. To decipher how tralokinumab inhibits the effects of IL-13, we determined the structure of tralokinumab Fab in complex with human IL-13 to 2 Å resolution. The structure analysis reveals that tralokinumab prevents IL-13 from binding to both IL-13Rα1 and IL-13Rα2. This is supported by biochemical ligand-receptor interaction assay data. The tralokinumab epitope is mainly composed of residues in helices D and A of IL-13. It is mostly light chain complementarity-determining regions that are driving paratope interactions; the variable light complementarity-determining region 2 plays a key role by providing residue contacts for a network of hydrogen bonds and a salt bridge in the core of binding. The key residues within the paratope contributing to binding were identified as Asp50, Asp51, Ser30 and Lys31. This study demonstrates that tralokinumab prevents the IL-13 pharmacodynamic effect by binding to IL-13 helices A and D, thus preventing IL-13 from interacting with IL-13Rα1 and IL-13Rα2. Copyright © 2016 AstraZeneca. Published by Elsevier Ltd.. All rights reserved.
Interleukin-13 is involved in the formation of liver fibrosis in Clonorchis sinensis-infected mice.
Xu, Yanquan; Liang, Pei; Bian, Meng; Chen, Wenjun; Wang, Xiaoyun; Lin, Jinsi; Shang, Mei; Qu, Hongling; Wu, Zhongdao; Huang, Yan; Yu, Xinbing
2016-07-01
Clonorchiasis is a chronic infection disease often accompanied by formation of liver fibrosis. Previous study has identified that Clonorchis sinensis (C. sinensis, Cs) infection and CsRNASET2 (a member of CsESPs) immunization can drive Th2 immune response. IL-13, a multifunctional Th2 cytokine, has been widely confirmed to be profibrotic mediator. We want to determine whether IL-13 is involved in the generation of liver fibrosis during C. sinensis infection. A part of mice were infected with C. sinensis or immunized with CsRNASET2, respectively. Another part of mice were intravenously injected with rIL-13. Liver tissues of C. sinensis-infected mice were stained with hematoxylin-eosin and Masson's trichrome, respectively. The transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1 in the livers of infected mice and rIL-13-treated mice were measured by quantitative RT-PCR. Besides, splenocytes of C. sinensis-infected and CsRNASET2-immunized mice were isolated, respectively. The levels of IL-13 in splenocytes were detected by ELISA. Our results displayed that the livers of C. sinensis-infected mice had serious chronic inflammation and collagen deposition. The transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1 in the livers of C. sinensis-infected mice were obviously increased. Splenocytes from both C. sinensis-infected and CsRNASET2-immunized mice expressed high levels of IL-13. Moreover, rIL-13 treatment markedly promoted the transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1. These data implied that hepatic fibrosis was formed in the livers of C. sinensis-infected mice, and IL-13 induced by C. sinensis infection and CsRNASET2 immunization might favor this progression.
Quantification of the "global" authigenic carbonate δ13C value and implications for carbon cycling
Loyd, S. J.
2017-12-01
Relationships among early Earth ocean chemistry, atmospheric chemistry and the evolution/radiation of life have been inferred from carbon isotope compositions (δ13C) of marine carbonates. Under steady-state conditions, the isotope compositions of marine carbonates reflect both the amount and δ13C of carbon entering and leaving the oceans. Recently the traditional "two-output" (marine carbonate and organic matter) mass-balance equation has been modified to include a third, authigenic carbonate output term. However, the formation mechanisms of authigenic carbonates remain poorly understood, particularly from a global prospective. The utility of the new mass-balance approach will be limited until authigenic carbonates are better characterized (e.g., through δ13C analyses). Authigenic carbonates form largely as a result of 1) the respiratory degradation of organic matter (e.g., sulfate reduction), 2) the oxidation of methane and 3) the production of methane. These major reaction pathways can produce authigenic carbonates with highly variable δ13C compositions (δ13Cac). Spatiotemporal variation in the extent and prevalence of different pathways therefore exert a first order control on "global" δ13Cac. Here, values are compiled from new and existing data sets and a modern, global δ13Cac is calculated. When calculated as an average of all data or an averaged mean of individual sites, this value is very similar to normal marine sedimentary organic matter. This finding suggests that marine sediments behave largely as closed systems in the context of organic matter degradation and carbonate authigenesis. In addition, the lack of significant difference between authigenic and organic δ13C implies that these two mass-balance output terms can be considered collectively in more recent time intervals. It may be appropriate to separate these two terms when characterizing more ancient settings when redox characteristics promoted more reducing organic matter degradation
Tung, Chen-Yin; Yin, Yun-Wen; Liu, Chia-Yun; Chang, Chia-Chen; Zhou, Yi-Ping
2017-07-01
To explore the employers' and promoters' perspective of health promotion quality according to the healthy workplace accreditation. We assessed the perspectives of 85 employers and 81 health promoters regarding the quality of health promotion at their workplaces. The method of measurement referenced the European Network for Workplace Health Promotion (ENWHP) quality criteria. In the large workplaces, the accredited corporation employers had a higher impression (P health promoters from different sized workplaces with or without accreditation (P > 0.05). It seems that employers' perspectives of healthy workplace accreditation surpassed employers from non-accredited workplaces. Specifically, large accredited corporations could share their successful experiences to encourage a more involved workplace in small-medium workplaces.
International Nuclear Information System (INIS)
Ahmad, N.; Hussain, S. T.; Abbas, S. M.; Khan, Y.; Muhammad, B.; Ali, N.
2013-01-01
The effect of Mn-promotion on high surface area Al-pillared montmorillonite (AlMMT) supported Co nanoparticles prepared by hydrothermal method have been investigated. A series of different weight% Mn-promoted Co nanoparticles were prepared and characterized by XRD, TPR, TGA, BET and SEM techniques. An increase in the surface area of MMT is observed with Al-pillaring. Fischer-Tropsch catalytic activity of the as prepared catalysts was studied in a fixed bed micro reactor at 225 .deg. C, H 2 /CO = 2 and at 1 atm pressure. The data showed that by the addition of Mn the selectivity of C 1 dropped drastically while that of C 2 -C 12 hydrocarbons increased significantly over all the Mn-promoted Co/AlMMT catalysts. The C 13 -C 20 hydrocarbons remained almost same for all the catalysts while the selectivity of C 21+ long chain hydrocarbons decreased considerably with the addition of Mn. The catalyst with 3.5%Mn showed lowest C 21+ and highest C 2 -C 12 hydrocarbons selectivity due to cracking of long chain hydrocarbons over acidic sites of MMT
Engineered Promoters for Potent Transient Overexpression.
Directory of Open Access Journals (Sweden)
Dan Y Even
Full Text Available The core promoter, which is generally defined as the region to which RNA Polymerase II is recruited to initiate transcription, plays a pivotal role in the regulation of gene expression. The core promoter consists of different combinations of several short DNA sequences, termed core promoter elements or motifs, which confer specific functional properties to each promoter. Earlier studies that examined the ability to modulate gene expression levels via the core promoter, led to the design of strong synthetic core promoters, which combine different core elements into a single core promoter. Here, we designed a new core promoter, termed super core promoter 3 (SCP3, which combines four core promoter elements (the TATA box, Inr, MTE and DPE into a single promoter that drives prolonged and potent gene expression. We analyzed the effect of core promoter architecture on the temporal dynamics of reporter gene expression by engineering EGFP expression vectors that are driven by distinct core promoters. We used live cell imaging and flow cytometric analyses in different human cell lines to demonstrate that SCPs, particularly the novel SCP3, drive unusually strong long-term EGFP expression. Importantly, this is the first demonstration of long-term expression in transiently transfected mammalian cells, indicating that engineered core promoters can provide a novel non-viral strategy for biotechnological as well as gene-therapy-related applications that require potent expression for extended time periods.
Development of a promoter shutoff system in Aspergillus oryzae using a sorbitol-sensitive promoter.
Oda, Ken; Terado, Shiho; Toyoura, Rieko; Fukuda, Hisashi; Kawauchi, Moriyuki; Iwashita, Kazuhiro
2016-09-01
Promoter shutoff is a general method for analyzing essential genes, but in the fungus Aspergillus oryzae, no tightly repressed promoters have been reported. To overcome the current limitations of conditional promoters, we examined sorbitol- and galactose-responsive genes using microarrays to identify regulatable genes with only minor physiological and genetic effects. We identified two sorbitol-induced genes (designated as sorA and sorB), cloned their promoters, and built a regulated egfp and brlA expression system. Growth medium-dependent enhanced green fluorescence protein (EGFP) fluorescence and conidiation were confirmed for egfp and brlA under the control of their respective promoters. We also used this shutoff system to regulate the essential rhoA, which demonstrated the expected growth inhibition under repressed growth conditions. Our new sorbitol promoter shutoff system developed can serve as a valuable new tool for essential gene analyses of filamentous fungi.
Conversion of the random amplified polymorphic DNA (RAPD ...
African Journals Online (AJOL)
Conversion of the random amplified polymorphic DNA (RAPD) marker UBC#116 linked to Fusarium crown and root rot resistance gene (Frl) into a co-dominant sequence characterized amplified region (SCAR) marker for marker-assisted selection of tomato.
