Sample records for kap promoter enhancer

  1. KAP1 promotes proliferation and metastatic progression of breast cancer cells.

    PubMed

    Addison, Joseph B; Koontz, Colton; Fugett, James H; Creighton, Chad J; Chen, Dongquan; Farrugia, Mark K; Padon, Renata R; Voronkova, Maria A; McLaughlin, Sarah L; Livengood, Ryan H; Lin, Chen-Chung; Ruppert, J Michael; Pugacheva, Elena N; Ivanov, Alexey V

    2015-01-15

    KAP1 (TRIM28) is a transcriptional regulator in embryonic development that controls stem cell self-renewal, chromatin organization, and the DNA damage response, acting as an essential corepressor for KRAB family zinc finger proteins (KRAB-ZNF). To gain insight into the function of this large gene family, we developed an antibody that recognizes the conserved zinc fingers linker region (ZnFL) in multiple KRAB-ZNF. Here, we report that the expression of many KRAB-ZNF along with active SUMOlyated KAP1 is elevated widely in human breast cancers. KAP1 silencing in breast cancer cells reduced proliferation and inhibited the growth and metastasis of tumor xenografts. Conversely, KAP1 overexpression stimulated cell proliferation and tumor growth. In cells where KAP1 was silenced, we identified multiple downregulated genes linked to tumor progression and metastasis, including EREG/epiregulin, PTGS2/COX2, MMP1, MMP2, and CD44, along with downregulation of multiple KRAB-ZNF proteins. KAP1-dependent stabilization of KRAB-ZNF required direct interactions with KAP1. Together, our results show that KAP1-mediated stimulation of multiple KRAB-ZNF contributes to the growth and metastasis of breast cancer. ©2014 American Association for Cancer Research.

  2. A KAP1 phosphorylation switch controls MyoD function during skeletal muscle differentiation.

    PubMed

    Singh, Kulwant; Cassano, Marco; Planet, Evarist; Sebastian, Soji; Jang, Suk Min; Sohi, Gurjeev; Faralli, Hervé; Choi, Jinmi; Youn, Hong-Duk; Dilworth, F Jeffrey; Trono, Didier

    2015-03-01

    The transcriptional activator MyoD serves as a master controller of myogenesis. Often in partnership with Mef2 (myocyte enhancer factor 2), MyoD binds to the promoters of hundreds of muscle genes in proliferating myoblasts yet activates these targets only upon receiving cues that launch differentiation. What regulates this off/on switch of MyoD function has been incompletely understood, although it is known to reflect the action of chromatin modifiers. Here, we identify KAP1 (KRAB [Krüppel-like associated box]-associated protein 1)/TRIM28 (tripartite motif protein 28) as a key regulator of MyoD function. In myoblasts, KAP1 is present with MyoD and Mef2 at many muscle genes, where it acts as a scaffold to recruit not only coactivators such as p300 and LSD1 but also corepressors such as G9a and HDAC1 (histone deacetylase 1), with promoter silencing as the net outcome. Upon differentiation, MSK1-mediated phosphorylation of KAP1 releases the corepressors from the scaffold, unleashing transcriptional activation by MyoD/Mef2 and their positive cofactors. Thus, our results reveal KAP1 as a previously unappreciated interpreter of cell signaling, which modulates the ability of MyoD to drive myogenesis. © 2015 Singh et al.; Published by Cold Spring Harbor Laboratory Press.

  3. How to operate a nuclear pore complex by Kap-centric control

    PubMed Central

    Lim, Roderick Y H; Huang, Binlu; Kapinos, Larisa E

    2015-01-01

    Nuclear pore complexes (NPCs) mediate molecular transport between the nucleus and cytoplasm in eukaryotic cells. Tethered within each NPC lie numerous intrinsically disordered proteins known as FG nucleoporins (FG Nups) that are central to this process. Over two decades of investigation has converged on a view that a barrier mechanism consisting of FG Nups rejects non-specific macromolecules while promoting the speed and selectivity of karyopherin (Kaps) receptors (and their cargoes). Yet, the number of NPCs in the cell is exceedingly small compared to the number of Kaps, so that in fact there is a high likelihood the pores are always populated by Kaps. Here, we contemplate a view where Kaps actively participate in regulating the selectivity and speed of transport through NPCs. This so-called “Kap-centric” control of the NPC accounts for Kaps as essential barrier reinforcements that play a prerequisite role in facilitating fast transport kinetics. Importantly, Kap-centric control reconciles both mechanistic and kinetic requirements of the NPC, and in so doing potentially resolves incoherent aspects of FG-centric models. On this basis, we surmise that Kaps prime the NPC for nucleocytoplasmic transport by fine-tuning the NPC microenvironment according to the functional needs of the cell. PMID:26338152

  4. Enhanced optical, thermal and piezoelectric behavior in dye doped potassium acid phthalate (KAP) single crystal

    NASA Astrophysics Data System (ADS)

    Rao, G. Babu; Rajesh, P.; Ramasamy, P.

    2017-06-01

    Dye inclusion crystals have attracted researchers in the context of crystal growth for applications in solid state lasers. Pure and 0.1 mol% amaranth doped KAP single crystals, were grown from aqueous solutions by slow evaporation technique at room temperature. The grown crystals are up to the dimension of 12×10×3 mm3. Attempt is made to improve the growth rate, optical, piezoelectric and photoconductive properties of pure KAP single crystal with addition of amaranth dye as a dopant. Various characterization studies were made for both pure and dye doped KAP. Thermal stability of the crystals is tested from thermogravimetric and differential thermal analysis (TG/DTA). There is only one endothermic peak indicating decomposition point. Higher optical transparency for dye doped KAP crystal was identified from the UV-vis spectrum. Etching studies showed an improvement in the optical quality of the KAP crystal after doping with amaranth dye. The positive photoconductive nature is observed from both pure and amaranth doped KAP.

  5. Radiation Protection Knowledge, Attitude, and Practice (KAP) in Interventional Radiology.

    PubMed

    Shabani, Fatemeh; Hasanzadeh, Hadi; Emadi, Alireza; Mirmohammadkhani, Majid; Bitarafan-Rajabi, Ahmad; Abedelahi, Ali; Bokharaeian, Mitra; Masoumi, Hamed; Seifi, Danial; Khani, Tahereh; Sanchooli, Mohamad; Moshfegh, Shima; Ziari, Abbas

    2018-03-01

    Due to increasing cardiac disease and its mortality rate, the frequency of cardiac imaging has grown and, as a result, interventional cardiologists potentially receive high radiation doses in cardiac examinations. This study aimed to assess the knowledge, attitude, and practice (KAP) level of radiation protection (RP) among interventional radiology staff in Iranian health care centers across the country. We used a validated questionnaire survey consisting of 30 multiple-choice questions to perform a cross-sectional study. Participants were healthcare personnel working professionally with radiation at different levels (i.e., secretary, radiology technologists, nurse, and physician). The questionnaire was divided into three sections to assess KAP regarding RP. Significant differences exist in RP KAP mean scores based on educational age (p < 0.050). There was no significant difference in RP KAP mean scores when looking at sex, practice age, and hospital type (p > 0.050). We found a significant difference between RP KAP mean scores and different regions (p < 0.050). Educational and practice age, sex, type of hospital, and geographical region affect he KAP of interventional radiology staff regarding RP. Since many of the subjective radiation harms for both medical team and patients, this can be easily controlled and prevented; a checkup for personnel of interventional radiology departments, considering samples from different parts of the country with different levels of education, continuous training, and practical courses may help map the status of KAP. The results of this study may also help authorized health physics officers design strategic plans to enhance the quality of such services in radiation departments.

  6. Radiation Protection Knowledge, Attitude, and Practice (KAP) in Interventional Radiology

    PubMed Central

    Shabani, Fatemeh; Hasanzadeh, Hadi; Emadi, Alireza; Mirmohammadkhani, Majid; Bitarafan-Rajabi, Ahmad; Abedelahi, Ali; Bokharaeian, Mitra; Masoumi, Hamed; Seifi, Danial; Khani, Tahereh; Sanchooli, Mohamad; Moshfegh, Shima; Ziari, Abbas

    2018-01-01

    Objectives Due to increasing cardiac disease and its mortality rate, the frequency of cardiac imaging has grown and, as a result, interventional cardiologists potentially receive high radiation doses in cardiac examinations. This study aimed to assess the knowledge, attitude, and practice (KAP) level of radiation protection (RP) among interventional radiology staff in Iranian health care centers across the country. Methods We used a validated questionnaire survey consisting of 30 multiple-choice questions to perform a cross-sectional study. Participants were healthcare personnel working professionally with radiation at different levels (i.e., secretary, radiology technologists, nurse, and physician). The questionnaire was divided into three sections to assess KAP regarding RP. Results Significant differences exist in RP KAP mean scores based on educational age (p < 0.050). There was no significant difference in RP KAP mean scores when looking at sex, practice age, and hospital type (p > 0.050). We found a significant difference between RP KAP mean scores and different regions (p < 0.050). Conclusions Educational and practice age, sex, type of hospital, and geographical region affect he KAP of interventional radiology staff regarding RP. Since many of the subjective radiation harms for both medical team and patients, this can be easily controlled and prevented; a checkup for personnel of interventional radiology departments, considering samples from different parts of the country with different levels of education, continuous training, and practical courses may help map the status of KAP. The results of this study may also help authorized health physics officers design strategic plans to enhance the quality of such services in radiation departments. PMID:29657683

  7. The Interaction of FABP with Kapα

    PubMed Central

    Amber-Vitos, Ortal; Kucherenko, Nataly; Nachliel, Esther; Gutman, Menachem; Tsfadia, Yossi

    2015-01-01

    Gene-activating lipophilic compounds are carried into the nucleus when loaded on fatty-acid-binding proteins (FABP). Some of these proteins are recognized by the α-Karyopherin (Kapα) through its nuclear localization signal (NLS) consisting of three positive residues that are not in a continuous sequence. The Importin system can distinguish between FABP loaded with activating and non-activating compounds. In the present study, we introduced molecular dynamics as a tool for clarifying the mechanism by which FABP4, loaded with activating ligand (linoleate) is recognized by Kapα. In the first phase, we simulated the complex between KapαΔIBB (termed “Armadillo”) that was crystallized with two NLS hepta-peptides. The trajectory revealed that the crystal-structure orientation of the peptides is rapidly lost and new interactions dominate. Though, the NLS sequence of FABP4 is cryptic, since the functional residues are not in direct sequence, implicating more than one possible conformation. Therefore, four possible docked conformations were generated, in which the NLS of FABP4 is interacting with either the major or the minor sites of Kapα, and the N → C vectors are parallel or anti-parallel. Out of these four basic starting positions, only the FABP4-minor site complex exhibited a large number of contact points. In this complex, the FABP interacts with the minor and the major sites, suppressing the self-inhibitory interaction of the Kapα, rendering it free to react with Kapβ. Finally, we propose that the transportable conformation generated an extended hydrophobic domain which expanded out of the boundary of the FABP4, allowing the loaded linoleate to partially migrate out of the FABP into a joint complex in which the Kapα contributes part of a combined binding pocket. PMID:26284534

  8. Establishment of stable cell line for inducing KAP1 protein expression.

    PubMed

    Liu, Xiaoyan; Khan, Md Asaduzzaman; Cheng, Jingliang; Wei, Chunli; Zhang, Lianmei; Fu, Junjiang

    2015-06-01

    Generation of the stable cell lines is a highly efficient tool in functional studies of certain genes or proteins, where the particular genes or proteins are inducibly expressed. The KRAB-associated protein-1 (KAP1) is an important transcription regulatory protein, which is investigated in several molecular biological studies. In this study, we have aimed to generate a stable cell line for inducing KAP1 expression. The recombinant plasmid pcDNA5/FRT/TO-KAP1 was constructed at first, which was then transfected into Flp-In™T-REx™-HEK293 cells to establish an inducible pcDNA5/FRT/TO-KAP1-HEK293 cell line. The Western blot analysis showed that the protein level of KAP1 is over-expressed in the established stable cell line by doxycycline induction, both dose and time dependently. Thus we have successfully established stable pcDNA5/FRT/TO-KAP1-HEK293 cell line, which can express KAP1 inducibly. This inducible cell line might be very useful for KAP1 functional studies.

  9. Evaluation of equivalent and effective dose by KAP for patient and orthopedic surgeon in vertebral compression fracture surgery

    NASA Astrophysics Data System (ADS)

    Santos, Felipe A.; Galeano, Diego C.; Santos, William S.; Silva, Ademir X.; Souza, Susana O.; Carvalho Júnior, Albérico B.

    2017-03-01

    Clinical scenarios were virtually modeled to estimate both the equivalent and effective doses normalized by KAP (Kerma Area Product) to vertebra compression fracture surgery in patient and surgeon. This surgery is known as kyphoplasty and involves the use of X-ray equipment, the C-arm, which provides real-time images to assist the surgeon in conducting instruments inserted into the patient and in the delivery of surgical cement into the fractured vertebra. The radiation transport code used was MCNPX (Monte Carlo N-Particle eXtended) and a pair of UFHADM (University of Florida Hybrid ADult Male) virtual phantoms. The developed scenarios allowed us to calculate a set of equivalent dose (HT) and effective dose (E) for patients and surgeons. In additional, the same scenario was calculated KAP in the tube output and was used for calculating conversion coefficients (E/KAP and HT/KAP). From the knowledge of the experimental values of KAP and the results presented in this study, it is possible to estimate absolute values of effective doses for different exposure conditions. In this work, we developed scenarios with and without the surgical table with the purpose of comparison with the existing data in the literature. The absence of the bed in the scenario promoted a percentage absolute difference of 56% in the patient effective doses in relation to scenarios calculated with a bed. Regarding the surgeon, the use of the personal protective equipment (PPE) reduces between 75% and 79% the effective dose and the use of the under table shield (UTS) reduces the effective dose of between 3% and 7%. All these variations emphasize the importance of the elaboration of virtual scenarios that approach the actual clinical conditions generating E/KAP and HT/KAP closer to the actual values.

  10. Phosphorylation of KRAB-associated Protein 1 (KAP1) at Tyr-449, Tyr-458, and Tyr-517 by Nuclear Tyrosine Kinases Inhibits the Association of KAP1 and Heterochromatin Protein 1α (HP1α) with Heterochromatin*

    PubMed Central

    Kubota, Sho; Fukumoto, Yasunori; Aoyama, Kazumasa; Ishibashi, Kenichi; Yuki, Ryuzaburo; Morinaga, Takao; Honda, Takuya; Yamaguchi, Noritaka; Kuga, Takahisa; Tomonaga, Takeshi; Yamaguchi, Naoto

    2013-01-01

    Protein tyrosine phosphorylation regulates a wide range of cellular processes at the plasma membrane. Recently, we showed that nuclear tyrosine phosphorylation by Src family kinases (SFKs) induces chromatin structural changes. In this study, we identify KRAB-associated protein 1 (KAP1/TIF1β/TRIM28), a component of heterochromatin, as a nuclear tyrosine-phosphorylated protein. Tyrosine phosphorylation of KAP1 is induced by several tyrosine kinases, such as Src, Lyn, Abl, and Brk. Among SFKs, Src strongly induces tyrosine phosphorylation of KAP1. Nucleus-targeted Lyn potentiates tyrosine phosphorylation of KAP1 compared with intact Lyn, but neither intact Fyn nor nucleus-targeted Fyn phosphorylates KAP1. Substitution of the three tyrosine residues Tyr-449/Tyr-458/Tyr-517, located close to the HP1 binding-motif, into phenylalanine ablates tyrosine phosphorylation of KAP1. Immunostaining and chromatin fractionation show that Src and Lyn decrease the association of KAP1 with heterochromatin in a kinase activity-dependent manner. KAP1 knockdown impairs the association of HP1α with heterochromatin, because HP1α associates with KAP1 in heterochromatin. Intriguingly, tyrosine phosphorylation of KAP1 decreases the association of HP1α with heterochromatin, which is inhibited by replacement of endogenous KAP1 with its phenylalanine mutant (KAP1-Y449F/Y458F/Y517F, KAP1–3YF). In DNA damage, KAP1–3YF repressed transcription of p21. These results suggest that nucleus-localized tyrosine kinases, including SFKs, phosphorylate KAP1 at Tyr-449/Tyr-458/Tyr-517 and inhibit the association of KAP1 and HP1α with heterochromatin. PMID:23645696

  11. LMP1-Induced Sumoylation Influences the Maintenance of Epstein-Barr Virus Latency through KAP1

    PubMed Central

    Moss, Charles Randall; Whitehurst, Christopher B.; Moody, Cary A.

    2015-01-01

    ABSTRACT As a herpesvirus, Epstein-Barr virus (EBV) establishes a latent infection that can periodically undergo reactivation, resulting in lytic replication and the production of new infectious virus. Latent membrane protein-1 (LMP1), the principal viral oncoprotein, is a latency-associated protein implicated in regulating viral reactivation and the maintenance of latency. We recently found that LMP1 hijacks the SUMO-conjugating enzyme Ubc9 via its C-terminal activating region-3 (CTAR3) and induces the sumoylation of cellular proteins. Because protein sumoylation can promote transcriptional repression, we hypothesized that LMP1-induced protein sumoylation induces the repression of EBV lytic promoters and helps maintain the viral genome in its latent state. We now show that with inhibition of LMP1-induced protein sumoylation, the latent state becomes less stable or leakier in EBV-transformed lymphoblastoid cell lines. The cells are also more sensitive to viral reactivation induced by irradiation, which results in the increased production and release of infectious virus, as well as increased susceptibility to ganciclovir treatment. We have identified a target of LMP1-mediated sumoylation that contributes to the maintenance of latency in this context: KRAB-associated protein-1 (KAP1). LMP1 CTAR3-mediated sumoylation regulates the function of KAP1. KAP1 also binds to EBV OriLyt and immediate early promoters in a CTAR3-dependent manner, and inhibition of sumoylation processes abrogates the binding of KAP1 to these promoters. These data provide an additional line of evidence that supports our findings that CTAR3 is a distinct functioning regulatory region of LMP1 and confirm that LMP1-induced sumoylation may help stabilize the maintenance of EBV latency. IMPORTANCE Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1) plays an important role in the maintenance of viral latency. Previously, we documented that LMP1 targets cellular proteins to be modified by a

  12. Kap121p-Mediated Nuclear Import Is Required for Mating and Cellular Differentiation in Yeast

    PubMed Central

    Leslie, Deena M.; Grill, Brock; Rout, Michael P.; Wozniak, Richard W.; Aitchison, John D.

    2002-01-01

    To further our understanding of how the nucleocytoplasmic transport machinery interfaces with its cargoes and how this affects cellular physiology, we investigated the molecular mechanisms of phenotypes associated with mutations in karyopherin Kap121p. Two previously unreported phenotypes of kap121 cells were observed: defects in mating and in the transition from the normal yeast form to the pseudohyphal, invasive form. In parallel, we searched for Kap121p cargoes by using Kap121p as a probe in overlay assays of yeast nuclear proteins. One of the major interacting proteins identified by this procedure was Ste12p, a transcription factor central to both the mating response and the pseudohyphal transition. We therefore investigated whether defects in these differentiation processes were due to an inability to import Ste12p. Both immunopurification and in vitro binding studies demonstrated that Ste12p interacted specifically with Kap121p in a Ran-GTP-sensitive manner and that Ste12p was mislocalized to the cytoplasm by inactivation of Kap121p in a temperature-sensitive mutant. The Kap121p-specific nuclear localization signal (NLS) of Ste12p was determined to reside within a C-terminal region of Ste12p. Furthermore, by overexpression of STE12 or expression of a STE12-cNLS fusion in kap121 cells, the invasive-growth defect and the mating defect were both suppressed. Together these data demonstrate that Ste12p is imported into nuclei by Kap121p and that mating and differentiation defects associated with kap121 mutants are primarily attributable to the mislocalization of Ste12p. PMID:11909949

  13. Structure-based nuclear import mechanism of histones H3 and H4 mediated by Kap123

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

    An, Sojin; Yoon, Jungmin; Kim, Hanseong

    Kap123, a major karyopherin protein of budding yeast, recognizes the nuclear localization signals (NLSs) of cytoplasmic histones H3 and H4 and translocates them into the nucleus during DNA replication. Mechanistic questions include H3- and H4-NLS redundancy toward Kap123 and the role of the conserved diacetylation of cytoplasmic H4 (K5ac and K12ac) in Kap123-mediated histone nuclear translocation. Here, we report crystal structures of full-length Kluyveromyces lactis Kap123 alone and in complex with H3- and H4-NLSs. Structures reveal the unique feature of Kap123 that possesses two discrete lysine-binding pockets for NLS recognition. Structural comparison illustrates that H3- and H4-NLSs share at leastmore » one of two lysine-binding pockets, suggesting that H3- and H4-NLSs are mutually exclusive. Additionally, acetylation of key lysine residues at NLS, particularly H4-NLS diacetylation, weakens the interaction with Kap123. These data support that cytoplasmic histone H4 diacetylation weakens the Kap123-H4-NLS interaction thereby facilitating histone Kap123-H3-dependent H3:H4/Asf1 complex nuclear translocation.« less

  14. SU-G-IeP3-01: Better Kerma-Area-Product (KAP) Estimation Using the System Parameters in Radiography and Fluoroscopy

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

    Kim, D; MacDougall, R

    2016-06-15

    Purpose: Accurate values for Kerma-Area-Product (KAP) are needed for patient dosimetry and quality control for exams utilizing radiographic and/or fluoroscopic imaging. The KAP measured using a typical direct KAP meter built with parallel-plate transmission ionization chamber is not precise and depends on the energy spectrum of diagnostic x-rays. This study compared the accuracy and reproducibility of KAP derived from system parameters with values measured with a direct KAP meter. Methods: IEC tolerance for displayed KAP is specified up to ± 35% above 2.5 Gy-cm{sup 2} and manufacturer’s specifications are typically ± 25%. KAP values from the direct KAP meter driftsmore » with time leading to replacement or re-calibration. More precise and consistent KAP is achievable utilizing a database of known radiation output for various system parameters. The integrated KAP meter was removed from a radiography system. A total of 48 measurements of air kerma were acquired at x-ray tube potential from 40 to 150 kVp with 10 kVp increment using ion chamber type external dosimeter at free-in-air geometry for four different types of filter combinations following the manufacturer’s service procedure. These data were used to create updated correction factors that determine air kerma computationally for given system parameters. Results of calculated KAP were evaluated against results using a calibrated ion chamber based dosimeter and a computed radiography imaging plate to measure x-ray field size. Results: The accuracy of calculated KAP from the system parameters was better within 4% deviation in all diagnostic x-ray tube potentials tested from 50 to 140 kVp. In contrast, deviations of up to 25% were measured from KAP displayed from the direct KAP meter. Conclusion: The “calculated KAP” approach provides the nominal advantage of improved accuracy and precision of displayed KAP as well as reduced cost of calibrating or replacing integrated KAP meters.« less

  15. The Nuclear Transport Factor Kap121 Is Required for Stability of the Dam1 Complex and Mitotic Kinetochore Bi-orientation.

    PubMed

    Cairo, Lucas V; Wozniak, Richard W

    2016-03-15

    The karyopherin (Kap) family of nuclear transport factors facilitates macromolecular transport through nuclear pore complexes (NPCs). The binding of Kaps to their cargos can also regulate, both temporally and spatially, the interactions of the cargo protein with interacting partners. Here, we show that the essential yeast Kap, Kap121, binds Dam1 and Duo1, components of the microtubule (MT)-associated Dam1 complex required for linking dynamic MT ends with kinetochores (KTs). Like mutations in the Dam1 complex, loss of Kap121 function compromises the formation of normal KT-MT attachments during mitosis. We show that the stability of the Dam1 complex in vivo is dependent on its association with Kap121. Furthermore, we show that the Kap121/Duo1 complex is maintained in the presence of RanGTP but Kap121 is released by the cooperative actions of RanGTP and tubulin. We propose that Kap121 stabilizes the Dam1 complex and participates in escorting it to spindle MTs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Effect of amaranth dye on the growth and properties of conventional and SR method grown KAP single crystals

    NASA Astrophysics Data System (ADS)

    Babu Rao, G.; P., Rajesh; Ramasamy, P.

    2018-04-01

    The 0.1 mol% amaranth added KAP single crystals were grown from aqueous solutions by both slow evaporation solution technique and Sankaranarayanan-Ramasamy method. The single crystal having dimension of 45 mm length and 12 mm diameter was grown with growth rate of 1.5 mm/day using SR method. 87 % transmittance is obtained for SR method grown amaranth added KAP single crystal. The high intense luminescence at 661 nm is obtained from amaranth added conventional and SR method grown KAP single crystal. The amaranth added KAP single crystal possesses good mechanical and laser damage threshold stability.

  17. URI Regulates KAP1 Phosphorylation and Transcriptional Repression via PP2A Phosphatase in Prostate Cancer Cells*

    PubMed Central

    Mita, Paolo; Savas, Jeffrey N.; Briggs, Erica M.; Ha, Susan; Gnanakkan, Veena; Yates, John R.; Robins, Diane M.; David, Gregory; Boeke, Jef D.; Garabedian, Michael J.; Logan, Susan K.

    2016-01-01

    URI (unconventional prefoldin RPB5 interactor protein) is an unconventional prefoldin, RNA polymerase II interactor that functions as a transcriptional repressor and is part of a larger nuclear protein complex. The components of this complex and the mechanism of transcriptional repression have not been characterized. Here we show that KAP1 (KRAB-associated protein 1) and the protein phosphatase PP2A interact with URI. Mechanistically, we show that KAP1 phosphorylation is decreased following recruitment of PP2A by URI. We functionally characterize the novel URI-KAP1-PP2A complex, demonstrating a role of URI in retrotransposon repression, a key function previously demonstrated for the KAP1-SETDB1 complex. Microarray analysis of annotated transposons revealed a selective increase in the transcription of LINE-1 and L1PA2 retroelements upon knockdown of URI. These data unveil a new nuclear function of URI and identify a novel post-transcriptional regulation of KAP1 protein that may have important implications in reactivation of transposable elements in prostate cancer cells. PMID:27780869

  18. 76 FR 56193 - KAP Analytics, LLC ; Supplemental Notice That Initial Market-Based Rate Filing Includes Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-12

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER11-4440-000] KAP Analytics... 204 Authorization This is a supplemental notice in the above-referenced proceeding of KAP Analytics... eSubscription link on the Web site that enables subscribers to receive e-mail notification when a...

  19. URI Regulates KAP1 Phosphorylation and Transcriptional Repression via PP2A Phosphatase in Prostate Cancer Cells.

    PubMed

    Mita, Paolo; Savas, Jeffrey N; Briggs, Erica M; Ha, Susan; Gnanakkan, Veena; Yates, John R; Robins, Diane M; David, Gregory; Boeke, Jef D; Garabedian, Michael J; Logan, Susan K

    2016-12-02

    URI (unconventional prefoldin RPB5 interactor protein) is an unconventional prefoldin, RNA polymerase II interactor that functions as a transcriptional repressor and is part of a larger nuclear protein complex. The components of this complex and the mechanism of transcriptional repression have not been characterized. Here we show that KAP1 (KRAB-associated protein 1) and the protein phosphatase PP2A interact with URI. Mechanistically, we show that KAP1 phosphorylation is decreased following recruitment of PP2A by URI. We functionally characterize the novel URI-KAP1-PP2A complex, demonstrating a role of URI in retrotransposon repression, a key function previously demonstrated for the KAP1-SETDB1 complex. Microarray analysis of annotated transposons revealed a selective increase in the transcription of LINE-1 and L1PA2 retroelements upon knockdown of URI. These data unveil a new nuclear function of URI and identify a novel post-transcriptional regulation of KAP1 protein that may have important implications in reactivation of transposable elements in prostate cancer cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. An arginine-rich motif of ring finger protein 4 (RNF4) oversees the recruitment and degradation of the phosphorylated and SUMOylated Krüppel-associated box domain-associated protein 1 (KAP1)/TRIM28 protein during genotoxic stress.

    PubMed

    Kuo, Ching-Ying; Li, Xu; Kong, Xiang-Qian; Luo, Cheng; Chang, Che-Chang; Chung, Yiyin; Shih, Hsiu-Ming; Li, Keqin Kathy; Ann, David K

    2014-07-25

    Krüppel-associated box domain-associated protein 1 (KAP1) is a universal transcriptional corepressor that undergoes multiple posttranslational modifications (PTMs), including SUMOylation and Ser-824 phosphorylation. However, the functional interplay of KAP1 PTMs in regulating KAP1 turnover during DNA damage response remains unclear. To decipher the role and cross-talk of multiple KAP1 PTMs, we show here that DNA double strand break-induced KAP1 Ser-824 phosphorylation promoted the recruitment of small ubiquitin-like modifier (SUMO)-targeted ubiquitin E3 ligase, ring finger protein 4 (RNF4), and subsequent RNF4-mediated, SUMO-dependent degradation. Besides the SUMO interacting motif (SIM), a previously unrecognized, but evolutionarily conserved, arginine-rich motif (ARM) in RNF4 acts as a novel recognition motif for selective target recruitment. Results from combined mutagenesis and computational modeling studies suggest that RNF4 utilizes concerted bimodular recognition, namely SIM for Lys-676 SUMOylation and ARM for Ser(P)-824 of simultaneously phosphorylated and SUMOylated KAP1 (Ser(P)-824-SUMO-KAP1). Furthermore, we proved that arginines 73 and 74 within the ARM of RNF4 are required for efficient recruitment to KAP1 or accelerated degradation of promyelocytic leukemia protein (PML) under stress. In parallel, results of bimolecular fluorescence complementation assays validated the role of the ARM in recognizing Ser(P)-824 in living cells. Taken together, we establish that the ARM is required for RNF4 to efficiently target Ser(P)-824-SUMO-KAP1, conferring ubiquitin Lys-48-mediated proteasomal degradation in the context of double strand breaks. The conservation of such a motif may possibly explain the requirement for timely substrate selectivity determination among a myriad of SUMOylated proteins under stress conditions. Thus, the ARM dynamically regulates the SIM-dependent recruitment of targets to RNF4, which could be critical to dynamically fine-tune the

  1. An Arginine-rich Motif of Ring Finger Protein 4 (RNF4) Oversees the Recruitment and Degradation of the Phosphorylated and SUMOylated Krüppel-associated Box Domain-associated Protein 1 (KAP1)/TRIM28 Protein during Genotoxic Stress*

    PubMed Central

    Kuo, Ching-Ying; Li, Xu; Kong, Xiang-Qian; Luo, Cheng; Chang, Che-Chang; Chung, Yiyin; Shih, Hsiu-Ming; Li, Keqin Kathy; Ann, David K.

    2014-01-01

    Krüppel-associated box domain-associated protein 1 (KAP1) is a universal transcriptional corepressor that undergoes multiple posttranslational modifications (PTMs), including SUMOylation and Ser-824 phosphorylation. However, the functional interplay of KAP1 PTMs in regulating KAP1 turnover during DNA damage response remains unclear. To decipher the role and cross-talk of multiple KAP1 PTMs, we show here that DNA double strand break-induced KAP1 Ser-824 phosphorylation promoted the recruitment of small ubiquitin-like modifier (SUMO)-targeted ubiquitin E3 ligase, ring finger protein 4 (RNF4), and subsequent RNF4-mediated, SUMO-dependent degradation. Besides the SUMO interacting motif (SIM), a previously unrecognized, but evolutionarily conserved, arginine-rich motif (ARM) in RNF4 acts as a novel recognition motif for selective target recruitment. Results from combined mutagenesis and computational modeling studies suggest that RNF4 utilizes concerted bimodular recognition, namely SIM for Lys-676 SUMOylation and ARM for Ser(P)-824 of simultaneously phosphorylated and SUMOylated KAP1 (Ser(P)-824-SUMO-KAP1). Furthermore, we proved that arginines 73 and 74 within the ARM of RNF4 are required for efficient recruitment to KAP1 or accelerated degradation of promyelocytic leukemia protein (PML) under stress. In parallel, results of bimolecular fluorescence complementation assays validated the role of the ARM in recognizing Ser(P)-824 in living cells. Taken together, we establish that the ARM is required for RNF4 to efficiently target Ser(P)-824-SUMO-KAP1, conferring ubiquitin Lys-48-mediated proteasomal degradation in the context of double strand breaks. The conservation of such a motif may possibly explain the requirement for timely substrate selectivity determination among a myriad of SUMOylated proteins under stress conditions. Thus, the ARM dynamically regulates the SIM-dependent recruitment of targets to RNF4, which could be critical to dynamically fine-tune the

  2. KAP Surveys and Dengue Control in Colombia: Disentangling the Effect of Sociodemographic Factors Using Multiple Correspondence Analysis

    PubMed Central

    Quintero, Juliana

    2016-01-01

    During the last few decades, several studies have analyzed and described knowledge, attitudes, and practices (KAP) of populations regarding dengue. However, few studies have applied geometric data analytic techniques to generate indices from KAP domains. Results of such analyses have not been used to determine the potential effects of sociodemographic variables on the levels of KAP. The objective was to determine the sociodemographic factors related to different levels of KAP regarding dengue in two hyper-endemic cities of Colombia, using a multiple correspondence analysis (MCA) technique. In the context of a cluster randomized trial, 3,998 households were surveyed in Arauca and Armenia between 2012 and 2013. To generate KAP indexes, we performed a MCA followed by a hierarchical cluster analysis to classify each score in different groups. A quantile regression for each of the score groups was conducted. KAP indexes explained 56.1%, 79.7%, and 83.2% of the variance, with means of 4.2, 1.4, and 3.2 and values that ranged from 1 to 7, 7 and 11, respectively. The highest values of the index denoted higher levels of knowledge and practices. The attitudes index did not show the same relationship and was excluded from the analysis. In the quantile regression, age (0.06; IC: 0.03, 0.09), years of education (0.14; IC: 0.06, 0.22), and history of dengue in the family (0.21; IC: 0.12, 0.31) were positively related to lower levels of knowledge regarding dengue. The effect of such factors gradually decreased or disappeared when knowledge was higher. The practices indexes did not evidence a correlation with sociodemographic variables. These results suggest that the transformation of categorical variables into a single index by the use of MCA is possible when analyzing knowledge and practices regarding dengue from KAP questionnaires. Additionally, the magnitude of the effect of socioeconomic variables on the knowledge scores varies according to the levels of knowledge, suggesting

  3. Kite Aerial Photography (KAP) as a Tool for Field Teaching

    ERIC Educational Resources Information Center

    Sander, Lasse

    2014-01-01

    Kite aerial photography (KAP) is proposed as a creative tool for geography field teaching and as a medium to approach the complexity of readily available geodata. The method can be integrated as field experiment, surveying technique or group activity. The acquired aerial images can instantaneously be integrated in geographic information systems…

  4. Ar-Ar dating and petrogenesis of the Early Miocene Taşkapı-Mecitli (Erciş-Van) granitoid, Eastern Anatolia Collisional Zone, Turkey

    NASA Astrophysics Data System (ADS)

    Oyan, Vural

    2018-06-01

    The Early Miocene Taşkapı-Mecitli granitoid that is located in the northern section of the Eastern Anatolia Collision Zone has typical I-type, metaluminous and calk-alkaline characteristics. It also contains mafic microgranular / magmatic enclaves (MMEs). New Ar-Ar dating results show that the age of the Taşkapı-Mecitli granitoid is ∼23 Ma and it crystallised in the Early Miocene, in contrast to its previously known Cretaceous age. Identical crystallisation ages (∼23 Ma), similar mineral assemblages and geochemical compositions, and indistinguishable isotopic compositions of MMEs and host rocks imply that the MMEs are most consistent with a cumulate origin formed at earlier stages of the same magmatic system that produced the Taşkapı-Mecitli granitoid. MELTS modelling suggests that magma of the Taşkapı-Mecitli granitoid was the result of fractionation under a crustal pressure of 4 kbar, with a H2O content of 1.5%. EC-AFC model calculation reveals that the Taşkapı-Mecitli granitoid includes from 0.5% to 2% crustal assimilation rates. These rates indicate that crustal contamination can be negligible when compared to fractional crystallisation in the evolution of the magma beneath the Taşkapı-Mecitli granitoid. The partial melting model calculations and MORB-normalised trace element concentrations of the least evolved samples of the Taşkapı-Mecitli granitoid are consistent with those of mafic melts obtained from partial melting of interacting mantle- lower crust with a melting degree of 18%. The age (23 Ma) of the post- or syn-collisional Taşkapı-Mecitli granitoid suggests that the collision between Arabian and Eurasian plates could be before/around ∼23 Ma (Late Oligocene to Early Miocene).

  5. Widespread Enhancer Activity from Core Promoters.

    PubMed

    Medina-Rivera, Alejandra; Santiago-Algarra, David; Puthier, Denis; Spicuglia, Salvatore

    2018-06-01

    Gene expression in higher eukaryotes is precisely regulated in time and space through the interplay between promoters and gene-distal regulatory regions, known as enhancers. The original definition of enhancers implies the ability to activate gene expression remotely, while promoters entail the capability to locally induce gene expression. Despite the conventional distinction between them, promoters and enhancers share many genomic and epigenomic features. One intriguing finding in the gene regulation field comes from the observation that many core promoter regions display enhancer activity. Recent high-throughput reporter assays along with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-related approaches have indicated that this phenomenon is common and might have a strong impact on our global understanding of genome organisation and gene expression regulation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Individual retrotransposon integrants are differentially controlled by KZFP/KAP1-dependent histone methylation, DNA methylation and TET-mediated hydroxymethylation in naïve embryonic stem cells.

    PubMed

    Coluccio, Andrea; Ecco, Gabriela; Duc, Julien; Offner, Sandra; Turelli, Priscilla; Trono, Didier

    2018-02-26

    The KZFP/KAP1 (KRAB zinc finger proteins/KRAB-associated protein 1) system plays a central role in repressing transposable elements (TEs) and maintaining parent-of-origin DNA methylation at imprinting control regions (ICRs) during the wave of genome-wide reprogramming that precedes implantation. In naïve murine embryonic stem cells (mESCs), the genome is maintained highly hypomethylated by a combination of TET-mediated active demethylation and lack of de novo methylation, yet KAP1 is tethered by sequence-specific KZFPs to ICRs and TEs where it recruits histone and DNA methyltransferases to impose heterochromatin formation and DNA methylation. Here, upon removing either KAP1 or the cognate KZFP, we observed rapid TET2-dependent accumulation of 5hmC at both ICRs and TEs. In the absence of the KZFP/KAP1 complex, ICRs lost heterochromatic histone marks and underwent both active and passive DNA demethylation. For KAP1-bound TEs, 5mC hydroxylation correlated with transcriptional reactivation. Using RNA-seq, we further compared the expression profiles of TEs upon Kap1 removal in wild-type, Dnmt and Tet triple knockout mESCs. While we found that KAP1 represents the main effector of TEs repression in all three settings, we could additionally identify specific groups of TEs further controlled by DNA methylation. Furthermore, we observed that in the absence of TET proteins, activation upon Kap1 depletion was blunted for some TE integrants and increased for others. Our results indicate that the KZFP/KAP1 complex maintains heterochromatin and DNA methylation at ICRs and TEs in naïve embryonic stem cells partly by protecting these loci from TET-mediated demethylation. Our study further unveils an unsuspected level of complexity in the transcriptional control of the endovirome by demonstrating often integrant-specific differential influences of histone-based heterochromatin modifications, DNA methylation and 5mC oxidation in regulating TEs expression.

  7. Economic inequality in nutritional knowledge, attitude and practice of Iranian households: The NUTRI-KAP study.

    PubMed

    Heshmat, Ramin; Salehi, Forouzan; Qorbani, Mostafa; Rostami, Mahsa; Shafiee, Gita; Ahadi, Zeinab; Khosravi, Shayesteh; Rezvani, Vahab; Sadeghi Ghotbabadi, Farzaneh; Ghaderpanahi, Maryam; Abdollahi, Zahra

    2016-01-01

    Background: Improper nutritional knowledge is one of the most important causes of nutritional problems, which can affect practice and cause more complications. The aim of this study was to assess the association between nutritional knowledge, attitude and practice (KAP) of Iranian households with socioeconomic status (SES). Methods: The study population was 14,136 households (57 clusters of 8 individuals in each province) who lived in urban and rural regions of 31 provinces of Iran. The sample size of the study was selected using multistage cluster sampling technique. A structured questionnaire and interview with the qualified person in each family was used to collect data. The questionnaire included demographic, SES and nutritional KAP questions. Using principle component analysis, some variables including household assets, occupation and education level of the heads of the families and respondents and the number of family members were used to construct family SES. The SES was categorized as good, moderate and weak. Pearson's Chi-square test was used to analyze categorical variables. Results: The percentage of knowledge about growing up, acquiring energy and being healthy as reasons for eating food was 24.1%, 44.8% and 54.7%, respectively. Only 69.7%, 60.5% and 52.5% of the participants had knowledge of identification of meat and legumes, grain and dairy group, respectively. More than 97% of the participants had a favorable attitude toward importance of nutrition in health. The nutritional knowledge linearly increased with increasing SES. Families with good SES significantly consumed more fruit, vegetable, dairy group, red meat, chicken and poultry, fish and egg while sugar consumption was significantly higher in families with weak SES (p<0.05). Conclusion: SES can influence the rate of nutritional KAP. Some policies should be considered to increase nutritional KAP especially in lower SES group in the society.

  8. Climatic significance of the ostracode fauna from the Pliocene Kap Kobenhavn Formation, north Greenland

    USGS Publications Warehouse

    Brouwers, E.M.; Jorgensen, N.O.; Cronin, T. M.

    1991-01-01

    The Kap Kobenhavn Formation crops out in Greenland at 80??N latitude and marks the most northerly onshore Pliocene locality known. The sands and silts that comprise the formation were deposited in marginal marine and shallow marine environments. An abundant and diverse vertebrate and invertebrate fauna and plant megafossil flora provide age and paleoclimatic constraints. The age estimated for the Kap Kobenhavn ranges from 2.0 to 3.0 million years old. Winter and summer bottom water paleotemperatures were estimated on the basis of the ostracode assemblages. The marine ostracode fauna in units B1 and B2 indicate a subfrigid to frigid marine climate, with estimated minimum sea bottom temperatures (SBT) of -2??C and estimated maximum SBT of 6-8??C. Sediments assigned to unit B2 at locality 72 contain a higher proportion of warm water genera, and the maximum SBT is estimated at 9-10??C. The marginal marine fauna in the uppermost unit B3 (locality 68) indicates a cold temperate to subfrigid marine climate, with an estimated minimum SBT of -2??C and an estimated maximum SBT ranging as high as 12-14??C. These temperatures indicated that, on the average, the Kap Kobenhavn winters in the late Pliocene were similar to or perhaps 1-2??C warmer than winters today and that summer temperatures were 7-8??C warmer than today. -from Authors

  9. Measurement and models of bent KAP(001) crystal integrated reflectivity and resolution (invited)

    NASA Astrophysics Data System (ADS)

    Loisel, G. P.; Wu, M.; Stolte, W.; Kruschwitz, C.; Lake, P.; Dunham, G. S.; Bailey, J. E.; Rochau, G. A.

    2016-11-01

    The Advanced Light Source beamline-9.3.1 x-rays are used to calibrate the rocking curve of bent potassium acid phthalate (KAP) crystals in the 2.3-4.5 keV photon-energy range. Crystals are bent on a cylindrically convex substrate with a radius of curvature ranging from 2 to 9 in. and also including the flat case to observe the effect of bending on the KAP spectrometric properties. As the bending radius increases, the crystal reflectivity converges to the mosaic crystal response. The X-ray Oriented Programs (xop) multi-lamellar model of bent crystals is used to model the rocking curve of these crystals and the calibration data confirm that a single model is adequate to reproduce simultaneously all measured integrated reflectivities and rocking-curve FWHM for multiple radii of curvature in both 1st and 2nd order of diffraction.

  10. Measurement and models of bent KAP(001) crystal integrated reflectivity and resolution (invited)

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

    Loisel, G. P., E-mail: gploise@sandia.gov; Wu, M.; Lake, P.

    2016-11-15

    The Advanced Light Source beamline-9.3.1 x-rays are used to calibrate the rocking curve of bent potassium acid phthalate (KAP) crystals in the 2.3-4.5 keV photon-energy range. Crystals are bent on a cylindrically convex substrate with a radius of curvature ranging from 2 to 9 in. and also including the flat case to observe the effect of bending on the KAP spectrometric properties. As the bending radius increases, the crystal reflectivity converges to the mosaic crystal response. The X-ray Oriented Programs (XOP) multi-lamellar model of bent crystals is used to model the rocking curve of these crystals and the calibration datamore » confirm that a single model is adequate to reproduce simultaneously all measured integrated reflectivities and rocking-curve FWHM for multiple radii of curvature in both 1st and 2nd order of diffraction.« less

  11. Chromatin loops as allosteric modulators of enhancer-promoter interactions.

    PubMed

    Doyle, Boryana; Fudenberg, Geoffrey; Imakaev, Maxim; Mirny, Leonid A

    2014-10-01

    The classic model of eukaryotic gene expression requires direct spatial contact between a distal enhancer and a proximal promoter. Recent Chromosome Conformation Capture (3C) studies show that enhancers and promoters are embedded in a complex network of looping interactions. Here we use a polymer model of chromatin fiber to investigate whether, and to what extent, looping interactions between elements in the vicinity of an enhancer-promoter pair can influence their contact frequency. Our equilibrium polymer simulations show that a chromatin loop, formed by elements flanking either an enhancer or a promoter, suppresses enhancer-promoter interactions, working as an insulator. A loop formed by elements located in the region between an enhancer and a promoter, on the contrary, facilitates their interactions. We find that different mechanisms underlie insulation and facilitation; insulation occurs due to steric exclusion by the loop, and is a global effect, while facilitation occurs due to an effective shortening of the enhancer-promoter genomic distance, and is a local effect. Consistently, we find that these effects manifest quite differently for in silico 3C and microscopy. Our results show that looping interactions that do not directly involve an enhancer-promoter pair can nevertheless significantly modulate their interactions. This phenomenon is analogous to allosteric regulation in proteins, where a conformational change triggered by binding of a regulatory molecule to one site affects the state of another site.

  12. Dextral strike-slip along the Kapıdağ shear zone (NW Turkey): evidence for Eocene westward translation of the Anatolian plate

    NASA Astrophysics Data System (ADS)

    Türkoğlu, Ercan; Zulauf, Gernold; Linckens, Jolien; Ustaömer, Timur

    2016-10-01

    The northern part of the Kapıdağ Peninsula (Marmara Sea, NW Turkey) is affected by the E-W trending Kapıdağ shear zone, which cuts through calc-alkaline granitoids of the Ocaklar pluton resulting in mylonitic orthogneiss. Macroscopic and microscopic shear-sense indicators, such as SC fabrics, shear bands, σ-clasts and mica fish, unequivocally suggest dextral strike-slip for the Kapıdağ shear zone. Based on petrographic data, deformation microfabrics of quartz and feldspar, and the slip systems in quartz, the dextral shearing should have been active at T = 500-300 °C and P < 5 kbar. Published K-Ar and 39Ar-40Ar cooling ages of hornblende and biotite suggest that cooling below 500-300 °C occurred during the Eocene (ca. 45-ca. 35 Ma), meaning that the Kapıdağ shear zone should have been active during Middle to Late Eocene times. The differential stress related to the shearing was <50 MPa as is indicated by the size of recrystallized quartz grains. Based on the new and published data, it is concluded that the westward movement of the Anatolian plate might have been active almost continuously from the Middle Eocene until recent times.

  13. An open randomized controlled clinical trial to evaluate ridge preservation and repair using SocketKAP(™) and SocketKAGE(™) : part 1-three-dimensional volumetric soft tissue analysis of study casts.

    PubMed

    Zadeh, Homayoun H; Abdelhamid, Alaa; Omran, Mostafa; Bakhshalian, Neema; Tarnow, Dennis

    2016-06-01

    The aims of this study were to evaluate (i) the efficacy of ridge preservation and repair involving SocketKAP(™) and SocketKAGE(™) devices following tooth removal; and (ii) ridge contour changes at 6 months post-extraction in intact sockets and sockets with dehiscence defects. Thirty-six patients required a total of 61 teeth to be extracted. Five cohorts were established with groups A-C involving intact sockets and groups D and E involving facial dehiscence: (A) Negative Control; (B) SocketKAP(™) alone; (C) Anorganic Bovine Bone Mineral (ABBM) + SocketKAP(™) ; (D) Negative Control; and (E) ABBM + SocketKAP(™)  + SocketKAGE(™) . Preoperative CBCT and laser-scanned casts were obtained. Teeth segmented from preoperative CBCT were merged with study cast images to allow for digital removal of teeth from the casts. Volumetric measurements of ridge contour were performed. Images of preoperative and 6 months post-operative casts were superimposed to measure ridge contour changes. Post-extraction contour loss occurred in all sockets primarily in the crestal 3 mm but was also detected up to 6 mm from alveolar crest. For intact sockets, SocketKAP(™) or SocketKAP(™)  + ABBM interventions led to greater percentages of remaining ridge contour when compared to controls. A significant difference favoring SocketKAP(™)  + SocketKAGE(™)  + ABBM treatment was observed for sockets with facial dehiscence when compared to controls. SocketKAP(™) , with or without ABBM, significantly limited post-extraction ridge contour loss in intact sockets. In the absence of a group treated with only the SocketKAGE(™) , it is not possible to determine its efficacy, although the combination of SocketKAGE(™)  + SocketKAP(™)  + ABBM was effective in limiting post-extraction ridge contour loss in sockets with dehiscence defects. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. [Evaluation of health education in primary school students from schistosomiasis-endemic areas around Poyang Lake by KAP hierarchical evaluation method].

    PubMed

    Zhu, Jing; Zhao, An; Wang, Li-Wei; Zhang, Wen-Xin; Huang, Chao-Qing; Tang, Qi-Qiang

    2013-10-01

    To quantitatively evaluate the intervention effect of schistosomiasis health education on the knowledge, attitude and behavior (KAP) among the primary school students. A questionnaire was designed to collect baseline data. Questionnairing was conducted among students of grades 3 and 4 from the Central Primary School, Liyuzhou Primary School, and Meichi Primary School in Wuxing Farm of Nanchang City in June 2010. Eighty-four students from Central Primary School were selected as experiment group, and 62 students in the other two schools served as control group. Health education intervention (knowledge lectures, information dissemination, intensive education and so on) was conducted for the students in experiment group from September 2010 to October 2011. Final KAP questionnaire survey was carried out after intervention. A KAP hierarchical evaluation method was used to calculate the KAP scores in the two groups before and after intervention. After health education, the total KAP score in experiment group increased from 8.40 before education to 9.36 (t = 2.994 4, P < 0.01), higher than that of the control (8.53, t = 5.335 5, P < 0.01). The scores of knowledge, attitude and behavior of schistosomiasis control increased from 6.16, 9.10, and 8.67 before education to 8.12, 9.86, and 9.45 after education in experiment group (t = 5.716 8, P < 0.01; t = 3.2764, P < 0.01; t = 3.276 4, P < 0.01), respectively. Compared to the experiment group, after health education the scores of knowledge (6.34, t = 3.517 5, P < 0.01) and attitude of schistosomiasis control (9.43, t = 2.311 9, P < 0.05) were lower in control group; but no significant difference was found on the score of behavior between the two groups. After health education, the scores of 26 indices in experiment group were higher than that of the control and before education. The health education intervention is effective for schistosomiasis control in the experiment school.

  15. Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks

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

    Fukumoto, Yasunori, E-mail: fukumoto@faculty.chiba-u.jp; Kuki, Kazumasa; Morii, Mariko

    2014-09-26

    Highlights: • Inhibition of Src family kinases decreased γ-H2AX signal. • Inhibition of Src family increased ATM-dependent phosphorylation of Chk2 and Kap1. • shRNA-mediated knockdown of Lyn increased phosphorylation of Kap1 by ATM. • Ectopic expression of Src family kinase suppressed ATM-mediated Kap1 phosphorylation. • Src is involved in upstream signaling for inactivation of ATM signaling. - Abstract: DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the processmore » by which cells recover from the DNA damage checkpoint, a process called checkpoint recovery. Here, we show that Src family kinases promote inactivation of ataxia telangiectasia mutated (ATM)-dependent checkpoint signaling during recovery from DNA double-strand breaks. Inhibition of Src activity increased ATM-dependent phosphorylation of Chk2 and Kap1. Src inhibition increased ATM signaling both in G2 phase and during asynchronous growth. shRNA knockdown of Lyn increased ATM signaling. Src-dependent nuclear tyrosine phosphorylation suppressed ATM-mediated Kap1 phosphorylation. These results suggest that Src family kinases are involved in upstream signaling that leads to inactivation of the ATM-dependent DNA damage checkpoint.« less

  16. An open randomized controlled clinical trial to evaluate ridge preservation and repair using SocketKAP(™) and SocketKAGE(™) : part 2 - three-dimensional alveolar bone volumetric analysis of CBCT imaging.

    PubMed

    Abdelhamid, Alaa; Omran, Mostafa; Bakhshalian, Neema; Tarnow, Dennis; Zadeh, Homayoun H

    2016-06-01

    The aims of this study were (i) to evaluate the efficacy of ridge preservation and repair procedures involving the application of SocketKAP(™) and SocketKAGE(™) devices following tooth removal and (ii) to evaluate alveolar bone volumetric changes at 6 months post-extraction in intact sockets or those with facial wall dehiscence defects using 3-dimensional pre- and postoperative CBCT data. Thirty-six patients required 61 teeth extracted. Five cohorts were established: Group A: Intact Socket Negative Control Group B: Intact Socket + SocketKAP(™) Group C: Intact Socket Filled with Anorganic Bovine Bone Mineral (ABBM) + SocketKAP(™) Group D: Facial Dehiscence Socket Negative Control Group E: Facial Dehiscence Socket Filled with ABBM + SocketKAP(™) + SocketKAGE(™) . Preoperative CBCT scans were obtained followed by digital subtraction of the test teeth. At 6 months post-extraction, another CBCT scan was obtained. The pre- and postoperative scans were then superimposed, allowing highly accurate quantitative determination of the 3D volumetric alveolar bone volume changes from baseline through 6 months. Significant volumetric bone loss occurred in all sockets, localized mainly in the 0-3 mm zone apical to the ridge crest. For intact sockets, SocketKAP(™) + ABBM treatment led to a statistically significant greater percentage of remaining mineralized tissue volume when compared to negative control group. A significant difference favoring SocketKAP(™) + SocketKAGE(™) + ABBM treatment was observed for sockets with facial dehiscence defects compared to the negative control group. SocketKAP(™) , with ABBM, appears effective in limiting post-extraction volumetric bone loss in intact sockets, while SocketKAP(™) + SocketKAGE + ABBM appears effective in limiting post-extraction bone loss in sockets with dehiscence defects. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Distinct roles of KAP1, HP1 and G9a/GLP in silencing of the two-cell-specific retrotransposon MERVL in mouse ES cells

    PubMed Central

    2013-01-01

    Background In mouse embryonic stem cells (mESCs), transcriptional silencing of numerous class I and II endogenous retroviruses (ERVs), including IAP, ETn and MMERVK10C, is dependent upon the H3K9 methyltransferase (KMTase) SETDB1/ESET and its binding partner KAP1/TRIM28. In contrast, the H3K9 KMTases G9a and GLP and HP1 proteins are dispensable for this process. Intriguingly, MERVL retroelements are actively transcribed exclusively in the two-cell (2C) embryo, but the molecular basis of silencing of these class III ERVs at later developmental stages has not been systematically addressed. Results Here, we characterized the roles of these chromatin factors in MERVL silencing in mESCs. While MMERVK10C and IAP ERVs are bound by SETDB1 and KAP1 and are induced following their deletion, MERVL ERVs show relatively low levels of SETDB1 and KAP1 binding and are upregulated exclusively following KAP1 depletion, indicating that KAP1 influences MERVL expression independent of SETDB1. In contrast to class I and class II ERVs, MERVL and MERVL LTR-driven genic transcripts are also upregulated following depletion of G9a or GLP, and G9a binds directly to these ERVs. Consistent with a direct role for H3K9me2 in MERVL repression, these elements are highly enriched for G9a-dependent H3K9me2, and catalytically active G9a is required for silencing of MERVL LTR-driven transcripts. MERVL is also derepressed in HP1α and HP1β KO ESCs. However, like KAP1, HP1α and HP1β are only modestly enriched at MERVL relative to IAP LTRs. Intriguingly, as recently shown for KAP1, RYBP, LSD1 and G9a-deficient mESCs, many genes normally expressed in the 2C embryo are also induced in HP1 KO mESCs, revealing that aberrant expression of a subset of 2C-specific genes is a common feature in each of these KO lines. Conclusions Our results indicate that G9a and GLP, which are not required for silencing of class I and II ERVs, are recruited to MERVL elements and play a direct role in silencing of these class

  18. Habit modification of potassium acid phthalate (KAP) single crystals by impurities

    NASA Astrophysics Data System (ADS)

    Murugakoothan, P.; Mohan Kumar, R.; Ushasree, P. M.; Jayavel, R.; Dhanasekaran, R.; Ramasamy, P.

    1999-12-01

    Nonlinear optical materials potassium dihydrogen phosphate (KDP), urea and L-arginine phosphate (LAP)-doped KAP crystals were grown by the slow cooling method. The LAP-doped crystals show pronounced habit modification compared to KDP and urea doping. The effect of these impurities on growth kinetics, surface morphology, habit modification, structure, optical and mechanical properties have been studied. Among the three impurities, urea doping yields high mechanical stability and optical transmission and for KDP and LAP doping there is a decrease in optical transmission.

  19. Knowledge, attitude, and practice (KAP) of 'teaching laboratory' technicians towards laboratory safety and waste management: a pilot interventional study.

    PubMed

    El-Gilany, A-H; El-Shaer, S; Khashaba, E; El-Dakroory, S A; Omar, N

    2017-06-01

    A quasi-experimental study was performed on 20 technicians working in the Faculty of Medicine, Mansoura University, Egypt. The knowledge, attitude, and practice (KAP) of laboratory technicians was measured before and two months after enrolling them in an intervention programme about laboratory best practice procedures. The programme addressed laboratory safety and medical waste management. The assessment was performed using a validated Arabic self-administered questionnaire. Pre- and post-intervention scores were compared using non-parametric tests. There are significant increases in the scores of KAP after implementation of the training programme. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  20. Genome-wide characterization of mammalian promoters with distal enhancer functions.

    PubMed

    Dao, Lan T M; Galindo-Albarrán, Ariel O; Castro-Mondragon, Jaime A; Andrieu-Soler, Charlotte; Medina-Rivera, Alejandra; Souaid, Charbel; Charbonnier, Guillaume; Griffon, Aurélien; Vanhille, Laurent; Stephen, Tharshana; Alomairi, Jaafar; Martin, David; Torres, Magali; Fernandez, Nicolas; Soler, Eric; van Helden, Jacques; Puthier, Denis; Spicuglia, Salvatore

    2017-07-01

    Gene expression in mammals is precisely regulated by the combination of promoters and gene-distal regulatory regions, known as enhancers. Several studies have suggested that some promoters might have enhancer functions. However, the extent of this type of promoters and whether they actually function to regulate the expression of distal genes have remained elusive. Here, by exploiting a high-throughput enhancer reporter assay, we unravel a set of mammalian promoters displaying enhancer activity. These promoters have distinct genomic and epigenomic features and frequently interact with other gene promoters. Extensive CRISPR-Cas9 genomic manipulation demonstrated the involvement of these promoters in the cis regulation of expression of distal genes in their natural loci. Our results have important implications for the understanding of complex gene regulation in normal development and disease.

  1. Effect of fluoroscopic X-ray beam spectrum on air-kerma measurement accuracy: implications for establishing correction coefficients on interventional fluoroscopes with KAP meters.

    PubMed

    Wunderle, Kevin A; Rakowski, Joseph T; Dong, Frank F

    2016-05-08

    The first goal of this study was to investigate the accuracy of the displayed reference plane air kerma (Ka,r) or air kerma-area product (Pk,a) over a broad spectrum of X-ray beam qualities on clinically used interventional fluoroscopes incorporating air kerma-area product meters (KAP meters) to measure X-ray output. The second goal was to investigate the accuracy of a correction coefficient (CC) determined at a single beam quality and applied to the measured Ka,r over a broad spectrum of beam qualities. Eleven state-of-the-art interventional fluoroscopes were evaluated, consisting of eight Siemens Artis zee and Artis Q systems and three Philips Allura FD systems. A separate calibrated 60 cc ionization chamber (external chamber) was used to determine the accuracy of the KAP meter over a broad range of clinically used beam qualities. For typical adult beam qualities, applying a single CC deter-mined at 100 kVp with copper (Cu) in the beam resulted in a deviation of < 5% due to beam quality variation. This result indicates that applying a CC determined using The American Association of Physicists in Medicine Task Group 190 protocol or a similar protocol provides very good accuracy as compared to the allowed ± 35% deviation of the KAP meter in this limited beam quality range. For interventional fluoroscopes dedicated to or routinely used to perform pediatric interventions, using a CC established with a low kVp (~ 55-60 kVp) and large amount of Cu filtration (~ 0.6-0.9 mm) may result in greater accuracy as compared to using the 100 kVp values. KAP meter responses indicate that fluoroscope vendors are likely normalizing or otherwise influencing the KAP meter output data. Although this may provide improved accuracy in some instances, there is the potential for large discrete errors to occur, and these errors may be difficult to identify.

  2. Enhancer-promoter interference and its prevention in transgenic plants

    USDA-ARS?s Scientific Manuscript database

    Transcriptional enhancer elements have been shown to override the specificity of nearby promoters in a position- and orientation-independent manner. This is problematic when multiple enhancers/promoters co-exist within a single transgenic construct as it has the potential to cause the mis-expressio...

  3. Socio-economic, Knowledge Attitude Practices (KAP), household related and demographic based appearance of non-dengue infected individuals in high dengue risk areas of Kandy District, Sri Lanka.

    PubMed

    Udayanga, Lahiru; Gunathilaka, Nayana; Iqbal, M C M; Pahalagedara, Kusumawathie; Amarasinghe, Upali S; Abeyewickreme, Wimaladharma

    2018-02-21

    Socio-economic, demographic factors and Knowledge Attitude Practices (KAPs) have been recognized as critical factors that influence the incidence and transmission of dengue epidemics. However, studies that characterize above features of a risk free or low risk population are rare. Therefore, the present study was conducted to characterize the household related, demographic, socio-economic factors and KAPs status of five selected dengue free communities. An analytical cross-sectional survey was conducted on selected demographic, socio-economic, household related and KAPs in five selected dengue free communities living in dengue risk areas within Kandy District, Central Province, Sri Lanka. Household heads of 1000 randomly selected houses were interviewed in this study. Chi-square test for independence, cluster analysis and Principal Coordinates (PCO) analysis were used for data analysis. Knowledge and awareness regarding dengue, (prevention of the vector breeding, bites of mosquitoes, disease symptoms and waste management) and attitudes of the community (towards home gardening, composting, waste management and maintenance of a clean and dengue free environment) are associated with the dengue free status of the study populations. The vector controlling authorities should focus on socio-economic, demographic and KAPs in stimulating the community to cooperate in the integrated vector management strategies to improve vector control and reduce transmission of dengue within Kandy District.

  4. Architectural and functional commonalities between enhancers and promoters

    PubMed Central

    Kim, Tae-Kyung; Shiekhattar, Ramin

    2015-01-01

    Summary With the explosion of genome-wide studies of regulated transcription, it has become clear that traditional definitions of enhancers and promoters need to be revisited. These control elements can now be characterized in terms of their local and regional architecture, their regulatory components including histone modifications and associated binding factors and their functional contribution to transcription. This review discusses unifying themes between promoters and enhancers in transcriptional regulatory mechanisms. PMID:26317464

  5. Intragenic Locus in Human PIWIL2 Gene Shares Promoter and Enhancer Functions.

    PubMed

    Skvortsova, Yulia V; Kondratieva, Sofia A; Zinovyeva, Marina V; Nikolaev, Lev G; Azhikina, Tatyana L; Gainetdinov, Ildar V

    2016-01-01

    Recently, more evidence supporting common nature of promoters and enhancers has been accumulated. In this work, we present data on chromatin modifications and non-polyadenylated transcription characteristic for enhancers as well as results of in vitro luciferase reporter assays suggesting that PIWIL2 alternative promoter in exon 7 also functions as an enhancer for gene PHYHIP located 60Kb upstream. This finding of an intragenic enhancer serving as a promoter for a shorter protein isoform implies broader impact on understanding enhancer-promoter networks in regulation of gene expression.

  6. Effectiveness of an educational program to promote pesticide safety among pesticide handlers of South India.

    PubMed

    Sam, Kishore Gnana; Andrade, Hira H; Pradhan, Lisa; Pradhan, Abhishek; Sones, Shashi J; Rao, Padma G M; Sudhakar, Christopher

    2008-05-01

    Occupational poisoning with pesticides is common in developing countries because farmers are often under trained, illiterate and consider it impractical and expensive to use safety equipment, especially in tropical climates. Greater benefit of education programs on prevention can be obtained if initiated in areas having higher occurrence of poisoning. Hence, the present study evaluated occurrence of poisoning and effectiveness of educational interventions among pesticide handlers in areas having high occurrence of occupational poisoning. Two villages of Udupi district of South India were identified by spot mapping and targeted for a public education program on safe handling of pesticides, the impact of which was assessed using a knowledge attitude and practice (KAP) questionnaire. Education was provided using a structured individualized training program to 74 pesticide handlers. Three point KAP assessments were carried out at baseline, immediately after training and after 1 month of training. Nonparametric Kruskal-Wallis tests and Friedmann tests were used to compare scores at different time points and between groups. Occurrence of occupation related poisoning was 33% and common in three villages of the district. The average baseline KAP score of 30.88 +/- 10.33 improved after education significantly (P < 0.001) at first follow-up 45.03 +/- 9.16 and at second follow-up 42.9 +/- 9.54. A decline of score between the first and second follow-up may be attributed to decline in knowledge retention. Demographics like gender, literacy and presence of children affected KAP score and there was no influence of geography, age or frequency of pesticide use. Educational intervention among pesticide handlers improved the KAP score for safe pesticide handling. We recommend that continuous education and training programs for agricultural workers will promote awareness and minimize the hazards of occupational pesticide exposure.

  7. Transvection Goes Live-Visualizing Enhancer-Promoter Communication between Chromosomes.

    PubMed

    Tsai, Albert; Singer, Robert H; Crocker, Justin

    2018-04-19

    Lim et al. (2018) use live imaging in Drosophila embryos to show that enhancers can drive transcription from promoters on another chromosome when they are in close proximity. In addition, they show that multiple promoters can access the same enhancer without competition, potentially sharing a pool of factors in a transcriptional "hub." Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Nutrition-Related Knowledge, Attitudes, and Practices (KAP) among Kindergarten Teachers in Chongqing, China: A Cross-Sectional Survey

    PubMed Central

    Liu, Dengyuan; Rao, Yunshuang; Yuan, Jun; Chen, Yao; Zhao, Yong

    2018-01-01

    Kindergarten teachers play an important role in providing kindergarten children with education on nutrition. However, few studies have been published on nutrition-related knowledge, attitudes, and practices (KAP) of Chinese kindergarten teachers. This study aimed to assess the nutrition-related knowledge, attitudes, and practices (KAP) of kindergarten teachers in Chongqing, China. Thus, a cross-sectional survey was conducted using a structured KAP model questionnaire administered to 222 kindergarten teachers, who were senior teachers from 80 kindergartens in 19 districts and 20 counties in Chongqing. Multiple regression analysis was used to analyze the influential factors. Among the participants, 54.2% were familiar with simple nutrition-related knowledge; only 9.9% of them were satisfied with their knowledge of childhood nutrition; and 97.7% of them had a positive attitude to learn nutrition-related knowledge. Only 38.7% of the participants had attended pediatric nutrition knowledge courses or training. Multiple regression analysis confirmed significant independent effects on the nutrition knowledge score (p < 0.0001) of respondents on age, type of residence, type of kindergarten, body mass index(BMI), professional training of kindergarten teachers, behavior of having ever participated in childhood nutrition education knowledge courses or training, and behavior of having ever paid attention to children’s nutrition knowledge. The model indicated that independent variables explained 45.4% (adjusted R2) of the variance found in the knowledge scores of respondents. While there were low levels of nutrition knowledge and training, it was still encouraging to note that there were positive attitudes towards acquiring nutrition-related knowledge among kindergarten teachers in Chongqing, China. These findings provide some implications that necessary training measures need to be carried out to improve the nutrition-related knowledge level among kindergarten teachers in

  9. Nutrition-Related Knowledge, Attitudes, and Practices (KAP) among Kindergarten Teachers in Chongqing, China: A Cross-Sectional Survey.