Jimarez, Teresa
Despite our national efforts to attract more students to the science, technology, engineering, and mathematics (STEM) fields, the number of students continues to be small. Empirical studies have suggested that in order to actively engage students in the science learning processes, lessons need to be designed which consider student prior experiences and provide a sound curriculum, within an environment promoting social interaction---that is, allowing for sharing and negotiation of those ideas which promote reflective thinking. These premises require an embedded assessment system that continuously provides feedback to both student and teacher. This technique allows adaptation and modification of lessons to better facilitate conceptual understanding. This study focused on the use of constructivist strategies that, when aligned, promoted conceptual understanding while facilitating development of science process skills. Skill development leads to meaningful learning, known to promote a change of attitude toward science. A mixed research design embedded in a case study approach was used to understand the complexity of the variables examined in this study. Both quantitative and qualitative methods of data collection were used to strengthen the validity and interpretation of the findings. Students from one of three ninth-grade physical science classes were selected for this study. The students numbered 29, 13 boys and 16 girls; the majority of these students were of Hispanic background. The analysis of data suggested that the use of constructivist strategies promotes conceptual understanding of science concepts and development of science process skills and a change of attitude towards science. This study concluded that selecting teaching and multiple assessment strategies is vital to engage students in science careers. Due to the limited nature of this case study, the researcher recommends a replication or followup with a different teacher and school, including a control
Gutierrez, Jorge; Larsen, Rasmus; Cintas, Luis M.; Kok, Jan; Hernandez, Pablo E.
Enterocin P (EntP), a sec-dependent bacteriocin from Enterococcus faecium P13, was produced by Lactococcus lactis. The EntP structural gene (entP) with or without the EntP immunity gene (entiP) was cloned in (1), plasmid pMG36c under control of the lactococcal constitutive promoter P-32, (2) in
Degradation of phorbol 12,13-diacetate in aqueous solution by gamma irradiation
International Nuclear Information System (INIS)
Kongmany, Santi; Furuta, Masakazu; Matsuura, Hiroto; Okuda, Shuichi; Imamura, Kiyoshi; Maeda, Yasuaki
2014-01-01
Phorbol esters (PEs) are highly toxic compounds that cause skin irritation, inflammation, and tumor promotion upon contact with humans or animals. These compounds are naturally present in Jatropha curcas L. To promote the use of J. curcas seed oil in bio-diesel production industries and reduce environmental concerns, it is necessary to find methods of degrading PEs. In this study, the degradation of phorbol 12,13-diacetate (PDA), as a representative PE, in aqueous solution at a concentration of 10 mg/L by 60 Co-γ-irradiation was investigated. The results demonstrate that PDA was effectively degraded by this treatment and the degradation efficiency increased with the absorbed dose within the range of 0.5–3 kGy. Complete degradation of PDA was achieved at a dose of 3 kGy. In the presence of radical scavengers (i.e., methanol, tert-butanol, 2-propanol), reactive species from water radiolysis were scavenged, and significant inhibition of PDA degradation was observed at absorbed doses less than 1 kGy. In the presence of nitrous oxide, the generation of hydroxyl radicals (·OH) was promoted during gamma irradiation and PDA degradation was drastically enhanced. - Highlights: • PDA in aqueous solution was effectively degraded by gamma irradiation. • Hydroxyl radical mainly contributed to PDA degradation. • Intermediate product produced from PDA degradation was further decomposed. • Gamma irradiation process can be useful for degrading phorbol esters in water
(/sup 13/N)ammonia in organic solvents; a potent synthetic precursor for /sup 13/N-labeling
Energy Technology Data Exchange (ETDEWEB)
Tominaga, Toshiyoshi; Hirobe, Masaaki; Suzuki, Kazutoshi; Inoue, Osamu; Irie, Toshiaki; Yamasaki, Toshio
1987-01-01
/sup 13/NH/sub 3/ in an organic solvent was prepared and its utility as a labeling precursor was studied. (/sup 13/N)adenine ((/sup 13/N)ADN), (/sup 13/N)nicotinamide ((/sup 13/N)NAM), (/sup 13/N)p-nitrophenyl carbamate ((/sup 13/N)NPC), and (/sup 13/N)L-glutamine ((/sup 13/N)Gln) were labeled utilizing this precursor. (/sup 13/N)ADN and (/sup 13/N)NAM were labeled in much better yields than from an aqueous solution of /sup 13/NH/sub 3/. (/sup 13/N)NPC and (/sup 13/N)Gln, which could not be labeled in an aqueous solution, were labeled in high radiochemical yields. Thus, the advantages of this precursor are the improvement of the labeling yield and the feasibility of labeling compounds unstable in aqueous conditions.
29 CFR 541.503 - Promotion work.
2010-07-01
... 29 Labor 3 2010-07-01 2010-07-01 false Promotion work. 541.503 Section 541.503 Labor Regulations... Outside Sales Employees § 541.503 Promotion work. (a) Promotion work is one type of activity often.... Promotion activities directed toward consummation of the employee's own sales are exempt. Promotional...
A systematic review of workplace health promotion interventions for increasing physical activity.
Malik, Sumaira H; Blake, Holly; Suggs, L Suzanne
2014-02-01
The benefits of an active lifestyle are widely documented, yet studies show that only a small proportion of adults engage in sufficient levels of physical activity. The workplace presents an ideal avenue for delivering initiatives to promote physical activity, overcoming commonly cited barriers such as a 'lack of time' and providing access to a large intersection of society. The purpose of this study was to (1) explore the types of interventions workplaces implement to promote physical activity among staff, (2) describe the characteristics of those interventions, (3) understand whether these interventions positively impact on activity levels, and (4) assess the methodological quality of studies. A systematic review of workplace physical activity interventions published up to April 2011 was conducted to identify types of interventions and their outcomes. Of the 58 studies included, the majority utilized health promotion initiatives. There were six physical activity/exercise interventions, 13 counselling/support interventions, and 39 health promotion messages/information interventions. Thirty-two of these studies showed a statistically significant increase in a measure of physical activity against a control group at follow-up. While the studies included in this review show some evidence that workplace physical activity interventions can be efficacious, overall the results are inconclusive. Despite the proliferation of research in this area, there is still a need for more well-designed studies to fully determine the effectiveness of workplace interventions for increasing physical activity and to identify the types of interventions that show the most promise. © 2013 The British Psychological Society.
DEFF Research Database (Denmark)
Seghezzi, Nicolas; Amar, Patrick; Købmann, Brian
2011-01-01
Streptomyces are bacteria of industrial interest whose genome contains more than 73% of bases GC. In order to define, in these GC-rich bacteria, specific sequence features of strong promoters, a library of synthetic promoters of various sequence composition was constructed in Streptomyces. To do so...... cloned into the promoter-probe plasmid pIJ487 just upstream of the promoter-less aphII gene that confers resistance to neomycin. This synthetic promoter library was transformed into Streptomyces lividans, and the resulting transformants were screened for their ability to grow in the presence of different...... projects. Thirty-eight promoters were sequenced, and the sequences of the 14 weakest and 14 strongest promoters were compared using the WebLogo software with small sample correction. This comparison revealed that the −10 box, the −10 extended motif as well as the spacer of the strong Streptomyces promoters...
International Nuclear Information System (INIS)
Xu, Guofeng; Li, Jianling; Xue, Qingrui; Dai, Yu; Zhou, Hongwei; Wang, Xindong; Kang, Feiyu
2014-01-01
A novel wet method of (NH 4 ) 3 AlF 6 coating was explored to enhance the electrochemical performance of Mn-based solid-solution cathode material 0.5Li 2 MnO 3 ·0.5LiNi 1/3 Co 1/3 Mn 1/3 O 2 . The X-ray powder diffraction patterns show that the coating material is pure-phase (NH 4 ) 3 AlF 6 and both pristine and coated samples can be indexed to hexagonal α-NaFeO 2 layered structure with space group of R-3 m. The field-emission scanning electron microscope images and the energy dispersive X-ray spectroscopy show that (NH 4 ) 3 AlF 6 is successfully coated on the surface of active particle. The (NH 4 ) 3 AlF 6 coated electrodes exhibit improved electrochemical performance, for instance, the initial charge-discharge efficiency was promoted by 5% (NH 4 ) 3 AlF 6 coating, the 1 wt.% and 3 wt.% coated electrodes deliver elevated cycling ability which is ascribed to the lower resistance between electrode and electrolyte as indicated by AC impedance measurement at different cycles. In addition, the coated-electrodes also give enhanced rate capability particularly for 1 wt.% NAF-coated electrode performing surprising capacity of 143.4 mAh g −1 at 5 C higher than that of 109.4 mAh g −1 for pristine electrode. Furthermore, the 1 wt.% NAF-coated electrode also shows improved cycle and rate performance at 55°C
Sood, Tanushri Jerath; Lagah, Swati Viviyan; Sharma, Ankita; Singla, Suresh Kumar; Mukesh, Manishi; Chauhan, Manmohan Singh; Manik, Radheysham; Palta, Prabhat
2017-10-01
We evaluated the suitability of 10 candidate internal control genes (ICGs), belonging to different functional classes, namely ACTB, EEF1A1, GAPDH, HPRT1, HMBS, RPS15, RPS18, RPS23, SDHA, and UBC for normalizing the real-time quantitative polymerase chain reaction (qPCR) data of blastocyst-stage buffalo embryos produced by hand-made cloning and in vitro fertilization (IVF). Total RNA was isolated from three pools, each of cloned and IVF blastocysts (n = 50/pool) for cDNA synthesis. Two different statistical algorithms geNorm and NormFinder were used for evaluating the stability of these genes. Based on gene stability measure (M value) and pairwise variation (V value), calculated by geNorm analysis, the most stable ICGs were RPS15, HPRT1, and ACTB for cloned blastocysts, HMBS, UBC, and HPRT1 for IVF blastocysts and RPS15, GAPDH, and HPRT1 for both the embryo types analyzed together. RPS18 was the least stable gene for both cloned and IVF blastocysts. Following NormFinder analysis, the order of stability was RPS15 = HPRT1>GAPDH for cloned blastocysts, HMBS = UBC>RPS23 for IVF blastocysts, and HPRT1>GAPDH>RPS15 for cloned and IVF blastocysts together. These results suggest that despite overlapping of the three most stable ICGs between cloned and IVF blastocysts, the panel of ICGs selected for normalization of qPCR data of cloned and IVF blastocyst-stage embryos should be different.