    PubMed

    Liu, Hongyan; Xu, Xianglong; Liu, Dengyuan; Rao, Yunshuang; Reis, Cesar; Sharma, Manoj; Yuan, Jun; Chen, Yao; Zhao, Yong

    2018-03-28

    Kindergarten teachers play an important role in providing kindergarten children with education on nutrition. However, few studies have been published on nutrition-related knowledge, attitudes, and practices (KAP) of Chinese kindergarten teachers. This study aimed to assess the nutrition-related knowledge, attitudes, and practices (KAP) of kindergarten teachers in Chongqing, China. Thus, a cross-sectional survey was conducted using a structured KAP model questionnaire administered to 222 kindergarten teachers, who were senior teachers from 80 kindergartens in 19 districts and 20 counties in Chongqing. Multiple regression analysis was used to analyze the influential factors. Among the participants, 54.2% were familiar with simple nutrition-related knowledge; only 9.9% of them were satisfied with their knowledge of childhood nutrition; and 97.7% of them had a positive attitude to learn nutrition-related knowledge. Only 38.7% of the participants had attended pediatric nutrition knowledge courses or training. Multiple regression analysis confirmed significant independent effects on the nutrition knowledge score ( p < 0.0001) of respondents on age, type of residence, type of kindergarten, body mass index(BMI), professional training of kindergarten teachers, behavior of having ever participated in childhood nutrition education knowledge courses or training, and behavior of having ever paid attention to children's nutrition knowledge. The model indicated that independent variables explained 45.4% (adjusted R²) of the variance found in the knowledge scores of respondents. While there were low levels of nutrition knowledge and training, it was still encouraging to note that there were positive attitudes towards acquiring nutrition-related knowledge among kindergarten teachers in Chongqing, China. These findings provide some implications that necessary training measures need to be carried out to improve the nutrition-related knowledge level among kindergarten teachers in

  10. A study of the knowledge, attitudes, and practices (KAP) of the women referred to health centers for cardiovascular disease (CVDs) and their risk factors.

    PubMed

    Mazloomy, Seyed Said; Baghianimoghadam, Mohammad Hosein; Ehrampoush, Mohammad Hasan; Baghianimoghadam, Behnam; Mazidi, Maysam; Mozayan, Mohammad Reza

    2014-01-01

    Hypertension, dyslipidemia, and diabetes are established risk factors for cardiovascular disease (CVD) morbidity and mortality. In the past decade a general increase in CVD risk factors in the population aged 65 and older, along with suboptimal control rates, have occurred. In this descriptive, cross-sectional study, the authors describe the knowledge, attitudes, and practices (KAP) of Iranian females regarding risk factors for CVD, in an attempt to help with the development of strategies to control risk factors and CVD. Participants were 200 women ages 15-49 referred to health centers in Yazd, selected from four different centers. Data were gathered through a questionnaire consisting of demographics and questions related to KAP. The validity of the questionnaire was determined by a health education specialist, with its reliability determined by piloting and measuring the related Cronbach's alpha (Alpha = 0.720). Measuring knowledge of CVD on a scale of 0-20, the mean knowledge score was 10.203.91. More than 76% of the participants knew that CVD is preventable. Ninety-one percent liked exercising and believed that exercising would make them feel better. The average mean scores for attitudes of participants toward CVD were 30.31 ± 3.21 out of 36. The authors conclude that there is a need for enhancing mothers' general knowledge about the disease, because of the increasing rates of CVD in females. This will lead to improvements in attitude and practice. Furthermore, learning in groups of 12 can be a beneficial educational method.

  11. Seroprevalence and "Knowledge, Attitudes and Practices" (KAPs) survey of endemic ovine brucellosis in Egypt.

    PubMed

    Hegazy, Yamen; Elmonir, Walid; Abdel-Hamid, Nour Hosny; Elbauomy, Essam Mohamed

    2016-01-07

    Between February and July 2014, a cross-sectional study to estimate the seroprevalence of brucellosis in sheep in the Kafrelsheikh district of Egypt was carried out, together with a survey of knowledge, attitudes and practices (KAPs) among local shepherds. A total of 273 serum samples were collected from 28 sheep flocks in 10 villages within the study area. These samples were analysed by the Rose Bengal Plate test (RBPT) test, with all positive samples being confirmed by complement fixation test (CFT). True seroprevalence was 20 % (95 % CI 15.3-24.7 %) with the prevalence of villages with at least one seropositive sheep estimated at 95.5 % (95 % CI 92.2-100 %); village flock seroprevalence ranged from 0 to 46.8 %. Results of the KAPs survey demonstrated that despite good knowledge regarding brucellosis being potentially present within their flocks, shepherds lacked knowledge regarding routes of livestock to humans disease transmission and the symptoms of brucellosis in humans. This lack of knowledge regarding disease transmission resulted in high-risk practices being widespread-practices such as assisting parturition without protective measures, throwing aborted material into water canals and a reluctance to remove animals that had aborted from the flock. This study proposes potential measures to reduce seroprevalence of brucellosis in sheep and reduce public health risks from brucellosis such as culling aborted livestock and educational campaigns among shepherds regarding disease risks and modes of transmission.

  12. 9 CFR 3.81 - Environment enhancement to promote psychological well-being.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Environment enhancement to promote..., Treatment, and Transportation of Nonhuman Primates 2 Facilities and Operating Standards § 3.81 Environment..., document, and follow an appropriate plan for environment enhancement adequate to promote the psychological...

  13. 9 CFR 3.81 - Environment enhancement to promote psychological well-being.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Environment enhancement to promote..., Treatment, and Transportation of Nonhuman Primates 2 Facilities and Operating Standards § 3.81 Environment..., document, and follow an appropriate plan for environment enhancement adequate to promote the psychological...

  14. 9 CFR 3.81 - Environment enhancement to promote psychological well-being.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Environment enhancement to promote..., Treatment, and Transportation of Nonhuman Primates 2 Facilities and Operating Standards § 3.81 Environment..., document, and follow an appropriate plan for environment enhancement adequate to promote the psychological...

  15. The karyopherin Kap95 and the C-termini of Rfa1, Rfa2, and Rfa3 are necessary for efficient nuclear import of functional RPA complex proteins in Saccharomyces cerevisiae.

    PubMed

    Belanger, Kenneth D; Griffith, Amanda L; Baker, Heather L; Hansen, Jeanne N; Kovacs, Laura A Simmons; Seconi, Justin S; Strine, Andrew C

    2011-09-01

    Nuclear protein import in eukaryotic cells is mediated by karyopherin proteins, which bind to specific nuclear localization signals on substrate proteins and transport them across the nuclear envelope and into the nucleus. Replication protein A (RPA) is a nuclear protein comprised of three subunits (termed Rfa1, Rfa2, and Rfa3 in Saccharomyces cerevisiae) that binds single-stranded DNA and is essential for DNA replication, recombination, and repair. RPA associates with two different karyopherins in yeast, Kap95, and Msn5/Kap142. However, it is unclear which of these karyopherins is responsible for RPA nuclear import. We have generated GFP fusion proteins with each of the RPA subunits and demonstrate that these Rfa-GFP chimeras are functional in yeast cells. The intracellular localization of the RPA proteins in live cells is similar in wild-type and msn5Δ deletion strains but becomes primarily cytoplasmic in cells lacking functional Kap95. Truncating the C-terminus of any of the RPA subunits results in mislocalization of the proteins to the cytoplasm and a loss of protein-protein interactions between the subunits. Our data indicate that Kap95 is likely the primary karyopherin responsible for RPA nuclear import in yeast and that the C-terminal regions of Rfa1, Rfa2, and Rfa3 are essential for efficient nucleocytoplasmic transport of each RPA subunit.

  16. Enhancer Sharing Promotes Neighborhoods of Transcriptional Regulation Across Eukaryotes

    PubMed Central

    Quintero-Cadena, Porfirio; Sternberg, Paul W.

    2016-01-01

    Enhancers physically interact with transcriptional promoters, looping over distances that can span multiple regulatory elements. Given that enhancer–promoter (EP) interactions generally occur via common protein complexes, it is unclear whether EP pairing is predominantly deterministic or proximity guided. Here, we present cross-organismic evidence suggesting that most EP pairs are compatible, largely determined by physical proximity rather than specific interactions. By reanalyzing transcriptome datasets, we find that the transcription of gene neighbors is correlated over distances that scale with genome size. We experimentally show that nonspecific EP interactions can explain such correlation, and that EP distance acts as a scaling factor for the transcriptional influence of an enhancer. We propose that enhancer sharing is commonplace among eukaryotes, and that EP distance is an important layer of information in gene regulation. PMID:27799341

  17. [Effectiveness of social mobilization and social marketing in promoting NaFeEDTA-fortified soya sauce in adult women].

    PubMed

    Wang, Bo; Chen, Junshi; Zhan, Siyan; Sun, Jing; Li, Liming

    2011-05-01

    To assess the effectiveness of social mobilization and social marketing in promoting NaFeEDTA-fortified soy sauce in an iron deficient population. This study was an uncontrolled, community-based, before-after study, which was implemented in three counties of Shijiazhuang Municipality. The intervention was a social mobilization and social marketing strategy. Adult women older than 20 years of age participated in the evaluation protocol. The main outcomes included KAP relevant to IDA. Cross-sectional samples were used to assess the outcomes at baseline and 1 year later. Knowledge and attitudes of adult women had changed positively, and the percentage of women who had adopted NaFeEDTA-fortified soy sauce increased from 8.9% to 36.6% (P < 0.001). Social mobilization and social marketing had a positive impact on the KAP of adult women in the iron deficient population.

  18. Flux enhancement during ultrafiltration of produced water using turbulence promoter.

    PubMed

    Zhen, Xiang-hua; Yu, Shui-li; Wang, Bei-fu; Zheng, Hai-feng

    2006-01-01

    Concentration polarization and membrane fouling remain one of the major hurdles for the implementation of ultrafiltration of produced water. Although many applications for ultrafiltration were already suggested, only few were implemented on an industrial scale. Among those techniques, turbulence promoter can be more simple and effective in overcoming membrane fouling and enhancing membrane flux. As for the result that turbulence promoter increase fluid velocity, wall shear rates and produce secondary flows or instabilities, the influence of turbulence promoter was investigated on permeate flux during produced water ultrafiltration and the potential application of this arrangement for an industrial development. Experimental investigations were performed on 100 KDa molecular weight cut-off PVDF single-channel tubular membrane module using four kinds of turbulence promoters. It is observed that the significant flux enhancement in the range of 83%-164% was achieved while the hydraulic dissipated power per unit volume of permeate decreased from 31%-42%, which indicated that the using of turbulence promoter is more efficient than operation without the turbulence promoter. The effects of transmembrane pressure and cross-flow velocity with and without turbulence promoter were studied as well. Among the four kinds of turbulence promoters, winding inserts with 20.0 mm pitch and 1.0 mm wire diameter showed better performances than the others did.

  19. Radiation Protection Knowledge, Attitude and Practice (RP-KAP) as Predictors of Job Stress Among Radiation Workers in Tehran Province, Iran

    PubMed Central

    Alavi, S. Shohreh; Taghizadeh Dabbagh, Sima; Abbasi, Mahya; Mehrdad, Ramin

    2016-01-01

    Background In recent years, much attention has been paid to occupational stress, but relatively little or no research has been conducted on the influence of knowledge, attitude, and practice of radiation protection (RP-KAP) on job stress among radiation workers Objectives This study aims to assess job stress among health care workers in Iran who are occupationally exposed to radiation in order to determine the effects of KAP on self-protection against radiation on their job stress. Materials and Methods The population in this descriptive cross-sectional study comprised 670 healthcare workers, including 428 staff with a degree in radiology and 242 other medical personnel who were working in 16 hospitals affiliated with Tehran University of Medical Sciences (TUMS) in Tehran, Iran. The census method was used to sample the workers. In total, 264 staff with a degree in radiology and 149 other medical personnel completed the job content questionnaire (JCQ) and the RP-KAP questionnaire from May to November 2014. Results The prevalence rate of job stress was 22.5% based on calculation formulas and possible scores on the JCQ. Sex, RP-knowledge, attitude, practice, and in-service training predicted 41.8% of the variance in job stress. According to the results of the binary logistic regression, workers with higher scores on knowledge (OR = 0.82, 95% CI: 0.75 - 0.90), attitude (OR = 0.71, 95% CI: 0.63 - 0.82), and practice (OR = 0.78, 95% CI: 0.72 - 0.86) and those who had participated in training programs had significantly lower rates of job stress (OR = 0.51, 95% CI: 0.28 - 0.93). Conclusions The effects of RP knowledge, attitude, and practice on job stress were significant. In order to reduce job stress in radiation environments, ongoing training programs related to self-care and protection principles are recommended. PMID:28180020

  20. Radiation Protection Knowledge, Attitude and Practice (RP-KAP) as Predictors of Job Stress Among Radiation Workers in Tehran Province, Iran.

    PubMed

    Alavi, S Shohreh; Taghizadeh Dabbagh, Sima; Abbasi, Mahya; Mehrdad, Ramin

    2016-10-01

    In recent years, much attention has been paid to occupational stress, but relatively little or no research has been conducted on the influence of knowledge, attitude, and practice of radiation protection (RP-KAP) on job stress among radiation workers. This study aims to assess job stress among health care workers in Iran who are occupationally exposed to radiation in order to determine the effects of KAP on self-protection against radiation on their job stress. The population in this descriptive cross-sectional study comprised 670 healthcare workers, including 428 staff with a degree in radiology and 242 other medical personnel who were working in 16 hospitals affiliated with Tehran University of Medical Sciences (TUMS) in Tehran, Iran. The census method was used to sample the workers. In total, 264 staff with a degree in radiology and 149 other medical personnel completed the job content questionnaire (JCQ) and the RP-KAP questionnaire from May to November 2014. The prevalence rate of job stress was 22.5% based on calculation formulas and possible scores on the JCQ. Sex, RP-knowledge, attitude, practice, and in-service training predicted 41.8% of the variance in job stress. According to the results of the binary logistic regression, workers with higher scores on knowledge (OR = 0.82, 95% CI: 0.75 - 0.90), attitude (OR = 0.71, 95% CI: 0.63 - 0.82), and practice (OR = 0.78, 95% CI: 0.72 - 0.86) and those who had participated in training programs had significantly lower rates of job stress (OR = 0.51, 95% CI: 0.28 - 0.93). The effects of RP knowledge, attitude, and practice on job stress were significant. In order to reduce job stress in radiation environments, ongoing training programs related to self-care and protection principles are recommended.

  1. Diabetes and Diabetic Retinopathy: Knowledge, Attitude, Practice (KAP) among Diabetic Patients in A Tertiary Eye Care Centre

    PubMed Central

    Srinivasan, Nithin Keshav; John, Deepa; Rebekah, Grace; Kujur, Evon Selina; Paul, Padma

    2017-01-01

    Introduction Diabetic retinopathy is becoming an increasingly important cause of visual impairment in India. Many diabetic patients who come to our centre have undetected, advanced diabetic retinopathy. If diabetic retinopathy had been detected earlier in these patients, irreversible visual impairment could have been prevented. Aim To document Knowledge, Attitude and Practice (KAP) patterns of diabetic patients regarding diabetes and diabetic retinopathy, to determine association between them, and to identify barriers to compliance with follow up and treatment regimes. Materials and Methods This was a hospital-based, cross-sectional study, conducted at the Department of Ophthalmology at Christian Medical College, Vellore, Tamil Nadu, India, over a six-month period from June 2013 to November 2013. Two hundred and eighty eight diabetic patients, who fulfilled the eligibility criteria, were included in the study. KAP of patients was assessed using a 45-point, verbally administered questionnaire. Patients were placed in different categories, such as, ‘good/ poor’ knowledge, ‘positive/negative’ attitude and ‘good/poor’ practice. Data were analysed using Chi-square test and binary logistic regression, as appropriate. The proportion of patients with ‘good/poor’ knowledge, ‘positive/negative’ attitude and ‘good/poor’ practice, and the association between KAP were studied. Barriers to compliance with follow up/treatment regimes were identified. Results Out of the 288 patients in the study, 42% had good knowledge about diabetes, but only 4.5% had good knowledge about retinopathy. Good knowledge about diabetes was significantly associated with positive attitude towards diabetes and good practice patterns regarding retinopathy; awareness of retinopathy was also significantly associated with good practice. A total of 61.1% of patients did not have periodic eye examination; most common barrier identified was lack of awareness about the necessity for this

  2. γ-H2AX/53BP1/pKAP-1 foci and their linear tracks induced by in vitro exposure to radon and its progeny in human peripheral blood lymphocytes

    PubMed Central

    Ding, Defang; Zhang, Yaping; Wang, Jing; Wang, Xufei; Fan, Dunhuang; He, Linfeng; Zhang, Xuxia; Gao, Yun; Li, Qiang; Chen, Honghong

    2016-01-01

    The biodosimetric information is critical for evaluating the human health hazards caused by radon and its progeny. Here, we demonstrated that the formation of phosphorylated histone variant H2AX (γ-H2AX), p53-binding protein 1 (53BP1) and phosphorylated KRAB-associated protein 1 (pKAP-1) foci and their linear tracks in human peripheral blood lymphocytes (HPBLs) in vitro exposed to radon and its progeny were dependent on the cumulative absorbed dose of radon exposure but was unrelated to the concentration of radon. Among them, γ-H2AX foci and its linear tracks were the most sensitive indicators with the lowest estimable cumulative absorbed dose of 1.74 mGy from their linear dose-response curves and sustained for 12 h after termination of radon exposure. In addition, three types of foci showed an overdispersed non-Poisson distribution in HPBLs. The ratios of pKAP-1/γ-H2AX foci co-localization, 53BP1/γ-H2AX foci co-localization and 53BP1/pKAP-1 foci co-localization were significantly increased in HPBLs exposed to radon while they were unrelated to the cumulative dose of radon exposure, suggesting that γ-H2AX, pKAP-1 and 53BP1 play an important role in the repair of heterochromatic double-strand breaks. Altogether, our findings provide an experimental basis for estimating the biological dose of internal α-particle irradiation from radon and its progeny exposure in humans. PMID:27922110

  3. [Evaluation of promoting the oral cavity health measures of rural AIDS patients/HIV-carriers].

    PubMed

    Tao, Wei; Jiang, Yong

    2011-05-01

    To survey the status of oral cavity hygiene knowledge, attitude and practice (KAP) of rural acquired immunodeficiency syndrome (AIDS) patients and human immunodeficiency virus (HIV) carriers and take corresponding intervention measures to improve the oral health of these patients. From May to August in 2009, the methods of anonymous face to face structured interview and oral examination at the scene were carried out at the baseline in rural AIDS patients/HIV-carriers. According to the results of the survey, intervention measures were taken. The results of the intervention and the oral hygiene status were compared before and after the intervention. The oral health status of 82 AIDS patients and HIV-carriers were in poor before the intervention, and the knowledge of AIDS-related oral health of 76 AIDS patients and HIV-carriers was promoted after interventions, "scaling can spread AIDS" were 22 cases (27%), and after the intervention 41 patients (54%) think that can spread (χ(2) = 20.066, P < 0.001). The oral diseases of related AIDS were decreased dramatically, 68 patients (83%) had gingivitis before intervention and 47 cases (62%) after the intervention (χ(2) = 8.852, P = 0.003). The personal oral cavity hygiene and related oral KAP of AIDS caused by subjective factors had improved to different extent, "brushing teeth over 3 min at every turn", there were over 36 cases (44%) before intervention and 45 patients after intervention (59%) (χ(2) = 4.017, P = 0.045). The oral hygiene and KAP of AIDS patients and HIV-carriers in rural areas were poor and improved after intervention.

  4. Enhancer activity of Helitron in sericin-1 gene promoter from Bombyx mori.

    PubMed

    Huang, Ke; Li, Chun-Feng; Wu, Jie; Wei, Jun-Hong; Zou, Yong; Han, Min-Jin; Zhou, Ze-Yang

    2016-06-01

    Sericin is a kind of water-soluble protein expressed specifically in the middle silk gland of Bombyx mori. When the sericin-1 gene promoter was cloned and a transgenic vector was constructed to express a foreign protein, a specific Helitron, Bmhel-8, was identified in the sericin-1 gene promoter sequence in some genotypes of Bombyx mori and Bombyx mandarina. Given that the Bmhel-8 Helitron transposon was present only in some genotypes, it could be the source of allelic variation in the sericin-1 promoter. The length of the sericin-1 promoter sequence is approximately 1063 or 643 bp. The larger size of the sequence or allele is ascribed to the presence of Bmhel-8. Silkworm genotypes can be homozygous for either the shorter or larger promoter sequence or heterozygous, containing both alleles. Bmhel-8 in the sericin-1 promoter exhibits enhancer activity, as demonstrated by a dual-luciferase reporter system in BmE cell lines. Furthermore, Bmhel-8 displays enhancer activity in a sericin-1 promoter-driven gene expression system but does not regulate the tissue-specific expression of sericin-1. © 2016 Institute of Zoology, Chinese Academy of Sciences.

  5. Wellness Promotion in the Schools: Enhancing Students' Mental and Physical Health

    ERIC Educational Resources Information Center

    Miller, David N.; Gilman, Rich; Martens, Matthew P.

    2007-01-01

    Wellness promotion addresses both the reduction of disorder and disease and the enhancement of mental and physical health. There is increasing evidence of a strong and reciprocal relationship between mental and physical health, and linking these two areas may be particularly useful for promoting positive youth development in school contexts. This…

  6. Knowledge, attitudes and practices (KAP) relating to avian influenza in urban and rural areas of China

    PubMed Central

    2010-01-01

    Background Studies have revealed that visiting poultry markets and direct contact with sick or dead poultry are significant risk factors for H5N1 infection, the practices of which could possibly be influenced by people's knowledge, attitudes and practices (KAPs) associated with avian influenza (AI). To determine the KAPs associated with AI among the Chinese general population, a cross-sectional survey was conducted in China. Methods We used standardized, structured questionnaires distributed in both an urban area (Shenzhen, Guangdong Province; n = 1,826) and a rural area (Xiuning, Anhui Province; n = 2,572) using the probability proportional to size (PPS) sampling technique. Results Approximately three-quarters of participants in both groups requested more information about AI. The preferred source of information for both groups was television. Almost three-quarters of all participants were aware of AI as an infectious disease; the urban group was more aware that it could be transmitted through poultry, that it could be prevented, and was more familiar with the relationship between AI and human infection. The villagers in Xiuning were more concerned than Shenzhen residents about human AI viral infection. Regarding preventative measures, a higher percentage of the urban group used soap for hand washing whereas the rural group preferred water only. Almost half of the participants in both groups had continued to eat poultry after being informed about the disease. Conclusions Our study shows a high degree of awareness of human AI in both urban and rural populations, and could provide scientific support to assist the Chinese government in developing strategies and health-education campaigns to prevent AI infection among the general population. PMID:20170542

  7. Using social media to enhance career development opportunities for health promotion professionals.

    PubMed

    Roman, Leah A

    2014-07-01

    For health promotion professionals, social media offers many ways to engage with a broader range of colleagues; participate in professional development events; promote expertise, products, or services; and learn about career-enhancing opportunities such as funding and fellowships. Previous work has recommended "building networking into what you are already doing." This article provides updated and new social media resources, as well as practical examples and strategies to promote effective use of social media. Social media offers health promotion professionals cost-effective opportunities to enhance their career by building communities of practice, participating in professional development events, and enriching classroom learning. Developing the skills necessary to use social media for networking is important in the public health workforce, especially as social media is increasingly used in academic and practice settings. © 2014 Society for Public Health Education.

  8. CCAAT/enhancer-binding protein beta promotes osteoblast differentiation by enhancing Runx2 activity with ATF4.

    PubMed

    Tominaga, Hiroyuki; Maeda, Shingo; Hayashi, Makoto; Takeda, Shu; Akira, Shizuo; Komiya, Setsuro; Nakamura, Takashi; Akiyama, Haruhiko; Imamura, Takeshi

    2008-12-01

    Although CCAAT/enhancer-binding protein beta (C/EBPbeta) is involved in osteocalcin gene expression in osteoblast in vitro, the physiological importance of and molecular mechanisms governing C/EBPbeta in bone formation remain to be elucidated. In particular, it remains unclear whether C/EBPbeta acts as a homodimer or a heterodimer with other proteins during osteoblast differentiation. Here, deletion of the C/EBPbeta gene from mice resulted in delayed bone formation with concurrent suppression of chondrocyte maturation and osteoblast differentiation. The expression of type X collagen as well as chondrocyte hypertrophy were suppressed in mutant bone, providing new insight into the possible roles of C/EBPbeta in chondrocyte maturation. In osteoblasts, luciferase reporter, gel shift, DNAP, and ChIP assays demonstrated that C/EBPbeta heterodimerized with activating transcription factor 4 (ATF4), another basic leucine zipper transcription factor crucial for osteoblast maturation. This complex interacted and transactivated osteocalcin-specific element 1 (OSE1) of the osteocalcin promoter. C/EBPbeta also enhanced the synergistic effect of ATF4 and Runx2 on osteocalcin promoter transactivation by enhancing their interaction. Thus, our results provide evidence that C/EBPbeta is a crucial cofactor in the promotion of osteoblast maturation by Runx2 and ATF4.

  9. Eliminating Plasmodium falciparum in Hainan, China: a study on the use of behavioural change communication intervention to promote malaria prevention in mountain worker populations.

    PubMed

    He, Chang-hua; Hu, Xi-min; Wang, Guang-ze; Zhao, Wei; Sun, Ding-wei; Li, Yu-chun; Chen, Chun-xiang; Du, Jian-wei; Wang, Shan-qing

    2014-07-13

    In the island of Hainan, the great majority of malaria cases occur in mountain worker populations. Using the behavioral change communication (BCC) strategy, an interventional study was conducted to promote mountain worker malaria prevention at a test site. This study found the methods and measures that are suitable for malaria prevention among mountain worker populations. During the Plasmodium falciparum elimination stage in Hainan, a representative sampling method was used to establish testing and control sites in areas of Hainan that were both affected by malaria and had a relatively high density of mountain workers. Two different methods were used: a BCC strategy and a conventional strategy as a control. Before and after the intervention, house visits, core group discussions, and structural surveys were utilized to collect qualitative and quantitative data regarding mountain worker populations (including knowledge, attitudes, and practices [KAPs]; infection status; and serological data), and these data from the testing and control areas were compared to evaluate the effectiveness of BCC strategies in the prevention of malaria. In the BCC malaria prevention strategy testing areas, the accuracy rates of malaria-related KAP were significantly improved among mountain worker populations. The accuracy rates in the 3 aspects of malaria-related KAP increased from 37.73%, 37.00%, and 43.04% to 89.01%, 91.53%, and 92.25%, respectively. The changes in all 3 aspects of KAP were statistically significant (p < 0.01). In the control sites, the changes in the indices were not as marked as in the testing areas, and the change was not statistically significant (p > 0.05). Furthermore, in the testing areas, both the percentage testing positive in the serum malaria indirect fluorescent antibody test (IFAT) and the number of people inflicted decreased more significantly than in the control sites (p < 0.01). The use of the BCC strategy significantly improved the ability of mountain

  10. KAPS (kinematic assessment of passive stretch): a tool to assess elbow flexor and extensor spasticity after stroke using a robotic exoskeleton.

    PubMed

    Centen, Andrew; Lowrey, Catherine R; Scott, Stephen H; Yeh, Ting-Ting; Mochizuki, George

    2017-06-19

    Spasticity is a common sequela of stroke. Traditional assessment methods include relatively coarse scales that may not capture all characteristics of elevated muscle tone. Thus, the aim of this study was to develop a tool to quantitatively assess post-stroke spasticity in the upper extremity. Ninety-six healthy individuals and 46 individuals with stroke participated in this study. The kinematic assessment of passive stretch (KAPS) protocol consisted of passive elbow stretch in flexion and extension across an 80° range in 5 movement durations. Seven parameters were identified and assessed to characterize spasticity (peak velocity, final angle, creep (or release), between-arm peak velocity difference, between-arm final angle, between-arm creep, and between-arm catch angle). The fastest movement duration (600 ms) was most effective at identifying impairment in each parameter associated with spasticity. A decrease in peak velocity during passive stretch between the affected and unaffected limb was most effective at identifying individuals as impaired. Spasticity was also associated with a decreased passive range (final angle) and a classic 'catch and release' as seen through between-arm catch and creep metrics. The KAPS protocol and robotic technology can provide a sensitive and quantitative assessment of post-stroke elbow spasticity not currently attainable through traditional measures.

  11. Lipid Biomarker Records Across the Permian-Triassic Boundary from Kap Stosch, Greenland

    NASA Astrophysics Data System (ADS)

    Hays, L. E.; Love, G. D.; Foster, C. B.; Grice, K.; Summons, R. E.

    2006-12-01

    The end-Permian extinction was the most severe in the past 500 million years of the Earth's history and evidence that an oceanic anoxic event (OAE) occurred contemporaneously has been presented previously [1,2]. OAEs have, therefore, been proposed as responsible for the mass mortality, and if the anoxic ocean was also euxinic, the release of hydrogen sulfide during upwelling and/or transgression provides an extinction agent in the ocean as well as on land. Chlorobiaceae, as indicators of photic zone euxinia (PZE), utilize hydrogen sulfide as an electron donor for anoxygenic photosynthesis. The detection of isorenieratane and a series of short-chain monoaromatic aryl isoprenoids, biomarkers for Chlorobiaceae, in sediments indicates the presence of hydrogen sulfide in the photic zone of the water column during sediment deposition. The Kap Stosch area in Eastern Greenland was identified as a Permian-Triassic boundary (PTB) outcrop of homogeneous shale, silty shale, and siltstone facies [3]. Another late Permian section in Eastern Greenland, the Ravnefjeld Formation, has framboidal pyrites indicative of sulfidic deep water [4]. A sample suite from the Kap Stosch region was studied using standard organic geochemistry methods including stable isotopic analyses of organic carbon, Rock-Eval pyrolysis, and biomarker hydrocarbon analysis. Aryl isoprenoids, including isorenieratane, were present in all samples studied and the concentrations were observed to fluctuate in tandem with TOC, similar to other Mesozoic OAEs. The molecular ratios of pristane/phytane and hopanes/steranes as well as the 2-methyl-hopane index (2-MHI) fluctuated dramatically through this section as they do at the type section at Meishan and in the Perth Basin [5]. The 2-MHI shows an inverse pattern to the total aryl isoprenoids, perhaps indicative of instability in the form of primary productivity in the water column during euxinic episodes. This can result in nitrogen limitation and a competitive

  12. Direct interactions of OCA-B and TFII-I regulate immunoglobulin heavy-chain gene transcription by facilitating enhancer-promoter communication.

    PubMed

    Ren, Xiaodi; Siegel, Rachael; Kim, Unkyu; Roeder, Robert G

    2011-05-06

    B cell-specific coactivator OCA-B, together with Oct-1/2, binds to octamer sites in promoters and enhancers to activate transcription of immunoglobulin (Ig) genes, although the mechanisms underlying their roles in enhancer-promoter communication are unknown. Here, we demonstrate a direct interaction of OCA-B with transcription factor TFII-I, which binds to DICE elements in Igh promoters, that affects transcription at two levels. First, OCA-B relieves HDAC3-mediated Igh promoter repression by competing with HDAC3 for binding to promoter-bound TFII-I. Second, and most importantly, Igh 3' enhancer-bound OCA-B and promoter-bound TFII-I mediate promoter-enhancer interactions, in both cis and trans, that are important for Igh transcription. These and other results reveal an important function for OCA-B in Igh 3' enhancer function in vivo and strongly favor an enhancer mechanism involving looping and facilitated factor recruitment rather than a tracking mechanism. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Direct interactions of OCA-B and TFII-I regulate immunoglobulin heavy-chain gene transcription by facilitating enhancer-promoter communication

    PubMed Central

    Ren, Xiaodi; Siegel, Rachael; Kim, Unkyu; Roeder, Robert G.

    2011-01-01

    Summary B cell-specific coactivator OCA-B, together with Oct-1/2, binds to octamer sites in promoters and enhancers to activate transcription of immunoglobulin (Ig) genes, although the mechanisms underlying their roles in enhancer-promoter communication are unknown. Here, we demonstrate a direct interaction of OCA-B with transcription factor TFII-I, which binds to DICE elements in IgH promoters, that affects transcription at two levels. First, OCA-B relieves HDAC3-mediated IgH promoter repression by competing with HDAC3 for binding to promoter-bound TFII-I. Second, and most importantly, Igh 3′enhancer-bound OCA-B and promoter-bound TFII-I mediate promoter-enhancer interactions, in both cis and trans, that are important for Igh transcription. These and other results reveal an important function for OCA-B in Igh 3′enhancer function in vivo and strongly favor an enhancer mechanism involving looping and facilitated factor recruitment rather than a tracking mechanism. PMID:21549311

  14. CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function

    PubMed Central

    Guo, Ya; Xu, Quan; Canzio, Daniele; Shou, Jia; Li, Jinhuan; Gorkin, David U.; Jung, Inkyung; Wu, Haiyang; Zhai, Yanan; Tang, Yuanxiao; Lu, Yichao; Wu, Yonghu; Jia, Zhilian; Li, Wei; Zhang, Michael Q.; Ren, Bing; Krainer, Adrian R.; Maniatis, Tom; Wu, Qiang

    2015-01-01

    SUMMARY CTCF/cohesin play a central role in insulator function and higher-order chromatin organization of mammalian genomes. Recent studies identified a correlation between the orientation of CTCF-binding sites (CBSs) and chromatin loops. To test the functional significance of this observation, we combined CRISPR/Cas9-based genomic-DNA-fragment editing with chromosome-conformation-capture experiments to show that the location and relative orientations of CBSs determine the specificity of long-range chromatin looping in mammalian genomes, using protocadherin (Pcdh) and β-globin as model genes. Inversion of CBS elements within the Pcdh enhancer reconfigures the topology of chromatin loops between the distal enhancer and target promoters, and alters gene-expression patterns. Thus, although enhancers can function in an orientation-independent manner in reporter assays, in the native chromosome context the orientation of at least some enhancers carrying CBSs can determine both the architecture of topological chromatin domains and enhancer/promoter specificity. The findings reveal how 3D chromosome architecture can be encoded by genome sequence. PMID:26276636

  15. School based oral health promotional intervention: Effect on knowledge, practices and clinical oral health related parameters

    PubMed Central

    Gauba, Arjun; Bal, Ikreet Singh; Jain, Ashish; Mittal, Hitesh Chander

    2013-01-01

    Background: No organized school oral health program is existent in India. Aim: The aim of this study is to test the feasibility and efficacy of an economical school oral health promotional intervention with educational and preventive components. Settings and Design: School oral health promotional intervention carried out in one of the randomly selected school and evaluated through short duration prospective model. Materials and Methods: A total of 100 children with an age range of 10-12 years with no previous history of dental intervention were enrolled. Interventions comprised of oral health education (delivered through lecture and demonstrations by an undergraduate dental student) and topical antibacterial therapy (fluoride varnish and povidone iodine). Outcomes consisted of Knowledge and practices (KAP) regarding oral health, clinical oral health related parameters such as plaque index (PI), gingival index (GI) and caries activity as per Modified Snyder's test. These were reported at baseline, 3 weeks and 6 months follow-up examination by a calibrated examiner. Statistical Analysis: McNemar Bowker's test, Student's t-test, Pearson Chi-square tests were used. Results: Highly significant (P < 0.001) improvements in KAP scores, PI scores, GI scores and caries activity were reported at 3 weeks and 6 months follow-up examination. Conclusion: This small economical school oral health program positively influenced oral health related practices and parameters of oral health such as oral cleanliness, gingival health and caries activity. PMID:24403795

  16. Strategies for enhancing bioluminescent bacterial sensor performance by promoter region manipulation

    PubMed Central

    Bilic, Benny; Belkin, Shimshon

    2010-01-01

    Genetically engineered microbial reporter strains are based upon the fusion of an inducible sensing element upstream of a reporting element, so that the construct emits a dose-dependent signal when exposed to the inducing compound(s) or stress factor(s). In this communication1 we described several general approaches undertaken in order to enhance the sensing performance of such promoter::reporter fusions. Significant improvements in detection sensitivity, response kinetics and signal intensity were achieved by modi fication of the length of the promoter-containing DNA fragment, by random or site-directed mutagenesis and by promoter duplication. The general nature of these genetics manipulations makes them applicable to other types of promoter::reporter fusions. PMID:21326942

  17. Lifestyle Change Plus Dental Care (LCDC) program improves knowledge, attitude, and practice (KAP) toward oral health and diabetes mellitus among the elderly with type 2 diabetes.

    PubMed

    Saengtipbovorn, Saruta; Taneepanichskul, Surasak

    2015-03-01

    Currently, there is an increased prevalence of diabetes mellitus among the elderly. Chronic inflammation from diabetes mellitus effects glycemic control and increases risk of diabetes complications. To assess the effectiveness of a Lifestyle Change plus Dental Care (LCDC) program by improved knowledge, attitude, and practice (KAP) toward oral health and diabetes mellitus among the elderly with type 2 diabetes. A quasi-experimental study was conducted in two Health Centers (HC 54 intervention and HC 59 control) between October 2013 and April 2014. Sixty-six diabetic patients per health center were recruited. At baseline, the intervention group attended a 20-minute lifestyle and oral health education program, individual lifestyle counseling using motivational interviewing, application of self-regulation manual, and individual oral hygiene instruction. At 3-month follow-up, the intervention group received individual lifestyle counseling and oral hygiene instruction. The intervention group received booster education every visit by viewing a 15-minute educational video. The control group received the routine program. Participants were assessed at baseline, 3-month, and 6-month follow-up for knowledge, attitude, and practice (KAP) toward oral health and diabetes mellitus. Data was analyzed by using descriptive statistic, Chi-square test, Fisher's exact test, and repeated measure ANOVA. After the 6-month follow-up, repeated measure ANOVA analysis showed that participants in the intervention group had significantly higher knowledge and attitude toward oral health and diabetes mellitus. The participants in the intervention group were more likely to exercise, modify diet, have foot examinations, always wear covered shoes, participate in self-feet screening, use dental floss, and use inter-proximal brush than the control group with statistically significant differences. The combination of lifestyle change and dental care in one program improved knowledge, attitude

  18. Concomitant Mycobacterium tuberculosis infection promotes lung tumor growth through enhancing Treg development.

    PubMed

    Zhou, Yan; Hu, Zhangguo; Cao, Shuhui; Yan, Bo; Qian, Jialin; Zhong, Hua

    2017-08-01

    Lung cancer is the most common malignancy in humans. An increased population of CD4+Foxp3+ regulatory T cells (Tregs) in the tumor-associated microenvironment plays an important role in cancer immune evasion. The exact role and the involved mechanisms of concomitant H37Rv infection in non-small cell lung cancer (NSCLC) development are still not clear. Here, we showed that H37Rv infection promoted NSCLC cell growth with a higher percentage of Tregs found in draining lymph nodes. We also determined in vitro that H37Rv infection induced macrophage maturation and PD-L1 expression, which promoted Treg proportion, with enhanced proliferation suppression function. Mechanism analysis revealed that AKT-mTORC1 signal was important for PD-L1 expression induced by H37Rv infection. Suppressing of AKT-mTORC1 signal by rapamycin or raptor deficiency showed decreased PD-L1 levels which further reduced Treg proportion in a co-culture system. Finally, tumor-bearing mice injected with H37Rv plus rapamycin enhance the immune response of lung cancer compared with injected with H37Rv alone. This study demonstrated that concomitant H37Rv infection promote NSCLC tumor immune eacape through enhancing Treg proportion.

  19. Enhanced Shewanella biofilm promotes bioelectricity generation.

    PubMed

    Liu, Ting; Yu, Yang-Yang; Deng, Xiao-Peng; Ng, Chun Kiat; Cao, Bin; Wang, Jing-Yuan; Rice, Scott A; Kjelleberg, Staffan; Song, Hao

    2015-10-01

    Electroactive biofilms play essential roles in determining the power output of microbial fuel cells (MFCs). To engineer the electroactive biofilm formation of Shewanella oneidensis MR-1, a model exoelectrogen, we herein heterologously overexpressed a c-di-GMP biosynthesis gene ydeH in S. oneidensis MR-1, constructing a mutant strain in which the expression of ydeH is under the control of IPTG-inducible promoter, and a strain in which ydeH is under the control of a constitutive promoter. Such engineered Shewanella strains had significantly enhanced biofilm formation and bioelectricity generation. The MFCs inoculated with these engineered strains accomplished a maximum power density of 167.6 ± 3.6 mW/m(2) , which was ∼ 2.8 times of that achieved by the wild-type MR-1 (61.0 ± 1.9 mW/m(2) ). In addition, the engineered strains in the bioelectrochemical system at poised potential of 0.2 V vs. saturated calomel electrode (SCE) generated a stable current density of 1100 mA/m(2) , ∼ 3.4 times of that by wild-type MR-1 (320 mA/m(2) ). © 2015 Wiley Periodicals, Inc.

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

    Kamitani, Shinya; Ohbayashi, Norihiko; Ikeda, Osamu

    Signal transducers and activators of transcription (STATs) mediate cell proliferation, differentiation, and survival in immune responses, hematopoiesis, neurogenesis, and other biological processes. Recently, we showed that KAP1 is a novel STAT-binding partner that regulates STAT3-mediated transactivation. KAP1 is a universal co-repressor protein for the KRAB zinc finger protein superfamily of transcriptional repressors. In this study, we found KAP1-dependent repression of interferon (IFN)/STAT1-mediated signaling. We also demonstrated that endogenous KAP1 associates with endogenous STAT1 in vivo. Importantly, a small-interfering RNA-mediated reduction in KAP1 expression enhanced IFN-induced STAT1-dependent IRF-1 gene expression. These results indicate that KAP1 may act as an endogenous regulatormore » of the IFN/STAT1 signaling pathway.« less

  1. Improved muscle-derived expression of human coagulation factor IX from a skeletal actin/CMV hybrid enhancer/promoter.

    PubMed

    Hagstrom, J N; Couto, L B; Scallan, C; Burton, M; McCleland, M L; Fields, P A; Arruda, V R; Herzog, R W; High, K A

    2000-04-15

    Hemophilia B is caused by the absence of functional coagulation factor IX (F.IX) and represents an important model for treatment of genetic diseases by gene therapy. Recent studies have shown that intramuscular injection of an adeno-associated viral (AAV) vector into mice and hemophilia B dogs results in vector dose-dependent, long-term expression of biologically active F.IX at therapeutic levels. In this study, we demonstrate that levels of expression of approximately 300 ng/mL (6% of normal human F.IX levels) can be reached by intramuscular injection of mice using a 2- to 4-fold lower vector dose (1 x 10(11) vector genomes/mouse, injected into 4 intramuscular sites) than previously described. This was accomplished through the use of an improved expression cassette that uses the cytomegalovirus (CMV) immediate early enhancer/promoter in combination with a 1.2-kilobase portion of human skeletal actin promoter. These results correlated with enhanced levels of F.IX transcript and secreted F.IX protein in transduced murine C2C12 myotubes. Systemic F.IX expression from constructs containing the CMV enhancer/promoter alone was 120 to 200 ng/mL in mice injected with 1 x 10(11) vector genomes. Muscle-specific promoters performed poorly for F.IX transgene expression in vitro and in vivo. However, the incorporation of a sequence from the alpha-skeletal actin promoter containing at least 1 muscle-specific enhancer and 1 enhancer-like element further improved muscle-derived expression of F.IX from a CMV enhancer/promoter-driven expression cassette over previously published results. These findings will allow the design of a clinical protocol for therapeutic levels of F.IX expression with lower vector doses, thus enhancing efficacy and safety of the protocol. (Blood. 2000;95:2536-2542)

  2. Knowledge, Attitudes and Practices (KAP) on Rift Valley Fever among Pastoralist Communities of Ijara District, North Eastern Kenya

    PubMed Central

    Abdi, Ismail H.; Affognon, Hippolyte D.; Wanjoya, Anthony K.; Onyango-Ouma, Washington; Sang, Rosemary

    2015-01-01

    Outbreaks of Rift Valley fever (RVF), a mosquito-borne viral zoonosis, have previously been associated with unusually heavy rainfall and extensive flooding. The disease is a serious public health problem in Africa and the Middle East, and is a potential global health threat. In Kenya, outbreaks of the disease have disproportionately affected impoverished pastoralist communities. This study sought to assess the knowledge, attitudes and practices (KAP) regarding RVF among the pastoralists of North Eastern Kenya, and to establish the determinants of KAP on RVF. A cross-sectional study involving 392 pastoralists living in Ijara district (Masalani and Ijara wards) was carried out using an interview questionnaire. All respondents interviewed (100%) had heard about RVF disease. They recognized that the disease is dangerous (99%), and had a positive attitude towards vaccination of animals (77%). However, few respondents knew that abortion (11%) and high mortality of young animals (10%) were key signs of RVF in animals. Very few (4%) use any form of protection when handling sick animals to avoid infection. Significant factors associated with knowledge were being in a household with a history of RVF infection (OR = 1.262, 95% CI = 1.099–1.447), having more livestock (OR = 1.285, 95% CI = 1.175–1.404) and the place of residence, Masalani (OR = 0.526, 95% CI = 0.480–0.576). Overall knowledge score on RVF was found to be a significant predictor of good preventive practice of the disease (OR = 1.073, 95% CI = 1.047–1.101). Despite the positive attitude that pastoralist communities have towards the prevention of RVF, there exist gaps in knowledge and good practices on the disease. Therefore there is need for public health education to address these gaps, and to identify and facilitate the removal of barriers to behavioural change related to the prevention of RVF. PMID:26566218

  3. The promotion of environmental enhancement in Strategic Environmental Assessment

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

    McCluskey, Daniel, E-mail: daniel.mccluskey@casaplanning.co.u; Joao, Elsa, E-mail: elsa.joao@strath.ac.u

    2011-04-15

    This paper evaluates how the enhancement of positive environmental impacts has been considered and developed in Strategic Environmental Assessment (SEA) reports since the SEA Act in Scotland was introduced in 2005. Fifteen Environmental Reports on strategic actions prepared between 2006 and 2009 were scrutinized for this study, one of which pertained to national policy and the rest to responsible authority programmes, plans or strategies throughout Scotland. A four point scale was developed to evaluate the extent to which environmental enhancement promotion or measures were considered in the Environmental Reports: Thorough, Fair, Minimal and Absent. Results found that nine out ofmore » the 15 Environmental Reports studied were graded as 'minimal' or 'absent'. The paper concludes that in order for SEA to achieve its full potential, in addition to considering mitigation measures for negative environmental impacts, SEA practitioners and decision makers must begin to realize and exploit potential enhancement opportunities.« less

  4. Regulation of a mammalian gene bearing a CpG island promoter and a distal enhancer.

    PubMed

    Berrozpe, Georgina; Bryant, Gene O; Warpinski, Katherine; Ptashne, Mark

    2013-08-15

    A quantitative nucleosome occupancy assay revealed rules for nucleosome disposition in yeast and showed how disposition affects regulation of the GAL genes. Here, we show how those findings apply to the control of Kit, a mammalian gene. The Kit promoter lies in a CpG island, and its enhancer (active in mast cells) lies some 150 kb upstream. Nucleosomes form with especially high avidities at the Kit promoter, a reaction that, we surmise, ensures extremely low basal expression. In mast cells, transcriptional activators displace nucleosomes that are less tightly formed at the Kit enhancer. In turn, the active enhancer replaces a single Kit promoter nucleosome with the transcriptional machinery, thereby inducing transcription over 1,000-fold. As at the yeast GAL genes, the inhibitory effects of nucleosomes facilitate high factors of induction by mammalian activators working in the absence of specific repressors. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  5. [Regulation of sporulation by two-component system YvcPQ in Bacillus thuringiensis].

    PubMed

    Fan, Qingyun; Zhang, Shumeng; Gong, Yujing; He, Jin

    2017-01-04

    To study the regulation of sporulation controlled by two-component system (TCS) YvcPQ. β-galactosidase experiment was used to verify the regulation of YvcP on kapD expression; bacterial one-hybrid assay, EMSA and RT-qPCR were applied to study the regulation of AbrB on yvcPQ expression; markerless gene deletion coupled with spore count was used to reveal the influence of yvcPQ and kapD expressions on sporulation. transcriptional regulator AbrB up-regulated the expression of yvcPQ; YvcP promoted the expression of kapD to inhibit sporulation. AbrB up-regulated the transcription of yvcPQ operon, then the increased YvcP strengthened the transcriptional acitivation of sporulation inhibitor gene kapD, and subsequently inhibited sporulation.

  6. A Significant Increase of RNAi Efficiency in Human Cells by the CMV Enhancer with a tRNAlys Promoter

    PubMed Central

    Weiwei, Ma; Zhenhua, Xie; Feng, Liu; Hang, Ning; Yuyang, Jiang

    2009-01-01

    RNA interference (RNAi) is the process of mRNA degradation induced by double-stranded RNA in a sequence-specific manner. Different types of promoters, such as U6, H1, tRNA, and CMV, have been used to control the inhibitory effect of RNAi expression vectors. In the present study, we constructed two shRNA expression vectors, respectively, controlled by tRNAlys and CMV enhancer-tRNAlys promoters. Compared to the vectors with tRNAlys or U6 promoter, the vector with a CMV enhancer-tRNAlys promoter silenced pokemon more efficiently on both the mRNA and the protein levels. Meanwhile, the silencing of pokemon inhibited the proliferation of MCF7 cells, but the induction of apoptosis of MCF7 cells was not observed. We conclude that the CMV enhancer-tRNAlys promoter may be a powerful tool in driving intracellular expression of shRNA which can efficiently silence targeted gene. PMID:19859553

  7. Enhancing promotional strategies within social marketing programs: use of Web 2.0 social media.

    PubMed

    Thackeray, Rosemary; Neiger, Brad L; Hanson, Carl L; McKenzie, James F

    2008-10-01

    The second generation of Internet-based applications (i.e., Web 2.0), in which users control communication, holds promise to significantly enhance promotional efforts within social marketing campaigns. Web 2.0 applications can directly engage consumers in the creative process by both producing and distributing information through collaborative writing, content sharing, social networking, social bookmarking, and syndication. Web 2.0 can also enhance the power of viral marketing by increasing the speed at which consumers share experiences and opinions with progressively larger audiences. Because of the novelty and potential effectiveness of Web 2.0, social marketers may be enticed to prematurely incorporate related applications into promotional plans. However, as strategic issues such as priority audience preferences, selection of appropriate applications, tracking and evaluation, and related costs are carefully considered, Web 2.0 will expand to allow health promotion practitioners more direct access to consumers with less dependency on traditional communication channels.

  8. Enhanced transgene expression in rice following selection controlled by weak promoters.

    PubMed

    Zhou, Jie; Yang, Yong; Wang, Xuming; Yu, Feibo; Yu, Chulang; Chen, Juan; Cheng, Ye; Yan, Chenqi; Chen, Jianping

    2013-03-27

    Techniques that enable high levels of transgene expression in plants are attractive for the commercial production of plant-made recombinant pharmaceutical proteins or other gene transfer related strategies. The conventional way to increase the yield of desired transgenic products is to use strong promoters to control the expression of the transgene. Although many such promoters have been identified and characterized, the increase obtainable from a single promoter is ultimately limited to a certain extent. In this study, we report a method to magnify the effect of a single promoter by using a weak promoter-based selection system in transgenic rice. tCUP1, a fragment derived from the tobacco cryptic promoter (tCUP), was tested for its activity in rice by fusion to both a β-glucuronidase (GUS) reporter and a hygromycin phosphotransferase (HPT) selectable marker. The tCUP1 promoter allowed the recovery of transformed rice plants and conferred tissue specific expression of the GUS reporter, but was much weaker than the CaMV 35S promoter in driving a selectable marker for growth of resistant calli. However, in the resistant calli and regenerated transgenic plants selected by the use of tCUP1, the constitutive expression of green fluorescent protein (GFP) was dramatically increased as a result of the additive effect of multiple T-DNA insertions. The correlation between attenuated selection by a weak promoter and elevation of copy number and foreign gene expression was confirmed by using another relatively weak promoter from nopaline synthase (Nos). The use of weak promoter derived selectable markers leads to a high T-DNA copy number and then greatly increases the expression of the foreign gene. The method described here provides an effective approach to robustly enhance the expression of heterogenous transgenes through copy number manipulation in rice.

  9. Alternative growth promoters alter broiler gut microbiome and enhance body weight gain

    USDA-ARS?s Scientific Manuscript database

    Antibiotic growth promoters (AGPs) have commonly been used to enhance growth in poultry production. However, there has been increasing concern over the impact of AGPs use in food production on acquisition of antibiotic resistance in zoonotic bacterial pathogens through inter-bacterial transfer of an...

  10. Ginsenoside compound K promotes β-amyloid peptide clearance in primary astrocytes via autophagy enhancement.

    PubMed

    Guo, Jinhui; Chang, Li; Zhang, Xin; Pei, Sujuan; Yu, Meishuang; Gao, Jianlian

    2014-10-01

    The aim of the present study was to investigate the effect of ginsenoside compound K on β-amyloid (Aβ) peptide clearance in primary astrocytes. Aβ degradation in primary astrocytes was determined using an intracellular Aβ clearance assay. Aggregated LC3 in astrocyte cells, which is a marker for the level of autophagy, was detected using laser scanning confocal microscope. The effect of compound K on the mammalian target of rapamycin (mTOR)/autophagy pathway was determined using western blot analysis, and an enzyme-linked immunosorbent assay was used for Aβ detection. The results demonstrated that compound K promoted the clearance of Aβ and enhanced autophagy in primary astrocytes. In addition, it was found that phosphorylation of mTOR was inhibited by compound K, which may have contributed to the enhanced autophagy. In conclusion, compound K promotes Aβ clearance by enhancing autophagy via the mTOR signaling pathway in primary astrocytes.

  11. Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction.

    PubMed

    Whittle, N; Maurer, V; Murphy, C; Rainer, J; Bindreither, D; Hauschild, M; Scharinger, A; Oberhauser, M; Keil, T; Brehm, C; Valovka, T; Striessnig, J; Singewald, N

    2016-12-06

    Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory.

  12. Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction

    PubMed Central

    Whittle, N; Maurer, V; Murphy, C; Rainer, J; Bindreither, D; Hauschild, M; Scharinger, A; Oberhauser, M; Keil, T; Brehm, C; Valovka, T; Striessnig, J; Singewald, N

    2016-01-01

    Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory. PMID:27922638

  13. Knowledge, Attitudes, and Practices (KAP) of the Relationship between Air Pollution and Children’s Respiratory Health in Shanghai, China

    PubMed Central

    Wang, Rui; Yang, Yingying; Chen, Renjie; Kan, Haidong; Wu, Jinyi; Wang, Keran; Maddock, Jay E.; Lu, Yuanan

    2015-01-01

    To assess the status of, and factors associated with, residents’ knowledge, attitudes, and practices (KAP) related to air pollution and respiratory health of children in Shanghai, we conducted a cross-sectional survey. Demographic factors associated with residents’ knowledge were identified by multiple logistic regressions. The questionnaires were completed by 972 participants, half from the Shanghai Children Hospital and the other half from the Jiading communities. Half of the participants’ scores of knowledge and attitudes were equal or greater than 8.0 on a 9-point scale, over 75% of respondents’ practice scores were equal to or less than 4.0. Our studies demonstrated a significant difference of average knowledge scores between the two groups (t = 1.27, p < 0.05). The parents’ educational level (OR = 1.89, 2.48) and average annual household income (AAHI) (OR = 2.37, 2.40, 2.12) were the two strongest factors on knowledge awareness. In addition, statistical analysis revealed a significant difference between the two groups in their attitudes towards air quality and their perception of the government’s efforts to alleviate it. The hospital and community groups also showed significant differences in practices geared towards protecting their children’s health. Nearly 90% of the respondents agreed that improving air quality is the responsibility of every citizen, and the joint action of governments and all citizens should be utilized for enhanced control. In addition, more resources should be allocated towards providing citizens with appropriate practices to help lessen the effects of poor air quality. PMID:25664694

  14. The inhibition of IGF-1 signaling promotes proteostasis by enhancing protein aggregation and deposition.

    PubMed

    Moll, Lorna; Ben-Gedalya, Tziona; Reuveni, Hadas; Cohen, Ehud

    2016-04-01

    The discovery that the alteration of aging by reducing the activity of the insulin/IGF-1 signaling (IIS) cascade protects nematodes and mice from neurodegeneration-linked, toxic protein aggregation (proteotoxicity) raises the prospect that IIS inhibitors bear therapeutic potential to counter neurodegenerative diseases. Recently, we reported that NT219, a highly efficient IGF-1 signaling inhibitor, protects model worms from the aggregation of amyloid β peptide and polyglutamine peptides that are linked to the manifestation of Alzheimer's and Huntington's diseases, respectively. Here, we employed cultured cell systems to investigate whether NT219 promotes protein homeostasis (proteostasis) in mammalian cells and to explore its underlying mechanisms. We found that NT219 enhances the aggregation of misfolded prion protein and promotes its deposition in quality control compartments known as "aggresomes." NT219 also elevates the levels of certain molecular chaperones but, surprisingly, reduces proteasome activity and impairs autophagy. Our findings show that IGF-1 signaling inhibitors in general and NT219 in particular can promote proteostasis in mammalian cells by hyperaggregating hazardous proteins, thereby bearing the potential to postpone the onset and slow the progression of neurodegenerative illnesses in the elderly.-Moll, L., Ben-Gedalya, T., Reuveni, H., Cohen, E. The inhibition of IGF-1 signaling promotes proteostasis by enhancing protein aggregation and deposition. © FASEB.

  15. [Brd3 promotes IL-6 production via enhancing acetylase CBP recruitment and histone 3 acetylation within IL6 promoter].

    PubMed

    Ren, Wenhui; Sun, Donghao; Wang, Chunmei; Li, Nan

    2016-10-01

    Objective To investigate the role of bromodomain containing 3 (Brd3) in LPS-triggered interleukin-6 (IL-6) production in macrophages and the underlying mechanism. Methods CRISPR-Cas9 technology was used to screen an RAW264.7 cell line with Brd3 knockout (Brd3 -/- ). The Brd3 -/- cells were used as an experimental group, and the parential cells expressing wide-type Brd3 as a control group. The IL-6 level in cell culture supernatant was detected by ELISA after 100 ng/mL LPS challenging. Effect of Brd3 knockout on the expression and activation of signal pathways involved in IL-6 expression, including the NF-κB and mitogen-activated protein kinase (MAPK) pathways were examined by Western blot analysis. Chromatin immunoprecipitation (ChIP) assay was used to evaluate the recruitment of acetylase CREB-binding protein (CBP) to IL6 gene promoter and the acetylation level of histone 3 within IL6 gene promoter. Results LPS treatment significantly downregulated Brd3 expression in mouse peritoneal macrophages. LPS-induced production of IL-6 was significantly inhibited in Brd3 -/- macrophages. The expressions and activation of signal molecules within NF-κB and MAPK pathways were barely affected. Brd3 knockout significantly decreased the recruitment of acetylase CBP to IL6 gene promoter, and the acetylation level of histone3 within IL6 gene promoter was also repressed. Conclusion Brd3 promotes LPS-triggered IL-6 production via promoting the recruitment of CBP to IL6 promoter and enhancing the acetylation level of histone 3 within IL6 promoter.

  16. Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway.

    PubMed

    Li, Shang; Dang, Yuanye; Zhou, Xuelin; Huang, Bin; Huang, Xiaohui; Zhang, Zherui; Kwan, Yiu Wa; Chan, Shun Wan; Leung, George Pak Heng; Lee, Simon Ming Yuen; Hoi, Maggie Pui Man

    2015-11-16

    Formononetin is an isoflavone that has been shown to display estrogenic properties and induce angiogenesis activities. However, the interrelationship between the estrogenic properties and angiogenesis activities of formononetin are not well defined. In the present study, docking and enzymatic assay demonstrated that formononetin displayed direct binding to the ligand-binding domain (LBD) of estrogen receptor alpha (ERα) with an agonistic property. Results from Human Umbilical Vein Endothelial Cells (HUVEC) by using real-time migration xCELLigence system, immunofluorescence and western blotting provided strong evidences of formononetin induced endothelial cell migration and dramatic actin cytoskeleton spatial modification through ERα-enhanced-ROCK-II/MMP2/9 signaling pathways. In addition, results from co-immunoprecipitation suggested formononetin induced cell migration via recruiting of ERα/ROCK-II activated complex formation. More interestingly, in zebrafish embryo we observed that formononetin significantly promoted angiogenic sproutings in the subintestinal vessels (SIVs) that could be completely abolished by ROCK inhibitor. In this study, we elucidated the underlying mechanisms that formononetin produced proangiogenesis effects through an ERα-enhanced ROCK-II signaling pathways. Results from the present study also expand our knowledge about the enigmatic underlying mechanisms of phytoestrogenic compounds in the promotion of angiogenesis in relation to ERα and ROCK interaction in endothelial cells and their relationship with actin assembly and cell migration.

  17. Fatty acid oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C.

    PubMed

    Lin, Zhaoyu; Liu, Fei; Shi, Peiliang; Song, Anying; Huang, Zan; Zou, Dayuan; Chen, Qin; Li, Jianxin; Gao, Xiang

    2018-02-26

    Changes in metabolic pathway preferences are key events in the reprogramming process of somatic cells to induced pluripotent stem cells (iPSCs). The optimization of metabolic conditions can enhance reprogramming; however, the detailed underlying mechanisms are largely unclear. By comparing the gene expression profiles of somatic cells, intermediate-phase cells, and iPSCs, we found that carnitine palmitoyltransferase (Cpt)1b, a rate-limiting enzyme in fatty acid oxidation, was significantly upregulated in the early stage of the reprogramming process. Mouse embryonic fibroblasts isolated from transgenic mice carrying doxycycline (Dox)-inducible Yamanaka factor constructs were used for reprogramming. Various fatty acid oxidation-related metabolites were added during the reprogramming process. Colony counting and fluorescence-activated cell sorting (FACS) were used to calculate reprogramming efficiency. Fatty acid oxidation-related metabolites were measured by liquid chromatography-mass spectrometry. Seahorse was used to measure the level of oxidative phosphorylation. We found that overexpression of cpt1b enhanced reprogramming efficiency. Furthermore, palmitoylcarnitine or acetyl-CoA, the primary and final products of Cpt1-mediated fatty acid oxidation, also promoted reprogramming. In the early reprogramming process, fatty acid oxidation upregulated oxidative phosphorylation and downregulated protein kinase C activity. Inhibition of protein kinase C also promoted reprogramming. We demonstrated that fatty acid oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C activity in the early stage of the reprogramming process. This study reveals that fatty acid oxidation is crucial for the reprogramming efficiency.

  18. AML1/ETO trans-activates c-KIT expression through the long range interaction between promoter and intronic enhancer.

    PubMed

    Tian, Ying; Wang, Genjie; Hu, Qingzhu; Xiao, Xichun; Chen, Shuxia

    2018-04-01

    The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT. Gene expression analyses verify that c-KIT expression is significantly high in t(8;21) AML. Further ChIP-seq analysis and motif scanning identify two regulatory regions located in the promoter and intronic enhancer region of c-KIT, respectively. Both regions are enriched by co-factors of AML1/ETO, such as AML1, CEBPe, c-Jun, and c-Fos. Further luciferase reporter assays show that AML1/ETO trans-activates c-KIT promoter activity through directly recognizing the AML1 motif and the co-existence of co-factors. The induction of c-KIT promoter activity is reinforced with the existence of intronic enhancer region. Furthermore, ChIP-3C-qPCR assays verify that AML1/ETO mediates the formation of DNA-looping between the c-KIT promoter and intronic enhancer region through the long-range interaction. Collectively, our data uncover a novel transcriptional activity mechanism of AML1/ETO and enrich our knowledge of the onco-fusion protein mediated transcription regulation. © 2017 Wiley Periodicals, Inc.

  19. Pokemon promotes the invasiveness of hepatocellular carcinoma by enhancing MEF2D transcription.

    PubMed

    Kong, Jing; Liu, Xiaoping; Li, Xiangqian; Wu, Jinsheng; Wu, Ning; Chen, Jun; Fang, Fang

    2016-05-01

    Pokemon, a master oncogene crucial for the tumorigenicity and progression of a variety of cancers, has been demonstrated to enhance the proliferation and survival of hepatocellular carcinoma (HCC). However, the contribution of Pokemon to the invasiveness of HCC has not yet been studied. In this study, we employed HCC cells to investigate the role of Pokemon in the invasion of HCC with multidisciplinary approaches. Pokemon overexpression was found to be closely associated with invasion and intrahepatic metastasis of HCC in clinical specimens. Suppression of Pokemon attenuated the invasion of HCC cells by in vitro transwell and wound-healing assays. Myocyte enhancer factor 2D (MEF2D), an oncogene that can promote the invasiveness of HCC, was found to be underexpressed during Pokemon silencing in HCC cells. Restoration of MEF2D abolished the effect of Pokemon downregulation on the migration of HCC cells. Further experiments verified that Pokemon binds two putative recognition sites located within the upstream region of the MEF2D promoter and enhances its transcription. The association between Pokemon and MEF2D was further confirmed in HCC specimens. Animal experiments further confirmed that Pokemon downregulation attenuated the metastasis of HCC cells in mice. Collectively, Pokemon was found to enhance the migration and invasion of HCC by increasing MEF2D expression. Thus, targeting Pokemon and MEF2D may be an effective strategy to suppress the metastasis of HCC.

  20. A 1-kb bacteriophage lambda fragment functions as an insulator to effectively block enhancer-promoter interactions in Arabidopsis thaliana

    USDA-ARS?s Scientific Manuscript database

    The 35S cauliflower mosaic virus (CaMV) promoter contains an enhancer element that is able to override the tissue-, organ- and developmental-stage specificity of nearby promoters. Consequently, the precise control of transgene expression in transgenic plants, which often contain the 35S CaMV promot...

  1. Activation-dependent intrachromosomal interactions formed by the TNF gene promoter and two distal enhancers

    PubMed Central

    Tsytsykova, Alla V.; Rajsbaum, Ricardo; Falvo, James V.; Ligeiro, Filipa; Neely, Simon R.; Goldfeld, Anne E.

    2007-01-01

    Here we provide a mechanism for specific, efficient transcription of the TNF gene and, potentially, other genes residing within multigene loci. We identify and characterize highly conserved noncoding elements flanking the TNF gene, which undergo activation-dependent intrachromosomal interactions. These elements, hypersensitive site (HSS)−9 and HSS+3 (9 kb upstream and 3 kb downstream of the TNF gene, respectively), contain DNase I hypersensitive sites in naive, T helper 1, and T helper 2 primary T cells. Both HSS-9 and HSS+3 inducibly associate with acetylated histones, indicative of chromatin remodeling, bind the transcription factor nuclear factor of activated T cells (NFAT)p in vitro and in vivo, and function as enhancers of NFAT-dependent transactivation mediated by the TNF promoter. Using the chromosome conformation capture assay, we demonstrate that upon T cell activation intrachromosomal looping occurs in the TNF locus. HSS-9 and HSS+3 each associate with the TNF promoter and with each other, circularizing the TNF gene and bringing NFAT-containing nucleoprotein complexes into close proximity. TNF gene regulation thus reveals a mode of intrachromosomal interaction that combines a looped gene topology with interactions between enhancers and a gene promoter. PMID:17940009

  2. Disruption of the Abdominal-B Promoter Tethering Element Results in a Loss of Long-Range Enhancer-Directed Hox Gene Expression in Drosophila

    PubMed Central

    Ho, Margaret C. W.; Schiller, Benjamin J.; Akbari, Omar S.; Bae, Esther; Drewell, Robert A.