Bioceramic bone graft substitute for treatment of unicameral bone cysts.
Fillingham, Y A; Cvetanovich, G L; Haughom, B D; Erickson, B J; Gitelis, S
2016-08-01
To review the outcome of 12 patients who underwent debridement and injection of bioceramic for unicameral bone cyst (UBC). The resorption rate of the bioceramic was estimated by both traditional and novel methods. Records of 10 males and 2 females aged 6 to 34 years who underwent debridement and injection of bioceramic for UBC and were followed up for a mean of 41 (range, 26-57) months were reviewed. Functional outcome was assessed using the selfcompleted Musculoskeletal Tumor Society (MSTS) questionnaire. Radiological outcome was assessed using both original and modified Neer Outcome Rating System. The resorption rate of the bioceramic was estimated using both traditional and novel (ImageJ) methods. The mean MSTS score was 29.7 (range, 28-30) indicating excellent functional outcome. Of the 12 patients, 9 achieved complete healing and 3 had a residual cyst of 1%, 11%, and 52%. The last was considered a local recurrence, and the patient underwent repeat percutaneous injection of the bioceramic 1.5 years later and remained disease-free 4 years later. The mean resorption rate was 29% faster when estimated using the traditional rather than the ImageJ method (0.47 vs. 0.33 cm3/day, p=0.02). In the patient with recurrence, the resorption rate was faster than the average (0.68 vs. 0.33 cm3/day). A single percutaneous injection of the bioceramic for UBC achieved good functional and radiological outcome while avoiding donor-site morbidity.
Directory of Open Access Journals (Sweden)
Seyed Mohammad Mehdi Hazavehei
2014-09-01
Full Text Available Introduction: The present study as a systematic review investigated and analyzed interventions based on models and theories of health education and promotion in the field of physical activity in women. Materials and Methods: Three electronic databases, including Springer, Biomed Central and Science Direct were searched systematically. Only studies were selected that were quantitative, interventional and in English language as well as those that used at least one of the models and theories of health education and health promotion. Finally, 13 studies were reviewed that met the inclusion criteria and published from 2000 to 2013. Results: Of 13 studies reviewed, 10 studies measured levels of physical activity before and after the intervention, which nine interventions increased physical activity in the intervention group compared to the control group. Studies were conducted in different settings of health promotion including health care centers, community setting and workplace. The most widely used model was the Transtheoretical Model applied in eight of investigations. Conclusion: It is suggested to focus more on physical activity and duration of interventions to increase the efficacy of interventions. It is suggested to measure changes of physical activity habits in experimental and control groups in interventions based on the transtheoretical model to prepare a complementary scale to assess the efficacy of interventions. According to the results, no study had focused on changes in institutional policies or general health or providing changes in environment related to physical activity.
JUNGBRUNNEN1 Confers Drought Tolerance Downstream of the HD-Zip I Transcription Factor AtHB13
Directory of Open Access Journals (Sweden)
Saghar Ebrahimian-Motlagh
2017-12-01
Full Text Available Low water availability is the major environmental factor limiting growth and productivity of plants and crops and is therefore considered of high importance for agriculture affected by climate change. Identifying regulatory components controlling the response and tolerance to drought stress is thus of major importance. The NAC transcription factor (TF JUNGBRUNNEN1 (JUB1 from Arabidopsis thaliana extends leaf longevity under non-stress growth conditions, lowers cellular hydrogen peroxide (H2O2 level, and enhances tolerance against heat stress and salinity. Here, we additionally find that JUB1 strongly increases tolerance to drought stress in Arabidopsis when expressed from both, a constitutive (CaMV 35S and an abiotic stress-induced (RD29A promoter. Employing a yeast one-hybrid screen we identified HD-Zip class I TF AtHB13 as an upstream regulator of JUB1. AtHB13 has previously been reported to act as a positive regulator of drought tolerance. AtHB13 and JUB1 thereby establish a joint drought stress control module.
Sales promotions and food consumption.
Hawkes, Corinna
2009-06-01
Sales promotions are widely used to market food to adults, children, and youth. Yet, in contrast to advertising, practically no attention has been paid to their impacts on dietary behaviors, or to how they may be used more effectively to promote healthy eating. This review explores the available literature on the subject. The objective is to identify if and what literature exists, examine the nature of this literature, and analyze what can be learned from it about the effects of sales promotions on food consumption. The review finds that while sales promotions lead to significant sales increases over the short-term, this does not necessarily lead to changes in food-consumption patterns. Nevertheless, there is evidence from econometric modeling studies indicating that sales promotions can influence consumption patterns by influencing the purchasing choices of consumers and encouraging them to eat more. These effects depend on the characteristics of the food product, sales promotion, and consumer. The complexity of the effects means that sales promotions aiming to encourage consumption of nutritious foods need to be carefully designed. These conclusions are based on studies that use mainly sales data as a proxy for dietary intake. The nutrition (and economics) research communities should add to this existing body of research to provide evidence on the impact of sales promotions on dietary intake and related behaviors. This would help support the development of a sales promotion environment conducive to healthy eating.
Unicameral bone cyst of the proximal tibia in a five year old girl.
Tahririan, Mohammadali; Motiffard, Mehdi
2012-01-01
Unicameral bone cysts (UBCs) are benign, osteolytic lesions which are often asymptomatic and are commonly seen in the proximal of humerus and femur. The average age at diagnosis is 9-11 years and there is a male preponderance with a male-to-female ratio of approximately 2-2.5 to 1. We describe a case of 5-year-old girl who presented to orthopedic clinic with a 4-month history of painful limping. Plain radiography of the right knee demonstrated a well-defined lytic lesion in the proximal of the tibia. Open biopsy and then curettage and bone grafting with bone- substitute was performed. The diagnosis of this condition requires a high index of suspicion. This report demonstrates that all UBCs do not have the same clinical patterns and with adequate attention good results can be achieved.
Unicameral bone cyst of the proximal tibia in a five year old girl
Directory of Open Access Journals (Sweden)
Mohammadali Tahririan
2012-01-01
Full Text Available Unicameral bone cysts (UBCs are benign, osteolytic lesions which are often asymptomatic and are commonly seen in the proximal of humerus and femur. The average age at diagnosis is 9-11 years and there is a male preponderance with a male-to-female ratio of approximately 2-2.5 to 1. We describe a case of 5-year-old girl who presented to orthopedic clinic with a 4-month history of painful limping. Plain radiography of the right knee demonstrated a well-defined lytic lesion in the proximal of the tibia. Open biopsy and then curettage and bone grafting with bone- substitute was per-formed. The diagnosis of this condition requires a high index of suspicion. This report demonstrates that all UBCs do not have the same clinical patterns and with adequate attention good results can be achieved.
Ramirez-Garcés, Diana; Camborde, Laurent; Pel, Michiel J C; Jauneau, Alain; Martinez, Yves; Néant, Isabelle; Leclerc, Catherine; Moreau, Marc; Dumas, Bernard; Gaulin, Elodie
2016-04-01
To successfully colonize their host, pathogens produce effectors that can interfere with host cellular processes. Here we investigated the function of CRN13 candidate effectors produced by plant pathogenic oomycetes and detected in the genome of the amphibian pathogenic chytrid fungus Batrachochytrium dendrobatidis (BdCRN13). When expressed in Nicotiana, AeCRN13, from the legume root pathogen Aphanomyces euteiches, increases the susceptibility of the leaves to the oomycete Phytophthora capsici. When transiently expressed in amphibians or plant cells, AeCRN13 and BdCRN13 localize to the cell nuclei, triggering aberrant cell development and eventually causing cell death. Using Förster resonance energy transfer experiments in plant cells, we showed that both CRN13s interact with nuclear DNA and trigger plant DNA damage response (DDR). Mutating key amino acid residues in a predicted HNH-like endonuclease motif abolished the interaction of AeCRN13 with DNA, the induction of DDR and the enhancement of Nicotiana susceptibility to P. capsici. Finally, H2AX phosphorylation, a marker of DNA damage, and enhanced expression of genes involved in the DDR were observed in A. euteiches-infected Medicago truncatula roots. These results show that CRN13 from plant and animal eukaryotic pathogens promotes host susceptibility by targeting nuclear DNA and inducing DDR. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.
Automated 13CO2 analyzing system for the 13C breath test
International Nuclear Information System (INIS)
Suehiro, Makiko; Kuroda, Akira; Maeda, Masahiro; Hinaga, Kou; Watanabe, Hiroyuki.
1987-01-01
An automated 13 CO 2 analyzing system for the 13 C breath test was designed, built and evaluated. The system, which was designed to be controlled by a micro-computer, includes CO 2 purification, 13 CO 2 abundance measurement, data processing and data filing. This article gives the description of the whole system with flow charts. This system has proved to work well and it has become feasible to dispose of 5 to 6 CO 2 samples per hour. With such a system, the 13 C breath test will be carried out much more easily and will obtain much greater popularity. (author)
Arroyo-Jousse, Viviana; Garcia-Diaz, Diego F; Codner, Ethel; Pérez-Bravo, Francisco
2016-12-01
TNF-α is a pro-inflammatory cytokine that is involved in type 1 diabetes (T1D) pathogenesis. The TNFa gene is subject of epigenetic regulation in which folate and homocysteine are important molecules because they participate in the methionine cycle where the most important methyl group donor (S-adenosylmethionine) is formed. We investigated whether TNFa gene promoter methylation status in T1D patients was related to blood folate, homocysteine and TNF-α in a transversal case-control study. We studied T1D patients (n 25, mean=13·7 years) and healthy control subjects (n 25, mean=31·1 years), without T1D and/or other autoimmune diseases or direct family history of these diseases. A blood sample was obtained for determination of serum folate, plasma homocysteine and TNF-α concentrations. Whole blood was used for the extraction of DNA to determine the percentage of methylation by real-time PCR and melting-curve analysis. Results are expressed as means and standard deviations for parametric variables and as median (interquartile range) for non-parametric variables. T1D patients showed a higher TNFa gene promoter methylation (39·2 (sd 19·5) %) when compared with control subjects (25·4 (sd 13·7) %) (P=0·008). TNFa gene promoter methylation was positively associated only with homocysteine levels in T1D patients (r 0·55, P=0·007), but not in control subjects (r -0·122, P=0·872). To our knowledge, this is the first work that reports the methylation status of the TNFa gene promoter and its relationship with homocysteine metabolism in Chilean T1D patients without disease complications.
Duke, Jennifer C; Hansen, Heather; Kim, Annice E; Curry, Laurel; Allen, Jane
2014-07-10
The promotion of evidence-based cessation services through social media sites may increase their utilization by smokers. Data on social media adoption and use within tobacco control programs (TCPs) have not been reported. This study examines TCP use of and activity levels on social media, the reach of TCP sites, and the level of engagement with the content on sites. A cross-sectional descriptive study of state TCP social media sites and their content was conducted. In 2013, 60% (30/50) of TCPs were using social media. Approximately one-quarter (26%, 13/50) of all TCPs used 3 or more social media sites, 24% (12/50) used 2, and 10% (5/50) used 1 site. Overall, 60% (30/50) had a Facebook page, 36% (18/50) had a Twitter page, and 40% (20/50) had a YouTube channel. The reach of social media was different across each site and varied widely by state. Among TCPs with a Facebook page, 73% (22/30) had less than 100 likes per 100,000 adults in the state, and 13% (4/30) had more than 400 likes per 100,000 adults. Among TCPs with a Twitter page, 61% (11/18) had less than 10 followers per 100,000 adults, and just 1 state had more than 100 followers per 100,000 adults. Seven states (23%, 7/30) updated their social media sites daily. The most frequent social media activities focused on the dissemination of information rather than interaction with site users. Social media resources from a national cessation media campaign were promoted infrequently. The current reach of state TCP social media sites is low and most TCPs are not promoting existing cessation services or capitalizing on social media's interactive potential. TCPs should create an online environment that increases participation and 2-way communication with smokers to promote free cessation services.
2010-01-01
... promotion means any action, including paid advertising, technical assistance, and trade servicing activities... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1220.121 Section 1220.121 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND...
Jelsøe, Erling; Thualagant, Nicole; Holm, Jesper; Kjærgård, Bente; Andersen, Heidi Myglegård; From, Ditte-Marie; Land, Birgit; Pedersen, Kirsten Bransholm
2018-02-01
Based on previous studies and reflections collected from participants in a workshop at the 8th Nordic Health Promotion Research Network conference, we reveal current tendencies and discuss future challenges for health-promotion research regarding integration of sustainable development principles. Despite obvious interfaces and interactions between the two, our contention is that strategies for health promotion are not sufficiently integrated with strategies for sustainable development and that policies aimed at solving health or sustainability problems may therefore cause new, undesired and unforeseen environmental and health problems. As illustrated in previous research and as deliberated in the above-mentioned workshop, a number of barriers are identified. These are believed to be related to historical segregation, the conceptual understandings of health promotion and sustainable development, as well as the politics and implementation of policy goals in both areas. Three focal points are proposed as important challenges to address in future research: (a) the duality of health promotion and sustainability and how it can be handled in order to enhance mutually supportive processes between them; (b) the social dimension of sustainability and how it can be strengthened in the development of strategies for health promotion and sustainable development; and (c) exploring and identifying policy approaches and strategies for integrating health promotion and sustainable development.
Long non-coding RNA HOTAIR regulates proliferation and invasion ...
Indian Academy of Sciences (India)
2016-09-22
Sep 22, 2016 ... Retinoblastoma (Rb) is an eye cancer that originates from the retina, and the most ..... receptor, and Jagged1, the most common ligand in Notch signalling .... urothelial bladder cancer (UBC) patients can serve as bio- markers ...
TNFSF14 (LIGHT Exhibits Inflammatory Activities in Lung Fibroblasts Complementary to IL-13 and TGF-β
Directory of Open Access Journals (Sweden)
Ricardo da Silva Antunes
2018-03-01
Full Text Available The cytokine TNFSF14 [homologous to Lymphotoxin, exhibits Inducible expression and competes with HSV Glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes (LIGHT] has been shown in mouse models to be important for development of lung tissue remodeling that is characteristic of asthma, idiopathic pulmonary fibrosis (IPF, and systemic sclerosis (SSc. However, its cellular targets are not fully delineated. In the present report, we show that LTβR and HVEM, the receptors for LIGHT, are constitutively expressed in primary human lung fibroblasts (HLFs. We asked whether LIGHT could promote inflammatory and remodeling-relevant activity in HLFs and how this was similar to, or distinct from, IL-13 or TGF-β, two cytokines strongly implicated in the pathogenesis of asthma, IPF, and SSc. Accumulation of myofibroblasts expressing alpha smooth muscle actin is a feature of lung inflammatory diseases. LIGHT promoted cell cycle progression and proliferation of HLFs, but not alpha smooth muscle actin expression. In contrast, TGF-β upregulated alpha smooth muscle actin but did not drive their proliferation. LIGHT also increased the gene or protein expression of a number of proinflammatory mediators, including ICAM-1 and VCAM-1, IL-6 and GM-CSF, the chemokines CCL5 and 20, and CXCL5, 11, and 12, and lung remodeling-associated proteinases MMP-9 and ADAM8. These were dependent on LTβR but not HVEM. LIGHT displayed overlapping and synergistic activities with IL-13 for a number of the activities, but LIGHT additionally enhanced the gene expression of several molecules, including the innate cytokines IL-33 and TSLP, which were not upregulated by IL-13. Our results highlight the varied and pleiotropic effects of LIGHT in HLFs. LIGHT might then be a therapeutic target for modulation of inflammation and remodeling associated with asthma and other similar diseases of the lung that involve fibroblasts.
Qu, Liu; Yu, Yaqiong; Qiu, Lihong; Yang, Di; Yan, Lu; Guo, Jiajie; Jahan, Rabita
2017-01-01
ABSTRACT Porphyromonas endodontalis lipopolysaccharide (P.e LPS) is an important initiating factor for periapical inflammation and bone destruction. Matrix metalloproteinase-13 (MMP-13) has been shown to participate in the formation and diffusion of periapical bone lesion in chronic apical periodontitis. Sirtuin 1 (SIRT1) is a key regulator of inflammation in mammalian cells which suppresses the release of inflammatory mediators. This study aimed to explore the role of SIRT1 in regulating MMP-13 expression induced by P.e LPS in osteoblasts. P.e LPS stimulated MMP-13 expression in MC3T3-E1 cells. Knockdown of SIRT1 reinforced the increase of MMP-13mRNA expression induced by P.e LPS. SIRT1 activator resveratrol significantly reduced the expression of MMP-13 and SIRT1 inhibitor EX-527 enhanced the expression of MMP-13. Moreover, SIRT1 activation with resveratrol inhibited acetylation of NF-κB p65 and NF-κB transcriptional activity, which were enhanced by P.e LPS. In addition, NF-κB p65 was involved in P.e LPS-induced MMP-13 expression via directly binding to the MMP-13 promoter. However, SIRT1 activation significantly interfered with this binding. These findings strongly suggest that P.e LPS induces MMP-13 expression in osteoblasts, and SIRT1 suppresses this expression of MMP-13 through targeting NF-κB p65. This provides new insights into understanding the actions of SIRT1 on anti-inflammatory and anti-bone resorption activity. PMID:28473882
Qu, Liu; Yu, Yaqiong; Qiu, Lihong; Yang, Di; Yan, Lu; Guo, Jiajie; Jahan, Rabita
2017-01-01
Porphyromonas endodontalis lipopolysaccharide (P.e LPS) is an important initiating factor for periapical inflammation and bone destruction. Matrix metalloproteinase-13 (MMP-13) has been shown to participate in the formation and diffusion of periapical bone lesion in chronic apical periodontitis. Sirtuin 1 (SIRT1) is a key regulator of inflammation in mammalian cells which suppresses the release of inflammatory mediators. This study aimed to explore the role of SIRT1 in regulating MMP-13 expression induced by P.e LPS in osteoblasts. P.e LPS stimulated MMP-13 expression in MC3T3-E1 cells. Knockdown of SIRT1 reinforced the increase of MMP-13mRNA expression induced by P.e LPS. SIRT1 activator resveratrol significantly reduced the expression of MMP-13 and SIRT1 inhibitor EX-527 enhanced the expression of MMP-13. Moreover, SIRT1 activation with resveratrol inhibited acetylation of NF-κB p65 and NF-κB transcriptional activity, which were enhanced by P.e LPS. In addition, NF-κB p65 was involved in P.e LPS-induced MMP-13 expression via directly binding to the MMP-13 promoter. However, SIRT1 activation significantly interfered with this binding. These findings strongly suggest that P.e LPS induces MMP-13 expression in osteoblasts, and SIRT1 suppresses this expression of MMP-13 through targeting NF-κB p65. This provides new insights into understanding the actions of SIRT1 on anti-inflammatory and anti-bone resorption activity.
Preliminary tension effect on low-cycle fatigue of 40Kh13 steel in gaseous hydrogen
International Nuclear Information System (INIS)
Romaniv, A.N.