    2011-01-01

    There are many examples within gene complexes of transcriptional enhancers interacting with only a subset of target promoters. A number of molecular mechanisms including promoter competition, insulators and chromatin looping are thought to play a role in regulating these interactions. At the Drosophila bithorax complex (BX-C), the IAB5 enhancer specifically drives gene expression only from the Abdominal-B (Abd-B) promoter, even though the enhancer and promoter are 55 kb apart and are separated by at least three insulators. In previous studies, we discovered that a 255 bp cis-regulatory module, the promoter tethering element (PTE), located 5′ of the Abd-B transcriptional start site is able to tether IAB5 to the Abd-B promoter in transgenic embryo assays. In this study we examine the functional role of the PTE at the endogenous BX-C using transposon-mediated mutagenesis. Disruption of the PTE by P element insertion results in a loss of enhancer-directed Abd-B expression during embryonic development and a homeotic transformation of abdominal segments. A partial deletion of the PTE and neighboring upstream genomic sequences by imprecise excision of the P element also results in a similar loss of Abd-B expression in embryos. These results demonstrate that the PTE is an essential component of the regulatory network at the BX-C and is required in vivo to mediate specific long-range enhancer-promoter interactions. PMID:21283702

  3. Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters.

    PubMed

    Javierre, Biola M; Burren, Oliver S; Wilder, Steven P; Kreuzhuber, Roman; Hill, Steven M; Sewitz, Sven; Cairns, Jonathan; Wingett, Steven W; Várnai, Csilla; Thiecke, Michiel J; Burden, Frances; Farrow, Samantha; Cutler, Antony J; Rehnström, Karola; Downes, Kate; Grassi, Luigi; Kostadima, Myrto; Freire-Pritchett, Paula; Wang, Fan; Stunnenberg, Hendrik G; Todd, John A; Zerbino, Daniel R; Stegle, Oliver; Ouwehand, Willem H; Frontini, Mattia; Wallace, Chris; Spivakov, Mikhail; Fraser, Peter

    2016-11-17

    Long-range interactions between regulatory elements and gene promoters play key roles in transcriptional regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here, we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary hematopoietic cell types. We show that promoter interactions are highly cell type specific and enriched for links between active promoters and epigenetically marked enhancers. Promoter interactomes reflect lineage relationships of the hematopoietic tree, consistent with dynamic remodeling of nuclear architecture during differentiation. Interacting regions are enriched in genetic variants linked with altered expression of genes they contact, highlighting their functional role. We exploit this rich resource to connect non-coding disease variants to putative target promoters, prioritizing thousands of disease-candidate genes and implicating disease pathways. Our results demonstrate the power of primary cell promoter interactomes to reveal insights into genomic regulatory mechanisms underlying common diseases. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. NF-κB-Dependent Lymphoid Enhancer Co-option Promotes Renal Carcinoma Metastasis.

    PubMed

    Rodrigues, Paulo; Patel, Saroor A; Harewood, Louise; Olan, Ioana; Vojtasova, Erika; Syafruddin, Saiful E; Zaini, M Nazhif; Richardson, Emma K; Burge, Johanna; Warren, Anne Y; Stewart, Grant D; Saeb-Parsy, Kourosh; Samarajiwa, Shamith A; Vanharanta, Sakari

    2018-06-06

    Metastases, the spread of cancer cells to distant organs, cause the majority of cancer-related deaths. Few metastasis-specific driver mutations have been identified, suggesting aberrant gene regulation as a source of metastatic traits. However, how metastatic gene expression programs arise is poorly understood. Here, using human-derived metastasis models of renal cancer, we identify transcriptional enhancers that promote metastatic carcinoma progression. Specific enhancers and enhancer clusters are activated in metastatic cancer cell populations, and the associated gene expression patterns are predictive of poor patient outcome in clinical samples. We find that the renal cancer metastasis-associated enhancer complement consists of multiple coactivated tissue-specific enhancer modules. Specifically, we identify and functionally characterize a coregulatory enhancer cluster, activated by the renal cancer driver HIF2A and an NF-κB-driven lymphoid element, as a mediator of metastasis in vivo We conclude that oncogenic pathways can acquire metastatic phenotypes through cross-lineage co-option of physiologic epigenetic enhancer states. SIGNIFICANCE: Renal cancer is associated with significant mortality due to metastasis. We show that in metastatic renal cancer, functionally important metastasis genes are activated via co-option of gene regulatory enhancer modules from distant developmental lineages, thus providing clues to the origins of metastatic cancer. Cancer Discov; 8(7); 1-16. ©2018 AACR. ©2018 American Association for Cancer Research.

  5. Promotion of breast feeding in the community: impact of health education programme in rural communities in Nigeria.

    PubMed

    Davies-Adetugbo, A A

    1996-03-01

    Breast feeding has been recognized as a child survival strategy, while breast feeding programmes have been increasingly implemented in many communities. This study assesses the effectiveness of a breast feeding education programme launched through the primary health care programme in the rural communities of Nigeria. Late trimester pregnant women were enrolled into the study and given a questionnaire on knowledge, attitudes, and practices (KAP) about breast feeding. Women in the study group (n = 126) received breast feeding counselling before and after delivery, while those in control group (n = 130) did not receive any counselling. Both groups were monitored after delivery and followed with the KAP questionnaire. The results of the study showed marked improvements in the intervention group for colostrum feeding (p = 0.0000). Moreover, 31.6% of the mothers in the intervention group practised timely initiation of breast feeding compared to 5.6% of the controls, and the prevalence of exclusive breast feeding at 4 months was 39.8% in the intervention group compared to 13.9% for the controls. Multivariate analysis showed that the intervention was a powerful and the only significant predictor of the increase in breast feeding behaviours (p = 0.0000), and that an early initiation of breast feeding is a strong predictor of exclusive breast feeding at 4 months of age. It is concluded that breast feeding promotion in rural communities is feasible and can lead to behavioural changes.

  6. Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway

    PubMed Central

    Li, Shang; Dang, Yuanye; Zhou, Xuelin; Huang, Bin; Huang, Xiaohui; Zhang, Zherui; Kwan, Yiu Wa; Chan, Shun Wan; Leung, George Pak Heng; Lee, Simon Ming Yuen; Hoi, Maggie Pui Man

    2015-01-01

    Formononetin is an isoflavone that has been shown to display estrogenic properties and induce angiogenesis activities. However, the interrelationship between the estrogenic properties and angiogenesis activities of formononetin are not well defined. In the present study, docking and enzymatic assay demonstrated that formononetin displayed direct binding to the ligand-binding domain (LBD) of estrogen receptor alpha (ERα) with an agonistic property. Results from Human Umbilical Vein Endothelial Cells (HUVEC) by using real-time migration xCELLigence system, immunofluorescence and western blotting provided strong evidences of formononetin induced endothelial cell migration and dramatic actin cytoskeleton spatial modification through ERα-enhanced-ROCK-II/MMP2/9 signaling pathways. In addition, results from co-immunoprecipitation suggested formononetin induced cell migration via recruiting of ERα/ROCK-II activated complex formation. More interestingly, in zebrafish embryo we observed that formononetin significantly promoted angiogenic sproutings in the subintestinal vessels (SIVs) that could be completely abolished by ROCK inhibitor. In this study, we elucidated the underlying mechanisms that formononetin produced proangiogenesis effects through an ERα-enhanced ROCK-II signaling pathways. Results from the present study also expand our knowledge about the enigmatic underlying mechanisms of phytoestrogenic compounds in the promotion of angiogenesis in relation to ERα and ROCK interaction in endothelial cells and their relationship with actin assembly and cell migration. PMID:26568398

  7. Socio-demographic factors influencing knowledge, attitude and practice (KAP) regarding malaria in Bangladesh

    PubMed Central

    2012-01-01

    Background A clear understanding of the social and behavioral risk factors, and knowledge gaps, related to exposure to malaria are essential when developing guidelines and recommendations for more effective disease prevention in many malaria endemic areas of the world including Bangladesh and elsewhere in the South East Asia. To-date, the level of knowledge that human populations, residing in moderate to high malaria risk zones, have with respect to the basic pathogen transmission dynamics, risk factors for malaria or disease preventative strategies, has not been assessed in Bangladesh. The purpose of this study was to address this gap by conducting surveys of the knowledge, attitudes and practices (KAP) of people, from variable socio-demographic backgrounds, residing in selected rural malaria endemic areas in Bangladesh. Methods The KAP survey was conducted in portions of six different malaria endemic districts in Bangladesh from July to October 2011. The survey consisted of interviewing residence of these malaria endemic districts using a structured questionnaire and interviewers also completed observational checklists at each household where people were interviewed. The study area was further divided into two zones (1 and 2) based on differences in the physical geography and level of malaria endemicity in the two zones. Data from the questionnaires and observational checklists were analysised using Statistical Package for Social Sciences 16.0 (SPSS, Inc., Chicago, IL, USA). Results A total of 468 individuals from individual households were interviewed, and most respondents were female. Monthly incomes varied within and among the zones. It was found that 46.4% and 41% of respondents’ family had malaria within the past one year in zones 1 and 2, respectively. Nearly 86% of the respondents did not know the exact cause of malaria or the role of Anopheles mosquitoes in the pathogen’s transmission. Knowledge on malaria transmission and symptoms of the respondents

  8. Socio-demographic factors influencing knowledge, attitude and practice (KAP) regarding malaria in Bangladesh.

    PubMed

    Bashar, Kabirul; Al-Amin, H M; Reza, Md Selim; Islam, Muzahidul; Asaduzzaman; Ahmed, Touhid Uddin

    2012-12-18

    A clear understanding of the social and behavioral risk factors, and knowledge gaps, related to exposure to malaria are essential when developing guidelines and recommendations for more effective disease prevention in many malaria endemic areas of the world including Bangladesh and elsewhere in the South East Asia. To-date, the level of knowledge that human populations, residing in moderate to high malaria risk zones, have with respect to the basic pathogen transmission dynamics, risk factors for malaria or disease preventative strategies, has not been assessed in Bangladesh. The purpose of this study was to address this gap by conducting surveys of the knowledge, attitudes and practices (KAP) of people, from variable socio-demographic backgrounds, residing in selected rural malaria endemic areas in Bangladesh. The KAP survey was conducted in portions of six different malaria endemic districts in Bangladesh from July to October 2011. The survey consisted of interviewing residence of these malaria endemic districts using a structured questionnaire and interviewers also completed observational checklists at each household where people were interviewed. The study area was further divided into two zones (1 and 2) based on differences in the physical geography and level of malaria endemicity in the two zones. Data from the questionnaires and observational checklists were analysised using Statistical Package for Social Sciences 16.0 (SPSS, Inc., Chicago, IL, USA). A total of 468 individuals from individual households were interviewed, and most respondents were female. Monthly incomes varied within and among the zones. It was found that 46.4% and 41% of respondents' family had malaria within the past one year in zones 1 and 2, respectively. Nearly 86% of the respondents did not know the exact cause of malaria or the role of Anopheles mosquitoes in the pathogen's transmission. Knowledge on malaria transmission and symptoms of the respondents of zones 1 and 2 were

  9. Is Nigeria winning the battle against malaria? Prevalence, risk factors and KAP assessment among Hausa communities in Kano State.

    PubMed

    Dawaki, Salwa; Al-Mekhlafi, Hesham M; Ithoi, Init; Ibrahim, Jamaiah; Atroosh, Wahib M; Abdulsalam, Awatif M; Sady, Hany; Elyana, Fatin Nur; Adamu, Ado U; Yelwa, Saadatu I; Ahmed, Abdulhamid; Al-Areeqi, Mona A; Subramaniam, Lahvanya R; Nasr, Nabil A; Lau, Yee-Ling

    2016-07-08

    Malaria is one of the most severe global public health problems worldwide, particularly in Africa, where Nigeria has the greatest number of malaria cases. This community-based study was designed to investigate the prevalence and risk factors of malaria and to evaluate the knowledge, attitudes, and practices (KAP) regarding malaria among rural Hausa communities in Kano State, Nigeria. A cross-sectional community-based study was conducted on 551 participants from five local government areas in Kano State. Blood samples were collected and examined for the presence of Plasmodium species by rapid diagnostic test (RDT), Giemsa-stained thin and thick blood films, and PCR. Moreover, demographic, socioeconomic, and environmental information as well as KAP data were collected using a pre-tested questionnaire. A total of 334 (60.6 %) participants were found positive for Plasmodium falciparum. The prevalence differed significantly by age group (p < 0.01), but not by gender or location. A multivariate analysis showed that malaria was associated significantly with being aged 12 years or older, having a low household family income, not using insecticide treated nets (ITNs), and having no toilets in the house. Overall, 95.6 % of the respondents had prior knowledge about malaria, and 79.7, 87.6 and 95.7 % of them knew about the transmission, symptoms, and prevention of malaria, respectively. The majority (93.4 %) of the respondents considered malaria a serious disease. Although 79.5 % of the respondents had at least one ITN in their household, utilization rate of ITNs was 49.5 %. Significant associations between the respondents' knowledge concerning malaria and their age, gender, education, and household monthly income were reported. Malaria is still highly prevalent among rural Hausa communities in Nigeria. Despite high levels of knowledge and attitudes in the study area, significant gaps persist in appropriate preventive practices, particularly the use of ITNs

  10. Economic value analysis of the return from the Korean astronaut program and the science culture diffusion activity in Korea

    NASA Astrophysics Data System (ADS)

    Yi, Soyeon; Jang, Hyun-Jin; Lee, Hyo Suk; Yu, Jong-Phil; Kim, Soyeon; Lee, Joohee; Hur, Hee-Young

    2013-06-01

    In this study, we analyze the economic effects from the Korean Astronaut Program (KAP) and the subsequent Science Culture Diffusion Activity (SCDA). Korea has had a huge practical effect on the development of science and technology and has increased international awareness of Korea by producing Korea's first astronaut. There has also been a large, ripple effect on space related industries. In addition, the KAP has exercised a far-reaching influence on Korean society and culture by boosting all science and engineering and inspiring national pride. After the KAP, astronauts' outreach activities, such as lectures for the general public; interviews on television, newspapers and magazines; participating in children's science camps; and distributing publications and DVDs about astronaut program for general public, were instituted for diffusing science culture. Thus, positive effects such as the promotion of Korea's level of technology, student interest in science and engineering fields, and the expansion of the industrial base were reinforced after the KAP. This study is aimed at evaluating the economic significance and the value of return through analyzing the effects of the KAP and the subsequent Science Culture Diffusion Activity.

  11. Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval

    PubMed Central

    Ishikawa, Rie; Fukushima, Hotaka; Frankland, Paul W; Kida, Satoshi

    2016-01-01

    Forgetting of recent fear memory is promoted by treatment with memantine (MEM), which increases hippocampal neurogenesis. The approaches for treatment of post-traumatic stress disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of recent, but not remote, memories. Here we show that, following prolonged re-exposure to the conditioning context, enhancers of hippocampal neurogenesis, including MEM, promote forgetting of remote contextual fear memory. However, these interventions are ineffective following shorter re-exposures. Importantly, we find that long, but not short re-exposures activate gene expression in the hippocampus and induce hippocampus-dependent reconsolidation of remote contextual fear memory. Furthermore, remote memory retrieval becomes hippocampus-dependent after the long-time recall, suggesting that remote fear memory returns to a hippocampus dependent state after the long-time recall, thereby allowing enhanced forgetting by increased hippocampal neurogenesis. Forgetting of traumatic memory may contribute to the development of PTSD treatment. DOI: http://dx.doi.org/10.7554/eLife.17464.001 PMID:27669409

  12. Bacterial lipopolysaccharide binding enhances virion stability and promotes environmental fitness of an enteric virus

    PubMed Central

    Robinson, Christopher M.; Jesudhasan, Palmy R.; Pfeiffer, Julie K.

    2014-01-01

    Summary Enteric viruses, including poliovirus and reovirus, encounter a vast microbial community in the mammalian gastrointestinal tract, which has been shown to promote virus replication and pathogenesis. Investigating the underlying mechanisms, we find that poliovirus binds bacterial surface polysaccharides, which enhances virion stability and cell attachment by increasing binding to the viral receptor. Additionally, we identified a poliovirus mutant, VP1-T99K, with reduced lipopolysaccharide (LPS) binding. Although T99K and WT poliovirus cell attachment, replication and pathogenesis in mice are equivalent, following peroral inoculation of mice, VP1-T99K poliovirus was unstable in feces. Consequently, the ratio of mutant virus in feces is reduced following additional cycles of infection in mice. Thus, the mutant virus incurs a fitness cost when environmental stability is a factor. These data suggest that poliovirus binds bacterial surface polysaccharides, enhancing cell attachment and environmental stability, potentially promoting transmission to a new host. PMID:24439896

  13. [Sociocultural aspects of epilepsy in Madagascar. K.A.P. survey carried out in Antananarivo].

    PubMed

    Andriantseheno, L M; Rakotoarivony, M C

    2000-11-01

    A general population survey on knowledge, attitudes and practices (K.A.P.) concerning epilepsy was conducted from 1st July to 31st December 1997 in Antananarivo, a region representative of ecological and cultural patterns of the Malagasy "Highlands". The sample, randomly selected according to the two-step cluster method, recruited 1392 men and women aged 18 years and older who were interviewed with a 16-item questionnaire. Knowledge and practices have significantly evolved since 1983, when a similar study was conducted. More natural explanations are given for the condition and health-care seeking is more common. However, popular attitudes towards the epileptic patient remain contradictory: the majority of those interviewed claimed to be tolerant; work and marriage could be envisaged for the epileptic patient, but not total freedom of movement nor regular school attendance. A more active popularisation of the disease thus appears to be necessary. Since some 60% of people had a radio, broadcasting and church involvement would be the most effective means towards this end. Traditional practicer do not seem to have an overwhelming influence; rather, healthcare seeking behaviour was determined by the availability of service, the efficacy of the intervention and cost. To be representative of Madagascar as a whole, our data should be compared to those of other surveys in more culturally enclosed and disadvantaged areas.

  14. STAT3-Activated GM-CSFRα Translocates to the Nucleus and Protects CLL Cells from Apoptosis

    PubMed Central

    Li, Ping; Harris, David; Liu, Zhiming; Rozovski, Uri; Ferrajoli, Alessandra; Wang, Yongtao; Bueso-Ramos, Carlos; Hazan-Halevy, Inbal; Grgurevic, Srdana; Wierda, William; Burger, Jan; O'Brien, Susan; Faderl, Stefan; Keating, Michael; Estrov, Zeev

    2014-01-01

    Here it was determined that Chronic Lymphocytic Leukemia (CLL) cells express the α-subunit but not the β-subunit of the granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR/CSF3R). GM-CSFRα was detected on the surface, in the cytosol, and the nucleus of CLL cells via confocal microscopy, cell fractionation, and GM-CSFRα antibody epitope mapping. Because STAT3 is frequently activated in CLL and the GM-CSFRα promoter harbors putative STAT3 consensus binding sites, MM1 cells were transfected with truncated forms of the GM-CSFRα promoter, then stimulated with IL-6 to activate STAT3 to identify STAT3 binding sites. Chromatin immunoprecipitation (ChIP) and an electoromobility shift assay (EMSA) confirmed STAT3 occupancy to those promoter regions in both IL-6 stimulated MM1 and CLL cells. Transfection of MM1 cells with STAT3 siRNA or CLL cells with STAT3 shRNA significantly down-regulated GM-CSFRα mRNA and protein levels. RNA transcripts, involved in regulating cell-survival pathways, and the proteins KAP1 (TRIM28) and ISG15 co-immunoprecipitated with GM-CSFRα. GM-CSFRα-bound KAP1 enhanced the transcriptional activity of STAT3, whereas ISG15 inhibited the NF-κB pathway. Nevertheless, overexpression of GM-CSFRα protected MM1 cells from dexamethasone-induced apoptosis, and GM-CSFRα knockdown induced apoptosis in CLL cells, suggesting that GM-CSFRα provides a ligand-independent survival advantage. PMID:24836891

  15. Functional analysis of the Arabidopsis PLDZ2 promoter reveals an evolutionarily conserved low-Pi-responsive transcriptional enhancer element

    PubMed Central

    Oropeza-Aburto, Araceli; Cruz-Ramírez, Alfredo; Acevedo-Hernández, Gustavo J.; Pérez-Torres, Claudia-Anahí; Caballero-Pérez, Juan; Herrera-Estrella, Luis

    2012-01-01

    Plants have evolved a plethora of responses to cope with phosphate (Pi) deficiency, including the transcriptional activation of a large set of genes. Among Pi-responsive genes, the expression of the Arabidopsis phospholipase DZ2 (PLDZ2) is activated to participate in the degradation of phospholipids in roots in order to release Pi to support other cellular activities. A deletion analysis was performed to identify the regions determining the strength, tissue-specific expression, and Pi responsiveness of this regulatory region. This study also reports the identification and characterization of a transcriptional enhancer element that is present in the PLDZ2 promoter and able to confer Pi responsiveness to a minimal, inactive 35S promoter. This enhancer also shares the cytokinin and sucrose responsive properties observed for the intact PLDZ2 promoter. The EZ2 element contains two P1BS motifs, each of which is the DNA binding site of transcription factor PHR1. Mutation analysis showed that the P1BS motifs present in EZ2 are necessary but not sufficient for the enhancer function, revealing the importance of adjacent sequences. The structural organization of EZ2 is conserved in the orthologous genes of at least eight families of rosids, suggesting that architectural features such as the distance between the two P1BS motifs are also important for the regulatory properties of this enhancer element. PMID:22210906

  16. P1 interneurons promote a persistent internal state that enhances inter-male aggression in Drosophila

    PubMed Central

    Hoopfer, Eric D; Jung, Yonil; Inagaki, Hidehiko K; Rubin, Gerald M; Anderson, David J

    2015-01-01

    How brains are hardwired to produce aggressive behavior, and how aggression circuits are related to those that mediate courtship, is not well understood. A large-scale screen for aggression-promoting neurons in Drosophila identified several independent hits that enhanced both inter-male aggression and courtship. Genetic intersections revealed that 8-10 P1 interneurons, previously thought to exclusively control male courtship, were sufficient to promote fighting. Optogenetic experiments indicated that P1 activation could promote aggression at a threshold below that required for wing extension. P1 activation in the absence of wing extension triggered persistent aggression via an internal state that could endure for minutes. High-frequency P1 activation promoted wing extension and suppressed aggression during photostimulation, whereas aggression resumed and wing extension was inhibited following photostimulation offset. Thus, P1 neuron activation promotes a latent, internal state that facilitates aggression and courtship, and controls the overt expression of these social behaviors in a threshold-dependent, inverse manner. DOI: http://dx.doi.org/10.7554/eLife.11346.001 PMID:26714106

  17. MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression.

    PubMed

    Xu, Meixiang; Cross, Courtney E; Speidel, Jordan T; Abdel-Rahman, Sherif Z

    2016-10-01

    The O 6 -methylguanine-DNA methyltransferase (MGMT) protein removes O 6 -alkyl-guanine adducts from DNA. MGMT expression can thus alter the sensitivity of cells and tissues to environmental and chemotherapeutic alkylating agents. Previously, we defined the haplotype structure encompassing single nucleotide polymorphisms (SNPs) in the MGMT promoter/enhancer (P/E) region and found that haplotypes, rather than individual SNPs, alter MGMT promoter activity. The exact mechanism(s) by which these haplotypes exert their effect on MGMT promoter activity is currently unknown, but we noted that many of the SNPs comprising the MGMT P/E haplotypes are located within or in close proximity to putative transcription factor binding sites. Thus, these haplotypes could potentially affect transcription factor binding and, subsequently, alter MGMT promoter activity. In this study, we test the hypothesis that MGMT P/E haplotypes affect MGMT promoter activity by altering transcription factor (TF) binding to the P/E region. We used a promoter binding TF profiling array and a reporter assay to evaluate the effect of different P/E haplotypes on TF binding and MGMT expression, respectively. Our data revealed a significant difference in TF binding profiles between the different haplotypes evaluated. We identified TFs that consistently showed significant haplotype-dependent binding alterations (p ≤ 0.01) and revealed their role in regulating MGMT expression using siRNAs and a dual-luciferase reporter assay system. The data generated support our hypothesis that promoter haplotypes alter the binding of TFs to the MGMT P/E and, subsequently, affect their regulatory function on MGMT promoter activity and expression level.

  18. Promotion of chloroplast proliferation upon enhanced post-mitotic cell expansion in leaves.

    PubMed

    Kawade, Kensuke; Horiguchi, Gorou; Ishikawa, Naoko; Hirai, Masami Yokota; Tsukaya, Hirokazu

    2013-09-28

    Leaves are determinate organs; hence, precise control of cell proliferation and post-mitotic cell expansion is essential for their growth. A defect in cell proliferation often triggers enhanced post-mitotic cell expansion in leaves. This phenomenon is referred to as 'compensation'. Several lines of evidence from studies on compensation have shown that cell proliferation and post-mitotic cell expansion are coordinately regulated during leaf development. Therefore, compensation has attracted much attention to the mechanisms for leaf growth. However, our understanding of compensation at the subcellular level remains limited because studies of compensation have focused mainly on cellular-level phenotypes. Proper leaf growth requires quantitative control of subcellular components in association with cellular-level changes. To gain insight into the subcellular aspect of compensation, we investigated the well-known relationship between cell area and chloroplast number per cell in compensation-exhibiting lines, and asked whether chloroplast proliferation is modulated in response to the induction of compensation. We first established a convenient and reliable method for observation of chloroplasts in situ. Using this method, we analyzed Arabidopsis thaliana mutants fugu5 and angustifolia3 (an3), and a transgenic line KIP-RELATED PROTEIN2 overexpressor (KRP2 OE), which are known to exhibit typical features of compensation. We here showed that chloroplast number per cell increased in the subepidermal palisade tissue of these lines. We analyzed tetraploidized wild type, fugu5, an3 and KRP2 OE, and found that cell area itself, but not nuclear ploidy, is a key parameter that determines the activity of chloroplast proliferation. In particular, in the case of an3, we uncovered that promotion of chloroplast proliferation depends on the enhanced post-mitotic cell expansion. The expression levels of chloroplast proliferation-related genes are similar to or lower than that in the wild

  19. Promotion of chloroplast proliferation upon enhanced post-mitotic cell expansion in leaves

    PubMed Central

    2013-01-01

    Background Leaves are determinate organs; hence, precise control of cell proliferation and post-mitotic cell expansion is essential for their growth. A defect in cell proliferation often triggers enhanced post-mitotic cell expansion in leaves. This phenomenon is referred to as ‘compensation’. Several lines of evidence from studies on compensation have shown that cell proliferation and post-mitotic cell expansion are coordinately regulated during leaf development. Therefore, compensation has attracted much attention to the mechanisms for leaf growth. However, our understanding of compensation at the subcellular level remains limited because studies of compensation have focused mainly on cellular-level phenotypes. Proper leaf growth requires quantitative control of subcellular components in association with cellular-level changes. To gain insight into the subcellular aspect of compensation, we investigated the well-known relationship between cell area and chloroplast number per cell in compensation-exhibiting lines, and asked whether chloroplast proliferation is modulated in response to the induction of compensation. Results We first established a convenient and reliable method for observation of chloroplasts in situ. Using this method, we analyzed Arabidopsis thaliana mutants fugu5 and angustifolia3 (an3), and a transgenic line KIP-RELATED PROTEIN2 overexpressor (KRP2 OE), which are known to exhibit typical features of compensation. We here showed that chloroplast number per cell increased in the subepidermal palisade tissue of these lines. We analyzed tetraploidized wild type, fugu5, an3 and KRP2 OE, and found that cell area itself, but not nuclear ploidy, is a key parameter that determines the activity of chloroplast proliferation. In particular, in the case of an3, we uncovered that promotion of chloroplast proliferation depends on the enhanced post-mitotic cell expansion. The expression levels of chloroplast proliferation-related genes are similar to or

  20. Using a Synchronous Online Learning Environment to Promote and Enhance Transactional Engagement beyond the Classroom

    ERIC Educational Resources Information Center

    Wdowik, Steven

    2014-01-01

    Purpose: The purpose of this paper is to create a synchronous online learning community through the use of "Blackboard Collaborate!" to promote and enhance transactional engagement outside the classroom. Design/methodology/approach: This paper employs a quantitative and qualitative approach where data were sourced from a third year…

  1. Knowledge, attitudes and practices (KAP) of hygiene among school children in Angolela, Ethiopia.

    PubMed

    Vivas, A P; Gelaye, B; Aboset, N; Kumie, A; Berhane, Y; Williams, M A

    2010-06-01

    Poor hygiene practices and inadequate sanitary conditions play major roles in the increased burden of communicable diseases within developing countries. This study evaluated the KAP of hygiene among rural school children in Ethiopia and assessed the extent to which proper knowledge of hygiene was associated with personal hygiene characteristics. This cross-sectional study was comprised of 669 students who were interviewed by trained staff Participants were in grades 1-6 at Angolela Primary School, located in rural Ethiopia. Data consisted of hygiene and hand washing practices, knowledge about sanitation, personal hygiene characteristics, and presence of gastrointestinal parasitic infection. Results. Approximately 52% of students were classified as having adequate knowledge of proper hygiene. Most students reported hand washing before meals (99.0%), but only 36.2% reported using soap. Although 76.7% of students reported that washing hands after defecation was important, only 14.8% reported actually following this practice. Students with adequate knowledge of proper hygiene were more likely to have clean clothes (AOR 1.62, CI 1.14-2.29) and to have a lower risk of parasitic infection (AOR 0.78, CI 0.56-1.09) although statistical significance was not achieved for the latter Study findings underscore the need for more hand washing and hygiene education in schools; and provide objective evidence that may guide the development of comprehensive health and hygiene intervention programs in rural Ethiopian schools. Successful implementation of these programs is likely to substantially attenuate the transmissible disease burden borne by school children in rural settings.

  2. Web-based KAP Intervention on Office Ergonomics: A Unique Technique for Prevention of Musculoskeletal Discomfort in Global Corporate Offices.

    PubMed

    Madhwani, Kishore P; Nag, P K

    2017-01-01

    The purpose of this study was to evaluate web-based Knowledge, Attitude and Practice (KAP) intervention on office ergonomics - a unique method for prevention of musculoskeletal discomfort (MSD) - in corporate offices that influences behavior modification. With the increasing use of computers, laptops and hand-held communication devices globally among office employees, creating awareness on office ergonomics has become a top priority. Emphasis needs to be given on maintaining ideal work postures, ergonomic arrangement of workstations, optimizing chair functions, as well as performing desk stretches to reduce MSD arising from the use of these equipment, thereby promoting safe work practices at offices and home, as in the current scenario many employees work from home with flexible work hours. Hence, this justifies the importance of our study. To promote safe working by exploring cost-effective communication methods to achieve behavior change at distant sites when an on-site visit may not be feasible. An invitation was sent by the Medical and Occupational Health Team of a multinational corporation to all employees at their offices in Sri Lanka, Singapore, and Malaysia to take up an online Nordic questionnaire, a screening tool for musculoskeletal symptoms, shared in local languages on two occasions - baseline evaluation ( n = 240) and a follow-up evaluation after 3 months ( n = 203). After completing the baseline questionnaire, employees were immediately trained on correct postures and office ergonomics with animation graphics. The same questionnaire was sent again after a 12-week gap only to those employees who responded to the baseline questionnaire on initial assessment. Data collected were analyzed using the Statistical Package for the Social Sciences (SPSS) version 20.0 software and variables were compared using odds ratio as well as Chi-square test. Of the 203 employees who responded, 47.35% had some musculoskeletal symptoms. Among them 58.7% had lower back pain

  3. Promoting effects of chemical permeation enhancers on insulin permeation across TR146 cell model of buccal epithelium in vitro.

    PubMed

    Xue, Xiao-yan; Zhou, Ying; Chen, Ying-ying; Meng, Jing-ru; Jia, Min; Hou, Zheng; Bai, Hui; Mao, Xing-gang; Luo, Xiao-xing

    2012-04-01

    To find potential enhancers for facilitating the buccal delivery of insulin, a TR146 cell-culture model of buccal epithelium, cultured on commercially available insert plates, was used to evaluate the permeability-enhancing effects of several traditional and new types of chemical enhancers, including N-acetyl-L-cysteine (NAC), sodium deoxycholate (SDC), sodium nitroprusside (SNP), reduced glutathione (GSH), glutamine (Gln), chitosan (CS), L-arginine (Arg), 1-dodecylazacycloheptan-2-one (Azone), and soybean lecithin (SPC) (50 and 10 μg/mL respectively). Permeability studies were performed to determine the enhancing effects of these compounds on insulin permeation across the cell-culture model. The enhancing effects of the enhancers were assessed by calculating the apparent permeability coefficients and enhancement ratio. Cytotoxicity of the permeation enhancers at different concentrations was investigated by using the methylthiazolydiphenyl-tetrazolium bromide (MTT) assay. Results showed that 50 μg/mL of NAC, SDC, GSH, CS, Arg, Azone, SPC, SNP, and 10 μg/mL of SNP had a significant enhancing effect on promoting the transport of insulin across the TR146 cell model. MTT assays showed that 50 μg/mL of Gln, Azone, SDC, SNP, Arg, 10 μg/mL SDC, and Arg had obvious toxic effects on TR146 cells. Therefore, NAC, GSH, CS, SPC, and SNP appear to be safe, effective permeability enhancers that promote the transport of insulin across the TR146 cell-culture model of buccal epithelium and may be potential enhancers for buccal delivery of insulin with both low toxicity and high efficiency.

  4. Islet cells share promoter hypomethylation independently of expression, but exhibit cell-type-specific methylation in enhancers.

    PubMed

    Neiman, Daniel; Moss, Joshua; Hecht, Merav; Magenheim, Judith; Piyanzin, Sheina; Shapiro, A M James; de Koning, Eelco J P; Razin, Aharon; Cedar, Howard; Shemer, Ruth; Dor, Yuval

    2017-12-19

    DNA methylation at promoters is an important determinant of gene expression. Earlier studies suggested that the insulin gene promoter is uniquely unmethylated in insulin-expressing pancreatic β-cells, providing a classic example of this paradigm. Here we show that islet cells expressing insulin, glucagon, or somatostatin share a lack of methylation at the promoters of the insulin and glucagon genes. This is achieved by rapid demethylation of the insulin and glucagon gene promoters during differentiation of Neurogenin3 + embryonic endocrine progenitors, regardless of the specific endocrine cell-type chosen. Similar methylation dynamics were observed in transgenic mice containing a human insulin promoter fragment, pointing to the responsible cis element. Whole-methylome comparison of human α- and β-cells revealed generality of the findings: genes active in one cell type and silent in the other tend to share demethylated promoters, while methylation differences between α- and β-cells are concentrated in enhancers. These findings suggest an epigenetic basis for the observed plastic identity of islet cell types, and have implications for β-cell reprogramming in diabetes and diagnosis of β-cell death using methylation patterns of circulating DNA. Copyright © 2017 the Author(s). Published by PNAS.

  5. Enhancing Educators' Skills for Promoting Critical Thinking in Their Classroom Discourses: A Randomized Control Trial

    ERIC Educational Resources Information Center

    Gul, Raisa B.; Khan, Shehla; Ahmed, Azra; Cassum, Shanaz; Saeed, Tanveer; Parpio, Yasmin; Schopflocher, Donald; Profetto-McGrath, Joanne

    2014-01-01

    The literature reveals that educators find it challenging to foster critical thinking (CT) in their students if they have not learned how to use CT in their educational system or training. This paper reports findings from a national research project that was undertaken to enhance the educators' ability to promote CT in their teaching practices.…

  6. Music and Sign Language to Promote Infant and Toddler Communication and Enhance Parent-Child Interaction

    ERIC Educational Resources Information Center

    Colwell, Cynthia; Memmott, Jenny; Meeker-Miller, Anne

    2014-01-01

    The purpose of this study was to determine the efficacy of using music and/or sign language to promote early communication in infants and toddlers (6-20 months) and to enhance parent-child interactions. Three groups used for this study were pairs of participants (care-giver(s) and child) assigned to each group: 1) Music Alone 2) Sign Language…

  7. The School and Promotion of Children's Health-Enhancing Physical Activity: Perspectives from the United Kingdom

    ERIC Educational Resources Information Center

    Fox, Kenneth R.; Cooper, Ashley; McKenna, Jim

    2004-01-01

    The purpose of this article is to summarize the developing role and the challenges facing the British primary and secondary education sector in the promotion of children's health-enhancing physical activity. This is in the context of a public agenda on physical activity for health that grew steadily in stature throughout the 1990s and has…

  8. Electroacupuncture Promotes Remyelination after Cuprizone Treatment by Enhancing Myelin Debris Clearance

    PubMed Central

    Zhu, Keying; Sun, Jingxian; Kang, Zheng; Zou, Zaofeng; Wu, Gencheng; Wang, Jun

    2017-01-01

    Promoting remyelination is crucial for patients with demyelinating diseases including multiple sclerosis. However, it is still a circuitous conundrum finding a practical remyelinating therapy. Electroacupuncture (EA), originating from traditional Chinese medicine (TCM), has been widely used to treat CNS diseases all over the world, but the role of EA in demyelinating diseases is barely known. In this study, we examined the remyelinating properties and mechanisms of EA in cuprizone-induced demyelinating model, a CNS demyelinating murine model of multiple sclerosis. By feeding C57BL/6 mice with chow containing 0.2% cuprizone for 5 weeks, we successfully induce demyelination as proved by weight change, beam test, pole test, histomorphology, and Western Blot. EA treatment significantly improves the neurobehavioral performance at week 7 (2 weeks after withdrawing cuprizone chow). RNA-seq and RT-PCR results reveal up-regulated expression of myelin-related genes, and the expression of myelin associated protein (MBP, CNPase, and O4) are also increased after EA treatment, indicating therapeutic effect of EA on cuprizone model. It is widely acknowledged that microglia exert phagocytic effect on degraded myelin debris and clear these detrimental debris, which is a necessary process for subsequent remyelination. We found the remyelinating effect of EA is associated with enhanced clearance of degraded myelin debris as detected by dMBP staining and red oil O staining. Our further studies suggest that more microglia assemble in demyelinating area (corpus callosum) during the process of EA treatment, and cells inside corpus callosum are mostly in a plump, ameboid, and phagocytic shape, quite different from the ramified cells outside corpus callosum. RNA-seq result also unravels that most genes relating to positive regulation of phagocytosis (GO:0050766) are up-regulated, indicating enhanced phagocytic process after EA treatment. During the process of myelin debris clearance

  9. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction.

    PubMed

    Yan, Meiping; Zhang, Xinhua; Chen, Ao; Gu, Wei; Liu, Jie; Ren, Xiaojiao; Zhang, Jianping; Wu, Xiaoxiong; Place, Aaron T; Minshall, Richard D; Liu, Guoquan

    2017-11-01

    Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of leukocytes to endothelial cells and initiates subsequent signaling that promotes their transendothelial migration (TEM). Vascular endothelial (VE)-cadherin plays a critical role in endothelial cell-cell adhesion, thereby controlling endothelial permeability and leukocyte transmigration. This study aimed to determine the molecular signaling events that originate from the ICAM-1-mediated firm adhesion of neutrophils that regulate VE-cadherin's role as a negative regulator of leukocyte transmigration. We observed that ICAM-1 interacts with Src homology domain 2-containing phosphatase-2 (SHP-2), and SHP-2 down-regulation via silencing of small interfering RNA in endothelial cells enhanced neutrophil adhesion to endothelial cells but inhibited neutrophil transmigration. We also found that VE-cadherin associated with the ICAM-1-SHP-2 complex. Moreover, whereas the activation of ICAM-1 leads to VE-cadherin dissociation from ICAM-1 and VE-cadherin association with actin, SHP-2 down-regulation prevented ICAM-1-VE-cadherin association and promoted VE-cadherin-actin association. Furthermore, SHP-2 down-regulation in vivo promoted LPS-induced neutrophil recruitment in mouse lung but delayed neutrophil extravasation. These results suggest that SHP-2- via association with ICAM-1-mediates ICAM-1-induced Src activation and modulates VE-cadherin switching association with ICAM-1 or actin, thereby negatively regulating neutrophil adhesion to endothelial cells and enhancing their TEM.-Yan, M., Zhang, X., Chen, A., Gu, W., Liu, J., Ren, X., Zhang, J., Wu, X., Place, A. T., Minshall, R. D., Liu, G. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction. © FASEB.

  10. FBI-1 enhances ETS-1 signaling activity and promotes proliferation of human colorectal carcinoma cells.

    PubMed

    Zhu, Min; Li, Mingyang; Zhang, Fan; Feng, Fan; Chen, Weihao; Yang, Yutao; Cui, Jiajun; Zhang, Dong; Linghu, Enqiang

    2014-01-01

    In this study, we investigated a potential regulatory role of FBI-1 in transcription factor activity of ETS-1. The protein interaction was identified between ETS-1 and FBI-1 in lovo cells. The accumulating data showed that FBI-1 promoted the recruitment of ETS-1 to endogenous promoter of its target genes and increase ETS-1 accumulation in the nuclear. Our work also indicated that the FBI-1 enhances ETS-1 transcription factor activity via down-regulating p53-mediated inhibition on ETS-1. Further, FBI-1 plays a role in regulation of colorectal carcinoma cells proliferation. These findings supported that FBI-1 might be a potential molecule target for treating colorectal carcinoma.

  11. FBI-1 Enhances ETS-1 Signaling Activity and Promotes Proliferation of Human Colorectal Carcinoma Cells

    PubMed Central

    Chen, Weihao; Yang, Yutao; Cui, Jiajun; Zhang, Dong; Linghu, Enqiang

    2014-01-01

    In this study, we investigated a potential regulatory role of FBI-1 in transcription factor activity of ETS-1. The protein interaction was identified between ETS-1 and FBI-1 in lovo cells. The accumulating data showed that FBI-1 promoted the recruitment of ETS-1 to endogenous promoter of its target genes and increase ETS-1 accumulation in the nuclear. Our work also indicated that the FBI-1 enhances ETS-1 transcription factor activity via down-regulating p53-mediated inhibition on ETS-1. Further, FBI-1 plays a role in regulation of colorectal carcinoma cells proliferation. These findings supported that FBI-1 might be a potential molecule target for treating colorectal carcinoma. PMID:24857950

  12. [Profiles of factors enhancing teachers' occupational wellbeing and their use in health promoting schools].

    PubMed

    Woynarowska-Sołdan, Magdalena; Weziak-Białowolska, Dorota

    2012-01-01

    The aim of this article is to present the results of survey on general occupational being and factors contributing to the enhancement of teachers' occupational wellbeing. The authors also address the issue how to work out, analyze, present and use the survey results in health promotion at schools. Teachers of four selected health promoting schools (HPS) were surveyed and the results were analyzed. The Factors Enhancing Teachers's Occupational Wellbeing Scale was used. This instrument consisted of 45 statements on 5 subscales (working conditions, teachers' community, students' and parents' community, organization and workload, professional competences). They were measured from two points of view, the assessment of a current situation and the assessment of needs for the improvement. The scale was preceded by questions concerning the assessment of general occupational being and the assessment of general occupational being of other teachers at school. The self-assessment of the respondents' own and other teachers' occupational being was positive. The current situation related to factors influencing teachers' wellbeing was recognized by teachers as rather good and the need for change was rather low. There were differences between schools in the majority of analyzed factors. An easy method of analyzing data as numerical values and graphic profiles was proposed to be used in HPS. Factors influencing teachers' occupational wellbeing differed between schools. The results of their assessment should be analyzed in each school taking account of its individual context. The proposed instrument and method of data analysis are useful in the planning of teachers' health promotion projects, diagnosis of the initial status ("pre-test") and evaluation of their outcomes ("post-test").

  13. Enhancing the Mental Health Promotion Component of a Health and Personal Development Programme in Irish Schools

    ERIC Educational Resources Information Center

    Fitzpatrick, Carol; Conlon, Andrea; Cleary, Deirdre; Power, Mike; King, Frances; Guerin, Suzanne

    2013-01-01

    This study set out to examine the impact of a health and personal development programme (the Social, Personal and Health Education Programme) which had been "enhanced" by the addition of a mental health promotion component. Students aged 12-16 years attending 17 secondary schools were randomly allocated as clusters to participate in…

  14. Does Decentralisation Enhance a School's Role of Promoting Social Cohesion? Bosnian School Leaders' Perceptions of School Governance

    ERIC Educational Resources Information Center

    Komatsu, Taro

    2014-01-01

    This study seeks to understand whether and how decentralised school governance in Bosnia and Herzegovina (BiH) enhances the schools' role of promoting social cohesion. This includes increasing "horizontal" trust among different ethnic groups and "vertical" trust between civilians and public institutes. The study examined…

  15. [KAP research and intervention effects of health education on prevention and control of occupational diseases in occupational groups in Jinzhou, China].

    PubMed

    Wang, D H; Liu, X L; Quan, J K

    2016-04-20

    To investigate the current status of knowledge, attitude, and practice (KAP)on the prevention and control of occupational diseases in occupational groups in Jinzhou, China, and to evaluate the intervention effects of health education. Using the cluster random sampling method, 1000 workers who underwent occupational health examination in Jinzhou Center for Disease Control and Prevention from September 2014 to April 2015 were enrolled in this study. They were equally and randomly divided into intervention group and control group. The intervention group received health education for 6 months through bulletin board, promotion materials, expert lecture, Q&A session, and other relevant educational events. The questionnaire survey was performed before and after intervention. The control group received the questionnaire survey but not the health education. The overall awareness rate of prevention and control knowledge was 75.34% in 990 workers in Jinzhou, China. After the intervention, the intervention group had a significantly higher awareness rate of prevention and control knowledge than the control group (89.87%~98.86% vs 71.25%~80.82%, P<0.05); the intervention group had a significantly higher attitude accuracy for" whether occupational health examination is necessary or not" and " is willing to received the training on occupational health knowledge" than the control group(χ(2)=57.857, P<0.05; χ(2)=70.683, P<0.05); and the intervention group had a significantly higher rate of correct behavior for" whether help the business management personnel to carry out the prevention and control of occupational diseases or not" and"whether actively understand the occupational hazards of job" (χ(2)=102.186, P<0.05; χ(2)=91.159, P<0.05). Health education can significantly increase the awareness rate of prevention and control knowledge on occupational diseases in occupational groups in Jinzhou, China. However, the more structured and longterm comprehensive intervention is

  16. The combination of dimethoxycurcumin with DNA methylation inhibitor enhances gene re-expression of promoter-methylated genes and antagonizes their cytotoxic effect

    PubMed Central

    Hassan, Hazem E.; Keita, Jean-Arnaud; Narayan, Lawrence; Brady, Sean M.; Frederick, Richard; Carlson, Samuel; C. Glass, Karen; Natesan, Senthil; Buttolph, Thomm; Fandy, Tamer E.

    2016-01-01

    ABSTRACT Curcumin and its analogs exhibited antileukemic activity either as single agent or in combination therapy. Dimethoxycurcumin (DMC) is a more metabolically stable curcumin analog that was shown to induce the expression of promoter-methylated genes without reversing DNA methylation. Accordingly, co-treatment with DMC and DNA methyltransferase (DNMT) inhibitors could hypothetically enhance the re-expression of promoter-methylated tumor suppressor genes. In this study, we investigated the cytotoxic effects and epigenetic changes associated with the combination of DMC and the DNMT inhibitor decitabine (DAC) in primary leukemia samples and cell lines. The combination demonstrated antagonistic cytotoxic effects and was minimally cytotoxic to primary leukemia cells. The combination did not affect the metabolic stability of DMC. Although the combination enhanced the downregulation of nuclear DNMT proteins, the hypomethylating activity of the combination was not increased significantly compared to DAC alone. On the other hand, the combination significantly increased H3K27 acetylation (H3K27Ac) compared to the single agents near the promoter region of promoter-methylated genes. Furthermore, sequential chromatin immunoprecipitation (ChIP) and DNA pyrosequencing of the chromatin-enriched H3K27Ac did not show any significant decrease in DNA methylation compared to other regions. Consequently, the enhanced induction of promoter-methylated genes by the combination compared to DAC alone is mediated by a mechanism that involves increased histone acetylation and not through potentiation of the DNA hypomethylating activity of DAC. Collectively, our results provide the mechanistic basis for further characterization of this combination in leukemia animal models and early phase clinical trials. PMID:27588609

  17. Development and psychometric testing of the Knowledge, Attitudes and Practices (KAP) questionnaire among student Tuberculosis (TB) Patients (STBP-KAPQ) in China.

    PubMed

    Fan, Yahui; Zhang, Shaoru; Li, Yan; Li, Yuelu; Zhang, Tianhua; Liu, Weiping; Jiang, Hualin

    2018-05-08

    validity was supported through a significant difference between student TB patients and healthy students across all domains (p < 0.05). An instrument, "Knowledge, Attitudes and Practices Questionnaire among Student Tuberculosis Patients (STBP-KAPQ)" was developed. Psychometric testing indicated that it had adequate validity and reliability for use in KAP researches with student TB patients in China. The new tool might help public health researchers evaluate the level of KAP in student TB patients, and it could also be used to examine the effects of TB health education.

  18. Web-based KAP Intervention on Office Ergonomics: A Unique Technique for Prevention of Musculoskeletal Discomfort in Global Corporate Offices

    PubMed Central

    Madhwani, Kishore P.; Nag, P. K.

    2017-01-01

    Aims: The purpose of this study was to evaluate web-based Knowledge, Attitude and Practice (KAP) intervention on office ergonomics – a unique method for prevention of musculoskeletal discomfort (MSD) – in corporate offices that influences behavior modification. Background: With the increasing use of computers, laptops and hand-held communication devices globally among office employees, creating awareness on office ergonomics has become a top priority. Emphasis needs to be given on maintaining ideal work postures, ergonomic arrangement of workstations, optimizing chair functions, as well as performing desk stretches to reduce MSD arising from the use of these equipment, thereby promoting safe work practices at offices and home, as in the current scenario many employees work from home with flexible work hours. Hence, this justifies the importance of our study. Objective: To promote safe working by exploring cost-effective communication methods to achieve behavior change at distant sites when an on-site visit may not be feasible. Materials and Methods: An invitation was sent by the Medical and Occupational Health Team of a multinational corporation to all employees at their offices in Sri Lanka, Singapore, and Malaysia to take up an online Nordic questionnaire, a screening tool for musculoskeletal symptoms, shared in local languages on two occasions – baseline evaluation (n = 240) and a follow-up evaluation after 3 months (n = 203). After completing the baseline questionnaire, employees were immediately trained on correct postures and office ergonomics with animation graphics. The same questionnaire was sent again after a 12-week gap only to those employees who responded to the baseline questionnaire on initial assessment. Statistical Analysis Used: Data collected were analyzed using the Statistical Package for the Social Sciences (SPSS) version 20.0 software and variables were compared using odds ratio as well as Chi-square test. Results: Of the 203 employees

  19. Mechanical Stretching Promotes Skin Tissue Regeneration via Enhancing Mesenchymal Stem Cell Homing and Transdifferentiation.

    PubMed

    Liang, Xiao; Huang, Xiaolu; Zhou, Yiwen; Jin, Rui; Li, Qingfeng

    2016-07-01

    Skin tissue expansion is a clinical procedure for skin regeneration to reconstruct cutaneous defects that can be accompanied by severe complications. The transplantation of mesenchymal stem cells (MSCs) has been proven effective in promoting skin expansion and helping to ameliorate complications; however, systematic understanding of its mechanism remains unclear. MSCs from luciferase-Tg Lewis rats were intravenously transplanted into a rat tissue expansion model to identify homing and transdifferentiation. To clarify underlying mechanisms, a systematic approach was used to identify the differentially expressed genes between mechanically stretched human MSCs and controls. The biological significance of these changes was analyzed through bioinformatic methods. We further investigated genes and pathways of interest to disclose their potential role in mechanical stretching-induced skin regeneration. Cross sections of skin samples from the expanded group showed significantly more luciferase(+) and stromal cell-derived factor 1α (SDF-1α)(+), luciferase(+)keratin 14(+), and luciferase(+)CD31(+) cells than the control group, indicating MSC transdifferentiation into epidermal basal cells and endothelial cells after SDF-1α-mediated homing. Microarray analysis suggested upregulation of genes related to hypoxia, vascularization, and cell proliferation in the stretched human MSCs. Further investigation showed that the homing of MSCs was blocked by short interfering RNA targeted against matrix metalloproteinase 2, and that mechanical stretching-induced vascular endothelial growth factor A upregulation was related to the Janus kinase/signal transducer and activator of transcription (Jak-STAT) and Wnt signaling pathways. This study determines that mechanical stretching might promote skin regeneration by upregulating MSC expression of genes related to hypoxia, vascularization, and cell proliferation; enhancing transplanted MSC homing to the expanded skin; and

  20. 7 CFR 1215.16 - Promotion.

    Code of Federal Regulations, 2010 CFR

    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...

  1. Promotion of Water Channels for Enhanced Ion Transport in 14 nm Diameter Carbon Nanotubes.

    PubMed

    Sheng, Jiadong; Zhu, Qi; Zeng, Xian; Yang, Zhaohui; Zhang, Xiaohua

    2017-03-29

    Ion transport plays an important role in solar-to-electricity conversion, drug delivery, and a variety of biological processes. Carbon nanotube (CNT) is a promising material as an ion transporter in the applications of the mimicking of natural ion channels, desalination, and energy harvesting. Here, we demonstrate a unique, enhanced ion transport through a vertically aligned multiwall CNT membrane after the application of an electric potential across CNT membranes. Interestingly, electrowetting arising from the application of an electric potential is critical for the enhancement of overall ion transport rate through CNT membranes. The wettability of a liquid with high surface tension on the interior channel walls of CNTs increases during an electric potential treatment and promotes the formation of water channels in CNTs. The formation of water channels in CNTs induces an increase in overall ion diffusion through CNT membranes. This phenomenon is also related to a decrease in the charge transfer resistance of CNTs (R ct ) after an electric potential is applied. Correspondingly, the enhanced ion flow rate gives rise to an enhancement in the capacitive performance of CNT based membranes. Our observations might have profound impact on the development of CNT based energy storage devices as well as artificial ion channels.

  2. ROCK inhibition promotes microtentacles that enhance reattachment of breast cancer cells

    PubMed Central

    Bhandary, Lekhana; Whipple, Rebecca A.; Vitolo, Michele I.; Charpentier, Monica S.; Boggs, Amanda E.; Chakrabarti, Kristi R.; Thompson, Keyata N.; Martin, Stuart S.

    2015-01-01

    The presence of circulating tumor cells (CTCs) in blood predicts poor patient outcome and CTC frequency is correlated with higher risk of metastasis. Recently discovered, novel microtubule-based structures, microtentacles, can enhance reattachment of CTCs to the vasculature. Microtentacles are highly dynamic membrane protrusions formed in detached cells and occur when physical forces generated by the outwardly expanding microtubules overcome the contractile force of the actin cortex. Rho-associated kinase (ROCK) is a major regulator of actomyosin contractility and Rho/ROCK over-activation is implicated in tumor metastasis. ROCK inhibitors are gaining popularity as potential cancer therapeutics based on their success in reducing adherent tumor cell migration and invasion. However, the effect of ROCK inhibition on detached cells in circulation is largely unknown. In this study, we use breast tumor cells in suspension to mimic detached CTCs and show that destabilizing the actin cortex through ROCK inhibition in suspended cells promotes the formation of microtentacles and enhances reattachment of cells from suspension. Conversely, increasing actomyosin contraction by Rho over-activation reduces microtentacle frequency and reattachment. Although ROCK inhibitors may be effective in reducing adherent tumor cell behavior, our results indicate that they could inadvertently increase metastatic potential of non-adherent CTCs by increasing their reattachment efficacy. PMID:25749040

  3. The effectiveness of nutrition education: Applying the Health Belief Model in child-feeding practices to use pulses for complementary feeding in Southern Ethiopia.

    PubMed

    Mulualem, Demmelash; Henry, Carol J; Berhanu, Getenesh; Whiting, Susan J

    2016-01-01

    Complementary foods (CFs) in Ethiopia are cereal based and adding locally grown pulses (legumes) to CF would provide needed nutrients. To assess the effects of nutrition education (NEd) using Health Belief Model (HBM) in promoting pulses for CF, a 6-month quasi-experimental study was conducted in 160 mother-child pairs. Knowledge, attitude, and practice (KAP) questions were given to mothers at baseline, midline, and endline, along with anthropometric measurements of children. NEd involving discussions and recipe demonstrations was given twice monthly for 6 months to the intervention group (n = 80) while control mothers received usual education. At baseline, mothers' KAP scores were low at both sites; at 3 and 6 months of NEd, mean KAP scores of mothers increased (p < 0.05) compared to the control site. Significant improvements in children's mean weight, weight for height, and weight for age occurred in the intervention site only. Nutritional status of children improved after providing mothers with pulse-based NEd.

  4. Enhancement of extracellular expression of Bacillus naganoensis pullulanase from recombinant Bacillus subtilis: Effects of promoter and host.

    PubMed

    Song, Wan; Nie, Yao; Mu, Xiao Qing; Xu, Yan

    2016-08-01

    Pullulanase plays an important role in industrial applications of starch processing. However, extracellular production of pullulanase from recombinant Bacillus subtilis is yet limited due to the issues on regulatory elements of B. subtilis expression system. In this study, the gene encoding B. naganoensis pullulanase (PUL) was expressed in B. subtilis WB800 under the promoter PHpaII in the shuttle vector pMA0911. The extracellular activity of expressed pullulanase was 3.9 U ml(-1) from the recombinant B. subtilis WB800/pMA0911-PHpaII-pul. To further enhance the yield of PUL, the promoter PHpaII in pMA0911 was replaced by a stronger constitutive promoter P43. Then the activity was increased to 8.7 U ml(-1) from the recombinant B. subtilis WB800/pMA0911-P43-pul. Effect of host on pullulanase expression was further investigated by comparison between B. subtilis WB600 and B. subtilis WB800. In addition to the available B. subtilis WB800 recombinants, the constructed plasmids pMA0911-PHpaII-pul and pMA0911-P43-pul were transformed into B. subtilis WB600, respectively. Consequently, the extracellular production of PUL was significantly enhanced by B. subtilis WB600/pMA0911-P43-pul, resulting in the extracellular pullulanase activity of 24.5 U ml(-1). Therefore, promoter and host had an impact on pullulanase expression and their optimization would be useful to improve heterologous protein expression in B. subtilis. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. A cross-sectional survey to evaluate knowledge, attitudes and practices (KAP) regarding seasonal influenza vaccination among European travellers to resource-limited destinations

    PubMed Central

    2010-01-01

    Background Influenza is one of the most common vaccine-preventable diseases in travellers. By performing two cross-sectional questionnaire surveys during winter 2009 and winter 2010 among European travellers to resource-limited destinations, we aimed to investigate knowledge, attitudes and practices (KAP) regarding seasonal influenza vaccination. Methods Questionnaires were distributed in the waiting room to the visitors of the University of Zurich Centre for Travel' Health (CTH) in January and February 2009 and January 2010 prior to travel health counselling (CTH09 and CTH10). Questions included demographic data, travel-related characteristics and KAP regarding influenza vaccination. Data were analysed by using SPSS® version 14.0 for Windows. Differences in proportions were compared using the Chi-square test and the significance level was set at p ≤ 0.05. Predictors for seasonal and pandemic influenza vaccination were determined by multiple logistic regression analyses. Results With a response rate of 96.6%, 906 individuals were enrolled and 868 (92.5%) provided complete data. Seasonal influenza vaccination coverage was 13.7% (n = 119). Only 43 (14.2%) participants were vaccinated against pandemic influenza A/H1N1, mostly having received both vaccines simultaneously, the seasonal and pandemic one. Job-related purposes (44, 37%), age > 64 yrs (25, 21%) and recommendations of the family physician (27, 22.7%) were the most often reported reasons for being vaccinated. In the multiple logistic regression analyses of the pooled data increasing age (OR = 1.03, 95% CI 1.01 - 1.04), a business trip (OR = 0.39, 95% CI 0.17 - 0.92) and seasonal influenza vaccination in the previous winter seasons (OR = 12.91, 95% CI 8.09 - 20.58) were independent predictors for seasonal influenza vaccination in 2009 or 2010. Influenza vaccination recommended by the family doctor (327, 37.7%), travel to regions with known high risk of influenza (305, 35.1%), and influenza vaccination

  6. A cross-sectional survey to evaluate knowledge, attitudes and practices (KAP) regarding seasonal influenza vaccination among European travellers to resource-limited destinations.

    PubMed

    Pfeil, Alena; Mütsch, Margot; Hatz, Christoph; Szucs, Thomas D

    2010-07-07

    Influenza is one of the most common vaccine-preventable diseases in travellers. By performing two cross-sectional questionnaire surveys during winter 2009 and winter 2010 among European travellers to resource-limited destinations, we aimed to investigate knowledge, attitudes and practices (KAP) regarding seasonal influenza vaccination. Questionnaires were distributed in the waiting room to the visitors of the University of Zurich Centre for Travel' Health (CTH) in January and February 2009 and January 2010 prior to travel health counselling (CTH09 and CTH10). Questions included demographic data, travel-related characteristics and KAP regarding influenza vaccination. Data were analysed by using SPSS version 14.0 for Windows. Differences in proportions were compared using the Chi-square test and the significance level was set at p 64 yrs (25, 21%) and recommendations of the family physician (27, 22.7%) were the most often reported reasons for being vaccinated. In the multiple logistic regression analyses of the pooled data increasing age (OR = 1.03, 95% CI 1.01 - 1.04), a business trip (OR = 0.39, 95% CI 0.17 - 0.92) and seasonal influenza vaccination in the previous winter seasons (OR = 12.91, 95% CI 8.09 - 20.58) were independent predictors for seasonal influenza vaccination in 2009 or 2010.Influenza vaccination recommended by the family doctor (327, 37.7%), travel to regions with known high risk of influenza (305, 35.1%), and influenza vaccination required for job purposes (233

  7. Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters.

    PubMed

    Kumar, Vibhor; Rayan, Nirmala Arul; Muratani, Masafumi; Lim, Stefan; Elanggovan, Bavani; Xin, Lixia; Lu, Tess; Makhija, Harshyaa; Poschmann, Jeremie; Lufkin, Thomas; Ng, Huck Hui; Prabhakar, Shyam

    2016-05-01

    Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation. © 2016 Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

  8. Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters

    PubMed Central

    Kumar, Vibhor; Rayan, Nirmala Arul; Muratani, Masafumi; Lim, Stefan; Elanggovan, Bavani; Xin, Lixia; Lu, Tess; Makhija, Harshyaa; Poschmann, Jeremie; Lufkin, Thomas; Ng, Huck Hui; Prabhakar, Shyam

    2016-01-01

    Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation. PMID:26957309

  9. Zinc deficiency promotes cystitis-related bladder pain by enhancing function and expression of Cav3.2 in mice.

    PubMed

    Ozaki, Tomoka; Matsuoka, Junki; Tsubota, Maho; Tomita, Shiori; Sekiguchi, Fumiko; Minami, Takeshi; Kawabata, Atsufumi

    2018-01-15

    Ca v 3.2 T-type Ca 2+ channel activity is suppressed by zinc that binds to the extracellular histidine-191 of Ca v 3.2, and enhanced by H 2 S that interacts with zinc. Ca v 3.2 in nociceptors is upregulated in an activity-dependent manner. The enhanced Ca v 3.2 activity by H 2 S formed by the upregulated cystathionine-γ-lyase (CSE) is involved in the cyclophosphamide (CPA)-induced cystitis-related bladder pain in mice. We thus asked if zinc deficiency affects the cystitis-related bladder pain in mice by altering Ca v 3.2 function and/or expression. Dietary zinc deficiency for 2 weeks greatly decreased zinc concentrations in the plasma but not bladder tissue, and enhanced the bladder pain/referred hyperalgesia (BP/RH) following CPA at 200mg/kg, a subeffective dose, but not 400mg/kg, a maximal dose, an effect abolished by pharmacological blockade or gene silencing of Ca v 3.2. Acute zinc deficiency caused by systemic N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylendiamine (TPEN), a zinc chelator, mimicked the dietary zinc deficiency-induced Ca v 3.2-dependent promotion of BP/RH following CPA at 200mg/kg. CPA at 400mg/kg alone or TPEN plus CPA at 200mg/kg caused Ca v 3.2 overexpression accompanied by upregulation of Egr-1 and USP5, known to promote transcriptional expression and reduce proteasomal degradation of Ca v 3.2, respectively, in the dorsal root ganglia (DRG). The CSE inhibitor, β-cyano-l-alanine, prevented the BP/RH and upregulation of Ca v 3.2, Egr-1 and USP5 in DRG following TPEN plus CPA at 200mg/kg. Together, zinc deficiency promotes bladder pain accompanying CPA-induced cystitis by enhancing function and expression of Ca v 3.2 in nociceptors, suggesting a novel therapeutic avenue for treatment of bladder pain, such as zinc supplementation. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Test-Enhanced Learning: The Potential for Testing to Promote Greater Learning in Undergraduate Science Courses

    PubMed Central

    Brame, Cynthia J.; Biel, Rachel

    2015-01-01

    Testing within the science classroom is commonly used for both formative and summative assessment purposes to let the student and the instructor gauge progress toward learning goals. Research within cognitive science suggests, however, that testing can also be a learning event. We present summaries of studies that suggest that repeated retrieval can enhance long-term learning in a laboratory setting; various testing formats can promote learning; feedback enhances the benefits of testing; testing can potentiate further study; and benefits of testing are not limited to rote memory. Most of these studies were performed in a laboratory environment, so we also present summaries of experiments suggesting that the benefits of testing can extend to the classroom. Finally, we suggest opportunities that these observations raise for the classroom and for further research. PMID:25999314

  11. Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease.

    PubMed

    Khurana, Surender; Loving, Crystal L; Manischewitz, Jody; King, Lisa R; Gauger, Phillip C; Henningson, Jamie; Vincent, Amy L; Golding, Hana

    2013-08-28

    Vaccine-induced disease enhancement has been described in connection with several viral vaccines in animal models and in humans. We investigated a swine model to evaluate mismatched influenza vaccine-associated enhanced respiratory disease (VAERD) after pH1N1 infection. Vaccinating pigs with whole inactivated H1N2 (human-like) virus vaccine (WIV-H1N2) resulted in enhanced pneumonia and disease after pH1N1 infection. WIV-H1N2 immune sera contained high titers of cross-reactive anti-pH1N1 hemagglutinin (HA) antibodies that bound exclusively to the HA2 domain but not to the HA1 globular head. No hemagglutination inhibition titers against pH1N1 (challenge virus) were measured. Epitope mapping using phage display library identified the immunodominant epitope recognized by WIV-H1N2 immune sera as amino acids 32 to 77 of pH1N1-HA2 domain, close to the fusion peptide. These cross-reactive anti-HA2 antibodies enhanced pH1N1 infection of Madin-Darby canine kidney cells by promoting virus membrane fusion activity. The enhanced fusion activity correlated with lung pathology in pigs. This study suggests a role for fusion-enhancing anti-HA2 antibodies in VAERD, in the absence of receptor-blocking virus-neutralizing antibodies. These findings should be considered during the evaluation of universal influenza vaccines designed to elicit HA2 stem-targeting antibodies.

  12. 7 CFR 1220.121 - Promotion.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.121 Promotion. The term..., to enhance the image or desirability of soybeans or soybean products in domestic and foreign markets...