1984-01-01
Comparative bending tests of specimens deformed by tension at 65, 18 and 30% in hydrogen and vacuum were accomplished to reveal the effect of preliminary tension on low-cycle fatigue strength of 40Kh13 martensitic steel. It was found that small amounts of preliminary strains induced a considerable decrease in low-cycle durability in vacuum and hydrogen which was connected with developing defects arising at the early stages of plastic deformation. A rather high degree of preliminary tension promoted steel homogenization, hydrogen embrittlement decrease and service behaviour improvement
International Nuclear Information System (INIS)
Myung, Seung-Taek; Lee, Myung-Hun; Komaba, Shinichi; Kumagai, Naoaki; Sun, Yang-Kook
2005-01-01
In attempts to prepare layered Li[Ni 1/3 Co 1/3 Mn 1/3 ]O 2 , hydrothermal method was employed. The hydrothermal precursor, [Ni 1/3 Co 1/3 Mn 1/3 ](OH) 2 , was synthesized via a coprecipitation route. The sphere-shaped powder precursor was hydrothermally reacted with LiOH aqueous solution at 170 deg. C for 4 days in autoclave. From X-ray diffraction and scanning electron microscopic studies, it was found that the as-hydrothermally prepared powders were crystallized to layered α-NaFeO 2 structure and the particles had spherical shape. The as-prepared Li[Ni 1/3 Co 1/3 Mn 1/3 ]O 2 delivered an initial discharge of about 110 mA h g -1 due to lower crystallinity. Heat treatment of the hydrothermal product at 800 deg. C was significantly effective to improve the structural integrity, which consequently affected the increase in the discharge capacity to 157 (4.3 V cut-off) and 182 mA h g -1 (4.6 V cut-off) at 25 deg. C with good reversibility
Health promotion in the workplace
Directory of Open Access Journals (Sweden)
Sultan T Al-Otaibi
2016-01-01
Full Text Available The objective of this review was to describe the scientific evidence for coordinating health promotion at the workplace and to discuss the required future research in this field. Literature review from March 1990 to November 2014 was performed. Using the keywords ′health, promotion, worksite and workplace′, literature was searched in the following databases: Medline, PubMed and Google Scholar; with no time limit. There is emerging evidence that workplace health promotion enhances the effectiveness of effort to promote and protect workers′ health. It proves both cost-effective and cost-beneficial to health promotion at the worksite and subsequently further reduces absenteeism. However, future research is needed to identify the impact of other factors such as age, gender and race on workers′ exposure. There is also a need to develop valid tests to measure the outcome of these programmes at the workplace. Health promotion should be central to workplace planning and should be recognised as an integral part of proactive occupational health. Indeed, the workplace is viewed as one of the most popular venues for promoting health and preventing diseases among employees.
Sonawane, Poonam; Cho, Hwang Eui; Tagde, Ashujit; Verlekar, Dattesh; Yu, Alice L; Reynolds, C Patrick; Kang, Min H
2014-12-01
Isotretinoin (13-cis-retinoic acid; 13-cRA) is a differentiation inducer used to treat minimal residual disease after myeloablative therapy for high-risk neuroblastoma. However, more than 40% of children develop recurrent disease during or after 13-cRA treatment. The plasma concentrations of 13-cRA in earlier studies were considered subtherapeutic while 4-oxo-13-cis-RA (4-oxo-13-cRA), a metabolite of 13-cRA considered by some investigators as inactive, were greater than threefold higher than 13-cRA. We sought to define the metabolic pathways of 13-cRA and investigated the anti-tumour activity of its major metabolite, 4-oxo-13-cRA. Effects of 13-cRA and 4-oxo-13-cRA on human neuroblastoma cell lines were assessed by DIMSCAN and flow cytometry for cell proliferation, MYCN down-regulation by reverse transcription PCR and immunoblotting, and neurite outgrowth by confocal microscopy. 13-cRA metabolism was determined using tandem MS in human liver microsomes and in patient samples. Six major metabolites of 13-cRA were identified in patient samples. Of these, 4-oxo-13-cRA was the most abundant, and 4-oxo-13-cRA glucuronide was also detected at a higher level in patients. CYP3A4 was shown to play a major role in catalysing 13-cRA to 4-oxo-13-cRA. In human neuroblastoma cell lines, 4-oxo-13-cRA and 13-cRA were equi-effective at inducing neurite outgrowth, inhibiting proliferation, decreasing MYCN mRNA and protein, and increasing the expression of retinoic acid receptor-β mRNA and protein levels. We showed that 4-oxo-13-cRA is as active as 13-cRA against neuroblastoma cell lines. Plasma levels of both 13-cRA and 4-oxo-13-cRA should be evaluated in pharmacokinetic studies of isotretinoin in neuroblastoma. © 2014 The British Pharmacological Society.
Glucose metabolism in pigs expressing human genes under an insulin promoter.
Wijkstrom, Martin; Bottino, Rita; Iwase, Hayoto; Hara, Hidetaka; Ekser, Burcin; van der Windt, Dirk; Long, Cassandra; Toledo, Frederico G S; Phelps, Carol J; Trucco, Massimo; Cooper, David K C; Ayares, David
2015-01-01
Xenotransplantation of porcine islets can reverse diabetes in non-human primates. The remaining hurdles for clinical application include safe and effective T-cell-directed immunosuppression, but protection against the innate immune system and coagulation dysfunction may be more difficult to achieve. Islet-targeted genetic manipulation of islet-source pigs represents a powerful tool to protect against graft loss. However, whether these genetic alterations would impair islet function is unknown. On a background of α1,3-galactosyltransferase gene-knockout (GTKO)/human (h)CD46, additional genes (hCD39, human tissue factor pathway inhibitor, porcine CTLA4-Ig) were inserted in different combinations under an insulin promoter to promote expression in islets (confirmed by immunofluorescence). Seven pigs were tested for baseline and glucose/arginine-challenged levels of glucose, insulin, C-peptide, and glucagon. This preliminary study did not show definite evidence of β-cell deficiencies, even when three transgenes were expressed under the insulin promoter. Of seven animals, all were normoglycemic at fasting, and five of seven had normal glucose disposal rates after challenge. All animals exhibited insulin, C-peptide, and glucagon responses to both glucose and arginine challenge; however, significant interindividual variation was observed. Multiple islet-targeted transgenic expression was not associated with an overtly detrimental effect on islet function, suggesting that complex genetic constructs designed for islet protection warrants further testing in islet xenotransplantation models. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Directory of Open Access Journals (Sweden)
Matthew Thomas
2010-12-01
Full Text Available Objective – To determine the level of awareness of the Information Rx program by Georgia librarians and Georgia American College of Physicians (GACP members, and the use of Information Rx pads, with which physicians would “prescribe” information for their patients.Design – Descriptive (surveys and interviews.Setting – Georgia, U.S. Surveys were distributed and responded to online. The face-to-face interview locations were not specified.Subjects – One survey, which was provided to the Georgia American College of Physicians (GACP membership including internal medicine physicians and medical students interested in internal medicine, had 46 respondents. The second survey was sent to librarians who were members of the Georgia Public Library Service (GPLS and the Georgia Health Sciences Library Association (GHSLA. There were 72 public librarians, 14 hospital librarians and 13 academic medical librarians who responded (as well as 6 not specified in the article. A select group of four medical librarians was chosen for more in-depth interviews. The number of surveys sent out was not provided.Methods – Two online surveys, one for physicians and one for librarians, were administered. No information concerning response rate was provided. Face-to-face interviews with four academic medical librarians were conducted. No further information about the interviewing process was provided such as who conducted the interviews, methods used to ensure objectivity or consistency, or where the interviews were conducted.Main Results – Out of 46 GACP survey respondents, only 4 were familiar with the Information Rx program and only 2 of those had used the information Rx pads, neither of whom had referred anyone to a library for further assistance. The two who had not used the pads were either too busy or didn’t understand the program well enough. Of 105 librarian survey respondents, 46 had heard of Information Rx, 37 had received Information Rx promotional
Springer, Andrew E; Evans, Alexandra E
2016-01-01
Conducting a health needs assessment is an important if not essential first step for health promotion planning. This paper explores how health needs assessments may be further strengthened for health promotion planning via an assessment of environmental assets rooted in the multiple environments (policy, information, social and physical environments) that shape health and behavior. Guided by a behavioral-ecological perspective- one that seeks to identify environmental assets that can influence health behavior, and an implementation science perspective- one that seeks to interweave health promotion strategies into existing environmental assets, we present a basic framework for assessing environmental assets and review examples from the literature to illustrate the incorporation of environmental assets into health program design. Health promotion practitioners and researchers implicitly identify and apply environmental assets in the design and implementation of health promotion interventions;this paper provides foundation for greater intentionality in assessing environmental assets for health promotion planning.
Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit
Zampini, Valeria; Liu, Jian K; Diana, Marco A; Maldonado, Paloma P; Brunel, Nicolas; Dieudonné, Stéphane
2016-01-01
Synaptic currents display a large degree of heterogeneity of their temporal characteristics, but the functional role of such heterogeneities remains unknown. We investigated in rat cerebellar slices synaptic currents in Unipolar Brush Cells (UBCs), which generate intrinsic mossy fibers relaying
Szasz, George; Stuart, Freida; Maurice, William L.; Garry, Matthew
1977-01-01
The treatment of vaginismus was the subject of grand rounds in the Department of Obstetrics and Gynecology at Vancouver General Hospital. Staff members of the UBC Sex Therapy Unit participated in the presentation of a case of unconsummated marriage. PMID:21304871
Westhoff, E.; Witjes, J.A.; Fleshner, N.E.; Lerner, S.P.; Shariat, S.F.; Steineck, G.; Kampman, E.; Kiemeney, L.A.L.M.; Vrieling, A.