  13. A gene-specific non-enhancer sequence is critical for expression from the promoter of the small heat shock protein gene αB-crystallin

    PubMed Central

    2014-01-01

    Background Deciphering of the information content of eukaryotic promoters has remained confined to universal landmarks and conserved sequence elements such as enhancers and transcription factor binding motifs, which are considered sufficient for gene activation and regulation. Gene-specific sequences, interspersed between the canonical transacting factor binding sites or adjoining them within a promoter, are generally taken to be devoid of any regulatory information and have therefore been largely ignored. An unanswered question therefore is, do gene-specific sequences within a eukaryotic promoter have a role in gene activation? Here, we present an exhaustive experimental analysis of a gene-specific sequence adjoining the heat shock element (HSE) in the proximal promoter of the small heat shock protein gene, αB-crystallin (cryab). These sequences are highly conserved between the rodents and the humans. Results Using human retinal pigment epithelial cells in culture as the host, we have identified a 10-bp gene-specific promoter sequence (GPS), which, unlike an enhancer, controls expression from the promoter of this gene, only when in appropriate position and orientation. Notably, the data suggests that GPS in comparison with the HSE works in a context-independent fashion. Additionally, when moved upstream, about a nucleosome length of DNA (−154 bp) from the transcription start site (TSS), the activity of the promoter is markedly inhibited, suggesting its involvement in local promoter access. Importantly, we demonstrate that deletion of the GPS results in complete loss of cryab promoter activity in transgenic mice. Conclusions These data suggest that gene-specific sequences such as the GPS, identified here, may have critical roles in regulating gene-specific activity from eukaryotic promoters. PMID:24589182

  14. Peptide-modified chitosan hydrogels promote skin wound healing by enhancing wound angiogenesis and inhibiting inflammation

    PubMed Central

    Chen, Xionglin; Zhang, Min; Wang, Xueer; Chen, Yinghua; Yan, Yuan; Zhang, Lu; Zhang, Lin

    2017-01-01

    Cutaneous wound healing following trauma is a complex and dynamic process involving multiple overlapping events following trauma. Two critical elements affecting skin wound healing are neovascularization and inflammation. A nascent vessel can provide nutrition and oxygen to a healing wound. Therefore, treatments strategies that enhance angiogenesis and inhibit inflammation can promote skin wound healing. Previous studies have shown that the SIKVAV peptide (Ser-Ile-Lys-Val-Ala-Val) from laminin can promote angiogenesis in vitro. This study evaluated the effects of peptide SIKVAV-modified chitosan hydrogels on skin wound healing. We established skin wounds established in mice and treated them with SIKVAV-modified chitosan hydrogels. H&E staining showed that peptide-modified chitosan hydrogels accelerated the reepithelialization of wounds compared with the negative and positive controls. Immunohistochemistry analysis demonstrated that more myofibroblasts were deposited at wounds treated with peptide-modified chitosan hydrogels that at those treated with negative and positive controls. In addition, peptide-modified chitosan hydrogels promoted angiogenesis as well as keratinocyte proliferation and differentiation, but inhibited inflammation in skin wounds. Taken together, these results suggest that SIKVAV-modified chitosan hydrogels are a promising treatment component for healing-impaired wounds. PMID:28559985

  15. Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation

    PubMed Central

    Wong, Carmen P.; Rinaldi, Nicole A.; Ho, Emily

    2015-01-01

    Scope Zinc deficiency results in immune dysfunction and promotes systemic inflammation. The objective of this study was to examine the effects of zinc deficiency on cellular immune activation and epigenetic mechanisms that promote inflammation. This work is potentially relevant to the aging population given that age-related immune defects, including chronic inflammation, coincide with declining zinc status. Methods and results An in vitro cell culture system and the aged mouse model were used to characterize immune activation and DNA methylation profiles that may contribute to the enhanced proinflammatory response mediated by zinc deficiency. Zinc deficiency up-regulated cell activation markers ICAM1, MHC class II, and CD86 in THP1 cells, that coincided with increased IL1β and IL6 responses following LPS stimulation. A decreased zinc status in aged mice was similarly associated with increased ICAM1 and IL6 gene expression. Reduced IL6 promoter methylation was observed in zinc deficient THP1 cells, as well as in aged mice and human lymphoblastoid cell lines derived from aged individuals. Conclusion Zinc deficiency induced inflammatory response in part by eliciting aberrant immune cell activation and altered promoter methylation. Our results suggested potential interactions between zinc status, epigenetics, and immune function, and how their dysregulation could contribute to chronic inflammation. PMID:25656040

  16. Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement

    PubMed Central

    Looi, Chung Yen; Duta, Mihaela; Brem, Anna-Katharine; Huber, Stefan; Nuerk, Hans-Christoph; Cohen Kadosh, Roi

    2016-01-01

    Cognitive training offers the potential for individualised learning, prevention of cognitive decline, and rehabilitation. However, key research challenges include ecological validity (training design), transfer of learning and long-term effects. Given that cognitive training and neuromodulation affect neuroplasticity, their combination could promote greater, synergistic effects. We investigated whether combining transcranial direct current stimulation (tDCS) with cognitive training could further enhance cognitive performance compared to training alone, and promote transfer within a short period of time. Healthy adults received real or sham tDCS over their dorsolateral prefrontal cortices during two 30-minute mathematics training sessions involving body movements. To examine the role of training, an active control group received tDCS during a non-mathematical task. Those who received real tDCS performed significantly better in the game than the sham group, and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition. PMID:26902664

  17. Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement.

    PubMed

    Looi, Chung Yen; Duta, Mihaela; Brem, Anna-Katharine; Huber, Stefan; Nuerk, Hans-Christoph; Cohen Kadosh, Roi

    2016-02-23

    Cognitive training offers the potential for individualised learning, prevention of cognitive decline, and rehabilitation. However, key research challenges include ecological validity (training design), transfer of learning and long-term effects. Given that cognitive training and neuromodulation affect neuroplasticity, their combination could promote greater, synergistic effects. We investigated whether combining transcranial direct current stimulation (tDCS) with cognitive training could further enhance cognitive performance compared to training alone, and promote transfer within a short period of time. Healthy adults received real or sham tDCS over their dorsolateral prefrontal cortices during two 30-minute mathematics training sessions involving body movements. To examine the role of training, an active control group received tDCS during a non-mathematical task. Those who received real tDCS performed significantly better in the game than the sham group, and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition.

  18. The DUSP–Ubl domain of USP4 enhances its catalytic efficiency by promoting ubiquitin exchange

    PubMed Central

    Clerici, Marcello; Luna-Vargas, Mark P. A.; Faesen, Alex C.; Sixma, Titia K.

    2014-01-01

    Ubiquitin-specific protease USP4 is emerging as an important regulator of cellular pathways, including the TGF-β response, NF-κB signalling and splicing, with possible roles in cancer. Here we show that USP4 has its catalytic triad arranged in a productive conformation. Nevertheless, it requires its N-terminal DUSP–Ubl domain to achieve full catalytic turnover. Pre-steady-state kinetics measurements reveal that USP4 catalytic domain activity is strongly inhibited by slow dissociation of ubiquitin after substrate hydrolysis. The DUSP–Ubl domain is able to enhance ubiquitin dissociation, hence promoting efficient turnover. In a mechanism that requires all USP4 domains, binding of the DUSP–Ubl domain promotes a change of a switching loop near the active site. This ‘allosteric regulation of product discharge’ provides a novel way of regulating deubiquitinating enzymes that may have relevance for other enzyme classes. PMID:25404403

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

    PubMed

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

    2016-11-15

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

  20. Mining Halophytes for Plant Growth-Promoting Halotolerant Bacteria to Enhance the Salinity Tolerance of Non-halophytic Crops

    PubMed Central

    Etesami, Hassan; Beattie, Gwyn A.

    2018-01-01

    Salinity stress is one of the major abiotic stresses limiting crop production in arid and semi-arid regions. Interest is increasing in the application of PGPRs (plant growth promoting rhizobacteria) to ameliorate stresses such as salinity stress in crop production. The identification of salt-tolerant, or halophilic, PGPRs has the potential to promote saline soil-based agriculture. Halophytes are a useful reservoir of halotolerant bacteria with plant growth-promoting capabilities. Here, we review recent studies on the use of halophilic PGPRs to stimulate plant growth and increase the tolerance of non-halophytic crops to salinity. These studies illustrate that halophilic PGPRs from the rhizosphere of halophytic species can be effective bio-inoculants for promoting the production of non-halophytic species in saline soils. These studies support the viability of bioinoculation with halophilic PGPRs as a strategy for the sustainable enhancement of non-halophytic crop growth. The potential of this strategy is discussed within the context of ensuring sustainable food production for a world with an increasing population and continuing climate change. We also explore future research needs for using halotolerant PGPRs under salinity stress. PMID:29472908

  1. Enhancement of human ACAT1 gene expression to promote the macrophage-derived foam cell formation by dexamethasone.

    PubMed

    Yang, Li; Yang, Jin Bo; Chen, Jia; Yu, Guang Yao; Zhou, Pei; Lei, Lei; Wang, Zhen Zhen; Cy Chang, Catherine; Yang, Xin Ying; Chang, Ta Yuan; Li, Bo Liang

    2004-08-01

    In macrophages, the accumulation of cholesteryl esters synthesized by the activated acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1) results in the foam cell formation, a hallmark of early atherosclerotic lesions. In this study, with the treatment of a glucocorticoid hormone dexamethasone (Dex), lipid staining results clearly showed the large accumulation of lipid droplets containing cholesteryl esters in THP-1-derived macrophages exposed to lower concentration of the oxidized low-density lipoprotein (ox-LDL). More notably, when treated together with specific anti-ACAT inhibitors, the abundant cholesteryl ester accumulation was markedly diminished in THP-1-derived macrophages, confirming that ACAT is the key enzyme responsible for intracellular cholesteryl ester synthesis. RT-PCR and Western blot results indicated that Dex caused up-regulation of human ACAT1 expression at both the mRNA and protein levels in THP-1 and THP-1-derived macrophages. The luciferase activity assay demonstrated that Dex could enhance the activity of human ACAT1 gene P1 promoter, a major factor leading to the ACAT1 activation, in a cell-specific manner. Further experimental evidences showed that a glucocorticoid response element (GRE) located within human ACAT1 gene P1 promoter to response to the elevation of human ACAT1 gene expression by Dex could be functionally bound with glucocorticoid receptor (GR) proteins. These data supported the hypothesis that the clinical treatment with Dex, which increased the incidence of atherosclerosis, may in part due to enhancing the ACAT1 expression to promote the accumulation of cholesteryl esters during the macrophage-derived foam cell formation, an early stage of atherosclerosis.

  2. An enhancer located in a CpG-island 3' to the TCR/CD3-epsilon gene confers T lymphocyte-specificity to its promoter.

    PubMed Central

    Clevers, H; Lonberg, N; Dunlap, S; Lacy, E; Terhorst, C

    1989-01-01

    The gene encoding the CD3-epsilon chain of the T cell receptor (TCR/CD3) complex is uniquely transcribed in all T lymphocyte lineage cells. The human CD3-epsilon gene, when introduced into the mouse germ line, was expressed in correct tissue-specific fashion. The gene was then screened for T lymphocyte-specific cis-acting elements in transient chloramphenicol transferase assays. The promoter (-228 to +100) functioned irrespective of cell type. A 1225 bp enhancer with strict T cell-specificity was found in a DNase I hypersensitive site downstream of the last exon, 12 kb from the promoter. This site was present in T cells only. The CD3-epsilon enhancer did not display sequence similarity with the T cell-specific enhancer of CD3-delta, a related gene co-regulated with CD3-epsilon during intrathymic differentiation. The CD3-epsilon enhancer was unusual in that it constituted a CpG island, and was hypomethylated independent of tissue type. Two HTLV I-transformed T cell lines were identified in which the CD3-epsilon gene was not expressed, and in which the enhancer was inactive. Images PMID:2583122

  3. MLV integration site selection is driven by strong enhancers and active promoters

    PubMed Central

    LaFave, Matthew C.; Varshney, Gaurav K.; Gildea, Derek E.; Wolfsberg, Tyra G.; Baxevanis, Andreas D.; Burgess, Shawn M.

    2014-01-01

    Retroviruses integrate into the host genome in patterns specific to each virus. Understanding the causes of these patterns can provide insight into viral integration mechanisms, pathology and genome evolution, and is critical to the development of safe gene therapy vectors. We generated murine leukemia virus integrations in human HepG2 and K562 cells and subjected them to second-generation sequencing, using a DNA barcoding technique that allowed us to quantify independent integration events. We characterized >3 700 000 unique integration events in two ENCODE-characterized cell lines. We find that integrations were most highly enriched in a subset of strong enhancers and active promoters. In both cell types, approximately half the integrations were found in <2% of the genome, demonstrating genomic influences even narrower than previously believed. The integration pattern of murine leukemia virus appears to be largely driven by regions that have high enrichment for multiple marks of active chromatin; the combination of histone marks present was sufficient to explain why some strong enhancers were more prone to integration than others. The approach we used is applicable to analyzing the integration pattern of any exogenous element and could be a valuable preclinical screen to evaluate the safety of gene therapy vectors. PMID:24464997

  4. Biomaterials that promote cell-cell interactions enhance the paracrine function of MSCs.

    PubMed

    Qazi, Taimoor H; Mooney, David J; Duda, Georg N; Geissler, Sven

    2017-09-01

    Mesenchymal stromal cells (MSCs) secrete paracrine factors that play crucial roles during tissue regeneration. Whether this paracrine function is influenced by the properties of biomaterials in general, and those used for cell delivery in particular, largely remains unexplored. Here, we investigated if three-dimensional culture in distinct microenvironments - nanoporous hydrogels (mean pore size ∼5 nm) and macroporous scaffolds (mean pore size ∼120 μm) - affects the secretion pattern of MSCs, and consequently leads to differential paracrine effects on target progenitor cells such as myoblasts. We report that compared to MSCs encapsulated in hydrogels, scaffold seeded MSCs show an enhanced secretion profile and exert beneficial paracrine effects on various myoblast functions including migration and proliferation. Additionally, we show that the heightened paracrine effects of scaffold seeded cells can in part be attributed to N-cadherin mediated cell-cell interactions during culture. In hydrogels, this physical interaction between cells is prevented by the encapsulating matrix. Functionally blocking N-cadherin negatively affected the secretion profile and paracrine effects of MSCs on myoblasts, with stronger effects observed for scaffold seeded compared to hydrogel encapsulated cells. Together, these findings demonstrate that the therapeutic potency of MSCs can be enhanced by biomaterials that promote cell-cell interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Klucevsek, K.; Daley, J.; Darshan, M.S.

    We have investigated the nuclear import strategies of high-risk HPV18 L2 minor capsid protein. HPV18 L2 interacts with Kap {alpha}{sub 2} adapter, and Kap {beta}{sub 2} and Kap {beta}{sub 3} nuclear import receptors. Moreover, binding of RanGTP to either Kap {beta}{sub 2} or Kap {beta}{sub 3} inhibits their interaction with L2, suggesting that these Kap {beta}/L2 complexes are import competent. Mapping studies show that HPV18 L2 contains two NLSs: in the N-terminus (nNLS) and in the C-terminus (cNLS), both of which can independently mediate nuclear import. Both nNLS and cNLS form a complex with Kap {alpha}{sub 2}{beta}{sub 1} heterodimer andmore » mediate nuclear import via a classical pathway. The nNLS is also essential for the interaction of HPV18 L2 with Kap {beta}{sub 2} and Kap {beta}{sub 3}. Interestingly, both nNLS and cNLS interact with the viral DNA and this DNA binding occurs without nucleotide sequence specificity. Together, the data suggest that HPV18 L2 can interact via its NLSs with several Kaps and the viral DNA and may enter the nucleus via multiple import pathways mediated by Kap {alpha}{sub 2}{beta}{sub 1} heterodimers, Kap {beta}{sub 2} and Kap {beta}{sub 3}.« less

  6. Potential of wheat bran to promote indigenous microbial enhanced oil recovery.

    PubMed

    Zhan, Yali; Wang, Qinghong; Chen, Chunmao; Kim, Jung Bong; Zhang, Hongdan; Yoza, Brandon A; Li, Qing X

    2017-06-01

    Microbial enhanced oil recovery (MEOR) is an emerging oil extraction technology that utilizes microorganisms to facilitate recovery of crude oil in depleted petroleum reservoirs. In the present study, effects of wheat bran utilization were investigated on stimulation of indigenous MEOR. Biostimulation conditions were optimized with the response surface methodology. The co-application of wheat bran with KNO 3 and NH 4 H 2 PO 4 significantly promoted indigenous MEOR (IMEOR) and exhibited sequential aerobic (O-), facultative (A n -) and anaerobic (A 0 -) metabolic stages. The surface tension of fermented broth decreased by approximately 35%, and the crude oil was highly emulsified. Microbial community structure varied largely among and in different IMEOR metabolic stages. Pseudomonas sp., Citrobacter sp., and uncultured Burkholderia sp. dominated the O-, A n - and early A 0 -stages. Bacillus sp., Achromobacter sp., Rhizobiales sp., Alcaligenes sp. and Clostridium sp. dominated the later A 0 -stage. This study illustrated occurrences of microbial community succession driven by wheat bran stimulation and its industrial potential.

  7. Enhancing Resources at the Workplace with Health-Promoting Leadership.

    PubMed

    Jiménez, Paul; Bregenzer, Anita; Kallus, K Wolfgang; Fruhwirth, Bianca; Wagner-Hartl, Verena

    2017-10-20

    Leaders engaging in health-promoting leadership can influence their employees' health directly by showing health awareness or indirectly by changing working conditions. With health-promoting leadership, leaders are able to support a healthy working environment by providing resource-oriented working conditions for their employees to support their health. Changing working conditions in a health-supportive way can prevent possible negative consequences from critical working conditions (e.g., burnout risk). The present study examined the relationship between health-promoting leadership and the employees' resources, stress and burnout. To analyze our proposed model, structural equation modelling was conducted in two samples. The resulting model from the first sample of 228 Austrian workers was cross-validated and could be verified with the second sample (N = 263 Austrian workers). The results supported a model in which health-promoting leadership has a strong direct effect on the employees' resources and an indirect effect on stress and burnout, which was mediated by resources. The results indicate that health-promoting leadership describes the leaders' capability and dedication creating the right working conditions for their employees by increasing the employees' resources at the workplace. This in turn minimizes the risk of experiencing burnout.

  8. Enhancing Resources at the Workplace with Health-Promoting Leadership

    PubMed Central

    Bregenzer, Anita; Kallus, K. Wolfgang; Fruhwirth, Bianca; Wagner-Hartl, Verena

    2017-01-01

    Leaders engaging in health-promoting leadership can influence their employees’ health directly by showing health awareness or indirectly by changing working conditions. With health-promoting leadership, leaders are able to support a healthy working environment by providing resource-oriented working conditions for their employees to support their health. Changing working conditions in a health-supportive way can prevent possible negative consequences from critical working conditions (e.g., burnout risk). The present study examined the relationship between health-promoting leadership and the employees’ resources, stress and burnout. To analyze our proposed model, structural equation modelling was conducted in two samples. The resulting model from the first sample of 228 Austrian workers was cross-validated and could be verified with the second sample (N = 263 Austrian workers). The results supported a model in which health-promoting leadership has a strong direct effect on the employees’ resources and an indirect effect on stress and burnout, which was mediated by resources. The results indicate that health-promoting leadership describes the leaders’ capability and dedication creating the right working conditions for their employees by increasing the employees’ resources at the workplace. This in turn minimizes the risk of experiencing burnout. PMID:29053640

  9. Enhanced EJ Cell Killing of (125)I Radiation by Combining with Cytosine Deaminase Gene Therapy Regulated by Synthetic Radio-Responsive Promoter.

    PubMed

    Li, Ling; Zhang, Chun-li; Kang, Lei; Wang, Rong-Fu; Yan, Ping; Zhao, Qian; Yin, Lei; Guo, Feng-qin

    2015-10-01

    To investigate the enhancing effect of radionuclide therapy by the therapeutic gene placed under the control of radio-responsive promoter. The recombinant lentivirus E8-codA-GFP, including a synthetic radiation-sensitive promoter E8, cytosine deaminase (CD) gene, and green fluorescent protein gene, was constructed. The gene expression activated by (125)I radiation was assessed by observation of green fluorescence. The ability of converting 5-fluorocytosine (5-FC) to 5-fluorourial (5-FU) by CD enzyme was assessed by high-performance liquid chromatography. The viability of the infected cells exposed to (125)I in the presence of 5-FC was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the infected cells exposed to (125)I alone served as negative control and 5-FU as positive control. The recombinant lentiviral vector was constructed successfully. On exposure of infected cells to (125)I, green fluorescence can be observed and 5-FU can be detected. MTT assay showed that the survival rate for infected cells treated with (125)I was lower compared with the (125)I control group, but higher than the positive control group. The synthetic promoter E8 can induce the expression of downstream CD gene under (125)I radiation, and the tumor killing effect of (125)I can be enhanced by combining CD gene therapy with radiosensitive promoter.

  10. Enhancement of expression of survivin promoter-driven CD/TK double suicide genes by the nuclear matrix attachment region in transgenic gastric cancer cells.

    PubMed

    Niu, Ying; Li, Jian-Sheng; Luo, Xian-Run

    2014-01-25

    This work aimed to study a novel transgenic expression system of the CD/TK double suicide genes enhanced by the nuclear matrix attachment region (MAR) for gene therapy. The recombinant vector pMS-CD/TK containing the MAR-survivin promoter-CD/TK cassette was developed and transfected into human gastric cancer SGC-7901 cells. Expression of the CD/TK genes was detected by quantitative real-time PCR (qPCR) and Western blot. Cell viability and apoptosis were measured using the methyl thiazolyl tetrazolium (MTT) assay and flow cytometry. When the MAR fragment was inserted into the upstream of the survivin promoter, the qPCR result showed that the expression of the CD/TK genes significantly increased 7.7-fold in the transgenic SGC-7901 cells with plasmid pMS-CD/TK compared with that without MAR. MTT and flow cytometry analyses indicated that treatment with the prodrugs (5-FC+GCV) significantly decreased the cellular survival rate and enhanced the cellular apoptosis in the SGC-7901 cells. The expression of the CD/TK double suicide genes driven by the survivin promoter can be enhanced by the MAR fragment in human gastric cancer cells. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Knowledge, Attitude and Practices (KAP) Survey on Water, Sanitation and Hygiene in Selected Schools in Vhembe District, Limpopo, South Africa

    PubMed Central

    Sibiya, Jerry E.; Gumbo, Jabulani Ray

    2013-01-01

    This study assessed the knowledge, attitude and practices (KAP) of learners on issues related to water, sanitation and hygiene in selected schools in Vhembe District, South Africa. The methodology relied on a questionnaire, an inspection of sanitary facilities and discussion with the school authorities. The data was analyzed using the Statistical Package for Social Science. The study revealed that the level of knowledge about waterborne diseases was relatively high (76.7 ± 1.75%), but knowledge on transmission routes was inadequate. The majority of the respondents had no knowledge when it comes to water-based diseases and their prevention (78.4 ± 1.71%).The attitude and practice on hygiene was also found to be high (91.40 ± 1.16%). Some schools from the urban area had proper handwashing facilities, but there was no soap available. The borehole water quality for rural schools appeared clear, but the microbial quality was unknown. The water supply and sanitation facilities were inadequate in rural schools, with no handwashing areas and no sanitary bins for girls. Some schools had toilets with broken doors which did not offer privacy. The only water tap, located at the centre of the school premises, was not enough for the whole school community. PMID:23736657

  12. Does decentralisation enhance a school's role of promoting social cohesion? Bosnian school leaders' perceptions of school governance

    NASA Astrophysics Data System (ADS)

    Komatsu, Taro

    2014-05-01

    This study seeks to understand whether and how decentralised school governance in Bosnia and Herzegovina (BiH) enhances the schools' role of promoting social cohesion. This includes increasing "horizontal" trust among different ethnic groups and "vertical" trust between civilians and public institutes. The study examined secondary school leaders' perceptions regarding school board influence on social cohesion policies and practices, their interactions with school board members, and their accountability to the school-based governing body. The results show that school leaders and school boards, supposedly representing the interests of local stakeholders, did not appear to be actively engaged in the deliberate process of promoting social cohesion. While school directors tended to view themselves as being independent from the school boards, ethnically diverse school boards provided important support to proactive school leaders for their inter-group activities. Given that the central level is not providing initiatives to promote social cohesion and that BiH citizens appear to generally support social cohesion, decentralised school governance has the potential to improve social trust from the bottom up. To promote participatory school governance, the study recommends that BiH school leaders should be provided with opportunities to re-examine and redefine their professional accountability and to assist local stakeholders to improve their involvement in school governance.

  13. Enhanced precipitation promotes decomposition and soil C stabilization in semiarid ecosystems, but seasonal timing of wetting matters

    USGS Publications Warehouse

    Campos, Xochi; Germino, Matthew; de Graaff, Marie-Anne

    2017-01-01

    AimsChanging precipitation regimes in semiarid ecosystems will affect the balance of soil carbon (C) input and release, but the net effect on soil C storage is unclear. We asked how changes in the amount and timing of precipitation affect litter decomposition, and soil C stabilization in semiarid ecosystems.MethodsThe study took place at a long-term (18 years) ecohydrology experiment located in Idaho. Precipitation treatments consisted of a doubling of annual precipitation (+200 mm) added either in the cold-dormant season or in the growing season. Experimental plots were planted with big sagebrush (Artemisia tridentata), or with crested wheatgrass (Agropyron cristatum). We quantified decomposition of sagebrush leaf litter, and we assessed organic soil C (SOC) in aggregates, and silt and clay fractions.ResultsWe found that: (1) increased precipitation applied in the growing season consistently enhanced decomposition rates relative to the ambient treatment, and (2) precipitation applied in the dormant season enhanced soil C stabilization.ConclusionsThese data indicate that prolonged increases in precipitation can promote soil C storage in semiarid ecosystems, but only if these increases happen at times of the year when conditions allow for precipitation to promote plant C inputs rates to soil.

  14. Dual‑sensitive HRE/Egr1 promoter regulates Smac overexpression and enhances radiation‑induced A549 human lung adenocarcinoma cell death under hypoxia.

    PubMed

    Li, Chang-Feng; Chen, Li-Bo; Li, Dan-Dan; Yang, Lei; Zhang, Bao-Gang; Jin, Jing-Peng; Zhang, Ying; Zhang, Bin

    2014-08-01

    The aim of this study was to construct an expression vector carrying the hypoxia/radiation dual‑sensitive chimeric hypoxia response element (HRE)/early growth response 1 (Egr‑1) promoter in order to overexpress the therapeutic second mitochondria‑derived activator of caspases (Smac). Using this expression vector, the present study aimed to explore the molecular mechanism underlying radiotherapy‑induced A549 human lung adenocarcinoma cell death and apoptosis under hypoxia. The plasmids, pcDNA3.1‑Egr1‑Smac (pE‑Smac) and pcDNA3.1‑HRE/Egr-1‑Smac (pH/E‑Smac), were constructed and transfected into A549 human lung adenocarcinoma cells using the liposome method. CoCl2 was used to chemically simulate hypoxia, followed by the administration of 2 Gy X‑ray irradiation. An MTT assay was performed to detect cell proliferation and an Annexin V‑fluorescein isothiocyanate apoptosis detection kit was used to detect apoptosis. Quantitative polymerase chain reaction and western blot analyses were used for the detection of mRNA and protein expression, respectively. Infection with the pE‑Smac and pH/E‑Smac plasmids in combination with radiation and/or hypoxia was observed to enhance the expression of Smac. Furthermore, Smac overexpression was found to enhance the radiation‑induced inhibition of cell proliferation and promotion of cycle arrest and apoptosis. The cytochrome c/caspase‑9/caspase‑3 pathway was identified to be involved in this regulation of apoptosis. Plasmid infection in combination with X‑ray irradiation was found to markedly induce cell death under hypoxia. In conclusion, the hypoxia/radiation dual‑sensitive chimeric HRE/Egr‑1 promoter was observed to enhance the expression of the therapeutic Smac, as well as enhance the radiation‑induced inhibition of cell proliferation and promotion of cycle arrest and apoptosis under hypoxia. This apoptosis was found to involve the mitochondrial pathway.

  15. Social mobilization and social marketing to promote NaFeEDTA-fortified soya sauce in an iron-deficient population through a public-private partnership.

    PubMed

    Wang, Bo; Zhan, Siyan; Sun, Jing; Lee, Liming

    2009-10-01

    The present pilot project aimed to assess the effectiveness of social mobilization and social marketing in improving knowledge, attitudes and practices (KAP) and Fe status in an Fe-deficient population. In an uncontrolled, before-after, community-based study, social mobilization and social marketing strategies were applied. The main outcomes included KAP and Hb level and were measured at baseline, 1 year later and 2 years later. One urban county and two rural counties in Shijiazhuang Municipality, Hebei Province, China. Adult women older than 20 years of age and young children aged from 3 to 7 years were selected from three counties to attend the evaluation protocol. After 1 year, most knowledge and attitudes had changed positively towards the prevention and control of anaemia. The percentage of women who had adopted NaFeEDTA-fortified soya sauce increased from 8.9% to 36.6% (P < or = 0.001). After 2 years, Hb levels had increased substantially, by 9.0 g/l (P < or = 0.001) in adult women and 7.7 g/l (P < or = 0.001) in young children. Social mobilization and social marketing activities had a positive impact on the KAP of adult women, and resulted in marked improvements in Hb levels in both adult women and young children. This should be recommended as a national preventive strategy to prevent and control Fe deficiency and Fe-deficiency anaemia.

  16. TOP1MT deficiency promotes GC invasion and migration via the enhancements of LDHA expression and aerobic glycolysis.

    PubMed

    Wang, Hongqiang; Zhou, Rui; Sun, Li; Xia, Jianling; Yang, Xuchun; Pan, Changqie; Huang, Na; Shi, Min; Bin, Jianping; Liao, Yulin; Liao, Wangjun

    2017-11-01

    Aerobic glycolysis plays an important role in cancer progression. New target genes regulating cancer aerobic glycolysis must be explored to improve patient prognosis. Mitochondrial topoisomerase I ( TOP1MT ) deficiency suppresses glucose oxidative metabolism but enhances glycolysis in normal cells. Here, we examined the role of TOP1MT in gastric cancer (GC) and attempted to determine the underlying mechanism. Using in vitro and in vivo experiments and analyzing the clinicopathological characteristics of patients with GC, we found that TOP1MT expression was lower in GC samples than in adjacent nonmalignant tissues. TOP1MT knockdown significantly promoted GC migration and invasion in vitro and in vivo Importantly, TOP1MT silencing increased glucose consumption, lactate production, glucose transporter 1 expression and the epithelial-mesenchymal transition (EMT) in GC. Additionally, regulation of glucose metabolism induced by TOP1MT was significantly associated with lactate dehydrogenase A (LDHA) expression. A retrospective analysis of clinical data from 295 patients with GC demonstrated that low TOP1MT expression was associated with lymph node metastasis, recurrence and high mortality rates. TOP1MT deficiency enhanced glucose aerobic glycolysis by stimulating LDHA to promote GC progression. © 2017 The authors.

  17. Trithorax dependent changes in chromatin landscape at enhancer and promoter regions drive female puberty.

    PubMed

    Toro, Carlos A; Wright, Hollis; Aylwin, Carlos F; Ojeda, Sergio R; Lomniczi, Alejandro

    2018-01-04

    Polycomb group (PcG) proteins control the timing of puberty by repressing the Kiss1 gene in hypothalamic arcuate nucleus (ARC) neurons. Here we identify two members of the Trithorax group (TrxG) of modifiers, mixed-lineage leukemia 1 (MLL1), and 3 (MLL3), as central components of an activating epigenetic machinery that dynamically counteracts PcG repression. Preceding puberty, MLL1 changes the chromatin configuration at the promoters of Kiss1 and Tac3, two genes required for puberty to occur, from repressive to permissive. Concomitantly, MLL3 institutes a chromatin structure that changes the functional status of a Kiss1 enhancer from poised to active. RNAi-mediated, ARC-specific Mll1 knockdown reduced Kiss1 and Tac3 expression, whereas CRISPR-Cas9-directed epigenome silencing of the Kiss1 enhancer selectively reduced Kiss1 activity. Both interventions delay puberty and disrupt reproductive cyclicity. Our results demonstrate that an epigenetic switch from transcriptional repression to activation is crucial to the regulatory mechanism controlling the timing of mammalian puberty.

  18. Promoter-enhancer interactions identified from Hi-C data using probabilistic models and hierarchical topological domains.

    PubMed

    Ron, Gil; Globerson, Yuval; Moran, Dror; Kaplan, Tommy

    2017-12-21

    Proximity-ligation methods such as Hi-C allow us to map physical DNA-DNA interactions along the genome, and reveal its organization into topologically associating domains (TADs). As the Hi-C data accumulate, computational methods were developed for identifying domain borders in multiple cell types and organisms. Here, we present PSYCHIC, a computational approach for analyzing Hi-C data and identifying promoter-enhancer interactions. We use a unified probabilistic model to segment the genome into domains, which we then merge hierarchically and fit using a local background model, allowing us to identify over-represented DNA-DNA interactions across the genome. By analyzing the published Hi-C data sets in human and mouse, we identify hundreds of thousands of putative enhancers and their target genes, and compile an extensive genome-wide catalog of gene regulation in human and mouse. As we show, our predictions are highly enriched for ChIP-seq and DNA accessibility data, evolutionary conservation, eQTLs and other DNA-DNA interaction data.

  19. An enhancer-like region regulates hrp3 promoter stage-specific gene expression in the human malaria parasite Plasmodium falciparum

    PubMed Central

    López-Estraño, Carlos; Gopalakrishnan, Anusha M.; Semblat, Jean-Philippe; Fergus, M. Ross; Mazier, Dominique; Haldar, Kasturi

    2008-01-01

    The asexual blood stage of Plasmodium falciparum is comprised of morphologically distinct ring, trophozoite and schizont stages. Each of these developmental stages possesses a distinct pattern of gene expression. Regulation of P. falciparum gene expression is thought to occur, at least in part, at the promoter level. Previously, we have found that although the RNA of the P. falciparum hrp3 gene is only seen in ring-stage parasites, deletion of a specific sequensce in the 5’ end of the promoter region decreased ring-stage expression of hrp3 and enabled detection of its transcripts in trophozoite-stage parasites. In order to investigate this stage specific regulation of gene expression, we employed a series of nested deletions of the 1.7-kb hrp3 promoter. Firefly luciferase gene was used as a reporter to evaluate the role of promoter sequences in gene regulation. Using this approach, we identified a ring-stage specific regulatory region on the hrp3 promoter located between -1.7-kb and -1.1-kb from the ATG initiation codon. Small 100–150 bp truncations on this enhancer-like region failed to uncover discrete regulatory sequences, suggesting the multipartite nature of this element. The data presented in this study demonstrates that stage specific promoter activity of the hrp3 gene in P. falciparum blood stage parasites is supported, at least in-part, by a small promoter region that can function in the absence of a larger chromosomal context. PMID:17570541

  20. Bidirectional binding property of high glycine-tyrosine keratin-associated protein contributes to the mechanical strength and shape of hair.

    PubMed

    Matsunaga, Ryo; Abe, Ryota; Ishii, Daisuke; Watanabe, Shun-Ichi; Kiyoshi, Masato; Nöcker, Bernd; Tsuchiya, Masaru; Tsumoto, Kouhei

    2013-09-01

    Since their first finding in wool 50years ago, keratin-associated proteins (KAPs), which are classified into three groups; high sulfur (HS) KAPs, ultra high sulfur (UHS) KAPs, and high glycine-tyrosine (HGT) KAPs, have been the target of curiosity for scientists due to their characteristic amino acid sequences. While HS and UHS KAPs are known to function in disulfide bond crosslinking, the function of HGT KAPs remains unknown. To clarify the function as well as the binding partners of HGT KAPs, we prepared KAP8.1 and other KAP family proteins, the trichocyte intermediate filament proteins (IFP) K85 and K35, the head domain of K85, and the C subdomain of desmoplakin C-terminus (DPCT-C) and investigated the interactions between them in vitro. Western blot analysis and isothermal titration calorimetry (ITC) indicate that KAP8.1 binds to the head domain of K85, which is helically aligned around the axis of the intermediate filament (IF). From these results and transmission electron microscopy (TEM) observations of bundled filament complex in vitro, we propose that the helical arrangement of IFs found in the orthocortex, which is uniquely distributed on the convex fiber side of the hair, is regulated by KAP8.1. Structure-dependent binding of DPCT-C to trichocyte IFP was confirmed by Western blotting, ITC, and circular dichroism. Moreover, DPCT-C also binds to some HGT KAPs. It is probable that such bidirectional binding property of HGT KAPs contribute to the mechanical robustness of hair. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. NF-Y coassociates with FOS at promoters, enhancers, repetitive elements, and inactive chromatin regions, and is stereo-positioned with growth-controlling transcription factors

    PubMed Central

    Fleming, Joseph D.; Pavesi, Giulio; Benatti, Paolo; Imbriano, Carol; Mantovani, Roberto; Struhl, Kevin

    2013-01-01

    NF-Y, a trimeric transcription factor (TF) composed of two histone-like subunits (NF-YB and NF-YC) and a sequence-specific subunit (NF-YA), binds to the CCAAT motif, a common promoter element. Genome-wide mapping reveals 5000–15,000 NF-Y binding sites depending on the cell type, with the NF-YA and NF-YB subunits binding asymmetrically with respect to the CCAAT motif. Despite being characterized as a proximal promoter TF, only 25% of NF-Y sites map to promoters. A comparable number of NF-Y sites are located at enhancers, many of which are tissue specific, and nearly half of the NF-Y sites are in select subclasses of HERV LTR repeats. Unlike most TFs, NF-Y can access its target DNA motif in inactive (nonmodified) or polycomb-repressed chromatin domains. Unexpectedly, NF-Y extensively colocalizes with FOS in all genomic contexts, and this often occurs in the absence of JUN and the AP-1 motif. NF-Y also coassociates with a select cluster of growth-controlling and oncogenic TFs, consistent with the abundance of CCAAT motifs in the promoters of genes overexpressed in cancer. Interestingly, NF-Y and several growth-controlling TFs bind in a stereo-specific manner, suggesting a mechanism for cooperative action at promoters and enhancers. Our results indicate that NF-Y is not merely a commonly used proximal promoter TF, but rather performs a more diverse set of biological functions, many of which are likely to involve coassociation with FOS. PMID:23595228

  2. Brucella spp. infection in large ruminants in an endemic area of Egypt: cross-sectional study investigating seroprevalence, risk factors and livestock owner's knowledge, attitudes and practices (KAPs).

    PubMed

    Holt, Hannah R; Eltholth, Mahmoud M; Hegazy, Yamen M; El-Tras, Wael F; Tayel, Ahmed A; Guitian, Javier

    2011-05-19

    Brucellosis is regarded as one of the major zoonotic infections worldwide. It was first reported in Egypt in 1939 and is now endemic, the predominate species of Brucella in cattle and buffalo in Egypt is B. melitensis. The aim of the study was to estimate seroprevalence of Brucella spp. in cattle and buffalo reared in households in an Egyptian village, identify risk factors for animals testing seropositive and to assess the knowledge, attitudes and practices (KAPs) of livestock owners with regards to brucellosis. A cross-sectional study was carried out in a village in Menufiya Governorate of Egypt. In June and July 2009, 107 households were selected using systematic sample and all lactating cattle and buffalo present in the household were sampled and tested for antibodies against Brucella spp. In addition, a questionnaire collecting information on potential risk factors for Brucella spp. infection in cattle and buffalo was administered to the household member responsible for rearing the livestock. Between December 2009 and February 2010 households were revisited and a second questionnaire regarding KAPs associated with brucellosis was administered. True individual and household seroprevalence were estimated to be 11.0% (95% CI: 3.06% to 18.4%) and 15.5% (95% CI: 6.61% to 24.7%), respectively. Cattle and buffalo kept in a household with sheep and goats had 6.32 (95% CI: 1.44 to 27.9) times the odds of testing seropositive for Brucella spp., compared to cattle and buffalo that were not. Most participants in the study stated that livestock owners assist in the parturition of ruminants without wearing gloves and that some farmers sell animals which they suspect are Brucella infected to butchers or at market. Many participants made their livestock's milk into cheese and other dairy products without pasteurising it. Brucellosis was endemic at high levels, in the current study. Although livestock owners had good general knowledge of brucellosis, they still appeared to

  3. Brucella spp. infection in large ruminants in an endemic area of Egypt: cross-sectional study investigating seroprevalence, risk factors and livestock owner's knowledge, attitudes and practices (KAPs)

    PubMed Central

    2011-01-01

    Background Brucellosis is regarded as one of the major zoonotic infections worldwide. It was first reported in Egypt in 1939 and is now endemic, the predominate species of Brucella in cattle and buffalo in Egypt is B. melitensis. The aim of the study was to estimate seroprevalence of Brucella spp. in cattle and buffalo reared in households in an Egyptian village, identify risk factors for animals testing seropositive and to assess the knowledge, attitudes and practices (KAPs) of livestock owners with regards to brucellosis. Methods A cross-sectional study was carried out in a village in Menufiya Governorate of Egypt. In June and July 2009, 107 households were selected using systematic sample and all lactating cattle and buffalo present in the household were sampled and tested for antibodies against Brucella spp. In addition, a questionnaire collecting information on potential risk factors for Brucella spp. infection in cattle and buffalo was administered to the household member responsible for rearing the livestock. Between December 2009 and February 2010 households were revisited and a second questionnaire regarding KAPs associated with brucellosis was administered. Results True individual and household seroprevalence were estimated to be 11.0% (95% CI: 3.06% to 18.4%) and 15.5% (95% CI: 6.61% to 24.7%), respectively. Cattle and buffalo kept in a household with sheep and goats had 6.32 (95% CI: 1.44 to 27.9) times the odds of testing seropositive for Brucella spp., compared to cattle and buffalo that were not. Most participants in the study stated that livestock owners assist in the parturition of ruminants without wearing gloves and that some farmers sell animals which they suspect are Brucella infected to butchers or at market. Many participants made their livestock's milk into cheese and other dairy products without pasteurising it. Conclusions Brucellosis was endemic at high levels, in the current study. Although livestock owners had good general knowledge of

  4. Prediction of enhancer-promoter interactions via natural language processing.

    PubMed

    Zeng, Wanwen; Wu, Mengmeng; Jiang, Rui

    2018-05-09

    Precise identification of three-dimensional genome organization, especially enhancer-promoter interactions (EPIs), is important to deciphering gene regulation, cell differentiation and disease mechanisms. Currently, it is a challenging task to distinguish true interactions from other nearby non-interacting ones since the power of traditional experimental methods is limited due to low resolution or low throughput. We propose a novel computational framework EP2vec to assay three-dimensional genomic interactions. We first extract sequence embedding features, defined as fixed-length vector representations learned from variable-length sequences using an unsupervised deep learning method in natural language processing. Then, we train a classifier to predict EPIs using the learned representations in supervised way. Experimental results demonstrate that EP2vec obtains F1 scores ranging from 0.841~ 0.933 on different datasets, which outperforms existing methods. We prove the robustness of sequence embedding features by carrying out sensitivity analysis. Besides, we identify motifs that represent cell line-specific information through analysis of the learned sequence embedding features by adopting attention mechanism. Last, we show that even superior performance with F1 scores 0.889~ 0.940 can be achieved by combining sequence embedding features and experimental features. EP2vec sheds light on feature extraction for DNA sequences of arbitrary lengths and provides a powerful approach for EPIs identification.

  5. SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response

    PubMed Central

    Mund, Andreas; Schubert, Tobias; Staege, Hannah; Kinkley, Sarah; Reumann, Kerstin; Kriegs, Malte; Fritsch, Lauriane; Battisti, Valentine; Ait-Si-Ali, Slimane; Hoffbeck, Anne-Sophie; Soutoglou, Evi; Will, Hans

    2012-01-01

    Survival time-associated plant homeodomain (PHD) finger protein in Ovarian Cancer 1 (SPOC1, also known as PHF13) is known to modulate chromatin structure and is essential for testicular stem-cell differentiation. Here we show that SPOC1 is recruited to DNA double-strand breaks (DSBs) in an ATM-dependent manner. Moreover, SPOC1 localizes at endogenous repair foci, including OPT domains and accumulates at large DSB repair foci characteristic for delayed repair at heterochromatic sites. SPOC1 depletion enhances the kinetics of ionizing radiation-induced foci (IRIF) formation after γ-irradiation (γ-IR), non-homologous end-joining (NHEJ) repair activity, and cellular radioresistance, but impairs homologous recombination (HR) repair. Conversely, SPOC1 overexpression delays IRIF formation and γH2AX expansion, reduces NHEJ repair activity and enhances cellular radiosensitivity. SPOC1 mediates dose-dependent changes in chromatin association of DNA compaction factors KAP-1, HP1-α and H3K9 methyltransferases (KMT) GLP, G9A and SETDB1. In addition, SPOC1 interacts with KAP-1 and H3K9 KMTs, inhibits KAP-1 phosphorylation and enhances H3K9 trimethylation. These findings provide the first evidence for a function of SPOC1 in DNA damage response (DDR) and repair. SPOC1 acts as a modulator of repair kinetics and choice of pathways. This involves its dose-dependent effects on DNA damage sensors, repair mediators and key regulators of chromatin structure. PMID:23034801

  6. Exploring plant growth-promotion actinomycetes from vermicompost and rhizosphere soil for yield enhancement in chickpea

    PubMed Central

    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

  7. Co-expression of interleukin 12 enhances antitumor effects of a novel chimeric promoter-mediated suicide gene therapy in an immunocompetent mouse model

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

    Xu, Yu, E-mail: xuyu1001@gmail.com; Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071; Liu, Zhengchun, E-mail: l135027@126.com

    Highlights: {yields} A novel chimeric promoter consisting of CArG element and hTERT promoter was developed. {yields} The promoter was characterized with radiation-inducibility and tumor-specificity. {yields} Suicide gene system driven by the promoter showed remarkable cytotoxicity in vitro. {yields} Co-expression of IL12 enhanced the promoter mediated suicide gene therapy in vivo. -- Abstract: The human telomerase reverse transcriptase (hTERT) promoter has been widely used in target gene therapy of cancer. However, low transcriptional activity limited its clinical application. Here, we designed a novel dual radiation-inducible and tumor-specific promoter system consisting of CArG elements and the hTERT promoter, resulting in increased expressionmore » of reporter genes after gamma-irradiation. Therapeutic and side effects of adenovirus-mediated horseradish peroxidase (HRP)/indole-3-acetic (IAA) system downstream of the chimeric promoter were evaluated in mice bearing Lewis lung carcinoma, combining with or without adenovirus-mediated interleukin 12 (IL12) gene driven by the cytomegalovirus promoter. The combination treatment showed more effective suppression of tumor growth than those with single agent alone, being associated with pronounced intratumoral T-lymphocyte infiltration and minor side effects. Our results suggest that the combination treatment with HRP/IAA system driven by the novel chimeric promoter and the co-expression of IL12 might be an effective and safe target gene therapy strategy of cancer.« less

  8. Stromal adipocyte enhancer-binding protein (AEBP1) promotes mammary epithelial cell hyperplasia via proinflammatory and hedgehog signaling.

    PubMed

    Holloway, Ryan W; Bogachev, Oleg; Bharadwaj, Alamelu G; McCluskey, Greg D; Majdalawieh, Amin F; Zhang, Lei; Ro, Hyo-Sung

    2012-11-09

    Disruption of mammary stromal-epithelial communication leads to aberrant mammary gland development and induces mammary tumorigenesis. Macrophages have been implicated in carcinogenesis primarily by creating an inflammatory microenvironment, which promotes growth of the adjacent epithelial cells. Adipocyte enhancer-binding protein 1 (AEBP1), a novel proinflammatory mediator, promotes macrophage inflammatory responsiveness by inducing NF-κB activity, which has been implicated in tumor cell growth and survival by aberrant sonic hedgehog (Shh) expression. Here, we show that stromal macrophage AEBP1 overexpression results in precocious alveologenesis in the virgin AEBP1 transgenic (AEBP1(TG)) mice, and the onset of ductal hyperplasia was accelerated in AEBP1(TG) mice fed a high fat diet, which induces endogenous AEBP1 expression. Transplantation of AEBP1(TG) bone marrow cells into non-transgenic (AEBP1(NT)) mice resulted in alveolar hyperplasia with up-regulation of NF-κB activity and TNFα expression as displayed in the AEBP1(TG) mammary macrophages and epithelium. Shh expression was induced in AEBP1(TG) macrophages and RAW264.7 macrophages overexpressing AEBP1. The Shh target genes Gli1 and Bmi1 expression was induced in the AEBP1(TG) mammary epithelium and HC11 mammary epithelial cells co-cultured with AEBP1(TG) peritoneal macrophages. The conditioned AEBP1(TG) macrophage culture media promoted NF-κB activity and survival signal, Akt activation, in HC11 cells, whereas such effects were abolished by TNFα neutralizing antibody treatment. Furthermore, HC11 cells displayed enhanced proliferation in response to AEBP1(TG) macrophages and their conditioned media. Our findings highlight the role of AEBP1 in the signaling pathways regulating the cross-talk between mammary epithelium and stroma that could predispose the mammary tissue to tumorigenesis.

  9. Stromal Adipocyte Enhancer-binding Protein (AEBP1) Promotes Mammary Epithelial Cell Hyperplasia via Proinflammatory and Hedgehog Signaling*

    PubMed Central

    Holloway, Ryan W.; Bogachev, Oleg; Bharadwaj, Alamelu G.; McCluskey, Greg D.; Majdalawieh, Amin F.; Zhang, Lei; Ro, Hyo-Sung

    2012-01-01

    Disruption of mammary stromal-epithelial communication leads to aberrant mammary gland development and induces mammary tumorigenesis. Macrophages have been implicated in carcinogenesis primarily by creating an inflammatory microenvironment, which promotes growth of the adjacent epithelial cells. Adipocyte enhancer-binding protein 1 (AEBP1), a novel proinflammatory mediator, promotes macrophage inflammatory responsiveness by inducing NF-κB activity, which has been implicated in tumor cell growth and survival by aberrant sonic hedgehog (Shh) expression. Here, we show that stromal macrophage AEBP1 overexpression results in precocious alveologenesis in the virgin AEBP1 transgenic (AEBP1TG) mice, and the onset of ductal hyperplasia was accelerated in AEBP1TG mice fed a high fat diet, which induces endogenous AEBP1 expression. Transplantation of AEBP1TG bone marrow cells into non-transgenic (AEBP1NT) mice resulted in alveolar hyperplasia with up-regulation of NF-κB activity and TNFα expression as displayed in the AEBP1TG mammary macrophages and epithelium. Shh expression was induced in AEBP1TG macrophages and RAW264.7 macrophages overexpressing AEBP1. The Shh target genes Gli1 and Bmi1 expression was induced in the AEBP1TG mammary epithelium and HC11 mammary epithelial cells co-cultured with AEBP1TG peritoneal macrophages. The conditioned AEBP1TG macrophage culture media promoted NF-κB activity and survival signal, Akt activation, in HC11 cells, whereas such effects were abolished by TNFα neutralizing antibody treatment. Furthermore, HC11 cells displayed enhanced proliferation in response to AEBP1TG macrophages and their conditioned media. Our findings highlight the role of AEBP1 in the signaling pathways regulating the cross-talk between mammary epithelium and stroma that could predispose the mammary tissue to tumorigenesis. PMID:22995915

  10. Transcription regulation by distal enhancers

    PubMed Central

    Stadhouders, Ralph; van den Heuvel, Anita; Kolovos, Petros; Jorna, Ruud; Leslie, Kris; Grosveld, Frank; Soler, Eric

    2012-01-01

    Genome-wide chromatin profiling efforts have shown that enhancers are often located at large distances from gene promoters within the noncoding genome. Whereas enhancers can stimulate transcription initiation by communicating with promoters via chromatin looping mechanisms, we propose that enhancers may also stimulate transcription elongation by physical interactions with intronic elements. We review here recent findings derived from the study of the hematopoietic system. PMID:22771987

  11. Knowledge, attitudes and practices (KAP) regarding leptospirosis among residents of riverside settlements of Santa Fe, Argentina.

    PubMed

    Ricardo, Tamara; Bergero, Laura C; Bulgarella, Esteban P; Previtali, M Andrea

    2018-05-01

    Leptospirosis is a global and re-emerging zoonotic disease caused by Leptospira spirochetes that are shed into the environment by infected animals. Humans can get infected via contact with animal hosts or contaminated environment. In Argentina, the highest annual incidences were reported in the province of Santa Fe, where epidemic outbreaks occurred during flooding events. This study examined the knowledge, attitudes and practices (KAP) regarding leptospirosis among residents of riverside slum settlements from Santa Fe after a major flood. A cross-sectional questionnaire was administered to 113 residents of 3 riverside settlements from Santa Fe. The influence of knowledge and attitudes regarding leptospirosis on the likelihood that an individual will use preventive practices were evaluated using linear mixed-effects models. The majority of respondents (83.2%) had previously heard about leptospirosis; however specific knowledge about leptospirosis was limited. The results of the modeling efforts, show that the likelihood of using preventive practices was associated with having greater knowledge score, but not with more positive attitudes. We also found that females were more likely to use safer practices than males. Even though the majority of respondents had heard about leptospirosis, a high percentage of them had limited knowledge regarding the severity of the disease and its prevalence in the region. Our results suggest that public health interventions in these riverside communities should focus on educating the public on the multiple dimensions of leptospirosis in order to attain greater adherence to preventive practices instead of intending to change the perceptions or attitudes towards the disease, which did not have a significant influence. The key challenge lies in identifying effective strategies to reach the high risk group for leptospirosis here that is male fishermen, who spend most of the time in precarious campsites on the river islands.

  12. [Knowledge, attitude and practice (KAP) of foodborne parasitic diseases among middle school students in Xuzhou City].

    PubMed

    Qi, Zhou; Ya-Peng, Liu; Li, Li

    2017-12-26

    To investigate the status of knowledge, attitude and practice (KAP) of foodborne parasitic diseases among middle school students in Xuzhou City, so as to provide a reference to the health education. A total of four middle schools were selected and their students were investigated with the basic information questionnaire and questions of foodborne parasitic diseases. The awareness rates of parasitic diseases, hazards and transmission were 56.50%, 66.33% and 70.50% respectively. The awareness rates of transmission of the diseases in the senior high school students and urban students were higher than those in the junior middle school students and rural students ( χ 2 = 8.684, 8.470, both P < 0.05). The formation rates of not drinking raw water and not eating raw food were higher among the female students than those among the male students ( χ 2 = 7.675, 15.230, both P < 0.05). The formation rate of not eating raw food was higher among the senior high school students than that among the junior middle school students ( χ 2 = 49.276, P < 0.001), and the formation rates of washing hands before meals and not keeping pets were higher among the urban students than those among the rural students ( χ 2 = 5.833, 13.443, both P < 0.05). Totally 64.83% of the students would not eat food that might be infected with foodborne parasites, and the proportion of girls was higher than that of the boys ( χ 2 = 11.690, P < 0.05), and 20.5% of the students would suggest others not eating food that might be infected with foodborne parasites, and 81% of the students would plan to get rid of bad habits. The cognition of foodborne parasitic diseases is poor among the middle school students in Xuzhou City. The health education work on foodborne parasitic diseases should be strengthened.

  13. Designing a Culturally Appropriate Visually Enhanced Low-Text Mobile Health App Promoting Physical Activity for Latinos: A Qualitative Study.

    PubMed

    Bender, Melinda S; Martinez, Suzanna; Kennedy, Christine

    2016-07-01

    Rapid proliferation of smartphone ownership and use among Latinos offers a unique opportunity to employ innovative visually enhanced low-text (VELT) mobile health applications (mHealth app) to promote health behavior change for Latinos at risk for lifestyle-related diseases. Using focus groups and in-depth interviews with 16 promotores and 5 health care providers recruited from California clinics, this qualitative study explored perceptions of visuals for a VELT mHealth app promoting physical activity (PA) and limiting sedentary behavior (SB) for Latinos. In this Phase 1 study, participants endorsed visuals portraying PA guidelines and recommended visuals depicting family and socially oriented PA. Overall, participants supported a VELT mHealth app as an alternative to text-based education. Findings will inform the future Phase 2 study development of a culturally appropriate VELT mHealth app to promote PA for Latinos, improve health literacy, and provide an alternative to traditional clinic text-based health education materials. © The Author(s) 2015.

  14. Complementary Public Service Announcements as a Strategy for Enhancing the Impact of Health-Promoting Messages in Fictional Television Programs.

    PubMed

    Bavin, Lynda M; Owens, R Glynn

    2018-05-01

    Research suggests that health-promoting storylines in developed nations' fictional television programs can have a beneficial impact on viewers' beliefs, attitudes, intentions, or behaviors. The sizes of the effects are generally modest; however, the audience reach is substantial. Given that many fictional programs may hold the prolonged attention of millions of viewers, it is of value to examine potential strategies for enhancing the persuasive impact of their health-promoting storylines. Complementary public service announcements may be a promising strategy. This randomized experimental study (N = 310) examined the effects of viewing a complementary public service announcement after an organ donation story in an episode of Grey's Anatomy. Results indicated that the public service announcement enhanced the beneficial impact of the story on viewers' discussion behavior (about one's organ donor wishes), discussion intention, and perceived learning. This experimental study is the first to examine the effects of viewing a non-character public service announcement after a health-related storyline in a developed nation's fictional program compared to viewing the same episode of the program on its own. It is important for future research to examine whether these findings replicate for different health issues and with a nationally representative sample.

  15. Effect of a health education program on reduction of pediculosis in school girls at Amphoe Muang, Khon Kaen Province, Thailand.

    PubMed

    Yingklang, Manachai; Sengthong, Chatchawan; Haonon, Ornuma; Dangtakot, Rungtiwa; Pinlaor, Porntip; Sota, Chulaporn; Pinlaor, Somchai

    2018-01-01

    Pediculosis caused by head lice (Pediculus humanus capitis) infestation is still an important health problem in schoolchildren, especially girls, worldwide, including in Thailand. Although pediculicidal agents effectively kill head lice, the re-infestation rate is still high. Thus, prevention is an important strategy for any sustainable control program. We aimed to develop and evaluate the efficacy of a health education program for increasing knowledge, changing attitudes and promoting preventive practices to reduce prevalence of pediculosis among school girls in Amphoe Muang, Khon Kaen, northeastern Thailand. Six schools were selected using multistage simple randomization and were allocated into intervention or control groups. A total of 267 girls was enrolled from these schools. A "knowledge, attitude and practice" (KAP) questionnaire, consent forms and health education materials were constructed and tested by experts and in one pilot school before the main investigation. Baseline prevalence of adult lice and nits was determined. The health education package was given only to the intervention group. The KAP questionnaire was re-evaluated at two months after intervention. At baseline, the prevalence and intensity of head lice infestation, and the KAP scores did not differ significantly between the two groups. After re-evaluation at two months, the KAP score was significantly greater in the intervention group. A significant decrease of the infestation rate from 59% to 44% was observed in the intervention group, whereas infestation increased in the control group (from 56% to 65%). The incidence of new cases in the intervention group (6.14%) was lower than in the control group (12.62%). These findings indicated that the newly-established health education package is an effective tool for increasing KAP and reducing head lice infestation in school girls. Efforts to combat pediculosis in schoolchildren elsewhere may consider including this, or a similar, health

  16. Oxygen-isotope exchange and mineral alteration in gabbros of the Lower Layered Series, Kap Edvard Holm Complex, East Greenland

    USGS Publications Warehouse

    Fehlhaber, Kristen L.; Bird, Dennis K.

    1991-01-01

    Multiple intrusions of gabbros, mafic dikes, and syenites in the Kap Edvard Holm Complex gave rise to prolonged circulation of meteoric hydrothermal solutions and extreme isotope exchange and mineral alteration in the 3600-m-thick Lower Layered Series gabbros. In the Lower Layered Series, δ18O of plagioclase varies from +0.3‰ to -5.8‰, and it decreases with an increase in the volume of secondary talc, chlorite, and actinolite. In the same gabbros, pyroxenes have a more restricted range in δ18O, from 5.0‰ to 3.8‰ and values of δ18Opyroxene are independent of the abundance of secondary minerals, which ranges from 14% to 30%. These relations indicate that large amounts of water continued to flow through the rocks at temperatures of <500-600°C, altering the gabbros to assemblages of talc + chlorite + actinolite ± epidote ±albite and causing significant oxygen-isotope exchange in plagioclase, but not in pyroxene. The extensive low-temperature secondary mineralization and 18O depletion of plagioclase in the Lower Layered Series are associated with the later emplacement of dikes and gabbros and syenites, which created new fracture systems and provided heat sources for hydrothermal fluid circulation. This produced subsolidus mineral alteration and isotope exchange in the Lower Layered Series that are distinct from those in the Skaergaard and Cuillin gabbros of the North Atlantic Tertiary province, but are similar to those observed in some oceanic gabbros.

  17. Revisiting knowledge, attitudes and practice (KAP) on human papillomavirus (HPV) vaccination among female university students in Hong Kong.

    PubMed

    Leung, Jonathan Tin Chi; Law, Chi-Kin

    2018-04-03

    Despite cervical cancer can be preventable by HPV vaccination, little is known on its associated factors among young females in Hong Kong. This study aimed to investigate the present situation regarding the self-reported knowledge, attitudes and practice (KAP) of Human Papillomavirus (HPV) vaccination and to examine their associated factors among female university students in Hong Kong. 195 respondents were recruited to complete a self-administered questionnaire from two local universities through convenience sampling. 8.2% respondents indicated that family doctors as sources of knowledge of HPV and HPV vaccination. 59.0% of the sample identified more than four knowledge items, 82.6% thought that HPV vaccines can effectively prevent cervical cancer and 47.2% received HPV vaccination. Regression analyses found those at older age, thought that they might be infected by HPV and received HPV would have a higher level of knowledge. Those who knew HPV is sexually transmitted, thought may be infected by HPV and received HPV vaccination would have positive attitude on HPV vaccination. Those at older ages, knew their university provided discounted vaccination for female students, and were not afraid of the side effects were associated with HPV vaccination. Family doctors should take a more prominent role in disseminating accurate and precise information. Advocacies should be emphasised on the risk of HPV as a sexually transmitted disease and the availability of discounted and safe HPV vaccines in tertiary educational institutions to increase the uptake rate of HPV vaccines for first-year and non-health major university students.

  18. A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation.

    PubMed

    Cambon, Karine; Hansen, Stine M; Venero, Cesar; Herrero, A Isabel; Skibo, Galina; Berezin, Vladimir; Bock, Elisabeth; Sandi, Carmen

    2004-04-28

    The neural cell adhesion molecule (NCAM) plays a critical role in development and plasticity of the nervous system and is involved in the mechanisms of learning and memory. Here, we show that intracerebroventricular administration of the FG loop (FGL), a synthetic 15 amino acid peptide corresponding to the binding site of NCAM for the fibroblast growth factor receptor 1 (FGFR1), immediately after training rats in fear conditioning or water maze learning, induced a long-lasting improvement of memory. In primary cultures of hippocampal neurons, FGL enhanced the presynaptic function through activation of FGFR1 and promoted synapse formation. These results provide the first evidence for a memory-facilitating effect resulting from a treatment that mimics NCAM function. They suggest that increased efficacy of synaptic transmission and formation of new synapses probably mediate the cognition-enhancing properties displayed by the peptide.

  19. Acute Sleep Deprivation Enhances Post-Infection Sleep and Promotes Survival during Bacterial Infection in Drosophila

    PubMed Central

    Kuo, Tzu-Hsing; Williams, Julie A.

    2014-01-01

    Study Objectives: Sleep is known to increase as an acute response to infection. However, the function of this behavioral response in host defense is not well understood. To address this problem, we evaluated the effect of acute sleep deprivation on post-infection sleep and immune function in Drosophila. Setting: Laboratory. Participants: Drosophila melanogaster. Methods and Results: Flies were subjected to sleep deprivation before (early DEP) or after (late DEP) bacterial infection. Relative to a non-deprived control, flies subjected to early DEP had enhanced sleep after infection as well as increased bacterial clearance and survival outcome. Flies subjected to late DEP experienced enhanced sleep following the deprivation period, and showed a modest improvement in survival outcome. Continuous DEP (early and late DEP) throughout infection also enhanced sleep later during infection and improved survival. However, improved survival in flies subjected to late or continuous DEP did not occur until after flies had experienced sleep. During infection, both early and late DEP enhanced NFκB transcriptional activity as measured by a luciferase reporter (κB-luc) in living flies. Early DEP also increased NFκB activity prior to infection. Flies that were deficient in expression of either the Relish or Dif NFκB transcription factors showed normal responses to early DEP. However, the effect of early DEP on post-infection sleep and survival was abolished in double mutants, which indicates that Relish and Dif have redundant roles in this process. Conclusions: Acute sleep deprivation elevated NFκB-dependent activity, increased post-infection sleep, and improved survival during bacterial infection. Citation: Kuo TH, Williams JA. Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila. SLEEP 2014;37(5):859-869. PMID:24790264

  20. EPA Participates in Energy Roundtable with States, Tribes, Businesses and Environmental Groups to Enhance Coordination and Promote Responsible Domestic Production of Oil and Gas Resources

    EPA Pesticide Factsheets

    EPA News Release: EPA Participates in Energy Roundtable with States, Tribes, Businesses and Environmental Groups to Enhance Coordination and Promote Responsible Domestic Production of Oil and Gas Resources

  1. Database construction for PromoterCAD: synthetic promoter design for mammals and plants.

    PubMed

    Nishikata, Koro; Cox, Robert Sidney; Shimoyama, Sayoko; Yoshida, Yuko; Matsui, Minami; Makita, Yuko; Toyoda, Tetsuro

    2014-03-21

    Synthetic promoters can control a gene's timing, location, and expression level. The PromoterCAD web server ( http://promotercad.org ) allows the design of synthetic promoters to control plant gene expression, by novel arrangement of cis-regulatory elements. Recently, we have expanded PromoterCAD's scope with additional plant and animal data: (1) PLACE (Plant Cis-acting Regulatory DNA Elements), including various sized sequence motifs; (2) PEDB (Mammalian Promoter/Enhancer Database), including gene expression data for mammalian tissues. The plant PromoterCAD data now contains 22 000 Arabidopsis thaliana genes, 2 200 000 microarray measurements in 20 growth conditions and 79 tissue organs and developmental stages, while the new mammalian PromoterCAD data contains 679 Mus musculus genes and 65 000 microarray measurements in 96 tissue organs and cell types ( http://promotercad.org/mammal/ ). This work presents step-by-step instructions for adding both regulatory motif and gene expression data to PromoterCAD, to illustrate how users can expand PromoterCAD functionality for their own applications and organisms.

  2. Knowledge, attitude and practices for design for safety: A study on civil & structural engineers.

    PubMed

    Goh, Yang Miang; Chua, Sijie

    2016-08-01

    Design for safety (DfS) (also known as prevention through design, safe design and Construction (Design and Management)) promotes early consideration of safety and health hazards during the design phase of a construction project. With early intervention, hazards can be more effectively eliminated or controlled leading to safer worksites and construction processes. DfS is practiced in many countries, including Australia, the UK, and Singapore. In Singapore, the Manpower Ministry enacted the DfS Regulations in July 2015, which will be enforced from August 2016 onwards. Due to the critical role of civil and structural (C&S) engineers during design and construction, the DfS knowledge, attitude and practices (KAP) of C&S engineers have significant impact on the successful implementation of DfS. Thus, this study aims to explore the DfS KAP of C&S engineers so as to guide further research in measuring and improving DfS KAP of designers. During the study, it was found that there is a lack of KAP studies in construction management. Therefore, this study also aims to provide useful lessons for future applications of the KAP framework in construction management research. A questionnaire was developed to assess the DfS KAP of C&S engineers. The responses provided by 43 C&S engineers were analyzed. In addition, interviews with experienced construction professionals were carried out to further understand perceptions of DfS and related issues. The results suggest that C&S engineers are supportive of DfS, but the level of DfS knowledge and practices need to be improved. More DfS guidelines and training should be made available to the engineers. To ensure that DfS can be implemented successfully, there is a need to study the contractual arrangements between clients and designers and the effectiveness of different implementation approaches for the DfS process. The questionnaire and findings in this study provided the foundation for a baseline survey with larger sample size, which is

  3. Resistance to BmNPV via Overexpression of an Exogenous Gene Controlled by an Inducible Promoter and Enhancer in Transgenic Silkworm, Bombyx mori

    PubMed Central

    Jiang, Liang; Cheng, Tingcai; Zhao, Ping; Yang, Qiong; Wang, Genhong; Jin, Shengkai; Lin, Ping; Xiao, Yang; Xia, Qingyou

    2012-01-01

    The hycu-ep32 gene of Hyphantria cunea NPV can inhibit Bombyx mori nucleopolyhedrovirus (BmNPV) multiplication in co-infected cells, but it is not known whether the overexpression of the hycu-ep32 gene has an antiviral effect in the silkworm, Bombyx mori. Thus, we constructed four transgenic vectors, which were under the control of the 39 K promoter of BmNPV (39 KP), Bombyx mori A4 promoter (A4P), hr3 enhancer of BmNPV combined with 39 KP, and hr3 combined with A4P. Transgenic lines were created via embryo microinjection using practical diapause silkworm. qPCR revealed that the expression level of hycu-ep32 could be induced effectively after BmNPV infection in transgenic lines where hycu-ep32 was controlled by hr3 combined with 39 KP (i.e., HEKG). After oral inoculation of BmNPV with 3 × 105 occlusion bodies per third instar, the mortality with HEKG-B was approximately 30% lower compared with the non-transgenic line. The economic characteristics of the transgenic lines remained unchanged. These results suggest that overexpression of an exogenous antiviral gene controlled by an inducible promoter and enhancer is a feasible method for breeding silkworms with a high antiviral capacity. PMID:22870254

  4. MEG3 is a prognostic factor for CRC and promotes chemosensitivity by enhancing oxaliplatin-induced cell apoptosis.

    PubMed

    Li, Lixia; Shang, Jian; Zhang, Yupeng; Liu, Shi; Peng, Yanan; Zhou, Zhou; Pan, Huaqing; Wang, Xiaobing; Chen, Lipng; Zhao, Qiu

    2017-09-01

    A major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to oxaliplatin-based chemotherapy. Recently, studies have shown that long non-coding RNAs (lncRNAs) play an important role in drug resistance. Using HiSeq sequencing methods, we identified that lncRNAs show differential expression levels in oxaliplatin-resistant (OxR) and non-resistant CRC patients. RT-qPCR was then performed in tissues and serum samples, and lncRNA MEG3 was verified to be downregulated in non-responding patients and to have considerable discriminating potential to identify responding patients from non-responding patients. Moreover, decreased serum MEG3 expression was associated with poor chemoresponse and low survival rate in CRC patients receiving oxaliplatin treatment. Subsequently, OxR cell lines were established, and MEG3 was significantly downregulated in HT29 OxR and SW480 OxR cells. In addition, overexpression of MEG3 with pMEG3 reversed oxaliplatin resistance in both CRC cell lines. Flow cytometric apoptosis analysis indicated that MEG3 promoted CRC cell apoptosis. More importantly, MEG3 enhanced oxaliplatin‑induced cell cytotoxicity in CRC. In conclusion, our integrated approach demonstrated that decreased expression of lncRNA MEG3 in CRC confers potent poor therapeutic efficacy, and that MEG3 promotes chemosensitivity by enhancing oxaliplatin-induced cell apoptosis. Thus, overexpression of MEG3 may be a future direction by which to develop a novel therapeutic strategy to overcome oxaliplatin resistance of CRC patients.

  5. Plant Growth Promoting Rhizobacteria and Silicon Synergistically Enhance Salinity Tolerance of Mung Bean

    PubMed Central

    Mahmood, Sajid; Daur, Ihsanullah; Al-Solaimani, Samir G.; Ahmad, Shakeel; Madkour, Mohamed H.; Yasir, Muhammad; Hirt, Heribert; Ali, Shawkat; Ali, Zahir

    2016-01-01

    The present study explored the eco-friendly approach of utilizing plant-growth-promoting rhizobacteria (PGPR) inoculation and foliar application of silicon (Si) to improve the physiology, growth, and yield of mung bean under saline conditions. We isolated 18 promising PGPR from natural saline soil in Saudi Arabia, and screened them for plant-growth-promoting activities. Two effective strains were selected from the screening trial, and were identified as Enterobacter cloacae and Bacillus drentensis using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry and 16S rRNA gene sequencing techniques, respectively. Subsequently, in a 2-year mung bean field trial, using a randomized complete block design with a split-split plot arrangement, we evaluated the two PGPR strains and two Si levels (1 and 2 kg ha−1), in comparison with control treatments, under three different saline irrigation conditions (3.12, 5.46, and 7.81 dS m−1). The results indicated that salt stress substantially reduced stomatal conductance, transpiration rate, relative water content (RWC), total chlorophyll content, chlorophyll a, chlorophyll b, carotenoid content, plant height, leaf area, dry biomass, seed yield, and salt tolerance index. The PGPR strains and Si levels independently improved all the aforementioned parameters. Furthermore, the combined application of the B. drentensis strain with 2 kg Si ha−1 resulted in the greatest enhancement of mung bean physiology, growth, and yield. Overall, the results of this study provide important information for the benefit of the agricultural industry. PMID:27379151

  6. Enhancing health knowledge, health beliefs, and health behavior in Poland through a health promoting television program series.

    PubMed

    Chew, Fiona; Palmer, Sushma; Slonska, Zofia; Subbiah, Kalyani

    2002-01-01

    This study examined the impact of a health promoting television program series on health knowledge and the key factors of the health belief model (HBM) that have led people to engage in healthy behavior (exercising, losing weight, changing eating habits, and not smoking/quitting smoking). Using data from a posttest comparison field study with 15) viewers and 146 nonviewers in Poland, we found that hierarchical regression analysis showed stronger support for the HBM factors of efficacy, susceptibility, seriousness, and salience in their contribution toward health behavior among television viewers compared with nonviewers. Cues to action variables (including television viewing) and health knowledge boosted efficacy among viewers. Without the advantage of receiving health information from the television series, nonviewers relied on their basic disease fears on one hand, and interest in good health on the other to take steps toward becoming healthier. A health promoting television series can increase health knowledge and enhance health beliefs, which in turn contribute to healthy behaviors.

  7. TRIM24 promotes glioma progression and enhances chemoresistance through activation of the PI3K/Akt signaling pathway.

    PubMed

    Zhang, L-H; Yin, A-A; Cheng, J-X; Huang, H-Y; Li, X-M; Zhang, Y-Q; Han, N; Zhang, X

    2015-01-29

    The tripartite motif protein TRIM24 (tripartite motif-containing 24) has been found to play distinct roles in tumor development and progression, according to different tumor contexts. However, it remains elusive whether TRIM24 plays a role in malignant gliomas that are the most common and deadly primary brain tumors in adults. We report here that TRIM24 expression is positively correlated with glioma malignancy and is negatively associated with prognosis of patients with newly diagnosed glioblastoma, which is the most malignant form of gliomas but displays highly heterogeneous clinical outcome. The multivariate Cox regression analysis demonstrates the independent predictive value of TRIM24 expression level for overall and progression-free survival. Knockdown of TRIM24 suppresses cell proliferation, cell cycle progression, clone formation and in vivo tumor development, whereas overexpression of TRIM24 promotes cell growth. Chromatin immunoprecipitation, real-time reverse transcription-PCR and mutation analyses demonstrate that TRIM24 binds to the PIK3CA promoter via its PHD-Bromo domain to activate the transcription of PIK3CA gene, thus enhancing phosphatidylinositide 3-kinase (PI3K)/Akt signaling. The pan-PI3K inhibitor LY294002 and small interfering RNA targeting PIK3CA both abrogate the growth-promoting effect of TRIM24. Moreover, TRIM24 regulates the expression of DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) through PI3K/Akt/nuclear factor-κB signaling transduction and enhances resistance to temozolomide, the standard chemotherapeutic agent for glioblastoma. Finally, glioblastoma patients with low TRIM24 expression benefit from chemotherapy, whereas those with high TRIM24 expression do not have such benefit. Our results suggest that TRIM24 might serve as a potential prognostic marker and therapeutic target for the management of malignant gliomas.

  8. Amphiregulin enhances intercellular adhesion molecule-1 expression and promotes tumor metastasis in human osteosarcoma

    PubMed Central

    Liu, Ju-Fang; Tsao, Ya-Ting; Hou, Chun-Han

    2015-01-01

    Osteosarcoma is a common, high malignant, and metastatic bone cancer. Amphiregulin (AREG) has been associated with cancer cellular activities. However, the effect of AREG on metastasis activity in human osteosarcoma cells has yet to be determined. We determined that AREG increases the expression of intercellular adhesion molecule-1 (ICAM-1) through PI3K/Akt signaling pathway via its interaction with the epidermal growth factor receptor, thus resulting in the enhanced cell migration of osteosarcoma. Furthermore, AREG stimulation increased the association of NF-κB to ICAM-1 promoter which then up-regulated ICAM-1 expression. Finally, we observed that shRNA silencing of AREG decreased osteosarcoma metastasis in vivo. Our findings revealed a relationship between osteosarcoma metastatic potential and AREG expression and the modulating effect of AREG on ICAM-1 expression. PMID:26503469

  9. Crystal Structure of human Karyopherin β2 bound to the PY-NLS of Saccharomyces cerevisiae Nab2

    PubMed Central

    Soniat, Michael; Sampathkumar, Parthasarathy; Collett, Garen; Gizzi, Anthony S.; Banu, Radhika N.; Bhosle, Rahul C.; Chamala, Swetha; Chowdhury, Sukanya; Fiser, Andras; Glenn, Alan S.; Hammonds, James; Hillerich, Brandan; Khafizov, Kamil; Love, James D.; Matikainen, Bridget; Seidel, Ronald D.; Toro, Rafael; Kumar, P. Rajesh; Bonanno, Jeffery B.; Chook, Yuh Min; Almo, Steven C.

    2013-01-01

    Import-Karyopherin or Importin proteins bind nuclear localization signals (NLSs) to mediate the import of proteins into the cell nucleus. Karyopherin β2 or Kapβ2, also known as Transportin, is a member of this transporter family responsible for the import of numerous RNA binding proteins. Kapβ2 recognizes a targeting signal termed the PY-NLS that lies within its cargos to target them through the nuclear pore complex. The recognition of PY-NLS by Kapβ2 is conserved throughout eukaryotes. Kap104, the Kapβ2 homolog in Saccharomyces cerevisiae, recognizes PY-NLSs in cargos Nab2, Hrp1, and Tfg2. We have determined the crystal structure of Kapβ2 bound to the PY-NLS of the mRNA processing protein Nab2 at 3.05-Å resolution. A seven-residue segment of the PY-NLS of Nab2 is observed to bind Kapβ2 in an extended conformation and occupies the same PY-NLS binding site observed in other Kapβ2•PY-NLS structures. PMID:23535894

  10. Enhancing medical-surgical nursing practice: using practice tests and clinical examples to promote active learning and program evaluation.

    PubMed

    DuHamel, Martha B; Hirnle, Constance; Karvonen, Colleen; Sayre, Cindy; Wyant, Sheryl; Colobong Smith, Nancy; Keener, Sheila; Barrett, Shannon; Whitney, Joanne D

    2011-10-01

    In a 14-week medical-surgical nursing review course, two teaching strategies are used to promote active learning and assess the transfer of knowledge to nursing practice. Practice tests and clinical examples provide opportunities for participants to engage in self-assessment and reflective learning and enhance their nursing knowledge, skills, and practice. These strategies also contribute to program evaluation and are adaptable to a variety of course formats, including traditional classroom, web conference, and online self-study. Copyright 2011, SLACK Incorporated.

  11. Plant growth promoting rhizobacteria reduce aphid population and enhance the productivity of bread wheat.

    PubMed

    Naeem, Muhammad; Aslam, Zubair; Khaliq, Abdul; Ahmed, Jam Nazir; Nawaz, Ahmad; Hussain, Mubshar

    2018-04-24

    Plant growth promoting rhizobacteria increase plant growth and give protection against insect pests and pathogens. Due to the negative impact of chemical pesticides on environment, alternatives to these chemicals are needed. In this scenario, the biological methods of pest control offer an eco-friendly and an attractive option. In this study, the effect of two plant growth promoting rhizobacterial strains (Bacillus sp. strain 6 and Pseudomonas sp. strain 6K) on aphid population and wheat productivity was evaluated in an aphid susceptible (Pasban-90) and resistant (Inqlab-91) wheat cultivar. The seeds were inoculated with each PGPR strain, separately or the combination of both. The lowest aphid population (2.1tiller -1 ), and highest plant height (85.8cm), number of spikelets per spike (18), grains per spike (44), productive tillers (320m -2 ), straw yield (8.6Mgha -1 ), and grain yield (4.8Mgha -1 ) were achieved when seeds were inoculated with Bacillus sp. strain 6+Pseudomonas sp. strain 6K. The grain yield of both varieties was enhanced by 35.5-38.9% with seed inoculation with both bacterial strains. Thus, the combine use of both PGPR strains viz. Bacillus sp. strain 6+Pseudomonas sp. strain 6K offers an attractive option to reduce aphid population tied with better wheat productivity. Copyright © 2018 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

  12. miR-155 promotes cutaneous wound healing through enhanced keratinocytes migration by MMP-2.

    PubMed

    Yang, Longlong; Zheng, Zhao; Zhou, Qin; Bai, Xiaozhi; Fan, Lei; Yang, Chen; Su, Linlin; Hu, Dahai

    2017-04-01

    Inflammation, re-epithelization and tissue remodeling are three essential steps during wound healing. The re-epithelization process plays the most important role which mainly involves keratinocyte proliferation and migration. miR-155 has been reported to participate in cell migration and transformation, however, its function in skin wound healing is largely unknown. Here we hypothesize that overexpression of miR-155 at wound edges could accelerate wound healing mediated by enhanced keratinocyte migration. To test this hypothesis, direct local injection of miR-155 expression plasmid to wound edges was conducted to overexpress miR-155 in vivo. Results shown that miR-155 significantly promoted wound healing and re-epithelization compared to control, while did not affect wound contraction. Also, miR-155 overexpression accelerated primarily cultured keratinocyte migration in vitro, but had no effect on cell proliferation. Importantly, western blot analysis shown that MMP-2 was significantly upregulated whiles its inhibitor TIMP-1 downregulated after miR-155 treatment. Moreover, the use of ARP-101, an MMP-2 inhibitor, effectively attenuated the accelerative effects on cell migration induced by miR-155. Taken together, our results suggest that miR-155 has the promote effect on wound healing that is probably mediated by accelerating keratinocyte migration via upregulated MMP-2 level. This study provides a rationale for the therapeutic effect of miR-155 on wound healing.

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

    Kwon, Deukwoo; Little, Mark P.; Miller, Donald L.

    Purpose: To determine more accurate regression formulas for estimating peak skin dose (PSD) from reference air kerma (RAK) or kerma-area product (KAP). Methods: After grouping of the data from 21 procedures into 13 clinically similar groups, assessments were made of optimal clustering using the Bayesian information criterion to obtain the optimal linear regressions of (log-transformed) PSD vs RAK, PSD vs KAP, and PSD vs RAK and KAP. Results: Three clusters of clinical groups were optimal in regression of PSD vs RAK, seven clusters of clinical groups were optimal in regression of PSD vs KAP, and six clusters of clinical groupsmore » were optimal in regression of PSD vs RAK and KAP. Prediction of PSD using both RAK and KAP is significantly better than prediction of PSD with either RAK or KAP alone. The regression of PSD vs RAK provided better predictions of PSD than the regression of PSD vs KAP. The partial-pooling (clustered) method yields smaller mean squared errors compared with the complete-pooling method.Conclusion: PSD distributions for interventional radiology procedures are log-normal. Estimates of PSD derived from RAK and KAP jointly are most accurate, followed closely by estimates derived from RAK alone. Estimates of PSD derived from KAP alone are the least accurate. Using a stochastic search approach, it is possible to cluster together certain dissimilar types of procedures to minimize the total error sum of squares.« less

  14. Test-enhanced learning: the potential for testing to promote greater learning in undergraduate science courses.

    PubMed

    Brame, Cynthia J; Biel, Rachel

    2015-01-01

    Testing within the science classroom is commonly used for both formative and summative assessment purposes to let the student and the instructor gauge progress toward learning goals. Research within cognitive science suggests, however, that testing can also be a learning event. We present summaries of studies that suggest that repeated retrieval can enhance long-term learning in a laboratory setting; various testing formats can promote learning; feedback enhances the benefits of testing; testing can potentiate further study; and benefits of testing are not limited to rote memory. Most of these studies were performed in a laboratory environment, so we also present summaries of experiments suggesting that the benefits of testing can extend to the classroom. Finally, we suggest opportunities that these observations raise for the classroom and for further research. © 2015 C. J. Brame and R. Biel. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  15. Modification of the hTERT promoter by heat shock elements enhances the efficiency and specificity of cancer targeted gene therapy.

    PubMed

    Wang, Xiaolong; Zhou, PeiHua; Sun, XueJun; Wei, GuangBing; Zhang, Li; Wang, Hui; Yao, JianFeng; Jia, PengBo; Zheng, JianBao

    2016-05-01

    normal temperature conditions. The hTERT promoter is a potentially powerful tumour-specific promoter and gene therapy tool for cancer treatment. Incorporating heat-inducible therapeutic elements (8HSEs) into the hTERT promoter may enhance the efficiency and specificity of cancer targeting gene therapy under hyperthermic clinical conditions.

  16. [Ru(bipy)3]2+ nanoparticle-incorporate dental light cure resin to promote photobiomodulation therapy for enhanced vital pulp tissue repair

    NASA Astrophysics Data System (ADS)

    Mosca, Rodrigo C.; Young, Nicholas; Zeituni, Carlos A.; Arany, Praveen R.

    2018-02-01

    The use of nanoparticle on dental light cure resin is not new, currently several compounds (nanoadditives) are used to promote better communication between the restorative material and biological tissues. The interest for this application is growing up to enhance mechanical proprieties to dental tissue cells regeneration. Bioactive nanoparticles and complex compounds with multiple functions are the major target for optimizing the restorative materials. In this work, we incorporate [Ru(bipy)3]2+ nanoparticles, that absorbs energy at 450 nm (blue-light) and emits strongly at 620 nm (red-light), in PLGA Microspheres and insert it in Dental Light Cure Resin to promote the Photobiomodulation Therapy (PBM) effects to accelerate dental pulp repair by in vitro using cytotoxicity and proliferation assay.

  17. Enhancing the use of research in health-promoting, anti-racism policy.

    PubMed

    Ferdinand, Angeline S; Paradies, Yin; Kelaher, Margaret

    2017-07-11

    The Localities Embracing and Accepting Diversity (LEAD) programme was established to improve the health of ethnic minority communities through the reduction of racial discrimination. Local governments in the state of Victoria, Australia, were at the forefront of LEAD implementation in collaboration with leading state and national organisations. Key aims included expanding the available evidence regarding effective anti-racism interventions and facilitating the uptake of this evidence in organisational policies and practices. One rural and one metropolitan local government areas were selected to participate in LEAD. Key informant interviews and discussions were conducted with individuals who had participated in LEAD implementation and members of LEAD governance structures. Data were also collected on programme processes and implementation, partnership formation and organisational assessments. The LEAD model demonstrated both strengths and weaknesses in terms of facilitating the use of evidence in a complex, community-based health promotion initiative. Representation of implementing, funding and advisory bodies at different levels of governance enabled the input of technical advice and guidance alongside design and implementation. The representation structure assisted in ensuring the development of a programme that was acceptable to all partners and informed by the best available evidence. Simultaneous evaluation also enhanced perceived validity of the intervention, allowed for strategy correction when necessary and supported the process of double-loop organisational learning. However, due to the model's demand for simultaneous and intensive effort by various organisations, when particular elements of the intervention were not functional, there was a considerable loss of time and resources across the partner organisations. The complexity of the model also presented a challenge in ensuring clarity regarding roles, functions and the direction of the programme. The

  18. The Ties That Bind: Mapping the Dynamic Enhancer-Promoter Interactome

    DOE PAGES

    Spurrell, Cailyn H.; Dickel, Diane E.; Visel, Axel

    2016-11-17

    Coupling chromosome conformation capture to molecular enrichment for promoter-containing DNA fragments enables the systematic mapping of interactions between individual distal regulatory sequences and their target genes. Here in this Minireview, we describe recent progress in the application of this technique and related complementary approaches to gain insight into the lineage- and cell-type-specific dynamics of interactions between regulators and gene promoters.

  19. Poly-ADP-ribose polymerase inhibition enhances ischemic and diabetic wound healing by promoting angiogenesis.

    PubMed

    Zhou, Xin; Patel, Darshan; Sen, Sabyasachi; Shanmugam, Victoria; Sidawy, Anton; Mishra, Lopa; Nguyen, Bao-Ngoc

    2017-04-01

    Chronic nonhealing wounds are a major health problem for patients in the United States and worldwide. Diabetes and ischemia are two major risk factors behind impaired healing of chronic lower extremity wounds. Poly-ADP-ribose polymerase (PARP) is found to be overactivated with both ischemic and diabetic conditions. This study seeks a better understanding of the role of PARP in ischemic and diabetic wound healing, with a specific focus on angiogenesis and vasculogenesis. Ischemic and diabetic wounds were created in FVB/NJ mice and an in vitro scratch wound model. PARP inhibitor PJ34 was delivered to the animals at 10 mg/kg/d through implanted osmotic pumps or added to the culture medium, respectively. Animal wound healing was assessed by daily digital photographs. Animal wound tissues, peripheral blood, and bone marrow cells were collected at different time points for further analysis with Western blot and flow cytometry. Scratch wound migration and invasion angiogenesis assays were performed using human umbilical vein endothelial cells (HUVECs). Measurements were reported as mean ± standard deviation. Continuous measurements were compared by t-test. P < .05 was considered statistically significant. A significant increase in PARP activity was observed under ischemic and diabetic conditions that correlated with delayed wound healing and slower HUVEC migration. The beneficial effect of PARP inhibition with PJ34 on ischemic and diabetic wound healing was observed in both animal and in vitro models. In the animal model, the percentage of wound healing was significantly enhanced from 43% ± 6% to 71% ± 9% (P < .05) by day 7 with the addition of PJ34. PARP inhibition promoted angiogenesis at the ischemic and diabetic wound beds as evidenced by significantly higher levels of endothelial cell markers (vascular endothelial growth factor receptor 2 [VEGFR2] and endothelial nitric oxide synthase) in mice treated with PJ34 compared with controls. Flow cytometry

  20. WIND1 Promotes Shoot Regeneration through Transcriptional Activation of ENHANCER OF SHOOT REGENERATION1 in Arabidopsis[OPEN

    PubMed Central

    Ohnuma, Mariko; Kurata, Tetsuya; Nakata, Masaru; Ohme-Takagi, Masaru

    2017-01-01

    Many plant species display remarkable developmental plasticity and regenerate new organs after injury. Local signals produced by wounding are thought to trigger organ regeneration but molecular mechanisms underlying this control remain largely unknown. We previously identified an AP2/ERF transcription factor WOUND INDUCED DEDIFFERENTIATION1 (WIND1) as a central regulator of wound-induced cellular reprogramming in plants. In this study, we demonstrate that WIND1 promotes callus formation and shoot regeneration by upregulating the expression of the ENHANCER OF SHOOT REGENERATION1 (ESR1) gene, which encodes another AP2/ERF transcription factor in Arabidopsis thaliana. The esr1 mutants are defective in callus formation and shoot regeneration; conversely, its overexpression promotes both of these processes, indicating that ESR1 functions as a critical driver of cellular reprogramming. Our data show that WIND1 directly binds the vascular system-specific and wound-responsive cis-element-like motifs within the ESR1 promoter and activates its expression. The expression of ESR1 is strongly reduced in WIND1-SRDX dominant repressors, and ectopic overexpression of ESR1 bypasses defects in callus formation and shoot regeneration in WIND1-SRDX plants, supporting the notion that ESR1 acts downstream of WIND1. Together, our findings uncover a key molecular pathway that links wound signaling to shoot regeneration in plants. PMID:28011694

  1. Alternative Growth Promoters Modulate Broiler Gut Microbiome and Enhance Body Weight Gain

    PubMed Central

    Salaheen, Serajus; Kim, Seon-Woo; Haley, Bradd J.; Van Kessel, Jo Ann S.; Biswas, Debabrata

    2017-01-01

    Antibiotic growth promoters (AGPs) are frequently used to enhance weight-gain in poultry production. However, there has been increasing concern over the impact of AGP on the emergence of antibiotic resistance in zoonotic bacterial pathogens in the microbial community of the poultry gut. In this study, we adopted mass-spectrophotometric, phylogenetic, and shotgun-metagenomic approaches to evaluate bioactive phenolic extracts (BPE) from blueberry (Vaccinium corymbosum) and blackberry (Rubus fruticosus) pomaces as AGP alternatives in broilers. We conducted two trials with 100 Cobb-500 broiler chicks (in each trial) in four equal groups that were provided water with no supplementation, supplemented with AGP (tylosin, neomycin sulfate, bacitracin, erythromycin, and oxytetracycline), or supplemented with 0.1 g Gallic acid equivalent (GAE)/L or 1.0 g GAE/L (during the last 72 h before euthanasia) of BPE for 6 weeks. When compared with the control group (water only), the chickens supplemented with AGP and 0.1 g GAE/L of BPE gained 9.5 and 5.8% more body weight, respectively. The microbiomes of both the AGP- and BPE-treated chickens had higher Firmicutes to Bacteroidetes ratios. AGP supplementation appeared to be associated with higher relative abundance of bacteriophages and unique cecal resistomes compared with BPE supplementation or control. Functional characterization of cecal microbiomes revealed significant animal-to-animal variation in the relative abundance of genes involved in energy and carbohydrate metabolism. These findings established a baseline upon which mechanisms of plant-based performance enhancers in regulation of animal growth can be investigated. In addition, the data will aid in designing alternate strategies to improve animal growth performance and consequently production. PMID:29123512

  2. Survivin expression promotes VEGF-induced tumor angiogenesis via PI3K/Akt enhanced β-catenin/Tcf-Lef dependent transcription.

    PubMed

    Fernández, Jaime G; Rodríguez, Diego A; Valenzuela, Manuel; Calderon, Claudia; Urzúa, Ulises; Munroe, David; Rosas, Carlos; Lemus, David; Díaz, Natalia; Wright, Mathew C; Leyton, Lisette; Tapia, Julio C; Quest, Andrew Fg

    2014-09-09

    Early in cancer development, tumour cells express vascular endothelial growth factor (VEGF), a secreted molecule that is important in all stages of angiogenesis, an essential process that provides nutrients and oxygen to the nascent tumor and thereby enhances tumor-cell survival and facilitates growth. Survivin, another protein involved in angiogenesis, is strongly expressed in most human cancers, where it promotes tumor survival by reducing apoptosis as well as favoring endothelial cell proliferation and migration. The mechanisms by which cancer cells induce VEGF expression and angiogenesis upon survivin up-regulation remain to be fully established. Since the PI3K/Akt signalling and β-catenin-Tcf/Lef dependent transcription have been implicated in the expression of many cancer-related genes, including survivin and VEGF, we evaluated whether survivin may favor VEGF expression, release from tumor cells and induction of angiogenesis in a PI3K/Akt-β-catenin-Tcf/Lef-dependent manner. Here, we provide evidence linking survivin expression in tumor cells to increased β-catenin protein levels, β-catenin-Tcf/Lef transcriptional activity and expression of several target genes of this pathway, including survivin and VEGF, which accumulates in the culture medium. Alternatively, survivin downregulation reduced β-catenin protein levels and β-catenin-Tcf/Lef transcriptional activity. Also, using inhibitors of PI3K and the expression of dominant negative Akt, we show that survivin acts upstream in an amplification loop to promote VEGF expression. Moreover, survivin knock-down in B16F10 murine melanoma cells diminished the number of blood vessels and reduced VEGF expression in tumors formed in C57BL/6 mice. Finally, in the chick chorioallantoid membrane assay, survivin expression in tumor cells enhanced VEGF liberation and blood vessel formation. Importantly, the presence of neutralizing anti-VEGF antibodies precluded survivin-enhanced angiogenesis in this assay. These

  3. Wiki technology enhanced group project to promote active learning in a neuroscience course for first-year medical students: an exploratory study.

    PubMed

    Mi, Misa; Gould, Douglas

    2014-01-01

    A Wiki group project was integrated into a neuroscience course for first-year medical students. The project was developed as a self-directed, collaborative learning task to help medical students review course content and make clinically important connections. The goals of the project were to enhance students' understanding of key concepts in neuroscience, promote active learning, and reinforce their information literacy skills. The objective of the exploratory study was to provide a formative evaluation of the Wiki group project and to examine how Wiki technology was utilized to enhance active and collaborative learning of first-year medical students in the course and to reinforce information literacy skills.

  4. Platelet-Rich Fibrin Promotes Periodontal Regeneration and Enhances Alveolar Bone Augmentation

    PubMed Central

    Li, Qi; Pan, Shuang; Dangaria, Smit J.; Gopinathan, Gokul; Kolokythas, Antonia; Chu, Shunli; Geng, Yajun; Zhou, Yanmin; Luan, Xianghong

    2013-01-01

    In the present study we have determined the suitability of platelet-rich fibrin (PRF) as a complex scaffold for periodontal tissue regeneration. Replacing PRF with its major component fibrin increased mineralization in alveolar bone progenitors when compared to periodontal progenitors, suggesting that fibrin played a substantial role in PRF-induced osteogenic lineage differentiation. Moreover, there was a 3.6-fold increase in the early osteoblast transcription factor RUNX2 and a 3.1-fold reduction of the mineralization inhibitor MGP as a result of PRF application in alveolar bone progenitors, a trend not observed in periodontal progenitors. Subcutaneous implantation studies revealed that PRF readily integrated with surrounding tissues and was partially replaced with collagen fibers 2 weeks after implantation. Finally, clinical pilot studies in human patients documented an approximately 5 mm elevation of alveolar bone height in tandem with oral mucosal wound healing. Together, these studies suggest that PRF enhances osteogenic lineage differentiation of alveolar bone progenitors more than of periodontal progenitors by augmenting osteoblast differentiation, RUNX2 expression, and mineralized nodule formation via its principal component fibrin. They also document that PRF functions as a complex regenerative scaffold promoting both tissue-specific alveolar bone augmentation and surrounding periodontal soft tissue regeneration via progenitor-specific mechanisms. PMID:23586051

  5. Platelet-rich fibrin promotes periodontal regeneration and enhances alveolar bone augmentation.

    PubMed

    Li, Qi; Pan, Shuang; Dangaria, Smit J; Gopinathan, Gokul; Kolokythas, Antonia; Chu, Shunli; Geng, Yajun; Zhou, Yanmin; Luan, Xianghong

    2013-01-01

    In the present study we have determined the suitability of platelet-rich fibrin (PRF) as a complex scaffold for periodontal tissue regeneration. Replacing PRF with its major component fibrin increased mineralization in alveolar bone progenitors when compared to periodontal progenitors, suggesting that fibrin played a substantial role in PRF-induced osteogenic lineage differentiation. Moreover, there was a 3.6-fold increase in the early osteoblast transcription factor RUNX2 and a 3.1-fold reduction of the mineralization inhibitor MGP as a result of PRF application in alveolar bone progenitors, a trend not observed in periodontal progenitors. Subcutaneous implantation studies revealed that PRF readily integrated with surrounding tissues and was partially replaced with collagen fibers 2 weeks after implantation. Finally, clinical pilot studies in human patients documented an approximately 5 mm elevation of alveolar bone height in tandem with oral mucosal wound healing. Together, these studies suggest that PRF enhances osteogenic lineage differentiation of alveolar bone progenitors more than of periodontal progenitors by augmenting osteoblast differentiation, RUNX2 expression, and mineralized nodule formation via its principal component fibrin. They also document that PRF functions as a complex regenerative scaffold promoting both tissue-specific alveolar bone augmentation and surrounding periodontal soft tissue regeneration via progenitor-specific mechanisms.

  6. A standards-based, peer-reviewed teaching award to enhance a medical school's teaching environment and inform the promotions process.

    PubMed

    Searle, Nancy S; Teal, Cayla R; Richards, Boyd F; Friedland, Joan A; Weigel, Nancy L; Hernandez, Rachael A; Lomax, James W; Coburn, Michael; Nelson, Elizabeth A

    2012-07-01

    The authors provide the rationale, design, and description of a unique teaching award that has enhanced Baylor College of Medicine's teaching environment and become highly valued by the promotions and tenure (P&T) committee in determining a faculty member's readiness for promotion. This award is self-nominating and standards based. The primary purpose for development of the award was to provide the Baylor community and the P&T committee a method to understand and value the scholarship of teaching to the same degree that they understand and value the scholarship of discovery.The authors also present results from an internal evaluation of the program that included a survey and interviews. Between the inception of the award in 2001 and the internal review conducted in 2010, the award could have had an influence on the promotion of 130 of the recipients. Of the 130, 88 (65.6%) received this award before gaining their current rank (χ (1) = 16.3, P < .001). Stakeholders, including department chairs and members of the P&T committee, agreed that this award is valuable to those seeking promotion. Individual recipients stated that the award is good for the institution by encouraging reflection on teaching; increasing the recognition, importance, and value of teaching; encouraging the improvement of teaching skills; and providing a better understanding to others about what medical teachers really do. Of the 214 open-ended responses to survey questions of award recipients, more than half the comments were about the value of the award and its positive effect on promotion.

  7. The Ties That Bind: Mapping the Dynamic Enhancer-Promoter Interactome.

    PubMed

    Spurrell, Cailyn H; Dickel, Diane E; Visel, Axel

    2016-11-17

    Coupling chromosome conformation capture to molecular enrichment for promoter-containing DNA fragments enables the systematic mapping of interactions between individual distal regulatory sequences and their target genes. In this Minireview, we describe recent progress in the application of this technique and related complementary approaches to gain insight into the lineage- and cell-type-specific dynamics of interactions between regulators and gene promoters. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Initiation-promotion skin carcinogenesis and immunological competence.

    PubMed

    Curtis, G L; Stenbäck, F; Ryan, W L

    1975-10-01

    The immune competence of mice during initiation-promotion skin carcinogenesis was determined by skin allograft rejection and lymphocyte mitogenesis. The carcinogen 7, 12-dimethylbenzanthracene inhibited the cellular immune competence of mice while lymphocytes from croton oil treated mice had enhanced PWM response. Chlorphenesin, a stimulator of cellular immunity, was found to inhibit tumorigenesis in initiation-promotion skin carcinogenesis when injected during promotion.

  9. Insulators form gene loops by interacting with promoters in Drosophila.

    PubMed

    Erokhin, Maksim; Davydova, Anna; Kyrchanova, Olga; Parshikov, Alexander; Georgiev, Pavel; Chetverina, Darya

    2011-09-01

    Chromatin insulators are regulatory elements involved in the modulation of enhancer-promoter communication. The 1A2 and Wari insulators are located immediately downstream of the Drosophila yellow and white genes, respectively. Using an assay based on the yeast GAL4 activator, we have found that both insulators are able to interact with their target promoters in transgenic lines, forming gene loops. The existence of an insulator-promoter loop is confirmed by the fact that insulator proteins could be detected on the promoter only in the presence of an insulator in the transgene. The upstream promoter regions, which are required for long-distance stimulation by enhancers, are not essential for promoter-insulator interactions. Both insulators support basal activity of the yellow and white promoters in eyes. Thus, the ability of insulators to interact with promoters might play an important role in the regulation of basal gene transcription.

  10. Promoting communication with older adults: protocols for resolving interpersonal conflicts and for enhancing interactions with doctors.

    PubMed

    Weitzman, Patricia Flynn; Weitzman, Eben A

    2003-07-01

    In this paper, we review the importance of effective communication in older adulthood, and ideas for promoting it. We focus on theoretical and applied work in two communicative encounters that have particular relevance for older adult health, i.e., interpersonal conflict and visits with a healthcare provider. Little applied work has aimed to adapt training protocols for older adults in these two areas. We will present training protocols we have developed in constructive conflict resolution for older adults, and on enhancing doctor-patient communication. We present these protocols to stimulate ideas on the part of the reader on how to further develop and refine training efforts for older adults in effective communication.

  11. Efficiency of plant growth-promoting P-solubilizing Bacillus circulans CB7 for enhancement of tomato growth under net house conditions.

    PubMed

    Mehta, Preeti; Walia, Abhishek; Kulshrestha, Saurabh; Chauhan, Anjali; Shirkot, Chand Karan

    2015-01-01

    P-solubilizing bacterial isolate CB7 isolated from apple rhizosphere soil of Himachal Pradesh, India was identified as Bacillus circulans on the basis of phenotypic characteristics, biochemical tests, fatty acid methyl esters analysis, and 16S rRNA gene sequence. The isolate exhibited plant growth-promoting traits of P-solubilization, auxin, 1-aminocyclopropane-1-carboxylate deaminase activity, siderophore, nitrogenase activity, and antagonistic activity against Dematophora necatrix. In vitro studies revealed that P-solubilization and other plant growth-promoting traits were dependent on the presence of glucose in PVK medium and removal of yeast extract had no significant effect on plant growth-promoting traits. Plant growth-promoting traits of isolate CB7 were repressed in the presence of KH2 PO4 . P-solubilization activity was associated with the release of organic acids and a drop in the pH of the Pikovskaya's medium. HPLC analysis detected gluconic and citric acid as major organic acids in the course of P-solubilization. Remarkable increase was observed in seed germination (22.32%), shoot length (15.91%), root length (25.10%), shoot dry weight (52.92%) and root dry weight (31.4%), nitrogen (18.75%), potassium (57.69%), and phosphorus (22.22%) content of shoot biomass over control. These results demonstrate that isolate CB7 has the promising PGPR attributes to be developed as a biofertilizer to enhance soil fertility and promote plant growth. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Development of a promoter shutoff system in Aspergillus oryzae using a sorbitol-sensitive promoter.

    PubMed

    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.

  13. Petunia AGAMOUS enhancer-derived chimeric promoters specify a carpel-, stamen- and petal-specific expression pattern sufficient for engineering male and female sterility in tobacco

    USDA-ARS?s Scientific Manuscript database

    Previous studies have shown that the AtAGIP promoter derived from the Arabidopsis AGAMOUS (AG) second intron/enhancer specifies a carpel- and stamen-specific pattern of expression in its native host species but not in heterologous species, such as tobacco which restricts its application in the engin...

  14. Enhanced activation of the left hemisphere promotes normative decision making.

    PubMed

    Corser, Ryan; Jasper, John D

    2014-01-01

    Previous studies have reported that enhanced activation of the left cerebral hemisphere reduces risky-choice, attribute, and goal-framing effects relative to enhanced activation of the right cerebral hemisphere. The present study sought to extend these findings and show that enhanced activation of the left hemisphere also reduces violations of other normative principles, besides the invariance principle. Participants completed ratio bias (Experiment 1, N = 296) and base rate neglect problems (Experiment 2, N = 145) under normal (control) viewing or with the right or left hemisphere primarily activated by imposing a unidirectional gaze. In Experiment 1 we found that enhanced left hemispheric activation reduced the ratio bias relative to normal viewing and a group experiencing enhanced right hemispheric activation. In Experiment 2 enhanced left hemispheric activation resulted in using base rates more than normal viewing, but not significantly more than enhanced right hemispheric activation. Results suggest that hemispheric asymmetries can affect higher-order cognitive processes, such as decision-making biases. Possible theoretical accounts are discussed as well as implications for dual-process theories.

  15. Calibration methodology application of kerma area product meters in situ: Preliminary results

    NASA Astrophysics Data System (ADS)

    Costa, N. A.; Potiens, M. P. A.

    2014-11-01

    The kerma-area product (KAP) is a useful quantity to establish the reference levels of conventional X-ray examinations. It can be obtained by measurements carried out with a KAP meter on a plane parallel transmission ionization chamber mounted on the X-ray system. A KAP meter can be calibrated in laboratory or in situ, where it is used. It is important to use one reference KAP meter in order to obtain reliable quantity of doses on the patient. The Patient Dose Calibrator (PDC) is a new equipment from Radcal that measures KAP. It was manufactured following the IEC 60580 recommendations, an international standard for KAP meters. This study had the aim to calibrate KAP meters using the PDC in situ. Previous studies and the quality control program of the PDC have shown that it has good function in characterization tests of dosimeters with ionization chamber and it also has low energy dependence. Three types of KAP meters were calibrated in four different diagnostic X-ray equipments. The voltages used in the two first calibrations were 50 kV, 70 kV, 100 kV and 120 kV. The other two used 50 kV, 70 kV and 90 kV. This was related to the equipments limitations. The field sizes used for the calibration were 10 cm, 20 cm and 30 cm. The calibrations were done in three different cities with the purpose to analyze the reproducibility of the PDC. The results gave the calibration coefficient for each KAP meter and showed that the PDC can be used as a reference instrument to calibrate clinical KAP meters.

  16. The application of powerful promoters to enhance gene expression in industrial microorganisms.

    PubMed

    Zhou, Shenghu; Du, Guocheng; Kang, Zhen; Li, Jianghua; Chen, Jian; Li, Huazhong; Zhou, Jingwen

    2017-02-01

    Production of useful chemicals by industrial microorganisms has been attracting more and more attention. Microorganisms screened from their natural environment usually suffer from low productivity, low stress resistance, and accumulation of by-products. In order to overcome these disadvantages, rational engineering of microorganisms to achieve specific industrial goals has become routine. Rapid development of metabolic engineering and synthetic biology strategies provide novel methods to improve the performance of industrial microorganisms. Rational regulation of gene expression by specific promoters is essential to engineer industrial microorganisms for high-efficiency production of target chemicals. Identification, modification, and application of suitable promoters could provide powerful switches at the transcriptional level for fine-tuning of a single gene or a group of genes, which are essential for the reconstruction of pathways. In this review, the characteristics of promoters from eukaryotic, prokaryotic, and archaea microorganisms are briefly introduced. Identification of promoters based on both traditional biochemical and systems biology routes are summarized. Besides rational modification, de novo design of promoters to achieve gradient, dynamic, and logic gate regulation are also introduced. Furthermore, flexible application of static and dynamic promoters for the rational engineering of industrial microorganisms is highlighted. From the perspective of powerful promoters in industrial microorganisms, this review will provide an extensive description of how to regulate gene expression in industrial microorganisms to achieve more useful goals.

  17. Misconceptions about Ebola seriously affect the prevention efforts: KAP related to Ebola prevention and treatment in Kouroussa Prefecture, Guinea

    PubMed Central

    Buli, Benti Geleta; Mayigane, Landry Ndriko; Oketta, Julius Facki; Soumouk, Aguide; Sandouno, Tamba Emile; Camara, Bole; Toure, Mory Saidou; Conde, Aissata

    2015-01-01

    Introduction Guinea is the third hardest hit country in the region with 2,806 cases and 1,814 deaths as of January 11, 2015 after Sierra Leone and Liberia respectively. This KAP study was conducted in three sub-prefectures of Kouroussa in the Kankan region of Guinea from 15 December 2014 to 15 January 2015. It was conducted with the general objective of examining the knowledge, attitude and practice related to Ebola prevention and care among the public of Kouroussa Prefecture. Methods A cross-sectional study design was employed to collect quantitative data to examine knowledge, attitude and practice related to Ebola. Structured questionnaire was administered by trained data collectors who were supervised by doctors and epidemiologists from WHO and Africa Union. Data were collected from 358 individuals (93% response rate) and analyzed in STATA 13 while tables and graphs are used to display results. Results Over 96% of the respondents have ever heard about Ebola while only 76.2% believed the disease existed in Kouroussa. Avoiding physical contacts including hand shaking and contacts with body fluids, and early treatment of persons sick from Ebola were the two important prevention methods frequently mentioned (96.8% and 93.9%). Only 35.7% of respondents were found to have comprehensive knowledge about Ebola (composite of correctly accepting three methods of prevention (85%) and rejecting misconceptions (55.7%)). Conclusion The high level of knowledge about modes of transmission and prevention methods has not positively affected the level of comprehensive knowledge about Ebola. In contrast, the prevailing high level of misconceptions surrounding Ebola was found to be responsible for a low comprehensive knowledge. PMID:26740839

  18. Misconceptions about Ebola seriously affect the prevention efforts: KAP related to Ebola prevention and treatment in Kouroussa Prefecture, Guinea.

    PubMed

    Buli, Benti Geleta; Mayigane, Landry Ndriko; Oketta, Julius Facki; Soumouk, Aguide; Sandouno, Tamba Emile; Camara, Bole; Toure, Mory Saidou; Conde, Aissata

    2015-01-01

    Guinea is the third hardest hit country in the region with 2,806 cases and 1,814 deaths as of January 11, 2015 after Sierra Leone and Liberia respectively. This KAP study was conducted in three sub-prefectures of Kouroussa in the Kankan region of Guinea from 15 December 2014 to 15 January 2015. It was conducted with the general objective of examining the knowledge, attitude and practice related to Ebola prevention and care among the public of Kouroussa Prefecture. A cross-sectional study design was employed to collect quantitative data to examine knowledge, attitude and practice related to Ebola. Structured questionnaire was administered by trained data collectors who were supervised by doctors and epidemiologists from WHO and Africa Union. Data were collected from 358 individuals (93% response rate) and analyzed in STATA 13 while tables and graphs are used to display results. Over 96% of the respondents have ever heard about Ebola while only 76.2% believed the disease existed in Kouroussa. Avoiding physical contacts including hand shaking and contacts with body fluids, and early treatment of persons sick from Ebola were the two important prevention methods frequently mentioned (96.8% and 93.9%). Only 35.7% of respondents were found to have comprehensive knowledge about Ebola (composite of correctly accepting three methods of prevention (85%) and rejecting misconceptions (55.7%)). The high level of knowledge about modes of transmission and prevention methods has not positively affected the level of comprehensive knowledge about Ebola. In contrast, the prevailing high level of misconceptions surrounding Ebola was found to be responsible for a low comprehensive knowledge.

  19. Choline availability modulates human neuroblastoma cell proliferation and alters the methylation of the promoter region of the cyclin-dependent kinase inhibitor 3 gene

    PubMed Central

    Niculescu, Mihai D.; Yamamuro, Yutaka; Zeisel, Steven H.

    2006-01-01

    Choline is an important methyl donor and a component of membrane phospholipids. In this study, we tested the hypothesis that choline availability can modulate cell proliferation and the methylation of genes that regulate cell cycling. In several other model systems, hypomethylation of cytosine bases that are followed by a guanosine (CpG) sites in the promoter region of a gene is associated with increased gene expression. We found that in choline-deficient IMR-32 neuroblastoma cells, the promoter of the cyclin-dependent kinase inhibitor 3 gene (CDKN3) was hypomethylated. This change was associated with increased expression of CDKN3 and increased levels of its gene product, kinase-associated phosphatase (KAP), which inhibits the G1/S transition of the cell cycle by dephosphorylating cyclin-dependent kinases. Choline deficiency also reduced global DNA methylation. The percentage of cells that accumulated bromodeoxyuridine (proportional to cell proliferation) was 1.8 times lower in the choline-deficient cells than in the control cells. Phosphorylated retinoblastoma (p110) levels were 3 times lower in the choline-deficient cells than in control cells. These findings suggest that the mechanism whereby choline deficiency inhibits cell proliferation involves hypomethylation of key genes regulating cell cycling. This may be a mechanism for our previously reported observation that stem cell proliferation in hippocampus neuroepithelium is decreased in choline-deficient rat and mouse fetuses. PMID:15147518

  20. Overexpression of plasma membrane H+-ATPase in guard cells promotes light-induced stomatal opening and enhances plant growth.

    PubMed

    Wang, Yin; Noguchi, Ko; Ono, Natsuko; Inoue, Shin-ichiro; Terashima, Ichiro; Kinoshita, Toshinori

    2014-01-07

    Stomatal pores surrounded by a pair of guard cells in the plant epidermis control gas exchange between plants and the atmosphere in response to light, CO2, and the plant hormone abscisic acid. Light-induced stomatal opening is mediated by at least three key components: the blue light receptor phototropin (phot1 and phot2), plasma membrane H(+)-ATPase, and plasma membrane inward-rectifying K(+) channels. Very few attempts have been made to enhance stomatal opening with the goal of increasing photosynthesis and plant growth, even though stomatal resistance is thought to be the major limiting factor for CO2 uptake by plants. Here, we show that transgenic Arabidopsis plants overexpressing H(+)-ATPase using the strong guard cell promoter GC1 showed enhanced light-induced stomatal opening, photosynthesis, and plant growth. The transgenic plants produced larger and increased numbers of rosette leaves, with ∼42-63% greater fresh and dry weights than the wild type in the first 25 d of growth. The dry weights of total flowering stems of 45-d-old transgenic plants, including seeds, siliques, and flowers, were ∼36-41% greater than those of the wild type. In addition, stomata in the transgenic plants closed normally in response to darkness and abscisic acid. In contrast, the overexpression of phototropin or inward-rectifying K(+) channels in guard cells had no effect on these phenotypes. These results demonstrate that stomatal aperture is a limiting factor in photosynthesis and plant growth, and that manipulation of stomatal opening by overexpressing H(+)-ATPase in guard cells is useful for the promotion of plant growth.

  1. Interleukin-6 enhances cancer stemness and promotes metastasis of hepatocellular carcinoma via up-regulating osteopontin expression.

    PubMed

    Wang, Chao-Qun; Sun, Hao-Ting; Gao, Xiao-Mei; Ren, Ning; Sheng, Yuan-Yuan; Wang, Zheng; Zheng, Yan; Wei, Jin-Wang; Zhang, Kai-Li; Yu, Xin-Xin; Zhu, Yin; Luo, Qin; Yang, Lu-Yu; Dong, Qiong-Zhu; Qin, Lun-Xiu

    2016-01-01

    Interleukin-6 (IL-6), one of the most important inflammatory cytokines, plays a pivotal role in metastasis and stemness of solid tumors. However, the underlying mechanisms of IL-6 in HCC metastasis remain unclear. In the present study, we demonstrated that stemness and metastatic potential of HCC cells were significantly enhanced after IL-6 stimulation. IL-6 could induce expression of osteopontin (OPN), along with other stemness-related genes, including HIF1α, BMI1, and HEY1. Block of OPN induction could significantly abrogate the effect of IL-6 on stemness and metastasis of HCC cells. Furthermore, IL-6 level was positively correlated with OPN in HCC. Patients with high plasma IL-6 or OPN level had poorer prognosis. In multivariate analysis, IL-6 and OPN were demonstrated to be independent prognostic indicators for HCC patients, and their combination had a better prognostic performance than IL-6 or OPN alone. Collectively, our findings indicate that IL-6 could enhance stemness and promote metastasis of HCC via up-regulating OPN expression, which can be a potential therapeutic target for combating HCC metastasis, and the combination of IL-6 and OPN serves as a promising prognostic predictor for HCC.

  2. Uric acid promotes oxidative stress and enhances vascular endothelial cell apoptosis in rats with middle cerebral artery occlusion.

    PubMed

    Song, Chengfu; Zhao, Xiangdong

    2018-05-15

    In patients with cerebral infarction (CI), elevated serum uric acid (UA) level may exacerbate the occurrence and development of carotid atherosclerosis (AS). Our study intended to explore the underlying mechanism. We enrolled 86 patients with CI, and divided them into four groups: Non-AS, AS-mild, AS-moderate, and AS-severe groups; the levels of UA and oxidative stress-related factors in serum were detected. The middle cerebral artery occlusion (MCAO) model was used to stimulate CI in rats, and different doses of UA were administrated. The levels of oxidative stress-related factors in serum were detected. Hematoxylin & eosin (H&E) staining was used to observe the morphological alterations, and the apoptotic cell death detection kit was used to detect apoptotic cells. Increased UA concentration and enhanced oxidative stress were found in AS patients. H&E staining results showed that UA treatment exacerbated morphological damage in rats with MCAO, promoted oxidative stress, and enhanced vascular endothelial cell apoptosis in rats with MCAO. © 2017 The Author(s).

  3. Immunoglobulin kappa light chain gene promoter and enhancer are not responsible for B-cell restricted gene rearrangement.

    PubMed Central

    Goodhardt, M; Babinet, C; Lutfalla, G; Kallenbach, S; Cavelier, P; Rougeon, F

    1989-01-01

    We have produced transgenic mice which synthesize chimeric mouse-rabbit immunoglobulin (Ig) kappa light chains following in vivo recombination of an injected unrearranged kappa gene. The exogenous gene construct contained a mouse germ-line kappa variable (V kappa) gene segment, the mouse germ-line joining (J kappa) locus including the enhancer, and the rabbit b9 constant (C kappa) region. A high level of V-J recombination of the kappa transgene was observed in spleen of the transgenic mice. Surprisingly, a particularly high degree of variability in the exact site of recombination and the presence of non germ-line encoded nucleotides (N-regions) were found at the V-J junction of the rearranged kappa transgene. Furthermore, unlike endogenous kappa genes, rearrangement of the exogenous gene occurred in T-cells of the transgenic mice. These results show that additional sequences, other than the heptamer-nonamer signal sequences and the promoter and enhancer elements, are required to obtain stage- and lineage- specific regulation of Ig kappa light chain gene rearrangement in vivo. Images PMID:2508061

  4. Three year field test of a plant growth promoting rhizobacteria enhanced phytoremediation system at a land farm for treatment of hydrocarbon waste.

    PubMed

    Gurska, Jolanta; Wang, Wenxi; Gerhardt, Karen E; Khalid, Aaron M; Isherwood, David M; Huang, Xiao-Dong; Glick, Bernard R; Greenberg, Bruce M

    2009-06-15

    Phytoremediation of total petroleum hydrocarbons (TPH) has the potential to be a sustainable waste management technology if it can be proven to be effective in the field. Over the past decade, our laboratory has developed a system which utilizes plant growth promoting rhizobacteria (PGPR) enhanced phytoremediation (PEP) that, following extensive greenhouse testing, was shown to be effective at remediating TPH from soils. This system consists of physical soil manipulation and plant growth following seed inoculation with PGPR. PGPR elicit biomass increases, particularly in roots, by minimizing plant stress in highly contaminated soils. Extensive development of the root system enhances degradation of contaminants by the plants and supports an active rhizosphere that effectively promotes TPH degradation by a broad microbial consortium. Following promising greenhouse trials, field tests of PEP were performed over a period of three years at a Southern Ontario site (approximately 130 g kg(-1) TPH) used for land farming of refinery hydrocarbon waste for many years. The low molecular weight fractions (the Canadian Council of Ministers of the Environment (CCME) fractions 1 and 2) were removed through land farming and bioremediation; the high molecular weight, recalcitrant fractions (CCME fractions 3 and 4) remained at high levels in the soil. Using PEP, we substantially remediated fractions 3 and 4, and lowered TPH from 130 g kg(-1) to approximately 50 g kg(-1) over a three year period. The amount of plant growth and extent of oil remediation were consistently enhanced by PGPR.

  5. Inactivation of p27kip1 Promoted Nonspecific Inflammation by Enhancing Macrophage Proliferation in Islet Transplantation.

    PubMed

    Li, Yang; Ding, Xiaoming; Fan, Ping; Guo, Jian; Tian, Xiaohui; Feng, Xinshun; Zheng, Jin; Tian, Puxun; Ding, Chenguang; Xue, Wujun

    2016-11-01

    Islet transplantation suffers from low efficiency caused by nonspecific inflammation-induced graft loss after transplantation. This study reports increased islet loss and enhanced inflammatory response in p27-deficient mice (p27-/-) and proposes a possible mechanism. Compared with wild type, p27-/- mice showed more severe functional injury of islet, with increased serum levels of inflammatory cytokines IL-1 and TNF-α, inducing macrophage proliferation. Furthermore, the increased number, proapoptotic proteins, and nuclear factor-kappa b (NF-κB) phosphorylation status of the infiltrating macrophages were accompanied by increased TNF-α mRNA level of islet graft site in p27-/- mice. Moreover, in vitro, we found that macrophages were still activated and cocultured with islet and promoted islet loss even blocking the direct effect of TNF-α on islets. Malondialdehyde (MDA, an end product of lipid peroxidation) in islet and media were increased after cocultured with macrophages. p27 deficiency also increased macrophage proliferation and islet injury. Therefore, p27 inactivation promotes injury islet graft loss via the elevation of proliferation and inflammatory cytokines secretion in infiltrating macrophages which induced nonspecific inflammation independent of TNF-α/nuclear factor-kappa b pathway. This potentially represents a promising therapeutic target in improving islet graft survival.

  6. Plant growth-promoting actinobacteria: a new strategy for enhancing sustainable production and protection of grain legumes.

    PubMed

    Sathya, Arumugam; Vijayabharathi, Rajendran; Gopalakrishnan, Subramaniam

    2017-06-01

    Grain legumes are a cost-effective alternative for the animal protein in improving the diets of the poor in South-East Asia and Africa. Legumes, through symbiotic nitrogen fixation, meet a major part of their own N demand and partially benefit the following crops of the system by enriching soil. In realization of this sustainability advantage and to promote pulse production, United Nations had declared 2016 as the "International Year of pulses". Grain legumes are frequently subjected to both abiotic and biotic stresses resulting in severe yield losses. Global yields of legumes have been stagnant for the past five decades in spite of adopting various conventional and molecular breeding approaches. Furthermore, the increasing costs and negative effects of pesticides and fertilizers for crop production necessitate the use of biological options of crop production and protection. The use of plant growth-promoting (PGP) bacteria for improving soil and plant health has become one of the attractive strategies for developing sustainable agricultural systems due to their eco-friendliness, low production cost and minimizing consumption of non-renewable resources. This review emphasizes on how the PGP actinobacteria and their metabolites can be used effectively in enhancing the yield and controlling the pests and pathogens of grain legumes.

  7. Evolution of the Karyopherin-β Family of Nucleocytoplasmic Transport Factors; Ancient Origins and Continued Specialization

    PubMed Central

    O'Reilly, Amanda J.; Dacks, Joel B.; Field, Mark C.

    2011-01-01

    Background Macromolecular transport across the nuclear envelope (NE) is achieved through nuclear pore complexes (NPCs) and requires karyopherin-βs (KAP-βs), a family of soluble receptors, for recognition of embedded transport signals within cargo. We recently demonstrated, through proteomic analysis of trypanosomes, that NPC architecture is likely highly conserved across the Eukaryota, which in turn suggests conservation of the transport mechanisms. To determine if KAP-β diversity was similarly established early in eukaryotic evolution or if it was subsequently layered onto a conserved NPC, we chose to identify KAP-β sequences in a diverse range of eukaryotes and to investigate their evolutionary history. Results Thirty six predicted proteomes were scanned for candidate KAP-β family members. These resulting sequences were resolved into fifteen KAP-β subfamilies which, due to broad supergroup representation, were most likely represented in the last eukaryotic common ancestor (LECA). Candidate members of each KAP-β subfamily were found in all eukaryotic supergroups, except XPO6, which is absent from Archaeplastida. Phylogenetic reconstruction revealed the likely evolutionary relationships between these different subfamilies. Many species contain more than one representative of each KAP-β subfamily; many duplications are apparently taxon-specific but others result from duplications occurring earlier in eukaryotic history. Conclusions At least fifteen KAP-β subfamilies were established early in eukaryote evolution and likely before the LECA. In addition we identified expansions at multiple stages within eukaryote evolution, including a multicellular plant-specific KAP-β, together with frequent secondary losses. Taken with evidence for early establishment of NPC architecture, these data demonstrate that multiple pathways for nucleocytoplasmic transport were established prior to the radiation of modern eukaryotes but that selective pressure continues to sculpt

  8. Enhanced performance of the microalga Chlorella sorokiniana remotely induced by the plant growth-promoting bacteria Azospirillum brasilense and Bacillus pumilus

    PubMed Central

    Amavizca, Edgar; Bashan, Yoav; Ryu, Choong-Min; Farag, Mohamed A.; Bebout, Brad M.; de-Bashan, Luz E.

    2017-01-01

    Remote effects (occurring without physical contact) of two plant growth-promoting bacteria (PGPB) Azospirillum brasilense Cd and Bacilus pumilus ES4 on growth of the green microalga Chlorella sorokiniana UTEX 2714 were studied. The two PGPB remotely enhanced the growth of the microalga, up to six-fold, and its cell volume by about three-fold. In addition to phenotypic changes, both bacteria remotely induced increases in the amounts of total lipids, total carbohydrates, and chlorophyll a in the cells of the microalga, indicating an alteration of the microalga’s physiology. The two bacteria produced large amounts of volatile compounds, including CO2, and the known plant growth-promoting volatile 2,3-butanediol and acetoin. Several other volatiles having biological functions in other organisms, as well as numerous volatile compounds with undefined biological roles, were detected. Together, these bacteria-derived volatiles can positively affect growth and metabolic parameters in green microalgae without physical attachment of the bacteria to the microalgae. This is a new paradigm on how PGPB promote growth of microalgae which may serve to improve performance of Chlorella spp. for biotechnological applications. PMID:28145473

  9. Tissue kallikrein promotes cardiac neovascularization by enhancing endothelial progenitor cell functional capacity.

    PubMed

    Yao, Yuyu; Sheng, Zulong; Li, Yefei; Yan, Fengdi; Fu, Cong; Li, Yongjun; Ma, Genshan; Liu, Naifeng; Chao, Julie; Chao, Lee

    2012-08-01

    Tissue kallikrein (TK) has been demonstrated to improve neovasculogenesis after myocardial infarction (MI). In the present study, we examined the role and underlying mechanisms of TK in peripheral endothelial progenitor cell (EPC) function. Peripheral blood-derived mononuclear cells containing EPCs were isolated from rat. The in vitro effects of TK on EPC differentiation, apoptosis, migration, and vascular tube formation capacity were studied in the presence or absence of TK, kinin B(2) receptor antagonist (icatibant), and phosphatidylinositol-3 kinase inhibitor (LY294002). Apoptosis was evaluated by flow-cytometry analysis using Annexin V-FITC/PI staining, as well as western-blot analysis of Akt phosphorylation and cleaved caspase-3. Using an MI mouse model, we then examined the in vivo effects of human TK gene adenoviral vector (Ad.hTK) administration on the number of CD34(+)Flk-1(+) progenitors in the peripheral circulation, heart tissue, extent of vasculogenesis, and heart function. Administration of TK significantly increased the number of Dil-LDL/UEA-lectin double-positive early EPCs, as well as their migration and tube formation properties in vitro. Transduction of TK in cultured EPCs attenuated apoptosis induced by hypoxia and led to an increase in Akt phosphorylation and a decrease in cleaved caspase-3 levels. The beneficial effects of TK were blocked by pretreatment with icatibant and LY294002. The expression of recombinant human TK in the ischemic mouse heart significantly improved cardiac contractility and reduced infarct size 7 days after gene delivery. Compared with the Ad.Null group, Ad.hTK reduced mortality and preserved left ventricular function by increasing the number of CD34(+)Flk-1(+) EPCs and promoting the growth of capillaries and arterioles in the peri-infarct myocardium. These data provide direct evidence that TK promotes vessel growth by increasing the number of EPCs and enhancing their functional properties through the kinin B(2) receptor

  10. Loss of protein phosphatase 6 in mouse keratinocytes enhances K-rasG12D -driven tumor promotion.

    PubMed

    Kurosawa, Koreyuki; Inoue, Yui; Kakugawa, Yoichiro; Yamashita, Yoji; Kanazawa, Kosuke; Kishimoto, Kazuhiro; Nomura, Miyuki; Momoi, Yuki; Sato, Ikuro; Chiba, Natsuko; Suzuki, Mai; Ogoh, Honami; Yamada, Hidekazu; Miura, Koh; Watanabe, Toshio; Tanuma, Nobuhiro; Tachi, Masahiro; Shima, Hiroshi

    2018-05-14

    Here, we address the function of protein phosphatase 6 (PP6) loss on K-ras-initiated tumorigenesis in keratinocytes. To do so, we developed tamoxifen-inducible double mutant (K-ras G12D -expressing and Ppp6c-deficient) mice in which K-ras G12D expression is driven by the cytokeratin 14 (K14) promoter. Doubly-mutant mice showed early onset tumor formation in lip, nipples, external genitalia, anus and palms, and had to be sacrificed by three weeks after induction by tamoxifen, while comparably-treated K-ras G12D -expressing mice did not. HE-staining of lip tumors before euthanasia revealed that all were papillomas, some containing focal squamous cell carcinoma. Immunohistochemical analysis of lip of doubly-mutant versus K-ras G12D mice revealed that cell proliferation and cell size increased approximately two-fold relative to K-ras G12D -expressing mutants, and epidermal thickness of lip tissue greatly increased relative to that seen in K-ras G12D only mice. Moreover, AKT phosphorylation increased in K-ras G12D -expressing/Ppp6c-deficient cells, as did phosphorylation of the downstream effectors 4EBP1, S6, and GSK3, suggesting that protein synthesis and survival signals are enhanced in lip tissues of doubly-mutant mice. Finally, increased numbers of K14-positive cells were present in the suprabasal layer of doubly-mutant mice, indicating abnormal keratinocyte differentiation, and γH2AX-positive cells accumulated, indicating perturbed DNA repair. Taken together, Ppp6c deficiency enhances K-ras G12D -dependent tumor promotion. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

    PubMed

    Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

    2016-08-19

    Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

  12. DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ErbB signaling.

    PubMed

    Liao, Wen-Chieh; Liao, Chih-Kai; Tsai, You-Huan; Tseng, To-Jung; Chuang, Li-Ching; Lan, Chyn-Tair; Chang, Hung-Ming; Liu, Chiung-Hui

    2018-01-01

    Remodeling of the extracellular matrix (ECM) in the tumor microenvironment promotes glioma progression. Chondroitin sulfate (CS) proteoglycans appear in the ECM and on the cell surface, and can be catalyzed by dermatan sulfate epimerase to form chondroitin sulfate/dermatan sulfate (CS/DS) hybrid chains. Dermatan sulfate epimerase 1 (DSE) is overexpressed in many types of cancer, and CS/DS chains mediate several growth factor signals. However, the role of DSE in gliomas has never been explored. In the present study, we determined the expression of DSE in gliomas by consulting a public database and conducting immunohistochemistry on a tissue array. Our investigation revealed that DSE was upregulated in gliomas compared with normal brain tissue. Furthermore, high DSE expression was associated with advanced tumor grade and poor survival. We found high DSE expression in several glioblastoma cell lines, and DSE expression directly mediated DS chain formation in glioblastoma cells. Knockdown of DSE suppressed the proliferation, migration, and invasion of glioblastoma cells. In contrast, overexpression of DSE in GL261 cells enhanced these malignant phenotypes and in vivo tumor growth. Interestingly, we found that DSE selectively regulated heparin-binding EGF-like growth factor (HB-EGF)-induced signaling in glioblastoma cells. Inhibiting epidermal growth factor receptor (EGFR) and ErbB2 with afatinib suppressed DSE-enhanced malignant phenotypes, establishing the critical role of the ErbB pathway in regulating the effects of DSE expression. This evidence indicates that upregulation of DSE in gliomas contributes to malignant behavior in cancer cells. We provide novel insight into the significance of DS chains in ErbB signaling and glioma pathogenesis.

  13. Institutional barriers and strategies to health promotion: perspectives and experiences of Cape Verdean women health promoters.

    PubMed

    De Jesus, Maria

    2010-06-01

    Health promoters are critical resources in improving health care access and in providing culturally-responsive health education and interventions to members of medically underserved communities. Little is known about the barriers that impede their health-promoting practices and the strategies used to overcome these barriers. In-depth, semi-structured interviews were conducted with nine Cape Verdean women health promoters to examine their perspectives on barriers and strategies to health promotion. Findings revealed how their health promotion practice is influenced by a host of institutional barriers, including insufficient program funding, restrictive institutional policies, and a lack of culturally and linguistically appropriate health resources. Adaptive and resistant strategies used to counterbalance these barriers included forming supportive internal and external alliances, having a good mentor, and "making noise." A complete and effective model of health promotion must embrace not only individual-level factors, but also macro-level factors, thus emphasizing the need for institutional change to enhance health-promoting practices.