2018-01-01
Background: Urologists are frequently confronted with questions of urinary bladder cancer (UBC) patients about what they can do to improve their prognosis. Unfortunately, it is largely unknown which lifestyle factors can influence prognosis. Objective: To systematically review the available evidence
Cohen, Pieter A; Travis, John C; Keizers, Peter H J; Deuster, Patricia; Venhuis, Bastiaan J
2017-11-08
The United States Food and Drug Administration banned the stimulant 1,3-dimethylamylamine (1,3-DMAA) from dietary supplements and warned consumers that the stimulant can pose cardiovascular risks ranging from high blood pressure to heart attacks. We designed our study to determine if a new stimulant similar in structure to 1,3-DMAA has been introduced as an ingredient in supplements sold in the United States (US). We analyzed six brands of supplements that listed an ingredient on the label (e.g., Aconitum kusnezoffii, DMHA or 2-amino-isoheptane) that might refer to an analog of 1,3-DMAA. Supplements were analyzed by two separate laboratories using ultra-high-performance liquid chromatography mass spectrometry and reference standards. Two previously unidentified 1,3-DMAA analogs (2-amino-6-methylheptane [octodrine] and 1,4-dimethylamylamine [1,4-DMAA]) and two banned stimulants (1,3-DMAA and 1,3-dimethylbutylamine [1,3-DMBA]) were identified. Octodrine was found at a dose (±95% CI) of 72 ± 7.5 mg per serving. In Europe, octodrine was previously sold as a pharmaceutical in multi-ingredient medications at dosages from 8 to 33 mg. The quantity of octodrine found in our study was more than twice the largest pharmaceutical dose. The other new stimulant, 1,4-DMAA, has not previously been approved for human consumption, and its safety in humans is unknown. 1,4-DMAA was found at dosages between 21 ± 11 mg to 94 ± 48 mg per serving. In addition, two banned stimulants - 1,3-DMAA and 1,3-DMBA - were also identified: 24 ± 7.6 mg to 35 ± 11 mg of 1,3-DMAA and 51 ± 16 mg of 1,3-DMBA. In one product, 24 ± 7.6 mg of 1,3-DMAA was combined with 21 ± 11 mg of 1,4-DMAA. 1,3-DMAA has been investigated as potentially contributing to hemorrhagic strokes and sudden death, whereas the safety of 1,3-DMBA in humans is unknown. Two banned stimulants (1,3-DMAA and 1,3-DMBA) and two previously unidentified stimulants (1,4-DMAA and
78 FR 24239 - Temporary Mailing Promotion
2013-04-24
... POSTAL REGULATORY COMMISSION [Docket No. R2013-6; Order No. 1702] Temporary Mailing Promotion... offering a Technology Credit Promotion. This notice informs the public of the Postal Service's filing and... changes associated with offering a Technology Credit Promotion.\\1\\ The promotion is planned to begin on...
Feng, Hongxiang; Zhang, Zhenrong; Qing, Xin; Wang, Xiaowei; Liang, Chaoyang; Liu, Deruo
2016-02-01
Aberrant promoter hypermethylations of tumor suppressor genes are promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine methylation status at APC and RAR-β promoters in primary NSCLC, and whether they have any relationship with survival. APC and RAR-β promoter methylation status were determined in 41 NSCLC patients using methylation specific PCR. APC promoter methylation was detectable in 9 (22.0%) tumor samples and 6 (14.6%) corresponding non-tumor samples (P=0.391). RAR-β promoter methylation was detectable in 13 (31.7%) tumor samples and 4 (9.8%) corresponding non-tumor samples (P=0.049) in the NSCLC patients. APC promoter methylation was found to be associated with T stage (P=0.046) and nodal status (P=0.019) in non-tumor samples, and with smoking (P=0.004) in tumor samples. RAR-β promoter methylation was found associated with age (P=0.031) in non-tumor samples and with primary tumor site in tumor samples. Patients with APC promoter methylation in tumor samples showed significantly longer survival than patients without it (Log-rank P=0.014). In a multivariate analysis of prognostic factors, APC methylation in tumor samples was an independent prognostic factor (P=0.012), as were N1 positive lymph node number (P=0.025) and N2 positive lymph node number (P=0.06). Our study shows that RAR-β methylation detected in lung tissue may be used as a predictive marker for NSCLC diagnosis and that APC methylation in tumor sample may be a useful marker for superior survival in NSCLC patients. Copyright © 2015. Published by Elsevier Inc.
Pedrana, Alisa; Hellard, Margaret; Gold, Judy; Ata, Nadine; Chang, Shanton; Howard, Steve; Asselin, Jason; Ilic, Olivia; Batrouney, Colin; Stoove, Mark
2013-02-07
A growing number of health promotion interventions are taking advantage of the popularity and interactivity of new social media platforms to foster and engage communities for health promotion. However, few health promotion interventions using social networking sites (SNS) have been rigorously evaluated. "Queer as F**k"(QAF) began as pilot project in 2010 to deliver sexual health promotion via short "webisodes" on SNS to gay men. Now in its fifth season, QAF is among the few published examples internationally to demonstrate the sexual health promotion potential of SNS. The objective of this evaluation is to assess reach, interactivity, and engagement generated by QAF to inform future health interventions and evaluations using SNS. We undertook a mixed method process evaluation using an uncontrolled longitudinal study design that compared multiple measurements over time to assess changes in reach and engagement. We adapted evaluation methods from the health promotion, information systems, and creative spheres. We incorporated online usage statistics, interviews informed by user diary-scrapbooks, and user focus groups to assess intervention reach and engagement. During Series 1-3 (April 2010 to April 2011), 32 webisodes were posted on the QAF Facebook and YouTube pages. These webisodes attracted over 30,000 views; ranging from 124-3092 views per individual episode. By April 2011, the QAF Facebook page had 2929 predominantly male fans. Interview and focus group participants supported the balance of education and entertainment. They endorsed the narrative "soap opera" format as an effective way to deliver sexual health messages in an engaging, informative, and accessible manner that encouraged online peer discussion of sexual health and promoted community engagement. QAF offers a successful example of exploiting the reach, interactivity, and engagement potential of SNS; findings from this process evaluation provide a model to inform the delivery and evaluation of future
Aberrant gene promoter methylation associated with sporadic multiple colorectal cancer.
Directory of Open Access Journals (Sweden)
Victoria Gonzalo
Full Text Available BACKGROUND: Colorectal cancer (CRC multiplicity has been mainly related to polyposis and non-polyposis hereditary syndromes. In sporadic CRC, aberrant gene promoter methylation has been shown to play a key role in carcinogenesis, although little is known about its involvement in multiplicity. To assess the effect of methylation in tumor multiplicity in sporadic CRC, hypermethylation of key tumor suppressor genes was evaluated in patients with both multiple and solitary tumors, as a proof-of-concept of an underlying epigenetic defect. METHODOLOGY/PRINCIPAL FINDINGS: We examined a total of 47 synchronous/metachronous primary CRC from 41 patients, and 41 gender, age (5-year intervals and tumor location-paired patients with solitary tumors. Exclusion criteria were polyposis syndromes, Lynch syndrome and inflammatory bowel disease. DNA methylation at the promoter region of the MGMT, CDKN2A, SFRP1, TMEFF2, HS3ST2 (3OST2, RASSF1A and GATA4 genes was evaluated by quantitative methylation specific PCR in both tumor and corresponding normal appearing colorectal mucosa samples. Overall, patients with multiple lesions exhibited a higher degree of methylation in tumor samples than those with solitary tumors regarding all evaluated genes. After adjusting for age and gender, binomial logistic regression analysis identified methylation of MGMT2 (OR, 1.48; 95% CI, 1.10 to 1.97; p = 0.008 and RASSF1A (OR, 2.04; 95% CI, 1.01 to 4.13; p = 0.047 as variables independently associated with tumor multiplicity, being the risk related to methylation of any of these two genes 4.57 (95% CI, 1.53 to 13.61; p = 0.006. Moreover, in six patients in whom both tumors were available, we found a correlation in the methylation levels of MGMT2 (r = 0.64, p = 0.17, SFRP1 (r = 0.83, 0.06, HPP1 (r = 0.64, p = 0.17, 3OST2 (r = 0.83, p = 0.06 and GATA4 (r = 0.6, p = 0.24. Methylation in normal appearing colorectal mucosa from patients with multiple and solitary CRC showed no relevant
2006 Guidelines for Advancement and Promotion
HR Department
2006-01-01
1. General The Director-General has now fixed the guidelines and schedule for the 2006 annual advancement review in the framework of the Merit Advancement and Promotion Scheme (MAPS). Procedures are set out in Administrative Circular 26 (Rev. 6). All decisions will be made by 1 July 2006. These now include career path changes for staff in Career Paths A to D. Departments are invited to comply strictly with the target date for the completion of the annual interviews which this year has been fixed at 15 March 2006. Group Leader evaluations are expected to be finalized by 13 April 2006. Exceptions due to particular circumstances (e.g. long-term absences) must be documented. The annual appraisal report should be completed using the electronic version in the EDH system. 2. Budget guidelines Within the annual advancement budget, the guideline allocations have been defined by the Director-General on a departmental basis for staff in Career Paths A to E and on a CERN-wide basis for staff in Career Paths F and ...