  14. Institutional Barriers and Strategies to Health Promotion: Perspectives and Experiences of Cape Verdean Women Health Promoters

    PubMed Central

    2015-01-01

    Background Health promoters are critical resources in improving health care access and in providing culturally-responsive health education and interventions to members of medically underserved communities. Little is known about the barriers that impede their health-promoting practices and the strategies used to overcome these barriers. Methods In-depth, semi-structured interviews were conducted with nine Cape Verdean women health promoters to examine their perspectives on barriers and strategies to health promotion. Results Findings revealed how their health promotion practice is influenced by a host of institutional barriers, including insufficient program funding, restrictive institutional policies, and a lack of culturally and linguistically appropriate health resources. Adaptive and resistant strategies used to counterbalance these barriers included forming supportive internal and external alliances, having a good mentor, and “making noise.” Discussion A complete and effective model of health promotion must embrace not only individual-level factors, but also macro-level factors, thus emphasizing the need for institutional change to enhance health-promoting practices. PMID:18307042

  15. Comparison of the Effectiveness of Two Forms of the Enhancing Relationships in School Communities Project for Promoting Cooperative Conflict Resolution Education in Australian Primary Schools

    ERIC Educational Resources Information Center

    Trinder, Margot; Wertheim, Eleanor H.; Freeman, Elizabeth; Sanson, Ann; Richardson, Shanel; Hunt, Sue

    2010-01-01

    This study evaluated the Enhancing Relationships in School Communities (ERIS) Project which aimed to promote constructive conflict resolution (CR) in Australian primary school communities through professional development for core teams of three-five staff (n = 33 teachers). Twelve schools were randomly assigned to a full intervention (FI) group or…

  16. Malaria prevention knowledge, attitudes, and practices (KAP) among international flying pilots and flight attendants of a US commercial airline.

    PubMed

    Selent, Monica; de Rochars, Valery M Beau; Stanek, Danielle; Bensyl, Diana; Martin, Barbara; Cohen, Nicole J; Kozarsky, Phyllis; Blackmore, Carina; Bell, Teal R; Marano, Nina; Arguin, Paul M

    2012-12-01

    In 2010, malaria caused approximately 216 million infections in people and 655,000 deaths. In the United States, imported malaria cases occur every year, primarily in returning travelers and immigrants from endemic countries. In 2010, five Plasmodium falciparum malaria cases occurred among crew members of one US commercial airline company (Airline A). This investigation aimed to assess the malaria prevention knowledge, attitudes, and practices (KAP) of Airline A crew members to provide information for potential interventions. The web link to a self-administered on-line survey was distributed by internal company communications to Airline A pilots and flight attendants (FA) eligible for international travel. The survey collected demographic information as well as occupation, work history, and malaria prevention education. Of approximately 7,000 nonrandomly selected crew members, 220 FA and 217 pilots completed the survey (6%). Respondents correctly identified antimalarial medication (91% FA, 95% pilots) and insect repellents (96% FA, 96% pilots) as effective preventive measures. While in malaria-intense destinations, few FA and less than half of pilots always took antimalarial medication (4% FA, 40% pilots) yet many often spent greater than 30 minutes outdoors after sundown (71% FA, 66% pilots). Less than half in both groups always used insect repellents (46% FA, 47% pilots). Many respondents were unaware of how to get antimalarial medications (52% FA, 30% pilots) and were concerned about their side effects (61% FA, 31% pilots). Overall, FA and pilots demonstrated good knowledge of malaria prevention, but many performed risky activities while practicing only some recommended malaria preventive measures. Malaria prevention education should focus on advance notification if traveling to a malaria-endemic area, how to easily obtain antimalarial medications, and the importance of practicing all recommended preventive measures. © 2012 International Society of Travel

  17. DNA methylation of a PLPP3 MIR transposon-based enhancer promotes an osteogenic program in calcific aortic valve disease.

    PubMed

    Mkannez, Ghada; Gagné-Ouellet, Valérie; Nsaibia, Mohamed Jalloul; Boulanger, Marie-Chloé; Rosa, Mickael; Argaud, Deborah; Hadji, Fayez; Gaudreault, Nathalie; Rhéaume, Gabrielle; Bouchard, Luigi; Bossé, Yohan; Mathieu, Patrick

    2018-05-02

    Calcific aortic valve disease (CAVD) is characterized by the osteogenic transition of valve interstitial cells (VICs). In CAVD, lysophosphatidic acid (LysoPA), a lipid mediator with potent osteogenic activity, is produced in the aortic valve (AV) and is degraded by membrane-associated phospholipid phosphatases (PLPPs). We thus hypothesized that a dysregulation of PLPPs could participate to the osteogenic reprograming of VICs during CAVD. The expression of PLPPs was examined in human control and mineralized AVs and comprehensive analyses were performed to document the gene regulation and impact of PLPPs on the osteogenic transition of VICs. We found that PLPP3 gene and enzymatic activity were downregulated in mineralized AVs. Multidimensional gene profiling in 21 human AVs showed that expression of PLPP3 was inversely correlated with the level of 5-methylcytosine (5meC) located in an intronic mammalian interspersed repeat element (MIR). Bisulfite pyrosequencing in a larger series of 67 AVs confirmed that 5meC in intron 1 was increased by 2.2-fold in CAVD compared to control AVs. In isolated cells, epigenome editing with CRISPR-Cas9 system containing a deficient Cas9 fused with DNA methyltransferase (dCas9-DNMT) was used to increase 5meC in the intronic enhancer and showed that it reduced significantly the expression of PLPP3. Knockdown experiments showed that lower expression of PLPP3 in VICs promotes an osteogenic program. DNA methylation of a MIR-based enhancer downregulates the expression of PLPP3 and promotes the mineralization of the AV.

  18. Melatonin enhances thermotolerance by promoting cellular protein protection in tomato plants.

    PubMed

    Xu, Wen; Cai, Shu-Yu; Zhang, Yun; Wang, Yu; Ahammed, Golam Jalal; Xia, Xiao-Jian; Shi, Kai; Zhou, Yan-Hong; Yu, Jing-Quan; Reiter, Russel J; Zhou, Jie

    2016-11-01

    Melatonin is a pleiotropic signaling molecule that provides physiological protection against diverse environmental stresses in plants. Nonetheless, the mechanisms for melatonin-mediated thermotolerance remain largely unknown. Here, we report that endogenous melatonin levels increased with a rise in ambient temperature and that peaked at 40°C. Foliar pretreatment with an optimal dose of melatonin (10 μmol/L) or the overexpression of N-acetylserotonin methyltransferase (ASMT) gene effectively ameliorated heat-induced photoinhibition and electrolyte leakage in tomato plants. Both exogenous melatonin treatment and endogenous melatonin manipulation by overexpression of ASMT decreased the levels of insoluble and ubiquitinated proteins, but enhanced the expression of heat-shock proteins (HSPs) to refold denatured and unfolded proteins under heat stress. Meanwhile, melatonin also induced expression of several ATG genes and formation of autophagosomes to degrade aggregated proteins under the same stress. Proteomic profile analyses revealed that protein aggregates for a large number of biological processes accumulated in wild-type plants. However, exogenous melatonin treatment or overexpression of ASMT reduced the accumulation of aggregated proteins. Aggregation responsive proteins such as HSP70 and Rubisco activase were preferentially accumulated and ubiquitinated in wild-type plants under heat stress, while melatonin mitigated heat stress-induced accumulation and ubiquitination of aggregated proteins. These results suggest that melatonin promotes cellular protein protection through induction of HSPs and autophagy to refold or degrade denatured proteins under heat stress in tomato plants. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Palynofloral associations before and after the Permian-Triassic mass extinction, Kap Stosch, East Greenland

    NASA Astrophysics Data System (ADS)

    Schneebeli-Hermann, Elke; Hochuli, Peter A.; Bucher, Hugo

    2017-08-01

    The Permian-Triassic boundary (PTB) interval is known to document a major biodiversity crisis in the history of life. It is generally accepted that this crisis had a significant impact on marine invertebrates. The consequences for terrestrial ecosystems are still controversially discussed. Based on palynological analysis we present a high time resolution microfloral succession of the expanded Late Permian (Wuchiapingian)-Early Triassic (Dienerian) section from Kap Stosch, East Greenland. The quantitative distribution of palynomorphs (range charts and relative abundance data) allows for the differentiation of six distinct palynofloral associations. Ammonoids and conodonts provide independent age control for these assemblages. The Wuchiapingian association I, documented from the Ravnefjeld Formation, shows a typical Late Permian assemblage dominated by bisaccate and monosaccate pollen grains and Vittatina spp. It is separated from association II, present in the basal part of the Wordie Creek Formation, by an important hiatus. This association of Changhsingian or earliest Griesbachian age is characterised by the common occurrence of Ephedripites spp. and reduced abundance and diversity of Vittatina spp. Association III, dated as Griesbachian by the presence of ammonoids, is marked by high relative abundances of taeniate bisaccate pollen grains and high spore diversity. A distinct floral break occurs between the gymnosperm dominated Permian and Griesbachian floras and the lycopsid spore dominated Dienerian associations IV-VI. Ammonoid occurrences verify a Dienerian age for the latter associations. Association V is marked by the absence of non-taeniate bisaccate, striate monosaccate pollen grains, and Vittatina spp. Aratrisporites spp. a typical Triassic lycopsid spore occur consistently from this level onwards. Association VI is characterised by highest lycopsid spore abundances. Cluster analysis demonstrates that Griesbachian assemblages (associations II?-III) are

  20. Bacillus pumilus ES4: candidate plant growth-promoting bacterium to enhance establishment of plants in mine tailings

    PubMed Central

    de-Bashan, Luz E.; Hernandez, Juan-Pablo; Bashan, Yoav; Maier, Raina

    2014-01-01

    Three plant growth-promoting bacteria (PGPB; Bacillus pumilus ES4, B. pumilus RIZO1, and Azospirillum brasilense Cd) were tested for their ability to enhance plant growth and development of the native Sonoran Desert shrub quailbush (Atriplex lentiformis) and for their effect on the native bacterial community in moderately acidic, high-metal content (AHMT) and in neutral, low metal content natural tailings (NLMT) in controlled greenhouse experiments. Inoculation of quailbush with all three PGPB significantly enhanced plant growth parameters, such as germination, root length, dry weight of shoots and roots, and root/shoot ratio in both types of tailings. The effect of inoculation on the indigenous bacterial community by the most successful PGPB Bacillus pumilus ES4 was evaluated by denaturating gradient gel electrophoresis (PCR-DGGE) fingerprinting and root colonization was followed by specific fluorescent in situ hybridization (FISH). Inoculation with this strain significantly changed the bacterial community over a period of 60 days. FISH analysis showed that the preferred site of colonization was the root tips and root elongation area. This study shows that inoculation of native perennial plants with PGPB can be used for developing technologies for phytostabilizing mine tailings. PMID:25009362

  1. Self-Enhancement of Hepatitis C Virus Replication by Promotion of Specific Sphingolipid Biosynthesis

    PubMed Central

    Hirata, Yuichi; Ikeda, Kazutaka; Sudoh, Masayuki; Tokunaga, Yuko; Suzuki, Akemi; Weng, Leiyun; Ohta, Masatoshi; Tobita, Yoshimi; Okano, Ken; Ozeki, Kazuhisa; Kawasaki, Kenichi; Tsukuda, Takuo; Katsume, Asao; Aoki, Yuko; Umehara, Takuya; Sekiguchi, Satoshi; Toyoda, Tetsuya; Shimotohno, Kunitada; Soga, Tomoyoshi; Nishijima, Masahiro; Taguchi, Ryo; Kohara, Michinori

    2012-01-01

    Lipids are key components in the viral life cycle that affect host-pathogen interactions. In this study, we investigated the effect of HCV infection on sphingolipid metabolism, especially on endogenous SM levels, and the relationship between HCV replication and endogenous SM molecular species. We demonstrated that HCV induces the expression of the genes (SGMS1 and 2) encoding human SM synthases 1 and 2. We observed associated increases of both total and individual sphingolipid molecular species, as assessed in human hepatocytes and in the detergent-resistant membrane (DRM) fraction in which HCV replicates. SGMS1 expression had a correlation with HCV replication. Inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase (SPT) inhibitor, NA808, suppressed HCV-RNA production while also interfering with sphingolipid metabolism. Further, we identified the SM molecular species that comprise the DRM fraction and demonstrated that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication. Our results reveal that HCV alters sphingolipid metabolism to promote viral replication, providing new insights into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle. PMID:22916015

  2. Self-enhancement of hepatitis C virus replication by promotion of specific sphingolipid biosynthesis.

    PubMed

    Hirata, Yuichi; Ikeda, Kazutaka; Sudoh, Masayuki; Tokunaga, Yuko; Suzuki, Akemi; Weng, Leiyun; Ohta, Masatoshi; Tobita, Yoshimi; Okano, Ken; Ozeki, Kazuhisa; Kawasaki, Kenichi; Tsukuda, Takuo; Katsume, Asao; Aoki, Yuko; Umehara, Takuya; Sekiguchi, Satoshi; Toyoda, Tetsuya; Shimotohno, Kunitada; Soga, Tomoyoshi; Nishijima, Masahiro; Taguchi, Ryo; Kohara, Michinori

    2012-01-01

    Lipids are key components in the viral life cycle that affect host-pathogen interactions. In this study, we investigated the effect of HCV infection on sphingolipid metabolism, especially on endogenous SM levels, and the relationship between HCV replication and endogenous SM molecular species. We demonstrated that HCV induces the expression of the genes (SGMS1 and 2) encoding human SM synthases 1 and 2. We observed associated increases of both total and individual sphingolipid molecular species, as assessed in human hepatocytes and in the detergent-resistant membrane (DRM) fraction in which HCV replicates. SGMS1 expression had a correlation with HCV replication. Inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase (SPT) inhibitor, NA808, suppressed HCV-RNA production while also interfering with sphingolipid metabolism. Further, we identified the SM molecular species that comprise the DRM fraction and demonstrated that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication. Our results reveal that HCV alters sphingolipid metabolism to promote viral replication, providing new insights into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle.

  3. Transposon integration enhances expression of stress response genes.

    PubMed

    Feng, Gang; Leem, Young-Eun; Levin, Henry L

    2013-01-01

    Transposable elements possess specific patterns of integration. The biological impact of these integration profiles is not well understood. Tf1, a long-terminal repeat retrotransposon in Schizosaccharomyces pombe, integrates into promoters with a preference for the promoters of stress response genes. To determine the biological significance of Tf1 integration, we took advantage of saturated maps of insertion activity and studied how integration at hot spots affected the expression of the adjacent genes. Our study revealed that Tf1 integration did not reduce gene expression. Importantly, the insertions activated the expression of 6 of 32 genes tested. We found that Tf1 increased gene expression by inserting enhancer activity. Interestingly, the enhancer activity of Tf1 could be limited by Abp1, a host surveillance factor that sequesters transposon sequences into structures containing histone deacetylases. We found the Tf1 promoter was activated by heat treatment and, remarkably, only genes that themselves were induced by heat could be activated by Tf1 integration, suggesting a synergy of Tf1 enhancer sequence with the stress response elements of target promoters. We propose that the integration preference of Tf1 for the promoters of stress response genes and the ability of Tf1 to enhance the expression of these genes co-evolved to promote the survival of cells under stress.

  4. Transposon integration enhances expression of stress response genes

    PubMed Central

    Feng, Gang; Leem, Young-Eun; Levin, Henry L.

    2013-01-01

    Transposable elements possess specific patterns of integration. The biological impact of these integration profiles is not well understood. Tf1, a long-terminal repeat retrotransposon in Schizosaccharomyces pombe, integrates into promoters with a preference for the promoters of stress response genes. To determine the biological significance of Tf1 integration, we took advantage of saturated maps of insertion activity and studied how integration at hot spots affected the expression of the adjacent genes. Our study revealed that Tf1 integration did not reduce gene expression. Importantly, the insertions activated the expression of 6 of 32 genes tested. We found that Tf1 increased gene expression by inserting enhancer activity. Interestingly, the enhancer activity of Tf1 could be limited by Abp1, a host surveillance factor that sequesters transposon sequences into structures containing histone deacetylases. We found the Tf1 promoter was activated by heat treatment and, remarkably, only genes that themselves were induced by heat could be activated by Tf1 integration, suggesting a synergy of Tf1 enhancer sequence with the stress response elements of target promoters. We propose that the integration preference of Tf1 for the promoters of stress response genes and the ability of Tf1 to enhance the expression of these genes co-evolved to promote the survival of cells under stress. PMID:23193295

  5. Transcription regulation by distal enhancers: who's in the loop?

    PubMed

    Stadhouders, Ralph; van den Heuvel, Anita; Kolovos, Petros; Jorna, Ruud; Leslie, Kris; Grosveld, Frank; Soler, Eric

    2012-01-01

    Genome-wide chromatin profiling efforts have shown that enhancers are often located at large distances from gene promoters within the noncoding genome. Whereas enhancers can stimulate transcription initiation by communicating with promoters via chromatin looping mechanisms, we propose that enhancers may also stimulate transcription elongation by physical interactions with intronic elements. We review here recent findings derived from the study of the hematopoietic system.

  6. Health promotion health center project.

    PubMed

    Lee, Tae Wha; Lee, Chung Yul; Kim, Hee Soon; Ham, Ok Kyung

    2007-01-01

    As part of a major government support for health promotion, a health promotion health center (HPHC) project was launched at the national level in Korea. The purpose of the study was to describe this 2-year HPHC project within the framework of the Ottawa Charter for Health Promotion and to evaluate the preliminary outcomes of the community residents. A cross-sectional design was used. A total of 2,261 community residents participated in the survey, with 792 in HPHC sites and 1,469 in non-HPHC sites. The instrument included questions on participants' demographic characteristics, awareness, participation, health behavior (smoking, exercise, meat consumption, and blood pressure checkup), and satisfaction with the health promotion programs. The 5 main health promotion strategies of the Ottawa Charter were evident in the HPHCs. HPHCs were successful in enhancing awareness, participation, and satisfaction through their health promotion programs, although health behaviors were not significantly different between the 2 groups, except exercise. Ottawa Charter strategies embedded within the practice of the community health promotion activities were effective in increasing the short-term outcomes (awareness, participation, and satisfaction with health promotion programs), which is a promising finding for the development of health promotion behaviors in the future.

  7. IL-15 Enhances Activation and IGF-1 Production of Dendritic Epidermal T Cells to Promote Wound Healing in Diabetic Mice.

    PubMed

    Wang, Yangping; Bai, Yang; Li, Yashu; Liang, Guangping; Jiang, Yufeng; Liu, Zhongyang; Liu, Meixi; Hao, Jianlei; Zhang, Xiaorong; Hu, Xiaohong; Chen, Jian; Wang, Rupeng; Yin, Zhinan; Wu, Jun; Luo, Gaoxing; He, Weifeng

    2017-01-01

    Altered homeostasis and dysfunction of dendritic epidermal T cells (DETCs) contribute to abnormal diabetic wound healing. IL-15 plays important roles in survival and activation of T lymphocytes. Recently, reduction of epidermal IL-15 has been reported as an important mechanism for abnormal DETC homeostasis in streptozotocin -induced diabetic animals. However, the role of IL-15 in impaired diabetic wound healing remains unknown. Here, we found that, through rescuing the insufficient activation of DETCs, IL-15 increased IGF-1 production by DETCs and thereby promoted diabetic skin wound repair. Regulation of IGF-1 in DETCs by IL-15 was partly dependent on the mTOR pathway. In addition, expression of IL-15 and IGF-1 were positively correlated in wounded epidermis. Together, our data indicated that IL-15 enhanced IGF-1 production by DETCs to promoting diabetic wound repair, suggesting IL-15 as a potential therapeutic agent for managing diabetic wound healing.

  8. Epidermal Cadm1 expression promotes autoimmune alopecia via enhanced T cell adhesion and cytotoxicity.

    PubMed

    Giangreco, Adam; Hoste, Esther; Takai, Yoshimi; Rosewell, Ian; Watt, Fiona M

    2012-02-01

    Autoimmune alopecia is characterized by an extensive epidermal T cell infiltrate that mediates hair follicle destruction. We have investigated the role of cell adhesion molecule 1 (Cadm1; Necl2) in this disease. Cadm1 is expressed by epidermal cells and mediates heterotypic adhesion to lymphocytes expressing class 1-restricted T cell-associated molecule (CRTAM). Using a murine autoimmune alopecia model, we observed an increase in early-activated cytotoxic (CD8-restricted, CRTAM-expressing) T cells, which preferentially associated with hair follicle keratinocytes expressing Cadm1. Coculture with Cadm1-transduced MHC-matched APCs stimulated alopecic lymph node cells to release IL-2 and IFN-γ. Overexpression of Cadm1 in cultured human keratinocytes did not promote cytokine secretion, but led to increased adhesion of alopecic cytotoxic T cells and enhanced T cell cytotoxicity in an MHC-independent manner. Epidermal overexpression of Cadm1 in transgenic mice led to increased autoimmune alopecia susceptibility relative to nontransgenic littermate controls. Our findings reveal that Cadm1 expression in the hair follicle plays a role in autoimmune alopecia.

  9. Enhancing mutual accountability to promote quality, safety, and nurses' recovery from substance use disorders.

    PubMed

    Horton-Deutsch, Sara; McNelis, Angela; O'Haver Day, Pamela

    2011-12-01

    Year after year, the public view nurses at the top of the list of the most honest and ethical professionals. However, nurses impaired with substance use disorders are subject to the tremendous stigma associated with addiction. Successful treatment programs protect public safety and support nurses' recovery and reentry into practice. The purpose of this study was to explore the nurses' experience in an alternative-to-discipline treatment program, the Indiana State Nurses Assistance Program (ISNAP), administered by the Indiana State Nurses Association. For this study, focus groups were used to capture nurses' experience with the ISNAP, a nurse-monitoring program for substance use. Three focus groups were conducted with 25 participants. The overall theme of the focus groups was enhancing mutual accountability. Nurses' views were grouped into four major areas of importance, including accountability, clear expectations, addressing individual concerns, and educating others about substance use disorders. Nurses described how each of these factors supported and impeded their recovery. The findings support the need for further education and research on how to best promote and sustain recovery. 2011 Elsevier Inc. All rights reserved.

  10. [Intervention effect assessment of response to heatwave in communities of four cities, China].

    PubMed

    Li, Y H; Wang, Q Q; Lan, L; Luo, S Q; Fang, D K; He, J Y; Yang, C; Ding, Z; Cheng, Y B; Li, C C; Wu, Z; Yu, S Y; Jin, Y L

    2018-04-06

    Objective: To evaluate the intervention effects of response to heatwave in communities of four cities, China. Methods: Baseline survey on heatwave and climate change related knowledge, attitude and practice (KAP) was conducted in the pilot communities in Harbin, Nanjing, Shenzhen and Chongqing, using face-to-face questionnaire interview in November, 2011 to November, 2013. Finally, 1 604 residents were interviewed. Intervention measures were implemented in summers of 2013 and 2014, including delivering early warning information of heatwave health risk and launching health education and promotion. The second survey was conducted in same communities using the same questionnaire and sampling method as baseline survey in November, 2014, and 1 640 residents were interviewed. The Chi-square test was used to compare the demographic characteristics and KAP of community residents between before and after intervention, and the factors that affected the intervention effect were selected by logistic multiple stepwise regression model. Results: The age of the residents interviewed before and after intervention was (46.4 ± 15.5) years and (45.0 ± 15.9) years, respectively. Overall, the residents' awareness rates of heatwave before and after intervention were 70.5% (1 131/1 604) and 82.9% (1 359/1 640) (χ 2 =69.40, P< 0.001). The rate of residents who had wished to receive early warning information increased 6.3% (χ 2 =41.11, P< 0.001), which reached 94.6% (1 551/1 604) after intervention from 88.3% (1 416/1 604) in baseline survey. Both heatwave health risk early warning and health education had big impacts to residents. There were 92.7% (1 105 residents) among the 1 192 residents who had received the early warning information arrange work and rest time according to the early warning information and 93.0% (1 231 residents) among the 1 323 residents who knew about health education activities being conducted in community thought that the community health education activities

  11. Effectiveness of Educational Programs on Nutritional Behavior in Addicts Referring to Baharan Hospital, Zahedan (Eastern of IR Iran)

    PubMed Central

    Karajibani, Mansour; Montazerifar, Farzaneh; Dashipour, Alireza; Lashkaripour, Kobra; Abery, Maryam; Salari, Sajedeh

    2014-01-01

    Background: There are many factors which affect nutritional status of addicted such as lack o f knowledge, incorrect attitude toward modification of food pattern, and careless to food intake. Objectives: The aim of this study was to determine the effectiveness of educational program on nutritional behavior in addicts referring to Baharan hospital in Zahedan. Patients and Methods: Thirty-six addict patients were selected randomly. After recording general demographic data of patients, nutritional behaviors were determined. To determine the effectiveness of nutritional educational program, pre and post-tests were performed. Evaluation of nutritional behavior was determined as poor, fair and satisfactory levels. Statically analysis was performed by SPSS software. Results: Most addict patients had a medium level of education. Improvement in knowledge, attitude and practice (KAP) of patients after intervention was observed as follows; decreasing KAP in poor level (2.8% vs. 30.6%), (3% vs. 50%), (25% vs. 80.6%), respectively; also, increasing KAP in fair level (7% vs. 55.6 %), (15% vs. 15%), (19% vs. 7%), respectively and increasing KAP in satisfactory levels (77.8% vs. 13.8%), (50% vs. 8.3%), and (22.2% vs. 0%), respectively (P < 0.0001). There was a significant difference regarding the grade of KAP in patients based on gender, marital status, and education level after education (P < 0.0001). Conclusions: This study showed that nutritional KAP was improved in addicts. After intervention, there was a significant difference in the score of knowledge, attitude, and practice scores in patients in the current study. KAP was improved in patients after intervention including; decreased KAP in poor level and increased KAP in fair and satisfactory levels. This finding indicates that addict patients would like to modify their life style. PMID:25032162

  12. Health promotion and the freedom of the individual.

    PubMed

    Taylor, Gary; Hawley, Helen

    2006-03-01

    This article considers the extent to which health promotion strategies pose a threat to individual freedom. It begins by taking a look at health promotion strategies and at the historical development of health promotion in Britain. A theoretical context is then developed in which Berlin's distinction between negative and positive liberty is used alongside the ideas of John Stuart Mill, Charles Taylor and T.H. Green to discuss the politics of health promotion and to identify the implications of conflicting perspectives on freedom. The final section looks at current health promotion policy in Britain and beyond and argues that, if freedom is seen in terms of empowerment, health promotion can enhance individual freedom.

  13. Down-regulation of Transducin-Like Enhancer of Split protein 4 in hepatocellular carcinoma promotes cell proliferation and epithelial-Mesenchymal-Transition

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

    Wu, Xiao-cai; Xiao, Cui-cui; Li, Hua

    Background: Transducin-Like Enhancer of Split protein 4 (TLE4) has been reported to be involved in some subsets of acute myeloid leukemia and colorectal cancer. In the present study, we aimed to explore the role of TLE4 in tumorigenesis and cancer progression in hepatocellular carcinoma (HCC). Methods: The expression pattern of TLE4 in HCC was determined by Western-blot and qRT-PCR, gain-of-function and loss-of-function was used to explore the biological role of TLE4 in HCC cells. A xenograft model was established to confirm its effects on proliferation. Results: The protein expression levels of TLE4 were significantly down-regulated in HCC tissues compared tomore » matched adjacent normal liver tissues. In vitro, down-regulation of TLE4 in Huh7 or SMMC-7721 promoted cell proliferation and ectopical expression of TLE4 in Hep3B or Bel-7404 suppressed cell proliferation. In addition, the cell colony formation ability was enhanced after down-regulation of TLE4 expression in Huh-7 but suppressed after over-expression in Hep3B. Furthermore, down-regulation of TLE4 increased the cell invasion ability, as well as increased the expression level of Vimentin and decreased that of E-cadherin, indicating a phenotype of epithelial-mesenchymal transition (EMT) in HCC cells. On the contrary, ectopical expression of TLE4 in HCC cells decreased the cell invasion ability and inhibited EMT. In vivo, compared to control group, xenograft tumor volumes were significantly decreased in TLE4 overexpression group. Conclusions: These results demonstrated that TLE4 might play important regulatory roles in cellular proliferation and EMT process in HCC. - Highlights: • TLE4 is significantly down-regulated in HCC samples. • Down regulated of TLE4 in HCC cells promotes cell proliferation. • Down regulated of TLE4 in HCC cells promotes epithelial-to-mesenchymal transition.« less

  14. High level activity of the mouse CCAAT/enhancer binding protein (C/EBP alpha) gene promoter involves autoregulation and several ubiquitous transcription factors.

    PubMed Central

    Legraverend, C; Antonson, P; Flodby, P; Xanthopoulos, K G

    1993-01-01

    The promoter region of the mouse CCAAT-Enhancer Binding Protein (C/EBP alpha) gene is capable of directing high levels of expression of reporter constructs in various cell lines, albeit even in cells that do not express their endogenous C/EBP alpha gene. To understand the molecular mechanisms underlying this ubiquitous expression, we have characterized the promoter region of the mouse C/EBP alpha gene by a variety of in vitro and in vivo methods. We show that three sites related in sequence to USF, BTE and C/EBP binding sites and present in promoter region -350/+3, are recognized by proteins from rat liver nuclear extracts. The sequence of the C/EBP alpha promoter that includes the USF binding site is also capable of forming stable complexes with purified Myc+Max heterodimers and mutation of this site drastically reduces transcription of C/EBP alpha promoter luciferase constructs both in liver and non liver cell lines. In addition, we identify three novel protein-binding sites two of which display similarity to NF-1 and a NF kappa B binding sites. The region located between nucleotides -197 and -178 forms several heat-stable complexes with liver nuclear proteins in vitro which are recognized mainly by antibodies specific for C/EBP alpha. Furthermore, transient expression of C/EBP alpha and to a lesser extent C/EBP beta expression vectors, results in transactivation of a cotransfected C/EBP alpha promoter-luciferase reporter construct. These experiments support the notion that the C/EBP alpha gene is regulated by C/EBP alpha but other C/EBP-related proteins may also be involved. Images PMID:8493090

  15. Low-protein diet promotes sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

    PubMed

    Iishi, H; Tatsuta, M; Baba, M; Hirasawa, R; Sakai, N; Yano, H; Uehara, H; Nakaizumi, A

    1999-07-01

    Sodium chloride (NaCl) initiates and promotes experimental carcinogenesis in rats. We recently found that a high-protein diet attenuates NaCl-enhanced gastric carcinogenesis in Wistar rats. To investigate the effect of a purified low-protein diet on NaCl-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Wistar rats, rats were fed a purified diet with an equalized caloric content containing 1% or 2% NaCl and 25% casein (normal-protein diet) or 10% casein (low-protein diet) after oral treatment with MNNG for 25 weeks. In week 52, neither 1% nor 2% NaCl had a significant effect on gastric carcinogenesis in rats fed a normal-protein diet. However, oral administration of 2%, but not 1%, NaCl significantly increased the incidence of gastric cancers in rats fed a low-protein diet. Oral administration of 2% NaCl also significantly increased the bromodeoxyuridine (BrdU)-labeling index and the ornithine decarboxylase (ODC) activity and decreased apoptosis of gastric cancers in rats fed a low-protein diet. However, 2% NaCl had no significant effect on these three parameters in rats fed a normal-protein diet. These findings indicate that a low-protein diet enhances the effect of NaCl in gastric carcinogenesis and that this enhancement may be mediated by increased cell proliferation and reduced apoptosis of gastric cancers.

  16. Promotional Video Production in a Foreign Language Course.

    ERIC Educational Resources Information Center

    Fukushima, Tatsuya

    2002-01-01

    Discusses a technology-based project as a requirement for a traditional intermediate Japanese course at the University of Arkansas in which students worked in a small group to produce the university's promotional video in the target language, thus enhancing their Japanese language skills and promoting the program to the public. (Author/VWL)

  17. A future task for health-promotion research: Integration of health promotion and sustainable development.

    PubMed

    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.

  18. Enhanced immune response to a dual-promoter anti-caries DNA vaccine orally delivered by attenuated Salmonella typhimurium.

    PubMed

    Jiang, Hao; Hu, Yijun; Yang, Mei; Liu, Hao; Jiang, Guangshui

    2017-05-01

    The strength of immune responses induced by DNA vaccine is closely associated with the expression level of cloned antigens available to the antigen presenting cells (APCs). To acquire a larger and more persistent amount of antigen, a dual-promoter, which could double the target antigen output through its expression both in prokaryotic and eukaryotic cells, was employed in the constructed anti-caries DNA vaccine with attenuated Salmonella as mucosal delivery vector in this study. Here, both CMV and nirB promoters were included in the plasmid that harbors the genes encoding the functional epitopes of two virulence factors of S. mutans, i.e. the saliva-binding region (SBR) of PAc and the glucan-binding region (GBR) of glucosyltransferase-I (GTF-I). Delivered by attenuated Salmonella Typhimurium strain SL3261, the anti-caries vaccine was administered intragastrointestinally to BALB/c mice for evaluation of the effectiveness of this immune regime. Specific anti-SBR and anti-GBR antibodies were detected in the serum and saliva of experimental animals by week 3 after immunization. These immune responses were further enhanced after a booster vaccination at week 16. However, in mice receiving Salmonella expressing SBR and GBR under the control of nirB alone these antibody responses were significantly (P<0.01) lower. The serum IgG subclass profiles suggested a Th1/Th2-mixed but Th2 biased immune response to the cloned antigens, which was further confirmed by a significant increase in the Th1 (IFN-γ, IL-2) and Th2 (IL-4, IL-10) cytokines in splenocytes of immunized mice upon stimulation with SBR or GBR. To further determine the protective efficacy of these responses, a challenge test with S. mutans strain UA159 was performed in mice after the second immunization. Following challenge, mice immunized with Salmonella expressing SBR and GBR under the control of the CMV-nirB promoter showed a significant (P<0.01) reduction in the number of S. mutans in the dental plaque compared

  19. Guanabenz promotes neuronal survival via enhancement of ATF4 and parkin expression in models of Parkinson disease.

    PubMed

    Sun, Xiaotian; Aimé, Pascaline; Dai, David; Ramalingam, Nagendran; Crary, John F; Burke, Robert E; Greene, Lloyd A; Levy, Oren A

    2018-05-01

    Reduced function of parkin appears to be a central pathogenic event in Parkinson disease (PD). Increasing parkin levels enhances survival in models of PD-related neuronal death and is a promising therapeutic objective. Previously, we demonstrated that the transcription factor ATF4 promotes survival in response to PD-mimetic stressors by maintaining parkin levels. ATF4 translation is up-regulated by phosphorylation of the translation initiation factor eIF2α. The small molecule guanabenz enhances eIF2α phosphorylation by blocking the function of GADD34, a regulatory protein that promotes eIF2α dephosphorylation. We tested the hypothesis that guanabenz, by inhibiting GADD34 and consequently increasing eIF2α phosphorylation and elevating ATF4, would improve survival in models of PD by up-regulating parkin. We found that GADD34 is strongly induced by 6-OHDA, and that GADD34 localization is dramatically altered in dopaminergic substantia nigra neurons in PD cases. We further demonstrated that guanabenz attenuates 6-hydroxydopamine (6-OHDA) induced cell death of differentiated PC12 cells and primary ventral midbrain dopaminergic neurons in culture, and of dopaminergic neurons in the substantia nigra of mice. In culture models, guanabenz also increases eIF2α phosphorylation and ATF4 and parkin levels in response to 6-OHDA. Furthermore, if either ATF4 or parkin is silenced, then the protective effect of guanabenz is lost. We also found similar results in a distinct model of neuronal death: primary cultures of cortical neurons treated with the topoisomerase I inhibitor camptothecin, in which guanabenz limited camptothecin-induced neuronal death in an ATF4- and parkin-dependent manner. In summary, our data suggest that guanabenz and other GADD34 inhibitors could be used as therapeutic agents to boost parkin levels and thereby slow neurodegeneration in PD and other neurodegenerative conditions. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. 7SK-BAF axis controls pervasive transcription at enhancers

    PubMed Central

    Flynn, Ryan A.; Do, Brian T.; Rubin, Adam J.; Calo, Eliezer; Lee, Byron; Kuchelmeister, Hannes; Rale, Michael; Chu, Ci; Kool, Eric T.; Wysocka, Joanna; Khavari, Paul A.

    2016-01-01

    RNA functions at enhancers remain mysterious. Here we show that the 7SK small nuclear RNA (snRNA) inhibits enhancer transcription by modulating nucleosome position. 7SK occupies enhancers and super enhancers genome-wide in mouse and human cells, and 7SK is required to limit eRNA initiation and synthesis in a manner distinct from promoter pausing. Clustered elements at super enhancers uniquely require 7SK to prevent convergent transcription and DNA damage signaling. 7SK physically interacts with the BAF chromatin remodeling complex, recruit BAF to enhancers, and inhibits enhancer transcription by modulating chromatin structure. In turn, 7SK occupancy at enhancers coincides with Brd4 and is exquisitely sensitive to the bromodomain inhibitor JQ1. Thus, 7SK employs distinct mechanisms to counteract diverse consequences of pervasive transcription that distinguish super enhancers, enhancers, and promoters. PMID:26878240

  1. R521C and R521H mutations in FUS result in weak binding with Karyopherinβ2 leading to Amyotrophic lateral sclerosis: a molecular docking and dynamics study.

    PubMed

    Swetha, Rayapadi G; Ramaiah, Sudha; Anbarasu, Anand

    2017-08-01

    Fused in sarcoma (FUS) gene encodes the RNA binding protein FUS. This gene is mapped to chromosome 16p11.2. The FUS protein binds with karyopherineβ2 (Kapβ2) through its proline/tyrosine nuclear localization signal (PY-NLS) that helps in the localization of FUS protein within the nucleus. Arginine residue in 521 position (R521) of PY-NLS plays a vital role in the binding of FUS protein with Kapβ2. Mutations in this position (R521C and R521H) are the most predominant mutations associated with amyotrophic lateral sclerosis (ALS). However, the mechanism by which these mutations lead to ALS is poorly understood. We examined the binding behaviour of the mutants FUS (R521C) and FUS (R521H) with Kapβ2 through protein-protein docking and molecular dynamics simulation. The binding patterns of mutants were compared with the binding behaviour of wild FUS-Kapβ2. Our results suggest that these mutants have relatively weak binding affinity with Kapβ2 when compared with wild FUS-Kapβ2 as indicated by the lesser number of interactions found between the mutant FUS and Kapβ2. Hence, these mutations weakens the binding and this results in the cytoplasmic mislocalization of mutant FUS; and thereby it increases the severity of ALS.

  2. Structural and energetic basis of ALS-causing mutations in the atypical proline-tyrosine nuclear localization signal of the Fused in Sarcoma protein (FUS)

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

    Zhang, Zi Chao; Chook, Yuh Min

    Mutations in the proline/tyrosine–nuclear localization signal (PY-NLS) of the Fused in Sarcoma protein (FUS) cause amyotrophic lateral sclerosis (ALS). Here we report the crystal structure of the FUS PY-NLS bound to its nuclear import receptor Karyopherinβ2 (Kapβ2; also known as Transportin). The FUS PY-NLS occupies the structurally invariant C-terminal arch of Kapβ2, tracing a path similar to that of other characterized PY-NLSs. Unlike other PY-NLSs, which generally bind Kapβ2 in fully extended conformations, the FUS peptide is atypical as its central portion forms a 2.5-turn α-helix. The Kapβ2-binding epitopes of the FUS PY-NLS consist of an N-terminal PGKM hydrophobic motif,more » a central arginine-rich α-helix, and a C-terminal PY motif. ALS mutations are found almost exclusively within these epitopes. Each ALS mutation site makes multiple contacts with Kapβ2 and mutations of these residues decrease binding affinities for Kapβ2 (K D for wild-type FUS PY-NLS is 9.5 nM) up to ninefold. Thermodynamic analyses of ALS mutations in the FUS PY-NLS show that the weakening of FUS-Kapβ2 binding affinity, the degree of cytoplasmic mislocalization, and ALS disease severity are correlated.« less

  3. Factors promoting sustainable work in women with fibromyalgia.

    PubMed

    Palstam, Annie; Gard, Gunvor; Mannerkorpi, Kaisa

    2013-09-01

    To examine and describe the factors promoting sustainable work in women with fibromyalgia (FM). A qualitative interview study. Twenty-seven gainfully employed women with FM participated in five focus group interviews. Their median age was 52 years, ranging from 33 to 62. The interviews were recorded, transcribed verbatim and analysed by qualitative latent content analysis. Four categories were identified describing factors promoting sustainable work: the meaning of work and individual strategies were individual promoters while a favourable work environment and social support outside work were environmental promoters. The meaning of work included individual meaning and social meaning. The individual strategies included handling symptoms, the work day and long-term work life. A favourable work environment included the physical and psychosocial work environment. Social support outside work included societal and private social supports. Promoting factors for work were identified, involving individual and environmental factors. These working women with FM had developed advanced well-functioning strategies to enhance their work ability. The development of such strategies should be supported by health-care professionals as well as employers to promote sustainable work in women with FM. Work disability is a common consequence of fibromyalgia (FM). Working women with FM appear to have developed advanced well-functioning individual strategies to enhance their work ability. The development of individual strategies should be supported by health-care professionals as well as employers to promote sustainable work and health in women with FM.

  4. Influence of promoter/enhancer region haplotypes on MGMT transcriptional regulation: a potential biomarker for human sensitivity to alkylating agents.

    PubMed

    Xu, Meixiang; Nekhayeva, Ilona; Cross, Courtney E; Rondelli, Catherine M; Wickliffe, Jeffrey K; Abdel-Rahman, Sherif Z

    2014-03-01

    The O6-methylguanine-DNA methyltransferase gene (MGMT) encodes the direct reversal DNA repair protein that removes alkyl adducts from the O6 position of guanine. Several single-nucleotide polymorphisms (SNPs) exist in the MGMT promoter/enhancer (P/E) region. However, the haplotype structure encompassing these SNPs and their functional/biological significance are currently unknown. We hypothesized that MGMT P/E haplotypes, rather than individual SNPs, alter MGMT transcription and can thus alter human sensitivity to alkylating agents. To identify the haplotype structure encompassing the MGMT P/E region SNPs, we sequenced 104 DNA samples from healthy individuals and inferred the haplotypes using the data generated. We identified eight SNPs in this region, namely T7C (rs180989103), T135G (rs1711646), G290A (rs61859810), C485A (rs1625649), C575A (rs113813075), G666A (rs34180180), C777A (rs34138162) and C1099T (rs16906252). Phylogenetics and Sequence Evolution analysis predicted 21 potential haplotypes that encompass these SNPs ranging in frequencies from 0.000048 to 0.39. Of these, 10 were identified in our study population as 20 paired haplotype combinations. To determine the functional significance of these haplotypes, luciferase reporter constructs representing these haplotypes were transfected into glioblastoma cells and their effect on MGMT promoter activity was determined. Compared with the most common (reference) haplotype 1, seven haplotypes significantly upregulated MGMT promoter activity (18-119% increase; P < 0.05), six significantly downregulated MGMT promoter activity (29-97% decrease; P < 0.05) and one haplotype had no effect. Mechanistic studies conducted support the conclusion that MGMT P/E haplotypes, rather than individual SNPs, differentially regulate MGMT transcription and could thus play a significant role in human sensitivity to environmental and therapeutic alkylating agents.

  5. HNP-3 enhanced the antimicrobial activity of CIP by promoting ATP efflux from P. aeruginosa cells.

    PubMed

    Wang, Hao; Dong, Birong; Lou, Li

    2011-04-01

    To establish a novel strategy of P. aeruginosa control, we acquired recombination HNP-3 by gene recombination. Then we examined HNP-3 bio-activities and the influences of antimicrobial peptide on the efflux of ATP. Consequently, we obtained target protein with a molecular mass of 3,000 D consistent with the Anticipation. FIC index of Ciprofloxacin added HNP-3 was less than 0.5 and HNP3 synergistically cooperated with CIP to suppress P. aeruginosa colony formation revealed that there was significant synergy. ATP efflux was however up-regulated by low concentrations of HNP-3, although CIP did not exert any influence on ATP efflux. Conclusively, recombination protein HNP-3 displayed antimicrobial and synergic effects. HNP-3 enhanced the antimicrobial activity of CIP by promoting ATP efflux from P. aeruginosa cells and decreasing efflux of the drugs, which could have useful clinical applications.

  6. Lactosucrose attenuates intestinal inflammation by promoting Th2 cytokine production and enhancing CD86 expression in colitic rats.

    PubMed

    Zhou, Yan; Ruan, Zheng; Zhou, Xiaoli; Huang, Xiaoliu; Li, Hua; Wang, Ling; Zhang, Cui; Deng, Zeyuan; Wu, Guoyao; Yin, Yulong

    2015-01-01

    Some oligosaccharides have immunoregulatory and anti-inflammatory functions in the intestine. This study investigated the immunoregulatory effect of lactosucrose (LS) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitic rats. Alkaline phosphatase activity was increased but myeloperoxidase activity was decreased in the LS-TNBS group, as compared with the TNBS group (colitis rats without receiving LS). LS supplementation stimulated IL-4 and IL-10 production, while up-regulating CD86 expression in dendritic cells. LS supplementation reduced the ratio of CD80/CD86 and the ratio of IFN-γ/IL-4 compared to the TNBS group. Moreover, IFN-γ was significantly correlated with CD80 (r = 0.764, p < 0.01), whereas IL-4 was significantly correlated with CD86 (r = 0.489, p < 0.05). These results indicated that LS attenuated colitis by promoting the production of Th2-type cytokines and rebalancing the ratio of Th1/Th2 and that enhanced IL-4 production is correlated with enhanced CD86 expression in the gut. Therefore, LS is a functional food for patients with inflammatory bowel disease.

  7. Enhancing Rain Garden Design to Promote Nitrate Removal via Denitrification

    EPA Science Inventory

    Recommendations for rain garden media design typically specify high sand content and low organic matter content to promote infiltration and avoid excessive ponding. This design is effective at infiltrating stormwater and removing solids, heavy metals, phosphorus, and some specie...

  8. Tumor-derived exosomes promote tumor self-seeding in hepatocellular carcinoma by transferring miRNA-25-5p to enhance cell motility.

    PubMed

    Liu, Hao; Chen, Wei; Zhi, Xiao; Chen, En-Jiang; Wei, Tao; Zhang, Jian; Shen, Jian; Hu, Li-Qiang; Zhao, Bin; Feng, Xin-Hua; Bai, Xue-Li; Liang, Ting-Bo

    2018-05-22

    Tumor self-seeding occurs when circulating malignant cells reinfiltrate the original tumor. The process may breed more aggressive tumor cells, which may contribute to cancer progression. In this study, we observed tumor self-seeding in mouse xenograft models of hepatocellular carcinoma (HCC) for the first time. We confirmed that circulating tumor cell uptake of tumor-derived exosomes, which are increasingly recognized as key instigators of cancer progression by facilitating cell-cell communication, promoted tumor self-seeding by enhancing the invasive and migration capability of recipient HCC cells. Horizontal transfer of exosomal microRNA-25-5p to anoikis-resistant HCC cells significantly enhanced their migratory and invasive abilities, whereas inhibiting microRNA-25-5p alleviated these effects. Our experiments delineate an exosome-based novel pathway employed by functional microRNA from the original tumor cells that can influence the biological fate of circulating tumor cells.

  9. Fibroblast-derived CXCL12/SDF-1α promotes CXCL6 secretion and co-operatively enhances metastatic potential through the PI3K/Akt/mTOR pathway in colon cancer

    PubMed Central

    Ma, Jia-Chi; Sun, Xiao-Wen; Su, He; Chen, Quan; Guo, Tian-Kang; Li, Yuan; Chen, Xiao-Chang; Guo, Jin; Gong, Zhen-Qiang; Zhao, Xiao-Dan; Qi, Jian-Bo

    2017-01-01

    AIM To investigate the underlying mechanism by which CXCL12 and CXCL6 influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells. METHODS Western blotting was used to detect the expression of CXCL12 and CXCL6 in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and CXCL6 on proliferation and invasion of colon cancer cells and human umbilical vein endothelial cells (HUVECs) were determined by enzyme-linked immunosorbent assay, and proliferation and invasion assays. The angiogenesis of HUVECs through interaction with cancer cells and stromal cells was examined by angiogenesis assay. We eventually investigated activation of PI3K/Akt/mTOR signaling by CXCL12 involved in the metastatic process of colon cancer. RESULTS CXCL12 was expressed in DLD-1 cancer cells and fibroblasts. The secretion level of CXCL6 by colon cancer cells and HUVECs were significantly promoted by fibroblasts derived from CXCL12. CXCL6 and CXCL2 could significantly enhance HUVEC proliferation and migration (P < 0.01). CXCL6 and CXCL2 enhanced angiogenesis by HUVECs when cultured with fibroblast cells and colon cancer cells (P < 0.01). CXCL12 also enhanced the invasion of colon cancer cells. Stromal cell-derived CXCL12 promoted the secretion level of CXCL6 and co-operatively promoted metastasis of colon carcinoma through activation of the PI3K/Akt/mTOR pathway. CONCLUSION Fibroblast-derived CXCL12 enhanced the CXCL6 secretion of colon cancer cells, and both CXCL12 and CXCL6 co-operatively regulated the metastasis via the PI3K/Akt/mTOR signaling pathway. Blocking this pathway may be a potential anti-metastatic therapeutic target for patients with colon cancer. PMID:28811711

  10. [Health knowledge, health promoting behavior and factors influencing health promoting behavior of north korean defectors in South Korea].

    PubMed

    Choe, Myoung Ae; Yi, Myungsun; Choi, Jung An; Shin, Gisoo

    2012-10-01

    The purpose of this study was to identify health knowledge, health promoting behavior and factors influencing health promoting behavior of North Korean defectors in South Korea. Participants in this study were 410 North Korean defectors, over 20 years of age residing in Seoul. They were recruited by snowball sampling. Data were collected from April to June, 2010. Health knowledge, health promoting behavior, self-efficacy, perceived barriers to health promoting behavior and social support were measured by structured questionnaires, and perceived physical and mental health status were measured by one item with 10-point numeric rating scale. The data were analyzed using t-test, ANOVA, and multiple regression. Health knowledge, health promoting behavior, and perceived barriers to health promoting behavior were moderate while self-efficacy and social support were high. Factors influencing health promoting behavior of the participants were found to be self-efficacy, social support and perceived barrier to health promoting behavior. The results of this study indicate that nursing intervention programs enhancing self-efficacy, social support and reducing perceived barriers to health promoting behavior need to be developed for North Korean defectors in South Korea.

  11. Interest Matters: The Importance of Promoting Interest in Education.

    PubMed

    Harackiewicz, Judith M; Smith, Jessi L; Priniski, Stacy J

    2016-10-01

    Interest is a powerful motivational process that energizes learning, guides academic and career trajectories, and is essential to academic success. Interest is both a psychological state of attention and affect toward a particular object or topic, and an enduring predisposition to reengage over time. Integrating these two definitions, the four-phase model of interest development guides interventions that promote interest and capitalize on existing interests. Four interest-enhancing interventions seem useful: attention-getting settings, contexts evoking prior individual interest, problem-based learning, and enhancing utility value. Promoting interest can contribute to a more engaged, motivated, learning experience for students.

  12. ABCB5 promotes melanoma metastasis through enhancing NF-κB p65 protein stability.

    PubMed

    Wang, Shenghao; Tang, Li; Lin, Junyu; Shen, Zhongliang; Yao, Yikun; Wang, Wei; Tao, Shuai; Gu, Chenjian; Ma, Jie; Xie, Youhua; Liu, Yanfeng

    2017-10-07

    Melanoma is the most aggressive type of skin cancer. Melanoma has an extremely poor prognosis because of its high potential for vascular invasion, metastasis and recurrence. The mechanism of melanoma metastasis is not well understood. ATP-binding cassette sub-family B member 5 (ABCB5) plays a key role in melanoma growth. However, it is uncertain what function ABCB5 may exert in melanoma metastasis. In this report, we for the first time demonstrate ABCB5 as a crucial factor that promotes melanoma metastasis. ABCB5 positive (ABCB5 + ) malignant melanoma initiating cells (MMICs) display a higher metastatic potential compared with ABCB5 negative (ABCB5 - ) melanoma subpopulation. Knockdown of ABCB5 expression reduces melanoma cell migration and invasion in vitro and melanoma pulmonary metastasis in tumor xenograft mice. ABCB5 and NF-κB p65 expression levels are positively correlated in both melanoma tissues and cell lines. Consequently, ABCB5 activates the NF-κB pathway by inhibiting p65 ubiquitination to enhance p65 protein stability. Our finding highlights ABCB5 as a novel pro-metastasis factor and provides a potential therapeutic target for melanoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Occupational Hazards Education for Nursing Staff through Web-Based Learning

    PubMed Central

    Tung, Chen-Yin; Chang, Chia-Chen; Ming, Jin-Lain; Chao, Keh-Ping

    2014-01-01

    This study aims to explore the efficiency of using online education as an intervention measure to prevent occupational hazards in a clinical nursing setting. The subjects were 320 female nursing staff from two hospitals in Taiwan. The questionnaire results indicated that the subjects primarily experienced human factor occupational hazards, as well as psychological and social hazards. Specifically, 73.1% and 69.8% of the subjects suffered from poor sleep quality and low back pain, respectively. After web-based learning, the experimental group had higher post-test scores than the control group in terms of knowledge, attitudes, and practices (KAP). However, there was only a significant difference (p < 0.05) in their knowledge about the prevention of occupational hazards. It is suggested that an online discussion may enhance nursing staff’s participation in web-based learning, and further facilitate their comments on negative factors. The findings can highly promote nursing staff’s attitudes and practices toward preventing occupational hazards through web-based learning. PMID:25514154

  14. N-myc downstream-regulated gene 1 promotes oxaliplatin-triggered apoptosis in colorectal cancer cells via enhancing the ubiquitination of Bcl-2.

    PubMed

    Yang, Xiao; Zhu, Fan; Yu, Chaoran; Lu, Jiaoyang; Zhang, Luyang; Lv, Yanfeng; Sun, Jing; Zheng, Minhua

    2017-07-18

    N-myc downstream-regulated gene1 (NDRG1) has been identified as a potent tumor suppressor gene. The molecular mechanisms of anti-tumor activity of NDRG1 involve its suppressive effects on a variety of tumorigenic signaling pathways. The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. We first collected the clinical data of locally advanced rectal cancer (LARC) patients receiving oxaliplatin-based neoadjuvant chemotherapy in our medical center. Correlation analysis revealed that NDRG1 positively associated with the downstaging rates and prognosis of patients. Then, the effects of over-expression and depletion of NDRG1 gene on apoptosis of colorectal cancer were tested in vitro and in vivo. NDRG1 over-expression promoted apoptosis in colorectal cancer cells whereas depletion of NDRG1 resulted in resistance to oxaliplatin treatment. Furthermore, we observed that Bcl-2, a major anti-apoptotic protein, was regulated by NDRG1 at post-transcriptional level. By binding Protein kinase Cα (PKCα), a classical regulating factor of Bcl-2, NDRG1 enhanced the ubiquitination and degradation of Bcl-2, thus promoting apoptosis in CRC cells. In addition, NDRG1 inhibited tumor growth and promoted apoptosis in mouse xenograft model. In conclusion,NDRG1 promotes oxaliplatin-triggered apoptosis in colorectal cancer. Therefore, colorectal cancer patients can be stratified by the expression level of NDRG1. NDRG1-positive patients may benefit from oxaliplatin-containing chemotherapy regimens whereas those with negative NDRG1 expression should avoid the usage of this cytotoxic drug.

  15. MO-FG-CAMPUS-IeP1-04: Kerma Area Product Calculation for Non-Uniform X-Ray Fields Using a Skin Dose Tracking System

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

    Vijayan, S; Xiong, Z; Rudin, S

    Purpose: The functionality of the Dose-Tracking System (DTS) has been expanded to include the calculation of the Kerma-Area Product (KAP) for non-uniform x-ray fields such as result from the use of compensation filters during fluoroscopic procedures Methods: The DTS calculates skin dose during fluoroscopic interventions and provides a color-coded dose map on a patient-graphic model. The KAP is the integral of air kerma over the x-ray field and is usually measured with a transmission-ionization chamber that intercepts the entire x-ray beam. The DTS has been modified to determine KAP when there are beam non-uniformities that can be modeled. For example,more » the DTS includes models of the three compensation filters with tapered edges located in the collimator assembly of the Toshiba Infinix fluoroscopic C-Arm and can track their movement. To determine the air kerma after the filters, DTS includes transmission factors for the compensation filters as a function of kVp and beam filtration. A virtual KAP dosimeter is simulated in the DTS by an array of graphic vertices; the air kerma at each vertex is corrected by the field non-uniformity, which in this case is the attenuation factor for those rays which pass through the filter. The products of individual vertex air-kerma values for all vertices within the beam times the effective-area-per-vertex are summed for each x-ray pulse to yield the KAP per pulse and the cumulative KAP for the procedure is then calculated. Results: The KAP values estimated by DTS with the compensation filter inserted into the x-ray field agree within ± 6% with the values displayed on the fluoroscopy unit monitor, which are measured with a transmission chamber. Conclusion: The DTS can account for field non-uniformities such as result from the use of compensation filters in calculating KAP and can obviate the need for a KAP transmission ionization chamber. Partial support from NIH Grant R01-EB002873 and Toshiba Medical Systems Corp.« less

  16. Correlation Between Expression of Recombinant Proteins and Abundance of H3K4Me3 on the Enhancer of Human Cytomegalovirus Major Immediate-Early Promoter.

    PubMed

    Soo, Benjamin P C; Tay, Julian; Ng, Shirelle; Ho, Steven C L; Yang, Yuansheng; Chao, Sheng-Hao

    2017-08-01

    Role of epigenetic regulation in the control of gene expression is well established. The impact of several epigenetic mechanisms, such as DNA methylation and histone acetylation, on recombinant protein production in mammalian cells has been investigated recently. Here we investigate the correlation between the selected epigenetic markers and five trastuzumab biosimilar-producing Chinese hamster ovary (CHO) cell lines in which the expression of trastuzumab is driven by human cytomegalovirus (HCMV) major immediate-early (MIE) promoter. We chose the producing clones in which transcription was the determinative step for the production of recombinant trastuzumab. We found that the abundance of trimethylation of histone 3 at lysine 4 (H3K4Me3) on the enhancer of HCMV MIE promoter correlated well with the relative titers of recombinant trastuzumab among the clones. Such close correlation was not observed between the recombinant protein and other epigenetic markers examined in our study. Our results demonstrate that the HCMV MIE enhancer-bound H3K4Me3 epigenetic marker may be used as the epigenetic indicator to predict the relative production of recombinant proteins between the producing CHO cell lines.

  17. Time-bound promotions in Indian medical institutes: a mirage?

    PubMed

    Sukhlecha, Anupama

    2016-01-01

    Incentives, pay hikes and timely promotions enhance the job performance of an employee. In medical institutes, too, satisfied teachers would train students in a better way leading to better equipped doctors and ultimately, greater patient satisfaction. A study in Malaysia links high levels of satisfaction of employees with good salary, promotions, and incentives.

  18. Overexpression of a MADS-box gene from birch (Betula platyphylla) promotes flowering and enhances chloroplast development in transgenic tobacco.

    PubMed

    Qu, Guan-Zheng; Zheng, Tangchun; Liu, Guifeng; Wang, Wenjie; Zang, Lina; Liu, Huanzhen; Yang, Chuanping

    2013-01-01

    In this study, a MADS-box gene (BpMADS), which is an ortholog of AP1 from Arabidopsis, was isolated from birch (Betula platyphylla). Transgenic Arabidopsis containing a BpMADS promoter::GUS construct was produced, which exhibited strong GUS staining in sepal tissues. Ectopic expression of BpMADS significantly enhanced the flowering of tobacco (35S::BpMADS). In addition, the chloroplasts of transgenic tobacco exhibited much higher growth and division rates, as well rates of photosynthesis, than wild-type. A grafting experiment demonstrated that the flowering time of the scion was not affected by stock that overexpressed BpMADS. In addition, the overexpression of BpMADS resulted in the upregulation of some flowering-related genes in tobacco.

  19. Nurses and teachers: partnerships for green health promotion.

    PubMed

    Sendall, Marguerite C; Lidstone, John; Fleming, Marylou; Domocol, Michelle

    2013-07-01

    The term green health promotion is given to health promotion underpinned by the principles of ecological health and sustainability. Green health promotion is supported philosophically by global health promotion documents such as the 1986 Ottawa Charter for Health Promotion and the ecological public health movement. Green health promotion in schools means the practice, the principles of ecological health, and sustainability. A literature review revealed a paucity of publications about green health promotion in schools. Literature about nurses and health promotion in schools is generally found in nursing publications. Literature about ecological sustainability in schools is mostly found in teaching publications. This article explores the nexus between nursing and health promotion, and teachers and ecological sustainability. Collaborative partnerships between health and education do not capitalize on programs such as Health Promoting Schools and the School Based Youth Health Nurse Program in Queensland, Australia. The authors consider how collaborative partnerships between health and education in schools can work toward green health promotion. Nursing's approach to health promotion and education's approach to ecological sustainability need to be aligned to enhance green health promotion in schools. © 2013, American School Health Association.

  20. Engineering Promoter Architecture in Oleaginous Yeast Yarrowia lipolytica.

    PubMed

    Shabbir Hussain, Murtaza; Gambill, Lauren; Smith, Spencer; Blenner, Mark A

    2016-03-18

    Eukaryotic promoters have a complex architecture to control both the strength and timing of gene transcription spanning up to thousands of bases from the initiation site. This complexity makes rational fine-tuning of promoters in fungi difficult to predict; however, this very same complexity enables multiple possible strategies for engineering promoter strength. Here, we studied promoter architecture in the oleaginous yeast, Yarrowia lipolytica. While recent studies have focused on upstream activating sequences, we systematically examined various components common in fungal promoters. Here, we examine several promoter components including upstream activating sequences, proximal promoter sequences, core promoters, and the TATA box in autonomously replicating expression plasmids and integrated into the genome. Our findings show that promoter strength can be fine-tuned through the engineering of the TATA box sequence, core promoter, and upstream activating sequences. Additionally, we identified a previously unreported oleic acid responsive transcription enhancement in the XPR2 upstream activating sequences, which illustrates the complexity of fungal promoters. The promoters engineered here provide new genetic tools for metabolic engineering in Y. lipolytica and provide promoter engineering strategies that may be useful in engineering other non-model fungal systems.

  1. Gender-transformative health promotion for women: a framework for action

    PubMed Central

    Pederson, Ann; Greaves, Lorraine; Poole, Nancy

    2015-01-01

    Gender inequity is a pervasive global challenge to health equity. Health promotion, as a field, has paid only limited attention to gender inequity to date, but could be an active agent of change if gender equity became an explicit goal of health promotion research, policy and programmes. As an aspect of gendered health systems, health promotion interventions may maintain, exacerbate or reduce gender-related health inequities, depending upon the degree and quality of gender-responsiveness within the programme or policy. This article introduces a framework for gender-transformative health promotion that builds on understanding gender as a determinant of health and outlines a continuum of actions to address gender and health. Gender-transformative health promotion interventions could play a significant role in improving the lives of millions of girls and women worldwide. Gender-related principles of action are identified that extend the core principles of health promotion but reflect the significance of attending to gender in the development and use of evidence, engagement of stakeholders and selection of interventions. We illustrate the framework with examples from a range of women's health promotion activities, including cardiovascular disease prevention, tobacco control, and alcohol use. The literature suggests that gender-responsiveness will enhance the acceptance, relevance and effectiveness of health promotion interventions. By moving beyond responsiveness to transformation, gender-transformative health promotion could enhance both health and social outcomes for large numbers of women and men, girls and boys. PMID:25231058

  2. [Interactions of 1A2 insulator with promoter of hsp 70 gene in Drosophila melanogaster].

    PubMed

    Chetverina, D A; Elizar'ev, P V; Georgiev, P G; Erokhin, M M

    2013-04-01

    Insulators are regulatory DNA elements that participate in the modulation of the interactions between enhancers and promoters. Depending on the situation, insulators can either stabilize or destroy the contacts between enhancers and promoters. A possible explanation for the activity of insulators is their ability to directly interact with gene promoters. In the present study, it was demonstrated that, in model systems, a 1A2 insulator could interact with the core sequence of an hsp70 promoter. In this case, the insulator protein CP190 is found on the hsp70 promoter, which depends on the presence of an insulator in the transgene. The data obtained are consistent with the model, which implies that direct contacts between insulators and promoters make a considerable contribution to the modulation of the interactions between insulators and promoters.

  3. TALE-mediated modulation of transcriptional enhancers in vivo.

    PubMed

    Crocker, Justin; Stern, David L

    2013-08-01

    We tested whether transcription activator-like effectors (TALEs) could mediate repression and activation of endogenous enhancers in the Drosophila genome. TALE repressors (TALERs) targeting each of the five even-skipped (eve) stripe enhancers generated repression specifically of the focal stripes. TALE activators (TALEAs) targeting the eve promoter or enhancers caused increased expression primarily in cells normally activated by the promoter or targeted enhancer, respectively. This effect supports the view that repression acts in a dominant fashion on transcriptional activators and that the activity state of an enhancer influences TALE binding or the ability of the VP16 domain to enhance transcription. In these assays, the Hairy repression domain did not exhibit previously described long-range transcriptional repression activity. The phenotypic effects of TALER and TALEA expression in larvae and adults are consistent with the observed modulations of eve expression. TALEs thus provide a novel tool for detection and functional modulation of transcriptional enhancers in their native genomic context.

  4. Ecto-domain phosphorylation promotes functional recovery from spinal cord injury

    PubMed Central

    Suehiro, Kenji; Nakamura, Yuka; Xu, Shuai; Uda, Youichi; Matsumura, Takafumi; Yamaguchi, Yoshiaki; Okamura, Hitoshi; Yamashita, Toshihide; Takei, Yoshinori

    2014-01-01

    Inhibition of Nogo-66 receptor (NgR) can promote recovery following spinal cord injury. The ecto-domain of NgR can be phosphorylated by protein kinase A (PKA), which blocks activation of the receptor. Here, we found that infusion of PKA plus ATP into the damaged spinal cord can promote recovery of locomotor function. While significant elongation of cortical-spinal axons was not detectable even in the rats showing enhanced recovery, neuronal precursor cells were observed in the region where PKA plus ATP were directly applied. NgR1 was expressed in neural stem/progenitor cells (NSPs) derived from the adult spinal cord. Both an NgR1 antagonist NEP1-40 and ecto-domain phosphorylation of NgR1 promote neuronal cell production of the NSPs, in vitro. Thus, inhibition of NgR1 in NSPs can promote neuronal cell production, which could contribute to the enhanced recovery of locomotor function following infusion of PKA and ATP. PMID:24826969

  5. Pim-3 enhances melanoma cell migration and invasion by promoting STAT3 phosphorylation.

    PubMed

    Liu, Jing; Qu, Xinyu; Shao, Liwei; Hu, Yuan; Yu, Xin; Lan, Peixiang; Guo, Qie; Han, Qiuju; Zhang, Jian; Zhang, Cai

    2018-03-04

    Melanoma is the deadliest form of commonly encountered skin cancer, and has fast propagating and highly invasive characteristics. Pim-3, a highly expressed oncogene in melanoma, is a highly conserved serine/threonine kinase with various biological activities, such as proliferation-accelerating and anti-apoptosis effects on cancer progression. However, whether Pim-3 regulates melanoma metastasis has not been determined. Here, we constructed a Pim-3-silencing short hairpin RNA (sh-Pim-3), a TLR7-stimulating ssRNA and a dual-function vector containing a sh-Pim-3 and a ssRNA, and transfected them into the B16F10 melanoma cell line to investigate the effects of Pim-3 on migration and invasion in melanoma. We found that sh-Pim-3 inhibited B16F10 cell migration and invasion in vitro. In a tumor-bearing mouse model, sh-Pim-3 significantly downregulated pulmonary metastasis of B16F10 melanoma cell in vivo. Mechanistically, sh-Pim-3 inhibited metastasis by regulating the expression of genes related to epithelial-mesenchymal transition (EMT). Further study revealed that by promoting the phosphorylation of STAT3 (signal transducer and activator of transcription 3), Pim-3 induced the expression of Slug, Snail, and ZEB1, which enhanced EMT-related changes and induced melanoma migration and invasion. Our study suggests that Pim-3 is a potential effective target for melanoma therapy.