2006 Guidelines for Advancement and Promotion
HR Department
2006-01-01
1. General The Director-General has now fixed the guidelines and schedule for the 2006 annual advancement review in the framework of the Merit Advancement and Promotion Scheme (MAPS). Procedures are set out in Administrative Circular 26 (Rev. 6). All decisions will be made by 1 July 2006. These now include career path changes for staff in Career Paths A to D. Departments are invited to comply strictly with the target date for the completion of the annual interviews which this year has been fixed at 15 March 2006. Group Leader evaluations are expected to be finalized by 13 April 2006. Exceptions due to particular circumstances (e.g. long-term absences) must be documented. The annual appraisal report should be completed using the electronic version in the EDH system. 2. Budget guidelines Within the annual advancement budget, the guideline allocations have been defined by the Director-General on a departmental basis for staff in Career Paths A to E and on a CERN-wide basis for staff in Career Paths F and G...
Measuring the Cost of Supermarket Promotions
DEFF Research Database (Denmark)
Gao, Cixiu
2014-01-01
The widespread use of retail promotions and the magnitude of dollars spent on them call economists to examine the role of promotional costs in shaping the coordination of pricing and promotion decisions. In this study, I estimate the marginal cost of price promotion in the retail industry. The es...
Barroso, Raquel; Jiménez, Azucena; Pérez-Aguilar, M Carmen; Cabal, María-Paz; Valdés, Carlos
2016-03-04
1,3-Diaryl-3-trifluoromethylcyclopropenes and 2-aryl- or 2-alkyl-1,3-diaryl-3-trifluoromethylcyclopropenes are prepared in a very simple way by reaction between 1,1,1-trifluoroacetophenone tosylhydrazones and terminal or internal alkynes, respectively, in a base promoted process that does not require the presence of any metal catalyst. The essential role of the trifluoromethyl group, which enables the formation of the cyclopropenes instead of the expected pyrazoles, has been computationally investigated, suggesting the participation of a free carbene.
The use of (1-3) β-glucan along with itraconazole against canine refractory sporotrichosis.
Guterres, Karina Affeldt; de Matos, Caroline Bohnen; Osório, Luiza Da Gama; Schuch, Isabel Duarte; Cleff, Marlete Brum
2014-04-01
Sporotrichosis, caused by the Sporothrix schenckii fungal complex, is a zoonotic mycosis distributed worldwide. Itraconazole is the treatment of choice for domestic animals although some fungal isolates have shown resistance to this drug. The objective of this study was to report, for the first time, the use of (1-3) β-glucan along with itraconazole in the treatment of a canine with sporotrichosis caused by Sporothrix brasiliensis. The animal had ulcerated and crusted lesions, especially on the nasal planum. Clinical samples were collected for a complete blood count, cytological analysis of the lesion, and fungal culture. Based on the results of the laboratory examination, and after the fungal culture, antibiotic therapy and treatment with itraconazole were initiated. Two additional fungal cultures were performed, which were positive. After 7 months of the animal treatment with itraconazole, the S. brasiliensis culture was still positive, so that the itraconazole was associated with (1-3) β-glucan. After four weekly applications of glucan, the complete elimination of the fungus was observed based on the fungal culture negative results. The results show, therefore, that (1-3) β-glucan with itraconazole promoted the case resolution, and it may be considered a promising alternative for the treatment of sporotrichosis in cases of resistance to conventional therapy.
English, Lorna McLeod; Hsia, Jason; Malarcher, Ann
2016-10-01
We examined the change over time in tobacco advertising, promotion and sponsorship exposure and the concurrent changes in cigarette smoking behavior among students age 13 to 15years in two African countries with different anti-tobacco advertising, promotion and sponsorship policies. In South Africa, anti-tobacco advertising, promotion and sponsorship policies became more comprehensive over time and were more strictly enforced, whereas the partial anti-tobacco advertising, promotion and sponsorship policies adopted in Botswana were weakly enforced. We analyzed two rounds of Global Youth Tobacco Survey data from South Africa (1999, n=2342; 2011, n=3713) and in Botswana (2001, n=1073; 2008, n=1605). We assessed several indicators of tobacco advertising, promotion and sponsorship exposure along with prevalence of current cigarette smoking and smoking susceptibility for each data round. Logistic regression was used to examine changes over time in tobacco advertising, promotion and sponsorship exposure and smoking behavior in both countries. Between 1999 and 2011, South African students' exposure to tobacco advertising and sponsorship decreased significantly by 16% (p value, promotion was lower and did not decrease significantly. Botswanan students' tobacco advertising, promotion and sponsorship exposure did not change significantly between 2001 and 2008. South African students' prevalence of cigarette smoking decreased over time (OR, 0.68) as did susceptibility to smoking (OR, 0.75), but declines did not remain significant after adjusting for parents' and friends' smoking. In Botswana, students' prevalence of cigarette smoking increased significantly over time (OR, 1.84), as did susceptibility to smoking (OR, 2.71). Enforcement of strong anti-tobacco advertising, promotion and sponsorship policies is a vital component of effective tobacco control programs in Africa. Such regulations, if effectively implemented, can reduce tobacco advertising, promotion and sponsorship
The Clinician-Educator Pathway in Radiology: An Analysis of Institutional Promotion Criteria.
Jhala, Khushboo; Kim, Jisoo; Chetlen, Alison; Nickerson, Joshua P; Lewis, Petra J
2017-12-01
To provide radiology departmental promotional committees and vice chairs of education with a more global perspective on the types of academic activity valued by institutions to aid in their faculty mentoring and standardizing of the Clinician-Educator (ClinEd) pathway. Ninety-two research schools were ranked into three tiers. Ranking was correlated with the presence of a ClinEd track. Thirty promotion documents (ten from each tier) were analyzed to identify common criteria. Differences in guidelines between tiers were assessed by the frequency distribution of criteria. Tier 1 had a significantly greater proportion of schools with a ClinEd track than tier 2 (73% versus 44%, p < 0.05). Thirty-nine criteria were identified and organized into four categories teaching (13), scholarship (12), service/clinical excellence (7), and research (7). The top five included meeting presentations, trainee evaluations, leadership in committees, development of teaching methodologies and materials, and publication of book chapters. First and second tier schools were most similar in frequency distribution. The criteria for the ClinEd promotion track still vary across institutions, though many commonalities exist. A handful of innovative criteria reflect the changing structure of modern health care systems, such as incorporation of online teaching modules and quality improvement efforts. As health care changes, guidelines and incentive structures for faculty should change as well. The information gathered may provide promotion committees with a more global perspective on the types of academic activity valued by modern-day institutions to aid in the national standardization of this pathway and to assist in faculty mentoring. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.
Directory of Open Access Journals (Sweden)
Altenbuchner Josef
2011-10-01
Full Text Available Abstract Background Several vector systems have been developed to express any gene desired to be studied in Bacillus subtilis. Among them, the transcriptionally regulated promoters involved in carbohydrate utilization are a research priority. Expression systems based on Bacillus promoters for xylose, maltose, and mannose utilization, as well as on the heterologous E. coli lactose promoter, have been successfully constructed. The promoter of the mtlAFD operon for utilization of mannitol is another promising candidate for its use in expression vectors. In this study, we investigated the regulation of the mtl genes in order to identify the elements needed to construct a strong mannitol inducible expression system in B. subtilis. Results Regulation of the promoters of mtlAFD operon (PmtlA and mtlR (PmtlR encoding the activator were investigated by fusion to lacZ. Identification of the PmtlA and PmtlR transcription start sites revealed the σA like promoter structures. Also, the operator of PmtlA was determined by shortening, nucleotide exchange, and alignment of PmtlA and PmtlR operator regions. Deletion of the mannitol-specific PTS genes (mtlAF resulted in PmtlA constitutive expression demonstrating the inhibitory effect of EIICBMtl and EIIAMtl on MtlR in the absence of mannitol. Disruption of mtlD made the cells sensitive to mannitol and glucitol. Both PmtlA and PmtlR were influenced by carbon catabolite repression (CCR. However, a CcpA deficient mutant showed only a slight reduction in PmtlR catabolite repression. Similarly, using PgroE as a constitutive promoter, putative cre sites of PmtlA and PmtlR slightly reduced the promoter activity in the presence of glucose. In contrast, glucose repression of PmtlA and PmtlR was completely abolished in a ΔptsG mutant and significantly reduced in a MtlR (H342D mutant. Conclusions The mtl operon promoter (PmtlA is a strong promoter that reached a maximum of 13,000 Miller units with lacZ as a reporter on
Information technology in health promotion.
Lintonen, T P; Konu, A I; Seedhouse, D
2008-06-01
eHealth, the use of information technology to improve or enable health and health care, has recently been high on the health care development agenda. Given the vivid interest in eHealth, little reference has been made to the use of these technologies in the promotion of health. The aim of this present study was to conduct a review on recent uses of information technology in health promotion through looking at research articles published in peer-reviewed journals. Fifteen relevant journals with issues published between 2003 and June 2005 yielded altogether 1352 articles, 56 of which contained content related to the use of information technology in the context of health promotion. As reflected by this rather small proportion, research on the role of information technology is only starting to emerge. Four broad thematic application areas within health promotion were identified: use of information technology as an intervention medium, use of information technology as a research focus, use of information technology as a research instrument and use of information technology for professional development. In line with this rather instrumental focus, the concepts 'ePromotion of Health' or 'Health ePromotion' would come close to describing the role of information technology in health promotion.
2011-05-10
...: AMS-DA-08-0050] Dairy Promotion and Research Program; Importer Nominations to the Dairy Promotion and... to the Dairy Production Stabilization Act of 1983 (Dairy Act), as amended, and the Dairy Promotion... importer representation, initially two members, to the National Dairy Promotion and Research Board (Dairy...