  6. Dietary tributyrin, an HDAC inhibitor, promotes muscle growth through enhanced terminal differentiation of satellite cells.

    PubMed

    Murray, Robert L; Zhang, Wei; Iwaniuk, Marie; Grilli, Ester; Stahl, Chad H

    2018-05-01

    Muscle growth and repair rely on two main mechanisms - myonuclear accretion and subsequent protein accumulation. Altering the ability of muscle resident stem cells (satellite cells) to progress through their myogenic lineage can have a profound effect on lifetime muscle growth and repair. The use of the histone deacetylase (HDAC) inhibitor, butyrate, has had positive outcomes on the in vitro promotion of satellite cell myogenesis. In animal models, the use of butyrate has had promising results in treating myopathic conditions as well as improving growth efficiency, but the impact of dietary butyrate on satellite cells and muscle growth has not been elucidated. We investigated the impact of tributyrin, a butyrate prodrug, on satellite cell activity and muscle growth in a piglet model. Satellite cells from tributyrin-treated piglets had altered myogenic potential, and piglets receiving tributyrin had a ~40% increase in DNA:protein ratio after 21 days, indicating the potential for enhanced muscle growth. To assess muscle growth potential, piglets were supplemented tributyrin (0.5%) during either the neonatal phase (d1-d21) and/or the nursery phase (d21-d58) in a 2 × 2 factorial design. Piglets who received tributyrin during the neonatal phase had improved growth performance at the end of the study and had a ~10% larger loin eye area and muscle fiber cross-sectional area. Tributyrin treatment in the nursery phase alone did not have a significant effect on muscle growth or feed efficiency. These findings suggest that tributyrin is a potent promoter of muscle growth via altered satellite cell myogenesis. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  7. A novel lymphoid enhancer-binding factor 1-cytoglobin axis promotes extravasation of osteosarcoma cells into the lungs.

    PubMed

    Pongsuchart, Mongkol; Kuchimaru, Takahiro; Yonezawa, Sakiko; Tran, Diem Thi Phuong; Kha, Nguyen The; Hoang, Ngoc Thi Hong; Kadonosono, Tetsuya; Kizaka-Kondoh, Shinae

    2018-06-21

    Lung metastasis is a major cause of mortality in patients with osteosarcoma (OS). A better understanding of the molecular mechanism of OS lung metastasis may facilitate development of new therapeutic strategies to prevent the metastasis. We have established high- and low-metastatic sublines (LM8-H and LM8-L respectively) from Dunn OS cell line LM8 by using in vivo image-guided screening. Among the genes whose expression was significantly increased in LM8-H compared to LM8-L, the transcription factor lymphoid enhancer-binding factor 1 (LEF1) was identified as a factor that promotes LM8-H cell extravasation into the lungs. To identify downstream effectors of LEF1 that are involved in OS lung metastasis, 13 genes were selected based on the LM8 microarray data and genome-wide meta-analysis of a public database for OS patients. Among them, the cytoglobin (Cygb) gene was identified as a key effector in promoting OS extravasation into the lungs. CYGB overexpression increased the extravasation ability of LM8-L cells, whereas knocking out the Cygb gene in LM8-H cells reduced this ability. Our results uncovered a novel LEF1-CYGB axis in OS lung metastasis and may open a new avenue for developing therapeutic strategies to prevent OS lung metastasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. Incorporating performance improvement methods into a needs assessment: experience with a nutrition and exercise curriculum.

    PubMed

    Fluker, Shelly-Ann; Whalen, Ursula; Schneider, Jason; Cantey, Paul; Bussey-Jones, Jada; Brady, Donald; Doyle, Joyce P

    2010-09-01

    Clinical guidelines recommend that physicians counsel patients on diet and exercise; however, physician counseling remains suboptimal. To determine if incorporating performance improvement (PI) methodologies into a needs assessment for an internal medicine (IM) residency curriculum on nutrition and exercise counseling was feasible and enhanced our understanding of the curricular needs. One hundred and fifty-eight IM residents completed a questionnaire to assess their knowledge, attitudes, and practices (KAP) about nutrition and exercise counseling for hypertensive patients. Residents' baseline nutrition and exercise counseling rates were also obtained using chart abstraction. Fishbone diagrams were created by the residents to delineate perceived barriers to diet and exercise counseling. The KAP questionnaire was analyzed using descriptive statistics. Chart abstraction data was plotted on run charts and average counseling rates were calculated. Pareto charts were developed from the fishbone diagrams depicting the number of times each barrier was reported. Almost 90% of the residents reported counseling their hypertensive patients about diet and exercise more than 20% of the time on the KAP questionnaire. In contrast, chart abstraction revealed average counseling rates of 3% and 4% for nutrition and exercise, respectively. The KAP questionnaire exposed a clinical knowledge deficit, lack of familiarity with the national guidelines, and low self-efficacy. In contrast, the fishbone analysis highlighted patient apathy, patient co-morbidities, and time pressure as the major perceived barriers. We found that incorporating PI methods into a needs assessment for an IM residency curriculum on nutrition and exercise counseling for patients at risk of cardiovascular disease was feasible, provided additional information not obtained through other means, and provided the opportunity to pilot the use of PI techniques as an educational strategy and means of measuring outcomes. Our

  9. A dual switch controls bacterial enhancer-dependent transcription

    PubMed Central

    Wiesler, Simone C.; Burrows, Patricia C.; Buck, Martin

    2012-01-01

    Bacterial RNA polymerases (RNAPs) are targets for antibiotics. Myxopyronin binds to the RNAP switch regions to block structural rearrangements needed for formation of open promoter complexes. Bacterial RNAPs containing the major variant σ54 factor are activated by enhancer-binding proteins (bEBPs) and transcribe genes whose products are needed in pathogenicity and stress responses. We show that (i) enhancer-dependent RNAPs help Escherichia coli to survive in the presence of myxopyronin, (ii) enhancer-dependent RNAPs partially resist inhibition by myxopyronin and (iii) ATP hydrolysis catalysed by bEBPs is obligatory for functional interaction of the RNAP switch regions with the transcription start site. We demonstrate that enhancer-dependent promoters contain two barriers to full DNA opening, allowing tight regulation of transcription initiation. bEBPs engage in a dual switch to (i) allow propagation of nucleated DNA melting from an upstream DNA fork junction and (ii) complete the formation of the transcription bubble and downstream DNA fork junction at the RNA synthesis start site, resulting in switch region-dependent RNAP clamp closure and open promoter complex formation. PMID:22965125

  10. Leptin signaling enhances cell invasion and promotes the metastasis of human pancreatic cancer via increasing MMP-13 production.

    PubMed

    Fan, Yingchao; Gan, Yu; Shen, Yuling; Cai, Xiaojin; Song, Yanfang; Zhao, Fangyu; Yao, Ming; Gu, Jianren; Tu, Hong

    2015-06-30

    Emerging evidence has suggested that leptin, an adipokine related to energy homeostasis, plays a role in cancer growth and metastasis. However, its impact on pancreatic cancer is rarely studied. In this study, we found that leptin's functional receptor Ob-Rb was expressed in pancreatic cancer cell lines. Treatment with leptin enhanced the migration and invasion of pancreatic cancer cells but did not affect the proliferation of human pancreatic cancer cells. Leptin up-regulated the expression of matrix metalloproteinase-13 (MMP-13) via the JAK2/STAT3 signaling pathway. The overexpression of leptin was shown to significantly promote tumor growth and lymph node metastasis in a subcutaneous model and an orthotopic model of human pancreatic cancer, respectively. Furthermore, in human pancreatic cancer tissues, the expression of Ob-Rb was positively correlated with the MMP-13 level. The increased expression of either Ob-Rb or MMP-13 was significantly associated with lymph node metastasis and tended to be associated with the TNM stage in patients with pancreatic cancer. Our findings suggest that leptin enhances the invasion of pancreatic cancer through the increase in MMP-13 production, and targeting the leptin/MMP-13 axis could be an attractive therapeutic strategy for pancreatic cancer.

  11. Leptin signaling enhances cell invasion and promotes the metastasis of human pancreatic cancer via increasing MMP-13 production

    PubMed Central

    Shen, Yuling; Cai, Xiaojin; Song, Yanfang; Zhao, Fangyu; Yao, Ming; Gu, Jianren; Tu, Hong

    2015-01-01

    Emerging evidence has suggested that leptin, an adipokine related to energy homeostasis, plays a role in cancer growth and metastasis. However, its impact on pancreatic cancer is rarely studied. In this study, we found that leptin's functional receptor Ob-Rb was expressed in pancreatic cancer cell lines. Treatment with leptin enhanced the migration and invasion of pancreatic cancer cells but did not affect the proliferation of human pancreatic cancer cells. Leptin up-regulated the expression of matrix metalloproteinase-13 (MMP-13) via the JAK2/STAT3 signaling pathway. The overexpression of leptin was shown to significantly promote tumor growth and lymph node metastasis in a subcutaneous model and an orthotopic model of human pancreatic cancer, respectively. Furthermore, in human pancreatic cancer tissues, the expression of Ob-Rb was positively correlated with the MMP-13 level. The increased expression of either Ob-Rb or MMP-13 was significantly associated with lymph node metastasis and tended to be associated with the TNM stage in patients with pancreatic cancer. Our findings suggest that leptin enhances the invasion of pancreatic cancer through the increase in MMP-13 production, and targeting the leptin/MMP-13 axis could be an attractive therapeutic strategy for pancreatic cancer. PMID:25948792

  12. Elastic Network Model of a Nuclear Transport Complex

    NASA Astrophysics Data System (ADS)

    Ryan, Patrick; Liu, Wing K.; Lee, Dockjin; Seo, Sangjae; Kim, Young-Jin; Kim, Moon K.

    2010-05-01

    The structure of Kap95p was obtained from the Protein Data Bank (www.pdb.org) and analyzed RanGTP plays an important role in both nuclear protein import and export cycles. In the nucleus, RanGTP releases macromolecular cargoes from importins and conversely facilitates cargo binding to exportins. Although the crystal structure of the nuclear import complex formed by importin Kap95p and RanGTP was recently identified, its molecular mechanism still remains unclear. To understand the relationship between structure and function of a nuclear transport complex, a structure-based mechanical model of Kap95p:RanGTP complex is introduced. In this model, a protein structure is simply modeled as an elastic network in which a set of coarse-grained point masses are connected by linear springs representing biochemical interactions at atomic level. Harmonic normal mode analysis (NMA) and anharmonic elastic network interpolation (ENI) are performed to predict the modes of vibrations and a feasible pathway between locked and unlocked conformations of Kap95p, respectively. Simulation results imply that the binding of RanGTP to Kap95p induces the release of the cargo in the nucleus as well as prevents any new cargo from attaching to the Kap95p:RanGTP complex.

  13. URI Regulation of Androgen Receptor-Mediated Cell Growth

    DTIC Science & Technology

    2013-07-01

    R2TP/ Prefoldin -like cochaperone are involved in the cytoplasmic assembly of RNA polymerase II . Mol Cell 39, 912- 924. Chen, C.D., Welsbie, D.S., Tran...primers specific for the promoter of the chosen genes II . Test and titrate antibodies against the identified transcription factors in immuno...LNCaP prostate cancer cells ii . Measure KAP1 target gene expression changes (NOXA, p21, BAX) upon siRNA knockdown of ART-27 in LNCaP cells We

  14. Relapse Prevention in Health Promotion: Strategies and Long-Term Outcome.

    ERIC Educational Resources Information Center

    Gintner, Gary G.

    1988-01-01

    Reviews the efficacy of maintenance enhancement procedures to prevent relapse in smoking cessation, weight control, and exercise programs. Presents models of maintenance enhancement, reviews studies that have used relapse prevention strategies, and discusses ways of incorporating relapse prevention techniques into health promotion programs.…

  15. Enhancer Evolution across 20 Mammalian Species

    PubMed Central

    Villar, Diego; Berthelot, Camille; Aldridge, Sarah; Rayner, Tim F.; Lukk, Margus; Pignatelli, Miguel; Park, Thomas J.; Deaville, Robert; Erichsen, Jonathan T.; Jasinska, Anna J.; Turner, James M.A.; Bertelsen, Mads F.; Murchison, Elizabeth P.; Flicek, Paul; Odom, Duncan T.

    2015-01-01

    Summary The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution. PMID:25635462

  16. Rebamipide promotes healing of colonic ulceration through enhanced epithelial restitution.

    PubMed

    Takagi, Tomohisa; Naito, Yuji; Uchiyama, Kazuhiko; Okuda, Toshimitsu; Mizushima, Katsura; Suzuki, Takahiro; Handa, Osamu; Ishikawa, Takeshi; Yagi, Nobuaki; Kokura, Satoshi; Ichikawa, Hiroshi; Yoshikawa, Toshikazu

    2011-09-07

    To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro. Acute colitis was induced with trinitrobenzene sulfonic acid (TNBS) in male Wistar rats. Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration. The distal colon was removed to evaluate the various parameters of inflammation. Moreover, wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial (RIE) cells treated with rebamipide. Intracolonic administration of rebamipide accelerated TNBS-induced ulcer healing. Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide. The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signal-regulated kinase (ERK) and activation of Rho kinase. Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells, via ERK activation. Rebamipide might be a novel therapeutic approach for inflammatory bowel disease.

  17. Rebamipide promotes healing of colonic ulceration through enhanced epithelial restitution

    PubMed Central

    Takagi, Tomohisa; Naito, Yuji; Uchiyama, Kazuhiko; Okuda, Toshimitsu; Mizushima, Katsura; Suzuki, Takahiro; Handa, Osamu; Ishikawa, Takeshi; Yagi, Nobuaki; Kokura, Satoshi; Ichikawa, Hiroshi; Yoshikawa, Toshikazu

    2011-01-01

    AIM: To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro. METHODS: Acute colitis was induced with trinitrobenzene sulfonic acid (TNBS) in male Wistar rats. Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration. The distal colon was removed to evaluate the various parameters of inflammation. Moreover, wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial (RIE) cells treated with rebamipide. RESULTS: Intracolonic administration of rebamipide accelerated TNBS-induced ulcer healing. Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide. The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signal-regulated kinase (ERK) and activation of Rho kinase. CONCLUSION: Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells, via ERK activation. Rebamipide might be a novel therapeutic approach for inflammatory bowel disease. PMID:21987622

  18. Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies.

    PubMed

    Yadava, Koshika; Pattaroni, Céline; Sichelstiel, Anke K; Trompette, Aurélien; Gollwitzer, Eva S; Salami, Olawale; von Garnier, Christophe; Nicod, Laurent P; Marsland, Benjamin J

    2016-05-01

    Changes in the pulmonary microbiota are associated with progressive respiratory diseases including chronic obstructive pulmonary disease (COPD). Whether there is a causal relationship between these changes and disease progression remains unknown. To investigate the link between an altered microbiota and disease, we used a murine model of chronic lung inflammation that is characterized by key pathological features found in COPD and compared responses in specific pathogen-free (SPF) mice and mice depleted of microbiota by antibiotic treatment or devoid of a microbiota (axenic). Mice were challenged with LPS/elastase intranasally over 4 weeks, resulting in a chronically inflamed and damaged lung. The ensuing cellular infiltration, histological damage, and decline in lung function were quantified. Similar to human disease, the composition of the pulmonary microbiota was altered in diseased animals. We found that the microbiota richness and diversity were decreased in LPS/elastase-treated mice, with an increased representation of the genera Pseudomonas and Lactobacillus and a reduction in Prevotella. Moreover, the microbiota was implicated in disease development as mice depleted, or devoid, of microbiota exhibited an improvement in lung function, reduced inflammation, and lymphoid neogenesis. The absence of microbial cues markedly decreased the production of IL-17A, whereas intranasal transfer of fluid enriched with the pulmonary microbiota isolated from diseased mice enhanced IL-17A production in the lungs of antibiotic-treated or axenic recipients. Finally, in mice harboring a microbiota, neutralizing IL-17A dampened inflammation and restored lung function. Collectively, our data indicate that host-microbial cross-talk promotes inflammation and could underlie the chronicity of inflammatory lung diseases.

  19. Functional elements in the minimal promoter of the human proton-coupled folate transporter

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

    Stark, Michal; Gonen, Nitzan; Assaraf, Yehuda G., E-mail: assaraf@tx.technion.ac.il

    2009-10-09

    The proton-coupled folate transporter (PCFT) is the dominant intestinal folate transporter, however, its promoter has yet to be revealed. Hence, we here cloned a 3.1 kb fragment upstream to the first ATG of the human PCFT gene and generated sequential deletion constructs evaluated in luciferase reporter assay. This analysis mapped the minimal promoter to 157 bp upstream to the first ATG. Crucial GC-box sites were identified within the minimal promoter and in its close vicinity which substantially contribute to promoter activity, as their disruption resulted in 94% loss of luciferase activity. We also identified upstream enhancer elements including YY1 andmore » AP1 which, although distantly located, prominently transactivated the minimal promoter, as their inactivation resulted in 50% decrease in reporter activity. This is the first functional identification of the minimal PCFT promoter harboring crucial GC-box elements that markedly contribute to its transcriptional activation via putative interaction with distal YY1 and AP1 enhancer elements.« less

  20. Health Promoting Schools as Learning Sites for Physicians in-Training

    ERIC Educational Resources Information Center

    Dharamsi, Shafik; Woollard, Robert; Kendal, Paul; Okullo, Isaac; Macnab, Andrew J.

    2014-01-01

    Purpose: Although medical schools do well in preparing the next generation of practitioners to diagnose and clinically treat illness, they struggle in preparing them with capabilities in the areas of health promotion and disease prevention. Similarly, health promoting schools (HPS) face challenges in working to enhance the health and educational…

  1. Gender-transformative health promotion for women: a framework for action.

    PubMed

    Pederson, Ann; Greaves, Lorraine; Poole, Nancy

    2015-03-01

    Gender inequity is a pervasive global challenge to health equity. Health promotion, as a field, has paid only limited attention to gender inequity to date, but could be an active agent of change if gender equity became an explicit goal of health promotion research, policy and programmes. As an aspect of gendered health systems, health promotion interventions may maintain, exacerbate or reduce gender-related health inequities, depending upon the degree and quality of gender-responsiveness within the programme or policy. This article introduces a framework for gender-transformative health promotion that builds on understanding gender as a determinant of health and outlines a continuum of actions to address gender and health. Gender-transformative health promotion interventions could play a significant role in improving the lives of millions of girls and women worldwide. Gender-related principles of action are identified that extend the core principles of health promotion but reflect the significance of attending to gender in the development and use of evidence, engagement of stakeholders and selection of interventions. We illustrate the framework with examples from a range of women's health promotion activities, including cardiovascular disease prevention, tobacco control, and alcohol use. The literature suggests that gender-responsiveness will enhance the acceptance, relevance and effectiveness of health promotion interventions. By moving beyond responsiveness to transformation, gender-transformative health promotion could enhance both health and social outcomes for large numbers of women and men, girls and boys. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Integration of kerma-area product and cumulative air kerma determination into a skin dose tracking system for fluoroscopic imaging procedures

    NASA Astrophysics Data System (ADS)

    Vijayan, Sarath; Shankar, Alok; Rudin, Stephen; Bednarek, Daniel R.

    2016-03-01

    The skin dose tracking system (DTS) that we developed provides a color-coded mapping of the cumulative skin dose distribution on a 3D graphic of the patient during fluoroscopic procedures in real time. The DTS has now been modified to also calculate the kerma area product (KAP) and cumulative air kerma (CAK) for fluoroscopic interventions using data obtained in real-time from the digital bus on a Toshiba Infinix system. KAP is the integral of air kerma over the beam area and is typically measured with a large-area transmission ionization chamber incorporated into the collimator assembly. In this software, KAP is automatically determined for each x-ray pulse as the product of the air kerma/ mAs from a calibration file for the given kVp and beam filtration times the mAs per pulse times the length and width of the beam times a field nonuniformity correction factor. Field nonuniformity is primarily the result of the heel effect and the correction factor was determined from the beam profile measured using radio-chromic film. Dividing the KAP by the beam area at the interventional reference point provides the area averaged CAK. The KAP and CAK per x-ray pulse are summed after each pulse to obtain the total procedure values in real-time. The calculated KAP and CAK were compared to the values displayed by the fluoroscopy machine with excellent agreement. The DTS now is able to automatically calculate both KAP and CAK without the need for measurement by an add-on transmission ionization chamber.

  3. Overexpression of a MADS-Box Gene from Birch (Betula platyphylla) Promotes Flowering and Enhances Chloroplast Development in Transgenic Tobacco

    PubMed Central

    Qu, Guan-Zheng; Zheng, Tangchun; Liu, Guifeng; Wang, Wenjie; Zang, Lina; Liu, Huanzhen; Yang, Chuanping

    2013-01-01

    In this study, a MADS-box gene (BpMADS), which is an ortholog of AP1 from Arabidopsis, was isolated from birch (Betula platyphylla). Transgenic Arabidopsis containing a BpMADS promoter::GUS construct was produced, which exhibited strong GUS staining in sepal tissues. Ectopic expression of BpMADS significantly enhanced the flowering of tobacco (35S::BpMADS). In addition, the chloroplasts of transgenic tobacco exhibited much higher growth and division rates, as well rates of photosynthesis, than wild-type. A grafting experiment demonstrated that the flowering time of the scion was not affected by stock that overexpressed BpMADS. In addition, the overexpression of BpMADS resulted in the upregulation of some flowering-related genes in tobacco. PMID:23691043

  4. HMGB1 exacerbates experimental mouse colitis by enhancing innate lymphoid cells 3 inflammatory responses via promoted IL-23 production.

    PubMed

    Chen, Xiangyu; Li, Lingyun; Khan, Muhammad Noman; Shi, Lifeng; Wang, Zhongyan; Zheng, Fang; Gong, Feili; Fang, Min

    2016-11-01

    In inflammatory bowel diseases (IBD), high mobility group box 1 (HMGB1), as an endogenous inflammatory molecule, can promote inflammatory cytokines secretion by acting on TLR2/4 resulting in tissue damage. The underlying mechanisms remain unclear. Here we report a novel role of HMGB1 in controlling the maintenance and function of intestine-resident group-3 innate lymphoid cells (ILC3s) that are important innate effector cells implicated in mucosal homeostasis and IBD pathogenesis. We showed that mice treated with anti-HMGB1 Ab, or genetically deficient for TLR2 -/- or TLR4 -/- mice, displayed reduced intestinal inflammation. In these mice, the numbers of colonic ILC3s were significantly reduced, and the levels of IL-17 and IL-22 that can be secreted by ILC3s were also decreased in the colon tissues. Furthermore, HMGB1 promoted DCs via TLR2/4 signaling to produce IL-23, activating ILC3s to produce IL-17 and IL-22. Our data thus indicated that the HMGB1-TLR2/4-DCs-IL-23 cascade pathway enhances the functions of ILC3s to produce IL-17 and IL-22, and this signal way might play a vital role in the development of IBD.

  5. Double promoter expression systems for recombinant protein production by industrial microorganisms.

    PubMed

    Öztürk, Sibel; Ergün, Burcu Gündüz; Çalık, Pınar

    2017-10-01

    Using double promoter expression systems is a promising approach to increase heterologous protein production. In this review, current double promoter expression systems for the production of recombinant proteins (r-proteins) by industrially important bacteria, Bacillus subtilis and Escherichia coli; and yeasts, Saccharomyces cerevisiae and Pichia pastoris, are discussed by assessing their potentials and drawbacks. Double promoter expression systems need to be designed to maintain a higher specific product formation rate within the production domain. While bacterial double promoter systems have been constructed as chimeric tandem promoters, yeast dual promoter systems have been developed as separate expression cassettes. To increase production and productivity, the optimal transcriptional activity should be justified either by simultaneously satisfying the requirements of both promoters, or by consecutively stimulating the changeover from one to another in a biphasic process or via successive-iterations. Thus, considering the dynamics of a fermentation process, double promoters can be classified according to their operational mechanisms, as: i) consecutively operating double promoter systems, and ii) simultaneously operating double promoter systems. Among these metabolic design strategies, extending the expression period with two promoters activated under different conditions, or enhancing the transcriptional activity with two promoters activated under similar conditions within the production domain, can be applied independently from the host. Novel studies with new insights, which aim a rational systematic design and construction of dual promoter expression vectors with tailored transcriptional activity, will empower r-protein production with enhanced production and productivity. Finally, the current state-of-the-art review emphasizes the advantages of double promoter systems along with the necessity for discovering new promoters for the development of more

  6. Enhancing Quality Interventions Promoting Healthy Sexuality (EQUIPS): A Novel Application of Translational Research Methods

    PubMed Central

    Acosta, Joie; Ebener, Patricia; Driver, Jennifer; Keith, Jamie; Peebles, Dana

    2013-01-01

    Abstract Translational research is expanding, in part, because Evidence‐Based Programs or Practices (EBPs) are not adopted in many medical domains. However, little translational research exists on EBPs that are prevention programs delivered in nonclinical, community‐based settings. These organizations often have low capacity, which undermines implementation quality and outcomes. Rigorous translational research is needed in these settings so within a single study, capacity, implementation quality, and outcomes are measured and links between them tested. This paper overviews the study Enhancing Quality Interventions Promoting Healthy Sexuality (EQUIPS), which tests how well a community‐based setting (Boys & Girls Clubs) conducts an EBP called Making Proud Choices that aims to prevent teen pregnancy and sexually transmitted infections, with and without an implementation support intervention called Getting To Outcomes. The study design is novel as it assesses: Getting To Outcomes’ impact on capacity, implementation quality, and outcomes simultaneously and in both study conditions; will assess sustainability by measuring capacity and fidelity a year after the Getting To Outcomes support ends; and will operate on a large scale similar to many national initiatives. Many studies have not incorporated all these elements and thus EQUIPS could serve as a model for translational research in many domains. PMID:23751031

  7. Embryonic Stem Cell-Derived Exosomes Promote Endogenous Repair Mechanisms and Enhance Cardiac Function Following Myocardial Infarction

    PubMed Central

    Khan, Mohsin; Nickoloff, Emily; Abramova, Tatiana; Johnson, Jennifer; Verma, Suresh Kumar; Krishnamurthy, Prasanna; Mackie, Alexander Roy; Vaughan, Erin; Garikipati, Venkata Naga Srikanth; Benedict, Cynthia; Ramirez, Veronica; Lambers, Erin; Ito, Aiko; Gao, Erhe; Misener, Sol; Luongo, Timothy; Elrod, John; Qin, Gangjian; Houser, Steven R; Koch, Walter J; Kishore, Raj

    2015-01-01

    Rationale Embryonic stem cells (ESCs) hold great promise for cardiac regeneration but are susceptible to various concerns. Recently, salutary effects of stem cells have been connected to exosome secretion. ESCs have the ability to produce exosomes however their effect in the context of the heart is unknown. Objective Determine the effect of ESC-derived exosome for the repair of ischemic myocardium and whether c-kit+ CPCs function can be enhanced with ESC exosomes Methods and Results This study demonstrates that mouse ESC derived exosomes (mES Ex) possess ability to augment function in infarcted hearts. mES Ex enhanced neovascularization, cardiomyocyte survival and reduced fibrosis post infarction consistent with resurgence of cardiac proliferative response. Importantly, mES Ex augmented cardiac progenitor cell (CPC) survival, proliferation and cardiac commitment concurrent with increased c-kit+ CPCs in vivo 8 weeks after in vivo transfer along with formation of bonafide new cardiomyocytes in the ischemic heart. miRNA array revealed significant enrichment of miR290–295 cluster and particularly miR-294 in ESC exosomes. The underlying basis for the beneficial effect of mES Ex was tied to delivery of ESC specific miR-294 to CPCs promoting increased survival, cell cycle progression and proliferation. Conclusions mES Ex provide a novel cell free system that utilizes the immense regenerative power of ES cells while avoiding the risks associated with direct ES or ES derived cell transplantation and risk of teratomas. ESC exosomes possess cardiac regeneration ability and modulate both cardiomyocyte and CPC based repair programs in the heart. PMID:25904597

  8. Isolated Polynucleotides and Methods of Promoting a Morphology in a Fungus

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

    Lasure, Linda L; Dai, Ziyu

    2008-10-21

    The invention includes isolated polynucleotide molecules that are differentially expressed in a native fungus exhibiting a first morphology relative to the native fungus exhibiting a second morphology. The invention includes a method of enhancing a bioprocess utilizing a fungus. A transformed fungus is produced by transforming a fungus with a recombinant polynucleotide molecule. The recombinant polynucleotide molecule contains an isolated polynucleotide sequence linked operably to a promoter. The polynucleotide sequence is expressed to promote a first morphology. The first morphology of the transformed fungus enhances a bioprocess relative to the bioprocess utilizing a second morphology.

  9. Introducing modern technology to promote transparency in health services.

    PubMed

    Islam, Mohammad Shafiqul

    2015-01-01

    Quantitative indicators show that Bangladeshi maternal and child healthcare is progressing satisfactorily. However, healthcare quality is still inadequate. It is hypothesised that modern technology enhances healthcare quality. Therefore, the purpose of this paper is to investigate how modern technology such as electronic record keeping and the internet can contribute to enhancing Bangladeshi healthcare quality. This study also explores how socio-economic and political factors affect the healthcare quality. This paper is based on a qualitative case study involving 68 in-depth interviews with healthcare professionals, elected representatives, local informants and five focus group discussions with healthcare service users to understand technology's effect on health service quality. The study has been conducted in one rural and one urban service organisations to understand how various factors contribute differently to healthcare quality. The findings show that modern technology, such as the internet and electronic devices for record keeping, contribute significantly to enhancing health service transparency, which in turn leads to quality health and family planning services. The findings also show that information and communication technology (ICT) is an effective mechanism for reducing corruption and promoting transparency. However, resource constraints impact adversely on the introduction of technology, which leads to less transparent healthcare. Progress in education and general socio-economic conditions makes it suitable to enhance ICT usage, which could lead to healthcare transparency, but political and bureaucratic factors pose a major challenge to ensure transparency. This paper can be a useful guide for promoting governance and healthcare quality in developing countries including Bangladesh. It analyses the ICT challenges that healthcare staff face when promoting transparent healthcare. This paper provides a deeper understanding of transparency and healthcare

  10. Generation of a neurodegenerative disease mouse model using lentiviral vectors carrying an enhanced synapsin I promoter.

    PubMed

    Matsuzaki, Yasunori; Oue, Miho; Hirai, Hirokazu

    2014-02-15

    Certain inherited progressive neurodegenerative disorders, such as spinocerebellar ataxia (SCA), affect neurons in large areas of the central nervous system (CNS). The selective expression of disease-causing and therapeutic genes in susceptible regions and cell types is critical for the generation of animal models and development of gene therapies for these diseases. Previous studies have demonstrated the advantages of the short synapsin I (SynI) promoter (0.5 kb) as a neuron-specific promoter for robust transgene expression. However, the short SynI promoter has also shown some promoter activity in glia and a lack of transgene expression in significant areas of the CNS. New methods: To improve the SynI promoter, we used a SynI promoter that is twice as long (1.0 kb) as the short SynI promoter and incorporated a minimal CMV (minCMV) sequence. We observed that the 1.0 kb rat SynI promoter with minCMV [rSynI(1.0)-minCMV] exhibited robust promoter strength, excellent neuronal specificity and wide-ranging transgene expression throughout the CNS. Comparison with existing methods: Compared with the two previously reported short (0.5 kb) promoters, the new promoter was superior with respect to neuronal specificity and more efficiently transduced neurons. Moreover, transgenic mice expressing the mutant protein ATXN1[Q98], which causes SCA type 1 (SCA1), under the control of the rSynI(1.0)-minCMV promoter showed robust transgene expression specifically in neurons throughout the CNS and exhibited progressive ataxia. rSynI(1.0)-minCMV drives robust and neuron-specific transgene expression throughout the CNS and is therefore useful for viral vector-mediated neuron-specific gene delivery and generation of neuron-specific transgenic animals. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Promotion of health-enhancing physical activity in rheumatoid arthritis: a comparative study on healthcare providers in Italy, The Netherlands and Sweden.

    PubMed

    Brodin, Nina; Hurkmans, Emalie; DiMatteo, Luigi; Nava, Tiziana; Vliet Vlieland, Thea; Opava, Christina H

    2015-10-01

    The objectives of this study were to compare attitudes, practice of advice, perceived competencies and educational needs related to health-enhancing physical activity (HEPA) in rheumatoid arthritis (RA) among Dutch, Italian and Swedish healthcare providers (HCP) and to explore associations between these factors and age, gender and HEPA levels of HCP. Questionnaires were sent to 2939 HCP, members of their national rheumatology organizations. HEPA was assessed with the Short Questionnaire to Assess Health-Enhancing Physical Activity or the International Physical Activity Questionnaire; attitudes, practice of advice, perceived competencies and educational needs with a 23-item questionnaire. Overall response rate was 33 %. Ninety-five percent of HCP agreed that HEPA is an important health goal in RA. More Swedish HCP had positive attitudes to the attainability and safety of HEPA in RA. There were no differences between countries in practice of advice on HEPA to patients with RA in general or to those with recent onset disease, but more Italian HCP were reluctant to advise HEPA to patients with established disease. Of the total HCP, 36 to 60 % used public health guidelines to advise on HEPA, with Dutch HCP taking less advantage. Still they estimated a higher proportion of patients with RA to follow such advice. Italian HCP perceived their competencies the highest, but were also more interested in education to promote HEPA. Gender, age and HEPA performance had no association with attitudes toward HEPA, while a number of associations were found between these factors and practice of advice and perceived competencies. The differences found between HCP in the three countries might indicate the need for educational initiatives to improve HEPA promotion.

  12. Knowledge, attitude, and practices (KAP) and risk factors analysis related to cystic echinococcosis among residents in Tibetan communities, Xiahe County, Gansu Province, China.

    PubMed

    Li, Dan; Gao, Qi; Liu, Jian; Feng, Yu; Ning, Wenhua; Dong, Yanqing; Tao, Lixin; Li, Jingyi; Tian, Xiujun; Gu, Junchao; Xin, Deli

    2015-07-01

    Cystic echinococcosis (CE) is a global parasitic zoonosis caused by Echinococcus granulosus. The disease is highly endemic in western China, especially in Tibetan areas, because of poor economic development and hygiene conditions, limited community knowledge of CE, a large scale of dogs, and home slaughtering of livestock. Although many researchers have analyzed risk factors of CE transmission in Tibetan Plateau, there are rare reports of knowledge, attitude, and practice (KAP) of residents about CE in Tibetan communities. In our current study, community based cross-sectional study was conducted in three townships in Xiahe County, Gannan Tibetan Autonomous Prefectures of Gansu Province from May to September 2013. A total of 972 participants originating from Tibetan communities of 31 villages in the 3 townships were registered and data were collected using structured questionnaires. From the total of 972 study participants (457 males and 515 females), 65.9% heard of the disease CE. Most of them (96.1%) would like to accept CE inspection. About half of the peoples feed their dogs often and major of them do not play with the dogs. Risk factors included resident, knowing dog could be infected, knowing eating could be route of infection, oldest dog's age, usually feed your dog by self, feed dogs with internal organs. In general our findings showed that most of residents had positive attitude toward treatments of the disease, but their practice about disease prevention and control was low. Therefore, our study called for continued and strengthened education of changing the life style, especially the behaviors related to dogs. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Developing a set of strong intronic promoters for robust metabolic engineering in oleaginous Rhodotorula (Rhodosporidium) yeast species.

    PubMed

    Liu, Yanbin; Yap, Sihui Amy; Koh, Chong Mei John; Ji, Lianghui

    2016-11-25

    Red yeast species in the Rhodotorula/Rhodosporidium genus are outstanding producers of triacylglyceride and cell biomass. Metabolic engineering is expected to further enhance the productivity and versatility of these hosts for the production of biobased chemicals and fuels. Promoters with strong activity during oil-accumulation stage are critical tools for metabolic engineering of these oleaginous yeasts. The upstream DNA sequences of 6 genes involved in lipid biosynthesis or accumulation in Rhodotorula toruloides were studied by luciferase reporter assay. The promoter of perilipin/lipid droplet protein 1 gene (LDP1) displayed much stronger activity (4-11 folds) than that of glyceraldehyde-3-phosphate dehydrogenase gene (GPD1), one of the strongest promoters known in yeasts. Depending on the stage of cultivation, promoter of acetyl-CoA carboxylase gene (ACC1) and fatty acid synthase β subunit gene (FAS1) exhibited intermediate strength, displaying 50-160 and 20-90% levels of GPD1 promoter, respectively. Interestingly, introns significantly modulated promoter strength at high frequency. The incorporation of intron 1 and 2 of LDP1 (LDP1in promoter) enhanced its promoter activity by 1.6-3.0 folds. Similarly, the strength of ACC1 promoter was enhanced by 1.5-3.2 folds if containing intron 1. The intron 1 sequences of ACL1 and FAS1 also played significant regulatory roles. When driven by the intronic promoters of ACC1 and LDP1 (ACC1in and LDP1in promoter, respectively), the reporter gene expression were up-regulated by nitrogen starvation, independent of de novo oil biosynthesis and accumulation. As a proof of principle, overexpression of the endogenous acyl-CoA-dependent diacylglycerol acyltransferase 1 gene (DGA1) by LDP1in promoter was significantly more efficient than GPD1 promoter in enhancing lipid accumulation. Intronic sequences play an important role in regulating gene expression in R. toruloides. Three intronic promoters, LDP1in, ACC1in and FAS1in, are

  14. Antimicrobial peptide KSL-W promotes gingival fibroblast healing properties in vitro.

    PubMed

    Park, Hyun-Jin; Salem, Mabrouka; Semlali, Abdelhabib; Leung, Kai P; Rouabhia, Mahmoud

    2017-07-01

    We investigated the effect of synthetic antimicrobial decapeptide KSL-W (KKVVFWVKFK) on normal human gingival fibroblast growth, migration, collagen gel contraction, and α-smooth muscle actin protein expression. Results show that in addition to promoting fibroblast adhesion by increasing F-actin production, peptide KSL-W promoted cell growth by increasing the S and G2/M cell cycle phases, and enhanced the secretion of metalloproteinase (MMP)-1 and MMP-2 by upregulating MMP inhibitors, such as tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in fibroblasts. An in vitro wound healing assay confirmed that peptide KSL-W promoted fibroblast migration and contraction of a collagen gel matrix. We also demonstrated a high expression of α-smooth muscle actin by gingival fibroblasts being exposed to KSL-W. This work shows that peptide KSL-W enhances gingival fibroblast growth, migration, and metalloproteinase secretion, and the expression of α-smooth muscle actin, thus promoting wound healing. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Evaluation of the plant growth-promoting activity of Pseudomonas nitroreducens in Arabidopsis thaliana and Lactuca sativa.

    PubMed

    Trinh, Cao Son; Lee, Hyeri; Lee, Won Je; Lee, Seok Jin; Chung, Namhyun; Han, Juhyeong; Kim, Jongyun; Hong, Suk-Whan; Lee, Hojoung

    2018-06-01

    Pseudomonas nitroreducens: strain IHB B 13561 (PnIHB) enhances the growth of Arabidopsis thaliana and Lactuca sativa via the stimulation of cell development and nitrate absorption. Plant growth-promoting rhizobacteria (PGPR) enhance plant development through various mechanisms; they improve the uptake of soil resources by plants to greatly promote plant growth. Here, we used Arabidopsis thaliana seedlings and Lactuca sativa to screen the growth enhancement activities of a purified PGPR, Pseudomonas nitroreducens strain IHB B 13561 (PnIHB). When cocultivated with PnIHB, both species of plants exhibited notably improved growth, particularly in regard to biomass. Quantitative reverse transcription polymerase chain reaction analysis indicated high expression levels of the nitrate transporter genes, especially NRT2.1, which plays a major role in the high-affinity nitrate transport system in roots. Moreover, enhanced activity of the cyclin-B1 promoter was observed when wild-type 'Columbia-0' Arabidopsis seedlings were exposed to PnIHB, whereas upregulation of cyclin-B also occurred in the inoculated lettuce seedlings. Overall, these results suggest that PnIHB improves A. thaliana and L. sativa growth via specific pathways involved in the promotion of cell development and enhancement of nitrate uptake.

  16. STRONTIUM AS AN EFFICIENT PROMOTER FOR SUPPORTED PALLADIUM HYDROGENATION CATALYSTS

    EPA Science Inventory

    The effect of strontium promotion is studied for a series of supported palladium catalysts such as Pd/zeolite-β, Pd/Al2O3, Pd/SiO2, Pd/hydrotalcite and Pd/MgO. Strontium is found to be an effective promoter for enhancing the metal area, perce...

  17. Moderate UV Exposure Enhances Learning and Memory by Promoting a Novel Glutamate Biosynthetic Pathway in the Brain.

    PubMed

    Zhu, Hongying; Wang, Ning; Yao, Lei; Chen, Qi; Zhang, Ran; Qian, Junchao; Hou, Yiwen; Guo, Weiwei; Fan, Sijia; Liu, Siling; Zhao, Qiaoyun; Du, Feng; Zuo, Xin; Guo, Yujun; Xu, Yan; Li, Jiali; Xue, Tian; Zhong, Kai; Song, Xiaoyuan; Huang, Guangming; Xiong, Wei

    2018-06-14

    Sunlight exposure is known to affect mood, learning, and cognition. However, the molecular and cellular mechanisms remain elusive. Here, we show that moderate UV exposure elevated blood urocanic acid (UCA), which then crossed the blood-brain barrier. Single-cell mass spectrometry and isotopic labeling revealed a novel intra-neuronal metabolic pathway converting UCA to glutamate (GLU) after UV exposure. This UV-triggered GLU synthesis promoted its packaging into synaptic vesicles and its release at glutamatergic terminals in the motor cortex and hippocampus. Related behaviors, like rotarod learning and object recognition memory, were enhanced after UV exposure. All UV-induced metabolic, electrophysiological, and behavioral effects could be reproduced by the intravenous injection of UCA and diminished by the application of inhibitor or short hairpin RNA (shRNA) against urocanase, an enzyme critical for the conversion of UCA to GLU. These findings reveal a new GLU biosynthetic pathway, which could contribute to some of the sunlight-induced neurobehavioral changes. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Expression of a maize Myb transcription factor driven by a putative silk-specific promoter significantly enhances resistance to Helicoverpa zea in transgenic maize.

    PubMed

    Johnson, Eric T; Berhow, Mark A; Dowd, Patrick F

    2007-04-18

    Hi II maize (Zea mays) plants were engineered to express maize p1 cDNA, a Myb transcription factor, controlled by a putative silk specific promoter, for secondary metabolite production and corn earworm resistance. Transgene expression did not enhance silk color, but about half of the transformed plant silks displayed browning when cut, which indicated the presence of p1-produced secondary metabolites. Levels of maysin, a secondary metabolite with insect toxicity, were highest in newly emerged browning silks. The insect resistance of transgenic silks was also highest at emergence, regardless of maysin levels, which suggests that other unidentified p1-induced molecules likely contributed to larval mortality. Mean survivor weights of corn earworm larvae fed mature browning transgenic silks were significantly lower than weights of those fed mature nonbrowning transgenic silks. Some transgenic pericarps browned with drying and contained similar molecules found in pericarps expressing a dominant p1 allele, suggesting that the promoter may not be silk-specific.

  19. Promoting innovation: Enhancing transdisciplinary opportunities for medical and engineering students.

    PubMed

    Brazile, Tiffany; Hostetter Shoop, Glenda; McDonough, Christine M; Van Citters, Douglas W

    2018-01-30

    Addressing current healthcare challenges requires innovation and collaboration. Current literature provides limited guidance in promoting these skills in medical school. One approach involves transdisciplinary training in which students from different disciplines work together toward a shared goal. We assessed the need for such a curriculum at Dartmouth College. We surveyed medical and engineering students' educational values; learning experiences; professional goals; and interest in transdisciplinary education and innovation. Data were analyzed using descriptive statistics. Shared values among student groups included leadership development, innovation, collaboration, and resource sharing. Medical students felt their curriculum inadequately addressed creativity and innovation relative to their engineering counterparts (p < 0.05). Medical students felt less prepared for entrepreneurial activities (p < 0.05), while engineering students indicated a need for basic medical knowledge and patient-oriented design factors. Despite strong interest, collaboration was less than 50% of indicated interest. Medical and engineering students share an interest in the innovation process and need a shared curriculum to facilitate collaboration. A transdisciplinary course that familiarizes students with this process has the potential to promote physicians and engineers as leaders and innovators who can effectively work across industry lines. A transdisciplinary course was piloted in Spring 2017.

  20. Medicines Information and the Regulation of the Promotion of Pharmaceuticals.

    PubMed

    Leonardo Alves, Teresa; Lexchin, Joel; Mintzes, Barbara

    2018-05-02

    Many factors contribute to the inappropriate use of medicines, including not only a lack of information but also inaccurate and misleading promotional information. This review examines how the promotion of pharmaceuticals directly affects the prescribing and use of medicines. We define promotion broadly as all actions taken directly by pharmaceutical companies with the aim of enhancing product sales. We look in greater detail at promotion techniques aimed at prescribers, such as sales representatives, pharmaceutical advertisements in medical journals and use of key opinion leaders, along with the quality of information provided and the effects thereof. We also discuss promotion to the public, through direct-to-consumer advertising, and its effects. Finally, we consider initiatives to regulate promotion that come from industry, government and nongovernmental organizations.

  1. [Knowledge, attitudes and community practice during an outbreak of dengue in a town in Colombia, 2010].

    PubMed

    Castañeda, Oneida; Segura, Omar; Ramírez, Alba N

    2011-06-01

    17 cases of dengue were reported from the town of El Playón (7°28'15"-N/73°12'00"-W/altitude 510 masl) during epidemiological study weeks 5-6 and 12-13/2010. The Santander Department's Health Secretariat sought outbreak investigation and community knowledge-attitudes-practice (KAP) assessment on 16-4-2010 concerning a dengue fever outbreak in the town after an epidemiological surveillance committee had met; this was to strengthen local action regarding Aedes aegypti vector promotion-prevention-control. This was a descriptive outbreak investigation study using an active search for cases having clinical manifestations of dengue according to protocol definitions, an entomological survey and a KAP survey of 47 people selected by simple-random-sampling. Data was systematised and analysed using Epi-INFO (3.5.1) with measures of central tendency-male ratio, in-house Aegypti (IA), water-storage (WI) and Breatau (BI) indexes. 4,774 clinical records were examined. There were 67 records compatible with dengue, 24 cases were notified (75 % town-25 % department), 15 (63 %) being women and 9 (38 %) men. 20 (83 %) cases occurred in the urban area and 4 (17 %) in rural areas. Attack rate/cumulated incidence: initial=0.3 % (17/6 303), final=0.4 % (24/6 303), male ratio=1.5. 47 houses and 142 water-storage items proved positive: low water-stores=8.7 %(4/46), rubber tyres=8.3 %(1/12), others=4.4 %(2/45), plants=2.9 %(1/34). IA=5 %, WI=6%, BI=17%, taxonomy confirmed=15 %(7/47). 47 KAP, 36 (77 %) women, 11 (23 %) men; knowledge on disease, symptoms and signs 44 (94 %), eliminating larvae deposits 32(68 %), asked about dengue 3(6 %), informed about responsibilities related to control 25(53 %). The local community knows about risk factors and is aware of its responsibility regarding vector control. Community participation should be promoted using the ecosystem as a strategy for mosquito and dengue transmission control.

  2. Knowledge, attitudes and practices of food handlers in food safety: An integrative review.

    PubMed

    Zanin, Laís Mariano; da Cunha, Diogo Thimoteo; de Rosso, Veridiana Vera; Capriles, Vanessa Dias; Stedefeldt, Elke

    2017-10-01

    This study presents an overview of the relationship between knowledge, attitudes and practices (KAP) of food handlers with training in food safety, in addition to proposing reflections on the training of food handlers, considering its responsibility for food safety and health of consumers. The review was based on the integrative method. The descriptors used were: (food handler), (knowledge, attitudes and practice) and (training). Six databases were searched, 253 articles were consulted and 36 original articles were included. Fifty per cent of the articles pointed that there was no proper translation of knowledge into attitudes/practices or attitudes into practices after training. Knowledge, attitudes and practices of food handlers are important for identifying how efficient training in food safety is allowing prioritize actions in planning training. The evaluation of KAP is the first step to understand the food handler's point of view. After this evaluation other diagnostic strategies become necessary to enhance this understanding. Copyright © 2017. Published by Elsevier Ltd.

  3. Health seeking behavior of the mothers for the special care new-born unit discharged children: a comparative study.

    PubMed

    Jeet, Gursimer; Sharma, Atul; Mohanta, Tulika Goswami; Trakroo, Ajay

    2013-01-01

    Establishment of special care new-born units (SCNU) in hospitals not only serves to provide the intensive care to sick neonates, but presents with opportunities to enhance knowledge and modify attitude and practices of their parents through behavior change communication (BCC). A cross-sectional study was conducted in Dibrugarh District, Assam from January to June, 2011 to assess differences in health-care seeking behavior of these mothers from mothers of newborns who were born at home and mothers who had normal uneventful institutional deliveries. Mothers of 29 SCNU discharged, 34 institutions delivered and 26 home delivered children were interviewed using a semi-structured interview schedule and a knowledge, attitude and practice (KAP) survey tool. Mothers of children admitted to SCNU scored better in questions related to vaccination, contraception, protection of child from infections and cold and perceptions about traditional healers, but overall KAP scores in the three groups were not found significantly different.

  4. Enhanced performance feedback and patient participation to improve hand hygiene compliance of health-care workers in the setting of established multimodal promotion: a single-centre, cluster randomised controlled trial.

    PubMed

    Stewardson, Andrew James; Sax, Hugo; Gayet-Ageron, Angèle; Touveneau, Sylvie; Longtin, Yves; Zingg, Walter; Pittet, Didier

    2016-12-01

    Hand hygiene compliance of health-care workers remains suboptimal despite standard multimodal promotion, and evidence for the effectiveness of novel interventions is urgently needed. We aimed to assess the effect of enhanced performance feedback and patient participation on hand hygiene compliance in the setting of multimodal promotion. We did a single-centre, cluster randomised controlled trial at University of Geneva Hospitals (Geneva, Switzerland). All wards hosting adult, lucid patients, and all health-care workers and patients in these wards, were eligible. After a 15-month baseline period, eligible wards were assigned by computer-generated block randomisation (1:1:1), stratified by the type of ward, to one of three groups: control, enhanced performance feedback, or enhanced performance feedback plus patient participation. Standard multimodal hand hygiene promotion was done hospital-wide throughout the study. The primary outcome was hand hygiene compliance of health-care workers (according to the WHO Five Moments of Hand Hygiene) at the opportunity level, measured by direct observation (20-min sessions) by 12 validated infection control nurses, with each ward audited at least once every 3 months. This trial is registered with ISRCTN, number ISRCTN43599478. We randomly assigned 67 wards to the control group (n=21), enhanced performance feedback (n=24), or enhanced performance feedback plus patient participation (n=22) on May 19, 2010. One ward in the control group became a high-dependency unit and was excluded from analysis. During 1367 observation sessions, 12 579 hand hygiene opportunities were recorded. Between the baseline period (April 1, 2009, to June 30, 2010) and the intervention period (July 1, 2010, to June 30, 2012), mean hand hygiene compliance increased from 66% (95% CI 62-70) to 73% (70-77) in the control group (odds ratio [OR] 1·41, 95% CI 1·21-1·63), from 65% (62-69) to 75% (72-77) in the enhanced performance feedback group (1·61, 1·41-1

  5. Nurses' Knowledge and Attitudes about Pain: Personal and Professional Characteristics and Patient Reported Pain Satisfaction.

    PubMed

    Brant, Jeannine M; Mohr, Carla; Coombs, Nicholas C; Finn, Susan; Wilmarth, Estella

    2017-08-01

    Pain is a nursing sensitive indicator and yet pain is often not well managed in both hospital and ambulatory settings. Improving nurse knowledge and attitudes about pain may translate to improved patient outcomes. The objective of this study was to investigate knowledge and attitudes about pain (KAP) in nurses who work in diverse settings, professional and personal characteristics that predict KAP, and whether KAP correlated with patient satisfaction according to Hospital Consumer Assessment of Healthcare Providers (HCAHPS). Descriptive, cross-sectional, correlational study. A large integrated health care facility in the northwest. A total of 217 registered nurses working in acute, ambulatory, and long-term care. A Pain Knowledge and Attitudes Survey was administered to registered nurses in diverse settings. Scores were examined for personal and professional predictors of KAP and correlated with HCAHPS patient satisfaction surveys. Nurses scored an average of 72%; nurses in long-term care scored the highest. Having more than 5 years of nursing experience, being a certified nurse, and receiving pain education in the last year were predictive of a higher score on the KAP survey, which explained only 9.8% of the variance. Unit mean KAP scores were highly correlated with unit-based HCAHPS scores (r = 0.917, p = .01). Certified nurses scored higher on the KAP survey, consistent with other studies. This study suggests that having more knowledge and better attitudes about pain may improve patient satisfaction of pain. Further studies are needed that link knowledge and attitudes about pain to patient outcomes. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  6. A heterologous hormone response element enhances expression of rat beta-casein promoter-driven chloramphenicol acetyltransferase fusion genes in the mammary gland of transgenic mice.

    PubMed

    Greenberg, N M; Reding, T V; Duffy, T; Rosen, J M

    1991-10-01

    Previous studies have demonstrated that the entire rat beta-casein (R beta C) gene and a -524/+490 R beta C fragment-chloramphenicol acetyltransferase (CAT) fusion gene are expressed preferentially in the mammary gland of transgenic mice in a developmentally regulated fashion. However, transgene expression was infrequent, less than 1% of that observed for the endogenous gene, and varied as much as 500-fold, presumably due to the site of chromosomal integration. To determine whether a heterologous hormone-responsive enhancer could be used to increase both the level and frequency of expression in the mammary gland, a fragment derived from the mouse mammary tumor virus long terminal repeat containing four hormone response elements (HREs) was inserted into the R beta C promoter at a site not known to contain transcriptional regulatory elements. Transgenic mice generated which carried HRE-enhanced R beta C-CAT fusion genes expressed CAT activity in the mammary glands of all founder lines examined at levels that were on average 13-fold greater than for lines generated with similar constructs not carrying HREs. In the highest expressing line, the level of HRE-enhanced transgene expression was found to be developmentally regulated, increasing 14-fold in the mammary gland from virgin to day 10 of lactation. In this line, expression was also observed in the thymus and spleen; however, the level of CAT activity was 4-fold lower than in the mammary gland and was not developmentally regulated. In adrenalectomized mice, the administration of dexamethasone stimulated CAT expression in the mammary gland but not in the thymus and spleen. These studies demonstrate that in the context of the R beta C promoter, the HRE functions in the mammary gland to increase both the frequency and level of transgene expression.

  7. Finding Sales Promotion and Making Decision for New Product Based on Group Analysis of Edge-Enhanced Product Networks

    NASA Astrophysics Data System (ADS)

    Huang, Yi; Tan, Jianbin; Wu, Bin

    A novel method is proposed in this paper to find the promotive relationship of products from a network point of view. Firstly, a product network is built based on the dataset of handsets’ sale information collected from all outlets of a telecom operator of one province of China, with a period from Jan. 2006 to Jul. 2008. Then the edge enhanced model is applied on product network to divide all the products into several groups, according to which each outlet is assigned to class A or class B for a certain handset. Class A is defined as the outlet which sell the certain handset and contains all of handsets of its group, while other situation for class B which sell the certain handset too. It’s shown from the result of analysis on these two kinds of outlets that many handsets are sold better in outlets of class A than that of class B, even though the sales revenue of all these outlets in the time period is close. That is to say the handsets within a group would promote the sale for each other. Furthermore, a method proposed in this paper gives a way to find out the important attributes of the handsets which lead them to br divided into the same group, and it also explains how to add a new handset to an existing group and where would the new handset be sold best.

  8. Stronger enhancer II/core promoter activities of hepatitis B virus isolates of B2 subgenotype than those of C2 subgenotype

    PubMed Central

    Qin, Yanli; Zhou, Xueshi; Jia, Haodi; Chen, Chaoyang; Zhao, Weifeng; Zhang, Jiming; Tong, Shuping

    2016-01-01

    Hepatitis B virus (HBV) genotype C causes prolonged chronic infection and increased risk for liver cancer than genotype B. Our previous work revealed lower replication capacity of wild-type genotype C2 than B2 isolates. HBV DNA replication is driven by pregenomic RNA, which is controlled by core promoter (CP) and further augmented by enhancer I (ENI) and enhancer II (ENII). DNA fragments covering these regulatory elements were amplified from B2 and C2 isolates to generate luciferase reporter constructs. As ENII is fully embedded in CP, we inserted HBV DNA fragments in the sense orientation to determine their combined activities, and in the antisense orientation to measure enhancer activities alone. Genotype B2 isolates displayed higher ENI+ENII+CP, ENII+CP, and ENII activities, but not ENI or ENI+ENII activity, than C2 isolates. The higher ENII+CP activity was partly attributable to 4 positions displaying genotype-specific variability. Exchanging CP region was sufficient to revert the replication phenotypes of several B2 and C2 clones tested. These results suggest that a weaker ENII and/or CP at least partly accounts for the lower replication capacities of wild-type C2 isolates, which could drive the subsequent acquisition of CP mutations. Such mutations increase genome replication and are implicated in liver cancer development. PMID:27461034

  9. Stronger enhancer II/core promoter activities of hepatitis B virus isolates of B2 subgenotype than those of C2 subgenotype.

    PubMed

    Qin, Yanli; Zhou, Xueshi; Jia, Haodi; Chen, Chaoyang; Zhao, Weifeng; Zhang, Jiming; Tong, Shuping

    2016-07-27

    Hepatitis B virus (HBV) genotype C causes prolonged chronic infection and increased risk for liver cancer than genotype B. Our previous work revealed lower replication capacity of wild-type genotype C2 than B2 isolates. HBV DNA replication is driven by pregenomic RNA, which is controlled by core promoter (CP) and further augmented by enhancer I (ENI) and enhancer II (ENII). DNA fragments covering these regulatory elements were amplified from B2 and C2 isolates to generate luciferase reporter constructs. As ENII is fully embedded in CP, we inserted HBV DNA fragments in the sense orientation to determine their combined activities, and in the antisense orientation to measure enhancer activities alone. Genotype B2 isolates displayed higher ENI+ENII+CP, ENII+CP, and ENII activities, but not ENI or ENI+ENII activity, than C2 isolates. The higher ENII+CP activity was partly attributable to 4 positions displaying genotype-specific variability. Exchanging CP region was sufficient to revert the replication phenotypes of several B2 and C2 clones tested. These results suggest that a weaker ENII and/or CP at least partly accounts for the lower replication capacities of wild-type C2 isolates, which could drive the subsequent acquisition of CP mutations. Such mutations increase genome replication and are implicated in liver cancer development.

  10. Preserving and enhancing the functionality of highways in Texas : workshop.

    DOT National Transportation Integrated Search

    2010-01-01

    Workshop Objectives: : To promote the importance of Highway Functionality : To review functionality in highway lifecycle : To provide how to materials to preserve, maintain, and enhance functionality : To promote coordination be...

  11. Aberrant methylation of the MSH3 promoter and distal enhancer in esophageal cancer patients exposed to first-hand tobacco smoke.

    PubMed

    Vogelsang, Matjaz; Paccez, Juliano D; Schäfer, Georgia; Dzobo, Kevin; Zerbini, Luiz F; Parker, M Iqbal

    2014-11-01

    Polymorphisms in MSH3 gene confer risk of esophageal cancer when in combination with tobacco smoke exposure. The purpose of this study was to investigate the methylation status of MSH3 gene in esophageal cancer patients in order to further elucidate possible role of MSH3 in esophageal tumorigenesis. We applied nested methylation-specific polymerase chain reaction to investigate the methylation status of the MSH3 promoter in tumors and matching adjacent normal-looking tissues of 84 esophageal cancer patients from a high-risk South African population. The Cancer Genome Atlas data were used to examine DNA methylation profiles at 17 CpG sites located in the MSH3 locus. Overall, promoter methylation was detected in 91.9 % of tumors, which was significantly higher compared to 76.0 % in adjacent normal-looking esophageal tissues (P = 0.008). When samples were grouped according to different demographics (including age, gender and ethnicity) and smoking status of patients, methylation frequencies were found to be significantly higher in tumor tissues of Black subjects (P = 0.024), patients of 55-65 years of age (P = 0.032), males (P = 0.037) and tobacco smokers (P = 0.015). Furthermore, methylation of the MSH3 promoter was significantly more frequent in tumor samples from smokers compared to tumor samples from non-smokers [odds ratio (OR) = 31.9, P = 0.031]. The TCGA data confirmed significantly higher DNA methylation level at the MSH3 promoter region in tumors (P = 0.0024). In addition, we found evidence of an aberrantly methylated putative MSH3-associated distal enhancer element. Our results suggest that methylation of MSH3 together with exposure to tobacco smoke is involved in esophageal carcinogenesis. Due to the active role of the MSH3 protein in modulating chemosensitivity of cells, methylation of MSH3 should further be examined in association with the outcome of esophageal cancer treatment using anticancer drugs.

  12. Mental health promotion and the prevention of mental disorders in South Africa.

    PubMed

    Petersen, I; Bhana, A; Swartz, L

    2012-11-01

    The need for greater attention to mental health promotion and the prevention of mental disorders in South Africa is highlighted by the cycle of poverty and mental ill-health, the potential for social gains, the question of affordability of treatment in the face of the increasing burden of mental disorders, and the limitations of existing treatment methods. This article, which provides a desk review of the current status of mental health promotion and prevention of mental disorders in South Africa, suggests that South Africa has a number of policies that bode well for promoting mental health from infancy through to old age. There is, however, a need for programmatic interventions to promote resilience in vulnerable populations. Of note, is the need for programmes to address maternal depression and strengthen attachment and psychosocial stimulation during infancy, strengthen families, promote health enhancing school environments, and address intimate partner violence and build health enhancing social capital. Given the multifaceted nature of risk and protective influences, the need for a multi-sectoral plan of action is highlighted.

  13. Applying carbon dioxide, plant growth-promoting rhizobacterium and EDTA can enhance the phytoremediation efficiency of ryegrass in a soil polluted with zinc, arsenic, cadmium and lead.

    PubMed

    Guo, Junkang; Feng, Renwei; Ding, Yongzhen; Wang, Ruigang

    2014-08-01

    This study was conducted to investigate the use of elevated carbon dioxide (CO2), plant growth-promoting rhizobacterium Burkholderia sp. D54 (PGPR) and ethylenediaminetetraacetic acid (EDTA) to enhance the phytoextraction efficiency of ryegrass in response to multiple heavy metal (or metalloid)-polluted soil containing zinc (Zn), arsenic (As), cadmium (Cd) and lead (Pb). All of the single or combined CO2, PGPR and EDTA treatments promoted ryegrass growth. The stimulation of ryegrass growth by CO2 and PGPR could primarily be attributed to the regulation of photosynthesis rather than decreased levels of Zn, As and Cd in the shoots. Most treatments seemed to reduce the Zn, As and Cd contents in the shoots, which might be associated with enhanced shoot biomass, thus causing a "dilution effect" regarding their levels. The combined treatments seemed to perform better than single treatments in removing Zn, As, Cd and Pb from soil, judging from the larger biomass and relatively higher total amounts (TAs) of Zn, As, Cd and Pb in both the shoots and roots. Therefore, we suggest that the CO2 plus PGPR treatment will be suitable for removing Zn, As, Cd and Pb from heavy metal (or metalloid)-polluted soils using ryegrass as a phytoremediation material. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Knowledge, attitude, and practice of stroke among high school students in Nepal.

    PubMed

    Thapa, Lekhjung; Sharma, Nooma; Poudel, Ramesh Sharma; Bhandari, Tirtha Raj; Bhagat, Riwaz; Shrestha, Ashis; Shrestha, Shakti; Khatiwada, Dipendra; Caplan, Louis R

    2016-01-01

    Baseline stroke knowledge in a targeted population is indispensable to promote the effective stroke education. We report the baseline knowledge, attitude, and practice (KAP) of high school students with respect to stroke from Nepal. A self-structured questionnaire survey regarding KAP about stroke was conducted in high school students of 33 schools of Bharatpur, Nepal. Descriptive statistics including Chi-square test was used, and the significant variables were subjected to binary logistic regression. Among 1360 participants, 71.1% had heard or read about stroke; 30.2% knew someone with stroke. 39.3% identified brain as the organ affected. Sudden onset limb/s weakness/numbness (72%) and hypertension (74%) were common warning symptom and risk factor identified. 88.9% would take stroke patients to a hospital. Almost half participants (55.5%) felt ayurvedic treatment be effective. 44.8% felt stroke as a hindrance to a happy life and 86.3% believed that family care was helpful for early recovery. Students who identified at least one risk factor were 3.924 times ( P < 0.001, confidence interval [CI] = 1.867-8.247) or those who identified at least one warning symptom were 2.833 times ( P ≤ 0.023, CI = 1.156-6.944) more likely to take stroke patients to a hospital. KAP of high school Nepalese students regarding stroke was satisfactory, and the students having knowledge about the risk factors and warning symptoms were more likely to take stroke patients to a hospital. However, a few misconceptions persisted.

  15. Transcription through enhancers suppresses their activity in Drosophila

    PubMed Central

    2013-01-01

    Background Enhancer elements determine the level of target gene transcription in a tissue-specific manner, providing for individual patterns of gene expression in different cells. Knowledge of the mechanisms controlling enhancer action is crucial for understanding global regulation of transcription. In particular, enhancers are often localized within transcribed regions of the genome. A number of experiments suggest that transcription can have both positive and negative effects on regulatory elements. In this study, we performed direct tests for the effect of transcription on enhancer activity. Results Using a transgenic reporter system, we investigated the relationship between the presence of pass-through transcription and the activity of Drosophila enhancers controlling the expression of the white and yellow genes. The results show that transcription from different promoters affects the activity of enhancers, counteracting their ability to activate the target genes. As expected, the presence of a transcriptional terminator between the inhibiting promoter and the affected enhancer strongly reduces the suppression. Moreover, transcription leads to dislodging of the Zeste protein that is responsible for the enhancer-dependent regulation of the white gene, suggesting a 'transcription interference’ mechanism for this regulation. Conclusions Our findings suggest a role for pass-through transcription in negative regulation of enhancer activity. PMID:24279291

  16. Polymeric Precipitation Inhibitors Promote Fenofibrate Supersaturation and Enhance Drug Absorption from a Type IV Lipid-Based Formulation.