A Menagerie of Promotional Characters: Promoting Food to Children through Food Packaging
Hebden, Lana; King, Lesley; Kelly, Bridget; Chapman, Kathy; Innes-Hughes, Christine
2011-01-01
Objective: To determine the extent to which (1) promotional characters are used on food packaging for healthful and less-healthful food and (2) different companies use this persuasive marketing strategy. Design: Cross-sectional supermarket audit of all food and beverages featuring promotional characters on the packaging. Setting: Three Australian…
Tamminen, Nina; Solin, Pia; Stengård, Eija; Kannas, Lasse; Kettunen, Tarja
2017-07-01
In this study, we aimed to investigate what competencies are needed for mental health promotion in health sector practice in Finland. A qualitative study was carried out to seek the views of mental health professionals regarding mental health promotion-related competencies. The data were collected via two focus groups and a questionnaire survey of professionals working in the health sector in Finland. The focus groups consisted of a total of 13 professionals. Further, 20 questionnaires were received from the questionnaire survey. The data were analysed using the qualitative data analysis software ATLAS.ti Scientific Software Development GmbH, Berlin. A content analysis was carried out. In total, 23 competencies were identified and clustered under the categories of theoretical knowledge, practical skills, and personal attitudes and values. In order to promote mental health, it is necessary to have a knowledge of the principles and concepts of mental health promotion, including methods and tools for effective practices. Furthermore, a variety of skills-based competencies such as communication and collaboration skills were described. Personal attitudes and values included a holistic approach and respect for human rights, among others. The study provides new information on what competencies are needed to plan, implement and evaluate mental health promotion in health sector practice, with the aim of contributing to a more effective workforce. The competencies provide aid in planning training programmes and qualifications, as well as job descriptions and roles in health sector workplaces related to mental health promotion.
Health promotion: an ethical analysis.
Carter, Stacy M
2014-04-01
Thinking and practising ethically requires reasoning systematically about the right thing to do. Health promotion ethics - a form of applied ethics - includes analysis of health promotion practice and how this can be ethically justified. Existing frameworks can assist in such evaluation. These acknowledge the moral value of delivering benefits. But benefits need to be weighed against burdens, harms or wrongs, and these should be minimised: they include invading privacy, breaking confidentiality, restraining liberty, undermining self-determination or people's own values, or perpetuating injustice. Thinking about the ethics of health promotion also means recognising health promotion as a normative ideal: a vision of the good society. This ideal society values health, sees citizens as active and includes them in decisions that affect them, and makes the state responsible for providing all of its citizens, no matter how advantaged or disadvantaged, with the conditions and resources they need to be healthy. Ethicists writing about health promotion have focused on this relationship between the citizen and the state. Comparing existing frameworks, theories and the expressed values of practitioners themselves, we can see common patterns. All oppose pursuing an instrumental, individualistic, health-at-all-costs vision of health promotion. And all defend the moral significance of just processes: those that engage with citizens in a transparent, inclusive and open way. In recent years, some Australian governments have sought to delegitimise health promotion, defining it as extraneous to the role of the state. Good evidence is not enough to counter this trend, because it is founded in competing visions of a good society. For this reason, the most pressing agenda for health promotion ethics is to engage with communities, in a procedurally just way, about the role and responsibilities of the citizen and the state in promoting and maintaining good health.
1969-01-01
This is the insignia of the Apollo 13 lunar landing mission. Represented in the Apollo 13 emblem is Apollo, the sun god of Greek mythology, symbolizing how the Apollo flights have extended the light of knowledge to all mankind. The Latin phrase Ex Luna, Scientia means 'From the Moon, Knowledge'.
[Pathologic proximal femoral fractures in children in an unicameral bone cyst].
Havránek, P; Pesl, T; Bartonícek, J
2005-01-01
Proximal femoral fractures in children are rare, pathologic fractures being extremely rare. Despite many meanings these fractures are still "unsolved" there are some definite rules for treatment of true accidental injuries. Pathologic fractures are outstanding with their extremely rare incidence. The aim of the study is to overview a large clinical material, find out the incidence of this pathologic fracture, the extent and shape of the unicameral bone cyst (UBC), specific therapeutic approach, technical problems of eventual osteosynthesis, number of reoperations and sequels. Altogether 49 children with 50 accidental and pathologic fractures of proximal part of the femur treated in the Regional Pediatric Trauma Centre of the Department of Pediatric and Trauma Surgery, 3rd Faculty of Medicine, Charles University, Prague. Retrospective and prospective study of children (0 to 15 years of age) treated with proximal femoral accidental and pathologic fractures during the 20 year period (from August 1984 to November 2004). Classification of fractures according to Delbet and Colonna. Diagnosis of bone cyst with plain X-rays, eventually CT scans. During the 20 years period (August 1984 to November 2004) 49 children with 50 proximal femoral fractures were treated in the Department. Four patients sustained a pathologic fracture through an unicameral bone cyst. Two of these latter children were treated by an open reduction and osteosynthesis with the use of the proximal femoral AO-ASIF angled-plate and two children nonoperatively using skeletal traction because of impossibility of insertion of the osteosynthetic material without a damage of the growth plate. Subsequent operations of the UBC were necessary in these two children. All four patients recovered well without sequels. Pathologic fractures in UBC are usually treated nonoperatively and the cyst itself is treated after fracture healing. Proximal femoral impairment is the exception from this rule because of weigh bearing
Marketing instruments of foreign trade promotion
Directory of Open Access Journals (Sweden)
Bjelić Predrag
2011-01-01
Full Text Available Instruments of promotion as a part of marketing mix are usually associated with companies but more and more countries use this instrument in order to boost their exports. These foreign trade promotion instruments are now popular in many countries in the world since their use is not opposed to any World Trade Organization rules. Marketing instruments of trade promotions are the most important. They include National Exhibitions and National labels of origin and quality. In order to coordinate the application of these instruments countries have established national bodies for trade promotion. Many studies in the past had argued that national Agencies established to promote export did not had any real success, but recent studies indicate that they could have a significant impact on country export promotion. The result of this rise in impact of national export promotion agencies is due to international effort spearheaded by International Trade Center. The aim of this paper is to point out types and methods of marketing instruments application in trade promotion and to present the effectiveness of these instruments applications.
El-Awa, Fatimah M S; El Naga, Randa Abou; Labib, Sahar; Latif, Nisreen Abdel
2018-04-05
Tobacco use and placement of tobacco products in television (TV) productions and movies is a way to promote tobacco use while avoiding tobacco advertising bans that exist in most countries. The fact that such productions are broadcast widely and viewed by millions, including children and young people, is of concern. This paper reviews the evidence on the use of tobacco advertising, promotion and sponsorship (TAPS) in TV and films in the Eastern Mediterranean Region and the ways to combat it. Evidence from Egypt shows considerable and increasing use of tobacco products by actors on screen, including female actors, in programmes aired during Ramadan in 2015-2017. A study of Iranian movies in 2015 showed that tobacco scenes in Iranian movies were increasing. In 2014, the WHO Regional Office for the Eastern Mediterranean held a consultative meeting on TAPS in drama. The consultation recommended regulating the tobacco presence in movies and TV through complete implementation of Article 13 of the WHO FCTC, and raising the issue to the WHO FCTC Conference of the Parties. In 2016, the Conference of the Parties called on parties to consider scaling up the implementation of WHO FCTC Article 13 and monitoring the use of TAPS in entertainment media in accordance with national legislation. A comprehensive approach is essential to end the tobacco industry's use of TV productions and movies to promote their products. Copyright © World Health Organization (WHO) 2018. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).
Directory of Open Access Journals (Sweden)
Xiaoyan Wang
Full Text Available Extensive studies on floral transition in model species have revealed a network of regulatory interactions between proteins that transduce and integrate developmental and environmental signals to promote or inhibit the transition to flowering. Previous studies indicated FLOWERING PROMOTING FACTOR 1 (FPF1 gene was involved in the promotion of flowering, but the molecular mechanism was still unclear. Here, FPF1 homologous sequences were screened from diploid Gossypium raimondii L. (D-genome, n = 13 and Gossypium arboreum L. genome (A-genome, n = 13 databases. Orthologous genes from the two species were compared, suggesting that distinctions at nucleic acid and amino acid levels were not equivalent because of codon degeneracy. Six FPF1 homologous genes were identified from the cultivated allotetraploid Gossypium hirsutum L. (AD-genome, n = 26. Analysis of relative transcripts of the six genes in different tissues revealed that this gene family displayed strong tissue-specific expression. GhFPF1, encoding a 12.0-kDa protein (Accession No: KC832319 exerted more transcripts in floral apices of short-season cotton, hinting that it could be involved in floral regulation. Significantly activated APETALA 1 and suppressed FLOWERING LOCUS C expression were induced by over-expression of GhFPF1 in the Arabidopsis Columbia-0 ecotype. In addition, transgenic Arabidopsis displayed a constitutive shade-avoiding phenotype that is characterized by long hypocotyls and petioles, reduced chlorophyll content, and early flowering. We propose that GhFPF1 may be involved in flowering time control and shade-avoidance responses.
Liu, Hao; Wei, Nan; Wang, Zhou-fu; Wang, Xi-tang; Ma, Yan
2017-11-01
To improve their mechanical and thermal insulation properties, aluminum silicate fibrous materials with in situ synthesized K2Ti6O13 whiskers were prepared by firing a mixture of short aluminum silicate fibers and gel powders obtained from a sol-gel process. During the preparation process, the fiber surface was coated with K2Ti6O13 whiskers after the fibers were subjected to a heat treatment carried out at various temperatures. The effects of process parameters on the microstructure, compressive strength, and thermal conductivity were analyzed systematically. The results show that higher treatment temperatures and longer treatment durations promoted the development of K2Ti6O13 whiskers on the surface of aluminum silicate fibers; in addition, the intersection structure between whiskers modulated the morphology and volume of the multi-aperture structure among fibers, substantially increasing the fibers' compressive strength and reducing their heat conduction and convective heat transfer at high temperatures.