    PubMed

    Suys, Estelle J A; Chalmers, David K; Pouton, Colin W; Porter, Christopher J H

    2018-06-04

    The ability of lipid-based formulations (LBFs) to increase the solubilization, and prolong the supersaturation, of poorly water-soluble drugs (PWSDs) in the gastrointestinal (GI) fluids has generated significant interest in the past decade. One mechanism to enhance the utility of LBFs is to prolong supersaturation via the addition of polymers that inhibit drug precipitation (polymeric precipitation inhibitors or PPIs) to the formulation. In this work, we have evaluated the performance of a range of PPIs and have identified PPIs that are sufficiently soluble in LBF to allow the construction of single phase formulations. An in vitro model was first employed to assess drug (fenofibrate) solubilization and supersaturation on LBF dispersion and digestion. An in vitro-in situ model was subsequently employed to simultaneously evaluate the impact of PPI enhanced drug supersaturation on drug absorption in rats. The stabilizing effect of the polymers was polymer specific and most pronounced at higher drug loads. Polymers that were soluble in LBF allowed simple processing as single phase formulations, while formulations containing more hydrophilic polymers required polymer suspension in the formulation. The lipid-soluble polymers Eudragit (EU) RL100 and poly(propylene glycol) bis(2-aminopropyl ether) (PPGAE) and the water-soluble polymer hydroxypropylmethyl cellulose (HPMC) E4M were identified as the most effective PPIs in delaying fenofibrate precipitation in vitro. An in vitro model of lipid digestion was subsequently coupled directly to an in situ single pass intestinal perfusion assay to evaluate the influence of PPIs on fenofibrate absorption from LBFs in vivo. This coupled model allowed for real-time evaluation of the impact of supersaturation stabilization on absorptive drug flux and provided better discrimination between the different PPIs and formulations. In the presence of the in situ absorption sink, increased fenofibrate supersaturation resulted in increased drug

  17. Preserving and enhancing the functionality of highways in Texas : workshop.

    DOT National Transportation Integrated Search

    2010-01-01

    Workshop Objectives: To promote the importance of Highway Functionality To review functionality in highway lifecycle To provide how to materials to preserve, maintain, and enhance functionality To promote coordination between Tx...

  18. Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol promotes angiogenesis in a mouse model.

    PubMed

    Chen, Young-Bin; Lan, Ying-Wei; Hung, Tsai-Hsien; Chen, Lih-Geeng; Choo, Kong-Bung; Cheng, Winston T K; Lee, Hsuan-Shu; Chong, Kowit-Yu

    2015-07-01

    Several studies of stem cell-based gene therapy have indicated that long-lasting regeneration following vessel ischemia may be stimulated through VEGFA gene therapy and/or MSC transplantation for reduction of ischemic injury in limb ischemia and heart failure. The therapeutic potential of MSC transplantation can be further improved by genetically modifying MSCs with genes which enhance angiogenesis following ischemic injury. In the present study, we aimed to develop an approach in MSC-based therapy for repair and mitigation of ischemic injury and regeneration of damaged tissues in ischemic disease. HSP70 promoter-driven VEGFA expression was induced by resveratrol (RSV) in MSCs, and in combination with known RSV biological functions, the protective effects of our approach were investigated by using ex vivo aortic ring coculture system and a 3D scaffolds in vivo model. Results of this investigation demonstrated that HSP promoter-driven VEGFA expression in MSC increased approximately 2-fold over the background VEGFA levels upon HSP70 promoter induction by RSV. Exposure of HUVEC cells to medium containing MSC in which VEGFA had been induced by cis-RSV enhanced tube formation in the treated HUVEC cells. RSV-treated MSC cells differentiated into endothelial-like phenotypes, exhibiting markedly elevated expression of endothelial cell markers. These MSCs also induced aortic ring sprouting, characteristic of neovascular formation from pre-existing vessels, and additionally promoted neovascularization at the MSC transplantation site in a mouse model. These observations support a hypothesis that VEGFA expression induced by cis-RSV acting on the HSP70 promoter in transplanted MSC augments the angiogenic effects of stem cell gene therapy. The use of an inducible system also vastly reduces possible clinical risks associated with constitutive VEGFA expression.

  19. Health promotion competencies: providing a road map for health promotion to assume a prominent role in global health.

    PubMed

    Shilton, Trevor

    2009-06-01

    Understanding of health and its determinants is rapidly expanding and changing. The emergence of chronic diseases as the leading cause of global disease burden and improved understanding of social determinants of health has brought greater focus to the role of prevention in health. The IUHPE has shown outstanding leadership through the Galway Consensus Statement. Its three recommendations appropriately focus on stimulating dialogue, developing global consensus and communicating the results to key stakeholders. The IUHPE can further enhance progress of the statement by developing participative processes to ensure engagement and ownership by its members. The Galway Consensus Statement can be used to advance professional standards in global health promotion by: (1) providing a common language by which health promotion and its meaning can be communicated to others; (2) providing a framework for building capacity in the health promotion workforce and in the health workforce in general; (3) providing international consensus for consistency in university health promotion courses; (4) providing a framework for credentialing in health promotion; (5) better informing health promotion engagement with other significant workforce sectors and advancing partnership as a key way of working. A vital further application of the Galway Consensus Statement is to inform advocacy. Advocacy is vital to ensure health promotion is better resourced and prioritized by policy makers. Advocacy and communication are vital tools to highlight the evidence, establish the policy fit and infrastructure requirements of health promotion, and present health promotion solutions based on evidence of effectiveness.

  20. Priming of Spatial Distance Enhances Children's Creative Performance

    ERIC Educational Resources Information Center

    Liberman, Nira; Polack, Orli; Hameiri, Boaz; Blumenfeld, Maayan

    2012-01-01

    According to construal level theory, psychological distance promotes more abstract thought. Theories of creativity, in turn, suggest that abstract thought promotes creativity. Based on these lines of theorizing, we predicted that spatial distancing would enhance creative performance in elementary school children. To test this prediction, we primed…

  1. A novel approach to enhance biological nutrient removal using a culture supernatant from Micrococcus luteus containing resuscitation-promoting factor (Rpf) in SBR process.

    PubMed

    Liu, Yindong; Su, Xiaomei; Lu, Lian; Ding, Linxian; Shen, Chaofeng

    2016-03-01

    A culture supernatant from Micrococcus luteus containing resuscitation-promoting factor (SRpf) was used to enhance the biological nutrient removal of potentially functional bacteria. The obtained results suggest that SRpf accelerated the start-up process and significantly enhanced the biological nutrient removal in sequencing batch reactor (SBR). PO4 (3-)-P removal efficiency increased by over 12 % and total nitrogen removal efficiency increased by over 8 % in treatment reactor acclimated by SRpf compared with those without SRpf addition. The Illumina high-throughput sequencing analysis showed that SRpf played an essential role in shifts in the composition and diversity of bacterial community. The phyla of Proteobacteria and Actinobacteria, which were closely related to biological nutrient removal, were greatly abundant after SRpf addition. This study demonstrates that SRpf acclimation or addition might hold great potential as an efficient and cost-effective alternative for wastewater treatment plants (WWTPs) to meet more stringent operation conditions and legislations.

  2. Knowledge, attitudes and self-reported practices toward children oral health among mother's attending maternal and child's units, Salé, Morocco.

    PubMed

    Chala, Sanaa; Houzmali, Soumia; Abouqal, Redouane; Abdallaoui, Faïza

    2018-05-11

    The occurrence of severe dental caries is particularly prevalent and harmful in children. A better understanding of parental factors that may be indicators of children's risk of developing dental caries is important for the development of preventive measures. This study was conducted to assess knowledge, attitudes, and practices (KAP) of mothers in Salé, Morocco regarding oral health and their predictors. A cross-sectional KAP study was conducted of Mother and Child units in Salé, Morocco. Mothers attending the selected units from November 2014 to 29 January 2015 were recruited. Data were collected using a semi-structured questionnaire, administered by face-to-face interviews, to record socio-demographic factors and KAPs. The main outcome measures included knowledge about oral health diseases and preventive measures, and attitudes and practices related to oral health prevention measures and dental care. KAPs scores were then recoded based on responses and scores were determined for each KAP domain. Linear regression analysis was conducted to assess predictors of KAP scores. Among 502 mothers included, 140 (27.8%) were illiterate and 285 (60.9%) were aware that fluoride has a beneficial effect in caries prevention. Mothers' own practices about dental care were statistically related to their children's use of dental care services (p < 0.001). Multiple linear regression analysis revealed that the knowledge score was associated with mother's age (β = 0.05; 95% CI; p < 0.001), education level, and median income (β = 0.38; p = 0.04). Significant predictors of oral health-related practices were mother's education level and children's health status. Limited KAP scores were observed among the studied population. A great emphasis on oral health education and some risk factor modifications are recommended.

  3. Fluoroscopically guided transforaminal epidural steroid injections at a quaternary-care teaching institution: effect of trainee involvement and patient body mass index on fluoroscopy time and patient dose.

    PubMed

    Tiegs-Heiden, C A; Murthy, N S; Geske, J R; Diehn, F E; Schueler, B A; Wald, J T; Kaufmann, T J; Lehman, V T; Carr, C M; Amrami, K K; Morris, J M; Thielen, K R; Maus, T P

    2016-01-01

    To investigate whether there are differences in fluoroscopy time and patient dose for fluoroscopically guided lumbar transforaminal epidural steroid injections (TFESIs) performed by staff radiologists versus with trainees and to evaluate the effect of patient body mass index (BMI) on fluoroscopy time and patient dose, including their interactions with other variables. Single-level lumbar TFESIs (n=1844) between 1 January 2011 and 31 December 2013 were reviewed. Fluoroscopy time, reference point air kerma (Ka,r), and kerma area product (KAP) were recorded. BMI and trainee involvement were examined as predictors of fluoroscopy time, Ka,r, and KAP in models adjusted for age and gender in multivariable linear models. Stratified models of BMI groups by trainee presence were performed. Increased age was the only significant predictor of increased fluoroscopy time (p<0.0001). Ka,r and KAP were significantly higher in patients with a higher BMI (p<0.0001 and p=0.0009). When stratified by BMI, longer fluoroscopy time predicted increased Ka,r and KAP in all groups (p<0.0001). Trainee involvement was not a statistically significant predictor of fluoroscopy time or Ka,r in any BMI category. KAP was lower with trainees in the overweight group (p=0.0009) and higher in male patients for all BMI categories (p<0.02). Trainee involvement did not result in increased fluoroscopy time or patient dose. BMI did not affect fluoroscopy time; however, overweight and obese patients received significantly higher Ka,r and KAP. Male patients received a higher KAP in all BMI categories. Limiting fluoroscopy time and good collimation practices should be reinforced in these patients. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  4. The Role of Physical Activity Assessments for School-Based Physical Activity Promotion

    ERIC Educational Resources Information Center

    Welk, Gregory J.

    2008-01-01

    The emphasis in public health on lifestyle physical activity in recent years has focused attention on the promotion of lifetime physical activity as the primary objective of physical education. If used properly, physical activity and physical fitness assessments can enhance individual promotion of physical activity and also provide valuable…

  5. Impact of an intervention programme on knowledge, attitude and practice of healthcare staff regarding pharmaceutical waste management, Gaza, Palestine.

    PubMed

    Tabash, M I; Hussein, R A; Mahmoud, A H; El-Borgy, M D; Abu-Hamad, B A

    2016-09-01

    To assess knowledge, attitude and practice (KAP) of healthcare staff regarding pharmaceutical waste management; and to determine the impact of an educational programme on the KAP survey items. Pre-post-test intervention study. The pre-intervention phase was performed using a sample of 530 out of 1500 healthcare workers. A predesigned interview questionnaire was used to assess KAP. Next, an educational programme was designed and offered to a subsample of 69 healthcare workers. KAP were re-assessed for the programme attendees using the same interview questionnaire, both immediately (post-test) and six months after the end of the programme (follow-up test). The parametric paired sample t-test was used to assess the difference between pre-test and follow-up test results. Poor knowledge and poor practice levels (scores 50%) detected in the pre-intervention phase were found to improve to satisfactory levels (scores ≥75%) in the follow-up phase. Attitude was found to be positive (score ≥75%) in all phases of the study. The educational programme led to a significant improvement in KAP of healthcare staff regarding pharmaceutical waste management (P<0.001). Copyright © 2016. Published by Elsevier Ltd.

  6. Combining health promotion classroom lessons with health fair activities.

    PubMed

    Eliason, Kathy; True, Alexandra

    2004-02-01

    This article focuses on the important role of the school nurse in promoting healthy lifestyle choices through networking, resource identification, and working with community partners. "Everyone Is Healthy at Northeast" was a health promotion program designed and presented in two ways: classroom lessons and a health fair. There were interactive health promotion classroom lessons on topics such as proper hand washing, the effects of tobacco, and keeping one's heart healthy. These lessons were enhanced by community partners in delivering the healthy lifestyle message through a variety of teaching methods: music, interactive games, and hands-on visuals. The health promotion education program culminated in a schoolwide health fair that showcased the healthy lifestyle choice information at various stations. "Everyone Is Healthy at Northeast" was a success and promoted healthy lifestyle choices through creativity, collaboration, and support from the entire school community.

  7. HMGA2 promotes adipogenesis by activating C/EBPβ-mediated expression of PPARγ

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

    Xi, Yang; Shen, Wanjing; Ma, Lili

    Adipogenesis is orchestrated by a highly ordered network of transcription factors including peroxisome-proliferator activated receptor-gamma (PPARγ) and CCAAT-enhancer binding protein (C/EBP) family proteins. High mobility group protein AT-hook 2 (HMGA2), an architectural transcription factor, has been reported to play an essential role in preadipocyte proliferation, and its overexpression has been implicated in obesity in mice and humans. However, the direct role of HMGA2 in regulating the gene expression program during adipogenesis is not known. Here, we demonstrate that HMGA2 is required for C/EBPβ-mediated expression of PPARγ, and thus promotes adipogenic differentiation. We observed a transient but marked increase of Hmga2more » transcript at an early phase of differentiation of mouse 3T3-L1 preadipocytes. Importantly, Hmga2 knockdown greatly impaired adipocyte formation, while its overexpression promoted the formation of mature adipocytes. We found that HMGA2 colocalized with C/EBPβ in the nucleus and was required for the recruitment of C/EBPβ to its binding element at the Pparγ2 promoter. Accordingly, HMGA2 and C/EBPβ cooperatively enhanced the Pparγ2 promoter activity. Our results indicate that HMGA2 is an essential constituent of the adipogenic transcription factor network, and thus its function may be affected during the course of obesity. - Highlights: • Overexpression of HMGA2 has been implicated in obesity in mice and humans. • HMGA2 is required for adipocyte formation. • HMGA2 colocalizes with C/EBPβ and is required for C/EBPβ recruitment to Pparγ2 promoter. • HMGA2 and C/EBPβ cooperatively enhance the Pparγ2 promoter activity.« less

  8. A community-based approach to the promotion of breastfeeding in Mexico.

    PubMed

    Rodriguez-Garcia, R; Aumack, K J; Ramos, A

    1990-01-01

    A comprehensive education strategy is presented that links training, community education, research, and mass-media efforts to enhance breastfeeding practices. Breastfeeding promotion models, an administrative system, and lessons learned during the project are described. The keys to effective breastfeeding promotion are shown to be accurate information; appropriate education, training, and follow-up; and a supportive administrative system.

  9. The promotion and marketing of oxycontin: commercial triumph, public health tragedy.

    PubMed

    Van Zee, Art

    2009-02-01

    I focus on issues surrounding the promotion and marketing of controlled drugs and their regulatory oversight. Compared with noncontrolled drugs, controlled drugs, with their potential for abuse and diversion, pose different public health risks when they are overpromoted and highly prescribed. An in-depth analysis of the promotion and marketing of OxyContin illustrates some of the associated issues. Modifications of the promotion and marketing of controlled drugs by the pharmaceutical industry and an enhanced capacity of the Food and Drug Administration to regulate and monitor such promotion can have a positive impact on the public health.

  10. ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signaling

    PubMed Central

    Chakrabarti, Rumela; Wei, Yong; Hwang, Julie; Hang, Xiang; Blanco, Mario Andres; Choudhury, Abrar; Tiede, Benjamin; Romano, Rose-Anne; DeCoste, Christina; Mercatali, Laura; Ibrahim, Toni; Amadori, Dino; Kannan, Nagarajan; Eaves, Connie J; Sinha, Satrajit; Kang, Yibin

    2014-01-01

    Emerging evidence suggests that cancer is populated and maintained by tumor initiating cells (TICs) with stem-like properties similar to that of adult tissue stem cells. Despite recent advances, the molecular regulatory mechanisms that may be shared between normal and malignant stem cells remain poorly understood. Here we show that the ΔNp63 isoform of the Trp63 transcription factor promotes normal mammary stem cell (MaSC) activity by increasing the expression of the Wnt receptor Fzd7, thereby enhancing Wnt signaling. Importantly, Fzd7-dependent enhancement of Wnt signaling by ΔNp63 also governs tumor initiating activity of the basal subtype of breast cancer. These findings establish ΔNp63 as a key regulator of stem cells in both normal and malignant mammary tissues and provide direct evidence that breast cancer TICs and normal MaSCs share common regulatory mechanisms. PMID:25241036

  11. Proactive health consumerism: an important new tool for worksite health promotion.

    PubMed

    Johnson, Sara S; Cummins, Carol O; Evers, Kerry E; Prochaska, Janice M; Prochaska, James O

    2009-01-01

    Consumerism in health care has taken on the form of a major innovation among employers and health plans. Yet many of our efforts to enhance the skills and attitudes that enable consumerism have met with limited success. Proactive Health Consumerism is proposed as an approach that utilizes many of the hard-won lessons from health promotion research. Along with prerequisites that create the motivation and framework for increased health consumerism, this article provides a theory-driven example of a new tool for health promotion professionals to employ when enhancing the health consumer skills of working populations. Strategies for maximization of effectiveness and integration with supporting resources are also described.

  12. Teachers under Cover: Promoting the Personal Reading of Teachers.

    ERIC Educational Resources Information Center

    Cardarelli, Aldo F.

    1992-01-01

    Describes a program in which groups of middle school and junior high teachers read and discuss popular, best-selling literature, for the purposes of promoting their personal reading and enhancing school faculty camaraderie. (PRA)

  13. South Asian migrant women and HIV/STIs: knowledge, attitudes and practices and the role of sexual power.

    PubMed

    Gagnon, Anita J; Merry, Lisa; Bocking, Jacqueline; Rosenberg, Ellen; Oxman-Martinez, Jacqueline

    2010-01-01

    Differences in relationship power dynamics or migration factors may affect knowledge, attitudes, and practices (KAP) towards HIV/AIDS and sexually transmitted infections (STIs) in resettling Migrant women. A sample of 122 women and men born in India, Sri Lanka, Pakistan or Bangladesh and residing in Montreal completed questionnaires on HIV/STI KAP and decision-making power Within sexual relationships. Knowledge gaps and stigmatizing attitudes were found. STI/HIV information available in one's language and other educational strategies that consider women's Power may improve KAP among South Asian migrant women.

  14. Effective blocking of the white enhancer requires cooperation between two main mechanisms suggested for the insulator function.

    PubMed

    Kyrchanova, Olga; Maksimenko, Oksana; Stakhov, Viacheslav; Ivlieva, Tatyana; Parshikov, Alexander; Studitsky, Vasily M; Georgiev, Pavel

    2013-01-01

    Chromatin insulators block the action of transcriptional enhancers when interposed between an enhancer and a promoter. In this study, we examined the role of chromatin loops formed by two unrelated insulators, gypsy and Fab-7, in their enhancer-blocking activity. To test for this activity, we selected the white reporter gene that is activated by the eye-specific enhancer. The results showed that one copy of the gypsy or Fab-7 insulator failed to block the eye enhancer in most of genomic sites, whereas a chromatin loop formed by two gypsy insulators flanking either the eye enhancer or the reporter completely blocked white stimulation by the enhancer. However, strong enhancer blocking was achieved due not only to chromatin loop formation but also to the direct interaction of the gypsy insulator with the eye enhancer, which was confirmed by the 3C assay. In particular, it was observed that Mod(mdg4)-67.2, a component of the gypsy insulator, interacted with the Zeste protein, which is critical for the eye enhancer-white promoter communication. These results suggest that efficient enhancer blocking depends on the combination of two factors: chromatin loop formation by paired insulators, which generates physical constraints for enhancer-promoter communication, and the direct interaction of proteins recruited to an insulator and to the enhancer-promoter pair.

  15. Leaf saponins of Quillaja brasiliensis enhance long-term specific immune responses and promote dose-sparing effect in BVDV experimental vaccines.

    PubMed

    Cibulski, Samuel; Rivera-Patron, Mariana; Suárez, Norma; Pirez, Macarena; Rossi, Silvina; Yendo, Anna Carolina; de Costa, Fernanda; Gosmann, Grace; Fett-Neto, Arthur; Roehe, Paulo Michel; Silveira, Fernando

    2018-01-02

    Saponin-based adjuvants are promising adjuvants that enhance both humoral and T-cell-mediated immunity. One of the most used natural products as vaccine adjuvants are Quillaja saponaria bark saponins and its fraction named Quil A®. Despite that, its use has been restricted for human use due to safety issues. As an alternative, our group has been studying the congener species Quillaja brasiliensis saponins and its performance as vaccine adjuvants, which have shown to trigger humoral and cellular immune responses comparable to Quil A® but with milder side effects. Here, we studied a semi purified aqueous extract (AE) and a previously little characterized saponin-enriched fraction (QB-80) from Q. brasiliensis as vaccine adjuvants and an inactivated virus (bovine viral diarrhea virus, BVDV) antigen co-formulated in experimental vaccines in mice model. For the first time, we show the spectra pattern of the Q. brasiliensis saponins by MALDI-TOF, a novel and cost-effective method that could be used to characterize different batches during saponins production. Both AE and QB-80 exhibited noteworthy chemical similarities to Quil A®. In addition, the haemolytic activity and toxicity were assessed, showing that both AE and QB-80 were less toxic than Quil A®. When subcutaneously inoculated in mice, both fractions promoted long-term strong antibody responses encompassing specific IgG1 and IgG2a, enhanced the avidity of IgG antibodies, induced a robust DTH reaction and significantly increased IFN-ɣ production in T CD4 + and T CD8 + cells. Furthermore, we have proven herein that AE has the potential to promote dose-sparing, substantially reducing the dose of antigen required for the BVDV vaccines and still eliciting a mixed Th1/Th2 strong immune response. Based on these results, and considering that AE is a raw extract, easier and cheaper to produce than commercially available saponins, this product can be considered as candidate to be escalated from experimental to

  16. People Create Health: Effective Health Promotion is a Creative Process

    PubMed Central

    Cloninger, C. Robert; Cloninger, Kevin M.

    2015-01-01

    Effective health promotion involves the creative cultivation of physical, mental, social, and spiritual well-being. Efforts at health promotion produce weak and inconsistent benefits when it does not engage people to express their own goals and values. Likewise, health promotion has been ineffective when it relies only on instruction about facts regarding a healthy lifestyle, or focuses on reduction of disease rather than the cultivation of well-being. Meta-analysis of longitudinal studies and experimental interventions shows that improvements in subjective well-being lead to short-term and long-term reductions in medical morbidity and mortality, as well as to healthier functioning and longevity. However, these effects are inconsistent and weak (correlations of about 0.15). The most consistent and strong predictor of both subjective well-being and objective health status in longitudinal studies is a creative personality profile characterized by being highly self-directed, cooperative, and self-transcendent. There is a synergy among these personality traits that enhances all aspects of the health and happiness of people. Experimental interventions to cultivate this natural creative potential of people are now just beginning, but available exploratory research has shown that creativity can be enhanced and the changes are associated with widespread and profound benefits, including greater physical, mental, social, and spiritual well-being. In addition to benefits mediated by choice of diet, physical activity, and health care utilization, the effect of a creative personality on health may be partly mediated by effects on the regulation of heart rate variability. Creativity promotes autonomic balance with parasympathetic dominance leading to a calm alert state that promotes an awakening of plasticities and intelligences that stress inhibits. We suggest that health, happiness, and meaning can be cultivated by a complex adaptive process that enhances healthy functioning

  17. Mechanism of selective recruitment of RNA polymerases II and III to snRNA gene promoters.

    PubMed

    Dergai, Oleksandr; Cousin, Pascal; Gouge, Jerome; Satia, Karishma; Praz, Viviane; Kuhlman, Tracy; Lhôte, Philippe; Vannini, Alessandro; Hernandez, Nouria

    2018-05-01

    RNA polymerase II (Pol II) small nuclear RNA (snRNA) promoters and type 3 Pol III promoters have highly similar structures; both contain an interchangeable enhancer and "proximal sequence element" (PSE), which recruits the SNAP complex (SNAPc). The main distinguishing feature is the presence, in the type 3 promoters only, of a TATA box, which determines Pol III specificity. To understand the mechanism by which the absence or presence of a TATA box results in specific Pol recruitment, we examined how SNAPc and general transcription factors required for Pol II or Pol III transcription of SNAPc-dependent genes (i.e., TATA-box-binding protein [TBP], TFIIB, and TFIIA for Pol II transcription and TBP and BRF2 for Pol III transcription) assemble to ensure specific Pol recruitment. TFIIB and BRF2 could each, in a mutually exclusive fashion, be recruited to SNAPc. In contrast, TBP-TFIIB and TBP-BRF2 complexes were not recruited unless a TATA box was present, which allowed selective and efficient recruitment of the TBP-BRF2 complex. Thus, TBP both prevented BRF2 recruitment to Pol II promoters and enhanced BRF2 recruitment to Pol III promoters. On Pol II promoters, TBP recruitment was separate from TFIIB recruitment and enhanced by TFIIA. Our results provide a model for specific Pol recruitment at SNAPc-dependent promoters. © 2018 Dergai et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Characteristics of insufficiently active participants that benefit from health-enhancing physical activity (HEPA) promotion programs implemented in the sports club setting.

    PubMed

    Ooms, Linda; Leemrijse, Chantal; Collard, Dorine; Schipper-van Veldhoven, Nicolette; Veenhof, Cindy

    2018-06-01

    Health-enhancing physical activity (HEPA) promotion programs are implemented in sports clubs. The purpose of this study was to examine the characteristics of the insufficiently active participants that benefit from these programs. Data of three sporting programs, developed for insufficiently active adults, were used for this study. These sporting programs were implemented in different sports clubs in the Netherlands. Participants completed an online questionnaire at baseline and after six months (n = 458). Of this sample, 35.1% (n = 161) was insufficiently active (i.e. not meeting HEPA levels) at baseline. Accordingly, two groups were compared: participants who were insufficiently active at baseline, but increased their physical activity to HEPA levels after six months (activated group, n = 86) versus participants who were insufficiently active both at baseline and after six months (non-activated group, n = 75). Potential associated characteristics (demographic, social, sport history, physical activity) were included as independent variables in bivariate and multivariate logistic regression analyses. The percentage of active participants increased significantly from baseline to six months (from 64.9 to 76.9%, p < 0.05). The bivariate logistic regression analyses showed that participants in the activated group were more likely to receive support from family members with regard to their sport participation (62.8% vs. 42.7%, p = 0.02) and spent more time in moderate-intensity physical activity (128 ± 191 min/week vs. 70 ± 106 min/week, p = 0.02) at baseline compared with participants in the non-activated group. These results were confirmed in the multivariate logistic regression analyses: when receiving support from most family members, there is a 216% increase in the odds of being in the activated group (OR = 2.155; 95% CI: 1.118-4.154, p = 0.02) and for each additional 1 min/week spent in moderate-intensity physical

  19. Lymphatic exosomes promote dendritic cell migration along guidance cues

    PubMed Central

    Brown, Markus; Johnson, Louise A.; Leone, Dario A.; Majek, Peter; Senfter, Daniel; Bukosza, Nora; Asfour, Gabriele; Langer, Brigitte; Parapatics, Katja; Hong, Young-Kwon; Bennett, Keiryn L.; Sixt, Michael

    2018-01-01

    Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified >1,700 cargo proteins and revealed a dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory response of human dendritic cells along guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory behavior and thus promote directional migration of CX3CR1-expressing cells in complex tissue environments. PMID:29650776

  20. Promoted Fixation of Molecular Nitrogen with Surface Oxygen Vacancies on Plasmon-Enhanced TiO2 Photoelectrodes.

    PubMed

    Li, Chengcheng; Wang, Tuo; Zhao, Zhi-Jian; Yang, Weimin; Li, Jian-Feng; Li, Ang; Yang, Zhilin; Ozin, Geoffrey A; Gong, Jinlong

    2018-05-04

    A hundred years on, the energy-intensive Haber-Bosch process continues to turn the N 2 in air into fertilizer, nourishing billions of people while causing pollution and greenhouse gas emissions. The urgency of mitigating climate change motivates society to progress toward a more sustainable method for fixing N 2 that is based on clean energy. Surface oxygen vacancies (surface O vac ) hold great potential for N 2 adsorption and activation, but introducing O vac on the very surface without affecting bulk properties remains a great challenge. Fine tuning of the surface O vac by atomic layer deposition is described, forming a thin amorphous TiO 2 layer on plasmon-enhanced rutile TiO 2 /Au nanorods. Surface O vac in the outer amorphous TiO 2 thin layer promote the adsorption and activation of N 2 , which facilitates N 2 reduction to ammonia by excited electrons from ultraviolet-light-driven TiO 2 and visible-light-driven Au surface plasmons. The findings offer a new approach to N 2 photofixation under ambient conditions (that is, room temperature and atmospheric pressure). © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Spatial enhancer clustering and regulation of enhancer-proximal genes by cohesin

    PubMed Central

    Ing-Simmons, Elizabeth; Seitan, Vlad C.; Faure, Andre J.; Flicek, Paul; Carroll, Thomas; Dekker, Job; Fisher, Amanda G.; Lenhard, Boris

    2015-01-01

    In addition to mediating sister chromatid cohesion during the cell cycle, the cohesin complex associates with CTCF and with active gene regulatory elements to form long-range interactions between its binding sites. Genome-wide chromosome conformation capture had shown that cohesin's main role in interphase genome organization is in mediating interactions within architectural chromosome compartments, rather than specifying compartments per se. However, it remains unclear how cohesin-mediated interactions contribute to the regulation of gene expression. We have found that the binding of CTCF and cohesin is highly enriched at enhancers and in particular at enhancer arrays or “super-enhancers” in mouse thymocytes. Using local and global chromosome conformation capture, we demonstrate that enhancer elements associate not just in linear sequence, but also in 3D, and that spatial enhancer clustering is facilitated by cohesin. The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. Interestingly, ∼50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements. We propose a model for cohesin-dependent gene regulation in which spatial clustering of enhancer elements acts as a unified mechanism for both enhancer-promoter “connections” and “insulation.” PMID:25677180

  2. Secrets of long life: cross-cultural explorations in sustainably enhancing vitality and promoting longevity via elders' practice wisdom.

    PubMed

    Pesek, Todd; Reminick, Ronald; Nair, Murali

    2010-01-01

    In searching for different patterns of practice, lifestyle, and environment supportive of optimal health, we look to our elders around the world, who in the wisdom that has sustained them, we learn from with careful attention. Thirty-seven elders who live by their traditions participated in the present study. They assisted in the refinement of the methodology and collections and preparation of these data. These participants are well-respected, representative elders and traditional healers of their regions. These data, from study sites of the Eastern Afromontane and Albertine Rift region of Ethiopia, Africa; the Maya Mountains region of Belize, Central America; the Western Ghats region of India; and the Appalachian Mountains region of the United States, were grouped into three major categories: (1) philosophy, attitudes, and outlook, (2) lifestyle practices, and (3) dietary and nutritional practices. These elders demonstrate a relatively comprehensive but simple set of practices that can enhance our vitality and promote longevity sustainably. In essence, these practices, or practice wisdom, of our longest living elders, promote propagation of healthful lifestyles by following traditional ways and taking care of body, mind, spirit and our environment. Further field research among a larger cohort is required to fully generalize the findings of this study, but much of it is consistent with what we already know should be done. These data begin illustration of practice wisdom for implementation and serve to engage our universities, our hospitals, our industries, and our students, who we must position toward social change. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. CCDC106 promotes non-small cell lung cancer cell proliferation.

    PubMed

    Zhang, Xiupeng; Zheng, Qin; Wang, Chen; Zhou, Haijing; Jiang, Guiyang; Miao, Yuan; Zhang, Yong; Liu, Yang; Li, Qingchang; Qiu, Xueshan; Wang, Enhua

    2017-04-18

    Coiled-coil domain containing (CCDC) family members enhance tumor cell proliferation, and high CCDC protein levels correlate with unfavorable prognoses. Limited research demonstrated that CCDC106 may promote the degradation of p53/TP53 protein and inhibit its transactivity. The present study demonstrated that CCDC106 expression correlates with advanced TNM stage (P = 0.008), positive regional lymph node metastasis (P < 0.001), and poor overall survival (P < 0.001) in 183 non-small cell lung cancer cases. A549 and H1299 cells were selected as representative of CCDC106-low and CCDC106-high expressing cell lines, respectively. CCDC106 overexpression promoted A549 cell proliferation and xenograft tumor growth in nude mice, while siRNA-mediated CCDC106 knockdown inhibited H1299 cell proliferation. CCDC106 promoted AKT phosphorylation and upregulated the cell cycle-regulating proteins Cyclin A2 and Cyclin B1. Cell proliferation promoted by CCDC106 via Cyclin A2 and Cyclin B1 was rescued by treatment with the AKT inhibitor, LY294002. Our studies revealed that CCDC106 is associated with non-small cell lung cancer progression and unfavorable prognosis. CCDC106 enhanced Cyclin A2 and Cyclin B1 expression and promoted A549 and H1299 cell proliferation, which depended on AKT signaling. These results suggest that CCDC106 may be a novel target for lung cancer treatment.

  4. A randomized trial to evaluate the effectiveness of an individual, education-based safe transport program for drivers aged 75 years and older

    PubMed Central

    2013-01-01

    Background There are concerns over safety of older drivers due to increased crash involvement and vulnerability to injury. However, loss of driving privileges can dramatically reduce independence and quality of life for older members of the community. The aim of this trial is to examine the effectiveness of a safe transport program for drivers aged 75 years and older at reducing driving exposure but maintaining mobility. Methods and design A randomised trial will be conducted, involving 380 drivers aged 75 years and older, resident in urban and semi-rural areas of North-West Sydney. The intervention is an education program based on the Knowledge Enhances Your Safety (KEYS) program, adapted for the Australian context. Driving experience will be measured objectively using an in-vehicle monitoring device which includes a global positioning system (GPS) to assess driving exposure and an accelerometer to detect rapid deceleration events. Participation will be assessed using the Keele Assessment of Participation (KAP). Data will be analysed on an intention-to-treat basis; the primary outcomes include driving exposure, rapid deceleration events and scores for KAP. Secondary outcomes include self-reported measures of driving, socialisation, uptake of alternative forms of transport, depressive symptoms and mood. A detailed process evaluation will be conducted, including examination of the delivery of the program and uptake of alternative forms of transport. A subgroup analysis is planned for drivers with reduced function as characterized by established cut-off scores on the Drivesafe assessment tool. Discussion This randomised trial is powered to provide an objective assessment of the efficacy of an individually tailored education and alternative transportation program to promote safety of older drivers but maintain mobility. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12612000543886. PMID:23379593

  5. Amphiregulin enhances VEGF-A production in human chondrosarcoma cells and promotes angiogenesis by inhibiting miR-206 via FAK/c-Src/PKCδ pathway.

    PubMed

    Wang, Chao-Qun; Huang, Yu-Wen; Wang, Shih-Wei; Huang, Yuan-Li; Tsai, Chun-Hao; Zhao, Yong-Ming; Huang, Bi-Fei; Xu, Guo-Hong; Fong, Yi-Chin; Tang, Chih-Hsin

    2017-01-28

    Chondrosarcoma is the second most common primary malignancy of bone after myeloma and osteosarcoma. Chondrosarcoma development may be linked to angiogenesis, which is principally elicited by vascular endothelial growth factor-A (VEGF-A). The expression of VEGF-A has been recognized as a prognostic marker in angiogenesis. Amphiregulin (AR), an epidermal growth factor receptor ligand, promotes tumor proliferation, metastasis and angiogenesis. However, the role of AR in VEGF-A expression and angiogenesis in human chondrosarcoma remains largely unknown. This current study shows that AR promoted VEGF-A production and induced angiogenesis of human endothelial progenitor cells. Moreover, AR-enhanced VEGF-A expression and angiogenesis involved the FAK, c-Src and PKCδ signaling pathways, while miR-206 expression was negatively mediated by AR via the FAK, c-Src and PKCδ pathways. Our results illustrate the clinical significance between AR, VEGF-A and miR-206, as well as tumor stage, in human chondrosarcoma. AR may represent a novel therapeutic target in the metastasis and angiogenesis of chondrosarcoma. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. MicroRNA-26a/-26b-COX-2-MIP-2 Loop Regulates Allergic Inflammation and Allergic Inflammation-promoted Enhanced Tumorigenic and Metastatic Potential of Cancer Cells*

    PubMed Central

    Kwon, Yoojung; Kim, Youngmi; Eom, Sangkyung; Kim, Misun; Park, Deokbum; Kim, Hyuna; Noh, Kyeonga; Lee, Hansoo; Lee, Yun Sil; Choe, Jongseon; Kim, Young Myeong; Jeoung, Dooil

    2015-01-01

    Cyclooxgenase-2 (COX-2) knock-out mouse experiments showed that COX-2 was necessary for in vivo allergic inflammation, such as passive cutaneous anaphylaxis, passive systemic anaphylaxis, and triphasic cutaneous allergic reaction. TargetScan analysis predicted COX-2 as a target of miR-26a and miR-26b. miR-26a/-26b decreased luciferase activity associated with COX-2–3′-UTR. miR-26a/-26b exerted negative effects on the features of in vitro and in vivo allergic inflammation by targeting COX-2. ChIP assays showed the binding of HDAC3 and SNAIL, but not COX-2, to the promoter sequences of miR-26a and miR-26b. Cytokine array analysis showed that the induction of chemokines, such as MIP-2, in the mouse passive systemic anaphylaxis model occurred in a COX-2-dependent manner. ChIP assays showed the binding of HDAC3 and COX-2 to the promoter sequences of MIP-2. In vitro and in vivo allergic inflammation was accompanied by the increased expression of MIP-2. miR-26a/-26b negatively regulated the expression of MIP-2. Allergic inflammation enhanced the tumorigenic and metastatic potential of cancer cells and induced positive feedback involving cancer cells and stromal cells, such as mast cells, macrophages, and endothelial cells. miR-26a mimic and miR-26b mimic negatively regulated the positive feedback between cancer cells and stromal cells and the positive feedback among stromal cells. miR-26a/-26b negatively regulated the enhanced tumorigenic potential by allergic inflammation. COX-2 was necessary for the enhanced metastatic potential of cancer cells by allergic inflammation. Taken together, our results indicate that the miR26a/-26b-COX-2-MIP-2 loop regulates allergic inflammation and the feedback relationship between allergic inflammation and the enhanced tumorigenic and metastatic potential. PMID:25907560

  7. Promoting interprofessional learning and enhancing the pre-registration student experience through reciprocal cross professional peer tutoring.

    PubMed

    McLeod, Fiona; Jamison, Caroline; Treasure, Karen

    2018-05-01

    To improve collaboration and the quality of care, healthcare programmes are increasingly promoting interprofessional education thereby enabling students to learn with, from and about each other. A reciprocal peer learning model has developed among pre-registration physiotherapy and adult nursing students at Plymouth University, England. Embedded within the curriculum, it provides voluntary opportunities for year two students to become cross professional peer tutors to year one students while enhancing interprofessional understanding and skills acquisition. To explore participant experiences of two cross professional peer tutored clinical skills workshops delivered to a cohort of nursing (n = 67) and physiotherapy (n = 53) students in 2015. A mixed methods approach generated qualitative and quantitative data. Qualitative data was gathered via focus groups and individual interviews of peer tutors and learners (n = 27). These were recorded, transcribed and thematically analysed. The Readiness for Interprofessional Learning Scale questionnaire (n = 84) was completed before and after the workshops to consider any influence on students' attitudes towards interprofessional learning. Four themes evolved from thematic analysis; benefits of cross professional peer tutoring, interprofessional teamwork, quality of care and factors influencing the delivery of the workshops. Data showed students felt they developed greater understanding of interprofessional roles and acquired new skills. Peer tutors developed confidence in representing their profession while appearing to inspire early stage students. The Readiness for Interprofessional Learning Scale questionnaire data identified very positive attitudes towards interprofessional learning among the majority of students in both cohorts before and after the workshop. This study endorses the utility of enhancing the Higher Education experience by offering voluntary peer tutoring opportunities. Participating students

  8. Cognition-Enhancing Drugs

    PubMed Central

    Mehlman, Maxwell J

    2004-01-01

    New drugs that enhance cognition in cognitively healthy individuals present difficult public policy challenges. While their use is not inherently unethical, steps must be taken to ensure that they are safe, that they are widely available to promote equality of opportunity, and that individuals are free to decide whether or not to use them. PMID:15330974

  9. Enhancement of Bone-Marrow-Derived Mesenchymal Stem Cell Angiogenic Capacity by NPWT for a Combinatorial Therapy to Promote Wound Healing with Large Defect

    PubMed Central

    Ma, Zhanjun

    2017-01-01

    Poor viability of engrafted bone marrow mesenchymal stem cells (BMSCs) often hinders their application for wound healing, and the strategy of how to take full advantage of their angiogenic capacity within wounds still remains unclear. Negative pressure wound therapy (NPWT) has been demonstrated to be effective for enhancing wound healing, especially for the promotion of angiogenesis within wounds. Here we utilized combinatory strategy using the transplantation of BMSCs and NPWT to investigate whether this combinatory therapy could accelerate angiogenesis in wounds. In vitro, after 9-day culture, BMSCs proliferation significantly increased in NPWT group. Furthermore, NPWT induced their differentiation into the angiogenic related cells, which are indispensable for wound angiogenesis. In vivo, rat full-thickness cutaneous wounds treated with BMSCs combined with NPWT exhibited better viability of the cells and enhanced angiogenesis and maturation of functional blood vessels than did local BMSC injection or NPWT alone. Expression of angiogenesis markers (NG2, VEGF, CD31, and α-SMA) was upregulated in wounds treated with combined BMSCs with NPWT. Our data suggest that NPWT may act as an inductive role to enhance BMSCs angiogenic capacity and this combinatorial therapy may serve as a simple but efficient clinical solution for complex wounds with large defects. PMID:28243602

  10. Enhancing Doctors’ Competencies in Communication With and Activation of Older Patients: The Promoting Active Aging (PRACTA) Computer-Based Intervention Study

    PubMed Central

    Chylińska, Joanna; Lazarewicz, Magdalena; Rzadkiewicz, Marta; Jaworski, Mariusz; Adamus, Miroslawa; Haugan, Gørill; Lillefjell, Monica; Espnes, Geir Arild

    2017-01-01

    Background Demographic changes over the past decades call for the promotion of health and disease prevention for older patients, as well as strategies to enhance their independence, productivity, and quality of life. Objective Our objective was to examine the effects of a computer-based educational intervention designed for general practitioners (GPs) to promote active aging. Methods The Promoting Active Aging (PRACTA) study consisted of a baseline questionnaire, implementation of an intervention, and a follow-up questionnaire that was administered 1 month after the intervention. A total of 151 primary care facilities (response rate 151/767, 19.7%) and 503 GPs (response rate 503/996, 50.5%) agreed to participate in the baseline assessment. At the follow-up, 393 GPs filled in the questionnaires (response rate, 393/503, 78.1%), but not all of them took part in the intervention. The final study group of 225 GPs participated in 3 study conditions: e-learning (knowledge plus skills modelling, n=42), a pdf article (knowledge only, n=89), and control (no intervention, n=94). We measured the outcome as scores on the Patients Expectations Scale, Communication Scale, Attitude Toward Treatment and Health Scale, and Self-Efficacy Scale. Results GPs participating in e-learning demonstrated a significant rise in their perception of older patients’ expectations for disease explanation (Wald χ2=19.7, P<.001) and in perception of motivational aspect of older patients’ attitude toward treatment and health (Wald χ2=8.9, P=.03) in comparison with both the control and pdf article groups. We observed additional between-group differences at the level of statistical trend. GPs participating in the pdf article intervention demonstrated a decline in self-assessed communication, both at the level of global scoring (Wald χ2=34.5, P<.001) and at the level of 20 of 26 specific behaviors (all P<.05). Factors moderating the effects of the intervention were the number of patients per GP and

  11. NCOA1 promotes angiogenesis in breast tumors by simultaneously enhancing both HIF1α- and AP-1-mediated VEGFa transcription

    PubMed Central

    Qin, Li; Xu, Yan; Xu, Yixiang; Ma, Gang; Liao, Lan; Wu, Yelin; Li, Yi; Wang, Xian; Wang, Xiaosong; Jiang, Jun; Wang, Jin; Xu, Jianming

    2015-01-01

    Nuclear receptor coactivator 1 (NCOA1) is overexpressed in a subset of breast cancer and its increased expression positively correlates with disease recurrence and metastasis. Although NCOA1 is known to promote breast cancer metastasis through working with multiple transcription factors to upregulate the expression of Twist1, ITGA5, CSF-1, SDF1 and CXCR4, the role of NCOA1 in breast tumor angiogenesis has not been investigated. In this study, we found that the microvascular density (MVD) was significantly decreased and increased in Ncoa1-knockout and NCOA1-overexpressing mammary tumors, respectively, in several breast cancer mouse models. Knockout or knockdown of NCOA1 in breast cancer cell lines also markedly compromised their capability to induce angiogenesis in Matrigel plugs embedded subcutaneously in mice, while this compromised capability could be rescued by VEGFa treatment. At the molecular level, NCOA1 upregulates VEGFa expression in both mouse mammary tumors and cultured breast cancer cells, and it does so by associating with both c-Fos, which is recruited to the AP-1 site at bp −938 of the VEGFa promoter, and HIF1α, which is recruited to the HIF1α-binding element at bp −979 of the VEGFa promoter, to enhance VEGFa transcription. In 140 human breast tumors, high NCOA1 protein correlates with high MVD and patients with both high NCOA1 and high MVD showed significantly shorter survival time. In summary, this study revealed a novel mechanism that NCOA1 potentiates breast cancer angiogenesis through upregulating HIF1α and AP-1-mediated VEGFa expression, which reinforces the rational of targeting NCOA1 in controlling breast cancer progression and metastasis. PMID:26287601

  12. Myostatin promotes the wasting of human myoblast cultures through promoting ubiquitin-proteasome pathway-mediated loss of sarcomeric proteins.

    PubMed

    Lokireddy, Sudarsanareddy; Mouly, Vincent; Butler-Browne, Gillian; Gluckman, Peter D; Sharma, Mridula; Kambadur, Ravi; McFarlane, Craig

    2011-12-01

    Myostatin is a negative regulator of skeletal muscle growth and in fact acts as a potent inducer of "cachectic-like" muscle wasting in mice. The mechanism of action of myostatin in promoting muscle wasting has been predominantly studied in murine models. Despite numerous reports linking elevated levels of myostatin to human skeletal muscle wasting conditions, little is currently known about the signaling mechanism(s) through which myostatin promotes human skeletal muscle wasting. Therefore, in this present study we describe in further detail the mechanisms behind myostatin regulation of human skeletal muscle wasting using an in vitro human primary myotube atrophy model. Treatment of human myotube populations with myostatin promoted dramatic myotubular atrophy. Mechanistically, myostatin-induced myotube atrophy resulted in reduced p-AKT concomitant with the accumulation of active dephosphorylated Forkhead Box-O (FOXO1) and FOXO3. We further show that addition of myostatin results in enhanced activation of atrogin-1 and muscle-specific RING finger protein 1 (MURF1) and reduced expression of both myosin light chain (MYL) and myosin heavy chain (MYH). In addition, we found that myostatin-induced loss of MYL and MYH proteins is dependent on the activity of the proteasome and mediated via SMAD3-dependent regulation of FOXO1 and atrogin-1. Therefore, these data suggest that the mechanism through which myostatin promotes muscle wasting is very well conserved between species, and that myostatin-induced human myotube atrophy is mediated through inhibition of insulin-like growth factor (IGF)/phosphoinositide 3-kinase (PI3-K)/AKT signaling and enhanced activation of the ubiquitin-proteasome pathway and elevated protein degradation.

  13. Myocyte enhancer factor 2A promotes proliferation and its inhibition attenuates myogenic differentiation via myozenin 2 in bovine skeletal muscle myoblast

    PubMed Central

    Wang, Ya-Ning; Yang, Wu-Cai; Li, Pei-Wei; Wang, Hong-Bao; Zhang, Ying-Ying

    2018-01-01

    Myocyte enhancer factor 2A (MEF2A) is widely distributed in various tissues or organs and plays crucial roles in multiple biological processes. To examine the potential effects of MEF2A on skeletal muscle myoblast, the functional role of MFE2A in myoblast proliferation and differentiation was investigated. In this study, we found that the mRNA expression level of Mef2a was dramatically increased during the myogenesis of bovine skeletal muscle primary myoblast. Overexpression of MEF2A significantly promoted myoblast proliferation, while knockdown of MEF2A inhibited the proliferation and differentiation of myoblast. RT-PCR and western blot analysis revealed that this positive effect of MEF2A on the proliferation of myoblast was carried out by triggering cell cycle progression by activating CDK2 protein expression. Besides, MEF2A was found to be an important transcription factor that bound to the myozenin 2 (MyoZ2) proximal promoter and performed upstream of MyoZ2 during myoblast differentiation. This study provides the first experimental evidence that MEF2A is a positive regulator in skeletal muscle myoblast proliferation and suggests that MEF2A regulates myoblast differentiation via regulating MyoZ2. PMID:29698438

  14. The knowledge, attitudes and practices of parents of children with asthma in 29 cities of China: a multi-center study

    PubMed Central

    2013-01-01

    Background Asthma is becoming increasingly prevalent among children in China. Poor parent knowledge and attitudes often contribute to inappropriate management practices, leading to deficiencies in the care process. We aimed to document the knowledge, attitudes and practices (KAP) of parents of children with asthma and analyze how knowledge and attitudes relate to practices. Our secondary objective was to identify the factors associated with parent KAP scores. Methods A KAP questionnaire was distributed to parents caring for 2960 children (0–14 years) diagnosed with asthma for at least 3 months from China’s 29 provinces. A 50-item questionnaire was devised for this cross-sectional survey based on a comprehensive review of the subject. Questionnaires were scored on 30 items regarding parent asthma-related KAP, with one point for every correct response and a possible range of 0–13 for knowledge, 0–7 for attitudes and 0–10 for practices. Higher scores indicated better KAP. Chi-squared tests and logistic regression were used to identify factors associated with practices and combined KAP scores. Results The response rate was 83.95% (2485/2960). Only 18.31% (455/2485) of parents correctly answered ≥ 60% of the knowledge questions (mean = 5.69). Most (89.85%; 2226/2485) gave positive responses to ≥ 60% of the attitude questions (mean = 5.23) while 67.89% (1687/2485) correctly answered ≥ 60% of the practices questions (mean = 6.19). Knowledge and attitudes were positively associated with pulmonary function testing, regular physician visits, monitoring with a peak flow meter and the Children’s Asthma Control Test questionnaire, avoidance of asthma triggers, using an inhaled β2 receptor agonist and adherence to medication regimen (p ≤ 0.05). Attitudes were also associated with allergen testing. In logistic regression analysis, high KAP scores (dichotomized by a cut-off score of 18) were positively associated with food allergy, rhinitis, physician visits

  15. Correlating the degree of metal–promoter interaction to ethanol selectivity over MnRh/CNTs CO hydrogenation catalysts

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

    Liu, Jingjing; Guo, Zhao; Childers, David

    2014-05-01

    Multi-walled carbon nanotubes (MCNTs) were used as a support for Rh-based catalysts for high pressure (20 bar) CO hydrogenation. 3 wt% Rh/CNTs catalysts were loaded with 1 wt% and 2 wt% Mn promoter, respectively, in order to study the effect of metal–promoter interactions for ethanol synthesis. Both STEM and EXAFS results showed ≈1 nm Rh particles in promoted as well as the unpromoted catalysts, STEM and EELS results verified the enhanced metal–promoter interaction when the amount of Mn promoter increased from 1 wt% to 2 wt%. The enhancement in the degree of metal–promoter interaction leads to an increase in themore » ethanol selectivity. Moreover, due to the nature of CNTs (low Z number), the Mn–Rh interactions could be observed at atomic resolution during the STEM–EELS characterization, and the promoter phase is confirmed as Mn(II) oxide by XANES and EELS.« less

  16. The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia.

    PubMed

    Lee, Young Mok; Pan, Chi-Jiunn; Koeberl, Dwight D; Mansfield, Brian C; Chou, Janice Y

    2013-11-01

    Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious recombinant adeno-associated virus pseudotype 2/8 (rAAV8) vectors expressing human G6Pase-α have been independently developed. One is a single-stranded vector containing a 2864-bp of the G6PC promoter/enhancer (rAAV8-GPE) and the other is a double-stranded vector containing a shorter 382-bp minimal G6PC promoter/enhancer (rAAV8-miGPE). To identify the best construct, a direct comparison of the rAAV8-GPE and the rAAV8-miGPE vectors was initiated to determine the best vector to take forward into clinical trials. We show that the rAAV8-GPE vector directed significantly higher levels of hepatic G6Pase-α expression, achieved greater reduction in hepatic glycogen accumulation, and led to a better toleration of fasting in GSD-Ia mice than the rAAV8-miGPE vector. Our results indicated that additional control elements in the rAAV8-GPE vector outweigh the gains from the double-stranded rAAV8-miGPE transduction efficiency, and that the rAAV8-GPE vector is the current choice for clinical translation in human GSD-Ia. © 2013.

  17. The Drosophila gypsy Insulator Supports Transvection in the Presence of the vestigial Enhancer

    PubMed Central

    Rickels, Ryan; Labrador, Mariano

    2013-01-01

    Though operationally defined as cis-regulatory elements, enhancers can also communicate with promoters on a separate homolog in trans, a mechanism that has been suggested to account for the ability of certain alleles of the same gene to complement one another in a process otherwise known as transvection. This homolog-pairing dependent process is facilitated in Drosophila by chromatin-associated pairing proteins, many of which remain unknown and their mechanism of action uncharacterized. Here we have tested the role of the gypsy chromatin insulator in facilitating pairing and communication between enhancers and promoters in trans using a transgenic eGFP reporter system engineered to allow for targeted deletions in the vestigial Boundary Enhancer (vgBE) and the hsp70 minimal promoter, along with one or two flanking gypsy elements. We found a modest 2.5-3x increase in eGFP reporter levels from homozygotes carrying an intact copy of the reporter on each homolog compared to unpaired hemizygotes, although this behavior was independent of gypsy. However, detectable levels of GFP protein along the DV wing boundary in trans-heterozygotes lacking a single enhancer and promoter was only observed in the presence of two flanking gypsy elements. Our results demonstrate that gypsy can stimulate enhancer-promoter communication in trans throughout the genome in a context-dependent manner, likely through modulation of local chromatin dynamics once pairing has been established by other elements and highlights chromatin structure as the master regulator of this phenomenon. PMID:24236213

  18. Assessing Opportunities to Enhance Comprehensive Health Promotion and Wellness Programming in a State Community College System.

    PubMed

    Linnan, Laura A; Arandia, Gabriela; Naseer, Carolyn; Li, Jiang; Pomerantz, Meg; Diehl, Sandra J

    2017-01-01

    BACKGROUND North Carolina has the third largest community college system in the nation and reaches residents in all 100 counties. Few studies have focused on the health of employees who work at these institutions. We assessed the current status of and interest in supporting health promotion efforts among North Carolina Community College System members. METHODS North Carolina Community College System presidents completed a brief 15-item survey assessing support for and interest in offering health promotion programs. Wellness coordinators completed a 60-item questionnaire assessing current health promotion programming and organizational, environmental, and policy supports for health promotion efforts. Onsite interviews with a sub-sample of Wellness coordinators offered insights into important implementation considerations. We examined differences by campus size with Fisher's exact test. RESULTS All 58 presidents (100%) and 51 wellness coordinators (88%) completed surveys. Ten percent of colleges offered comprehensive employee health promotion programming. Most offered physical activity (70.6%), tobacco cessation (51.0%), weight loss/management (49.0%), and/or nutrition counseling (47.1%). Larger colleges were more likely to offer programming and environmental support. Nearly all presidents (89.7%) believed it is "very" or "extremely" important to offer health promotion programs to employees, and most (84%) were interested in promoting health through a university partnership. LIMITATIONS Despite very high survey response rates from presidents and wellness coordinators at each community college, onsite interviews were only done at select campuses, limiting the generalizability and scope of conclusions derived from interview data. CONCLUSION Community colleges in North Carolina are promising settings for promoting employee health. Findings identify resources, barriers, and technical assistance that could facilitate greater adoption and implementation of programs. ©2017

  19. Knowledge, attitude and practice of hygiene and sanitation in a Burundian refugee camp: implications for control of a Salmonella typhi outbreak.

    PubMed

    Nahimana, Marie-Rosette; Ngoc, Candide Tran; Olu, Olushayo; Nyamusore, Jose; Isiaka, Ayodeji; Ndahindwa, Vedaste; Dassanayake, Lakruwan; Rusanganwa, André

    2017-01-01

    A Salmonella typhi outbreak was reported in a Burundian refugee camp in Rwanda in October 2015. Transmission persisted despite increased hygiene promotion activities and hand-washing facilities instituted to prevent and control the outbreak. A knowledge, attitude and practice (KAP) study was carried out to assess the effectiveness of ongoing typhoid fever preventive interventions. A cross-sectional survey was conducted in Mahama Refugee Camp of Kirehe District, Rwanda from January to February 2016. Data were obtained through administration of a structured KAP questionnaire. Descriptive, bivariate and multivariate analysis was performed using STATA software. A total of 671 respondents comprising 264 (39.3%) males and 407 (60.7%) females were enrolled in the study. A comparison of hand washing practices before and after institution of prevention and control measures showed a 37% increase in the proportion of respondents who washed their hands before eating and after using the toilet (p < 0.001). About 52.8% of participants reported having heard about typhoid fever, however 25.9% had received health education. Only 34.6% and 38.6% of the respondents respectively knew how typhoid fever spreads and is prevented. Most respondents (98.2%) used pit latrines for disposal of feces. Long duration of stay in the camp, age over 35 years and being unemployed were statistically associated with poor hand washing practices. The findings of this study underline the need for bolstering up health education and hygiene promotion activities in Mahama and other refugee camp settings.

  20. Incorporating Performance Improvement Methods into a Needs Assessment: Experience with a Nutrition and Exercise Curriculum

    PubMed Central

    Whalen, Ursula; Schneider, Jason; Cantey, Paul; Bussey-Jones, Jada; Brady, Donald; Doyle, Joyce P.

    2010-01-01

    BACKGROUND Clinical guidelines recommend that physicians counsel patients on diet and exercise; however, physician counseling remains suboptimal. OBJECTIVES To determine if incorporating performance improvement (PI) methodologies into a needs assessment for an internal medicine (IM) residency curriculum on nutrition and exercise counseling was feasible and enhanced our understanding of the curricular needs. DESIGN AND PARTICIPANTS One hundred and fifty-eight IM residents completed a questionnaire to assess their knowledge, attitudes, and practices (KAP) about nutrition and exercise counseling for hypertensive patients. Residents’ baseline nutrition and exercise counseling rates were also obtained using chart abstraction. Fishbone diagrams were created by the residents to delineate perceived barriers to diet and exercise counseling. MAIN MEASURES The KAP questionnaire was analyzed using descriptive statistics. Chart abstraction data was plotted on run charts and average counseling rates were calculated. Pareto charts were developed from the fishbone diagrams depicting the number of times each barrier was reported. KEY RESULTS Almost 90% of the residents reported counseling their hypertensive patients about diet and exercise more than 20% of the time on the KAP questionnaire. In contrast, chart abstraction revealed average counseling rates of 3% and 4% for nutrition and exercise, respectively. The KAP questionnaire exposed a clinical knowledge deficit, lack of familiarity with the national guidelines, and low self-efficacy. In contrast, the fishbone analysis highlighted patient apathy, patient co-morbidities, and time pressure as the major perceived barriers. CONCLUSIONS We found that incorporating PI methods into a needs assessment for an IM residency curriculum on nutrition and exercise counseling for patients at risk of cardiovascular disease was feasible, provided additional information not obtained through other means, and provided the opportunity to pilot the

  1. [Macrophage colony stimulating factor enhances non-small cell lung cancer invasion and metastasis by promoting macrophage M2 polarization].

    PubMed

    Li, Y J; Yang, L; Wang, L P; Zhang, Y

    2017-06-23

    Objective: To investigate the key cytokine which polarizes M2 macrophages and promotes invasion and metastasis in non-small cell lung cancer (NSCLC). Methods: After co-culture with A549 cells in vitro, the proportion of CD14(+) CD163(+) M2 macrophages in monocytes and macrophage colony stimulating factor (M-CSF) levels in culture supernatant were detected by flow cytometry, ELISA assay and real-time qPCR, respectively. The effects of CD14(+) CD163(+) M2 macrophages on invasion of A549 cells and angiogenesis of HUVEC cells were measured by transwell assay and tubule formation assay, respectively. The clinical and prognostic significance of M-CSF expression in NSCLC was further analyzed. Results: The percentage of CD14(+) CD163(+) M2 macrophages in monocytes and the concentration of M-CSF in the supernatant followed by co-culture was (12.03±0.46)% and (299.80±73.76)pg/ml, respectively, which were significantly higher than those in control group [(2.80±1.04)% and (43.07±11.22)pg/ml, respectively, P < 0.05]. Human recombinant M-CSF promoted M2 polarization of macrophages in vitro . M2 macrophages enhanced the invasion of A549 cells (66 cells/field vs. 26 cells/field) and the angiogenesis of HUVEC cells (22 tubes/field vs. 8 tubes/field). The mRNA expression of M-CSF in stage Ⅰ-Ⅱ patients (16.23±4.83) was significantly lower than that in stage Ⅲ-Ⅳ (53.84±16.08; P <0.05). M-CSF levels were associated with poorer overall survival and disease-free survival in NSCLC patients ( P <0.05). Conclusions: Tumor-derived M-CSF can induce CD14(+) CD163(+) M2 polarization of macrophages, which can further promote the metastasis and angiogenesis of NSCLC. M-CSF could be used as a potential therapeutic target of NSCLC.

  2. Functional architecture of two exclusively late stage pollen-specific promoters in rice (Oryza sativa L.).

    PubMed

    Yan, Shuo; Wang, Zhongni; Liu, Yuan; Li, Wei; Wu, Feng; Lin, Xuelei; Meng, Zheng

    2015-07-01

    Late stage pollen-specific promoters are important tools in crop molecular breeding. Several such promoters, and their functional motifs, have been well characterized in dicotyledonous plants such as tomato and tobacco. However, knowledge about the functional architecture of such promoters is limited in the monocotyledonous plant rice. Here, pollen-late-stage-promoter 1 (PLP1) and pollen-late-stage-promoter 2 (PLP2) were characterized using a stable transformation system in rice. Histochemical staining showed that the two promoters exclusively drive GUS expression in late-stage pollen grains in rice. 5' deletion analysis revealed that four regions, including the -1159 to -720 and the -352 to -156 regions of PLP1 and the -740 to -557 and the -557 to -339 regions of PLP2, are important in maintaining the activity and specificity of these promoters. Motif mutation analysis indicated that 'AGAAA' and 'CAAT' motifs in the -740 to -557 region of PLP2 act as enhancers in the promoter. Gain of function experiments indicated that the novel TA-rich motif 'TACATAA' and 'TATTCAT' in the core region of the PLP1 and PLP2 promoters is necessary, but not sufficient, for pollen-specific expression in rice. Our results provide evidence that the enhancer motif 'AGAAA' is conserved in the pollen-specific promoters of both monocots and eudicots, but that some functional architecture characteristics are different.

  3. Enhancing Flower Color through Simultaneous Expression of the B-peru and mPAP1 Transcription Factors under Control of a Flower-Specific Promoter

    PubMed Central

    Kim, Da-Hye; Park, Sangkyu; Lee, Jong-Yeol; Ha, Sun-Hwa; Lim, Sun-Hyung

    2018-01-01

    Flower color is a main target for flower breeding. A transgenic approach for flower color modification requires a transgene and a flower-specific promoter. Here, we expressed the B-peru gene encoding a basic helix loop helix (bHLH) transcription factor (TF) together with the mPAP1 gene encoding an R2R3 MYB TF to enhance flower color in tobacco (Nicotiana tabacum L.), using the tobacco anthocyanidin synthase (ANS) promoter (PANS) to drive flower-specific expression. The transgenic tobacco plants grew normally and produced either dark pink (PANSBP_DP) or dark red (PANSBP_DR) flowers. Quantitative real time polymerase chain reaction (qPCR) revealed that the expression of five structural genes in the flavonoid biosynthetic pathway increased significantly in both PANSBP_DP and PANSBP_DR lines, compared with the non-transformed (NT) control. Interestingly, the expression of two regulatory genes constituting the active MYB-bHLH-WD40 repeat (WDR) (MBW) complex decreased significantly in the PANSBP_DR plants but not in the PANSBP_DP plants. Total flavonol and anthocyanin abundance correlated with flower color, with an increase of 1.6–43.2 fold in the PANSBP_DP plants and 2.0–124.2 fold in the PANSBP_DR plants. Our results indicate that combinatorial expression of B-peru and mPAP1 genes under control of the ANS promoter can be a useful strategy for intensifying flower color without growth retardation. PMID:29361688

  4. The needs of health promoters on a health promotion programme for families with adolescents orphaned by HIV and AIDS.

    PubMed

    Mthobeni, Maseapo P; Peu, Mmapheko D

    2013-02-01

    The South African communities has shown to have a challenge in accessing health services especially in rural areas; hence the national strategic objective 1.7 aimed at strengthening community systems to expand access to services using the community-based care programmes (NSP 2012-2016). The programmes enhance access to health services whilst promoting health and educating the community to improve health knowledge and work towards attaining a healthy living (NSP 2012-2016). However, the health promoters from the rural Hammanskraal region in the North West Province of South Africa often found themselves rendering the health promotion services in their communities with limited resources. This study aimed at exploring and describing the challenges faced by health promoters in implementing health promotion programmes for families with adolescents orphaned by HIV and AIDS. The study followed a qualitative design. Data was collected using focus group interviews. Participants were purposely selected by the social worker and the health promotion coordinator working at Hammanskraal. The process of data analysis was adapted from the eight steps of Tesch method of data analysis where categories, sub-categories and themes were isolated. The following categories emerged as the needs of health promoters on health promotion programmes for families with adolescents orphaned by HIV and AIDS, (1) financial needs, (2) resources, (3) basic life needs, (4) educational needs and (5) health promoter's needs. It is therefore recommended that equal distribution of resources: including medicine, equipment and finances, should be maintained in order to ensure non-interrupted services.

  5. Practicing health promotion in primary care -a reflective enquiry.

    PubMed

    Pati, S; Chauhan, A S; Mahapatra, S; Sinha, R; Pati, S

    2017-12-01

    Health promotion is an integral part of routine clinical practice. The physicians' role in improving the health status of the general population, through effective understanding and delivery of health promotion practice, is evident throughout the international literature. Data from India suggest that physicians have limited skills in delivering specific health promotion services. However, the data available on this is scarce. This study was planned to document the current health promotion knowledge, perception and practices of local primary care physicians in Odisha. An exploratory study was planned between the months of January - February 2013 in Odisha among primary care physicians working in government set up. This exploratory study was conducted, using a two-step self-administered questionnaire, thirty physicians practicing under government health system were asked to map their ideal and current health promotion practice, and potential health promotion elements to be worked upon to enhance the practice. The study recorded a significant difference between the mean of current and ideal health promotion practices. The study reported that physicians want to increase their practice on health education. We concluded that inclusion of health promotion practices in routine care is imperative for a strong healthcare system. It should be incorporated as a structured health promotion module in medical curriculum as well.

  6. Healthy Schools Promotion: An Experience in Thailand

    ERIC Educational Resources Information Center

    Erawan, Prawit

    2005-01-01

    The promotion of health education in schools has been operated continuously in Thailand with expecting to enhance a healthy society based on the definition of health under the new trend "A comprehensive and integrated health and social dimensions of body, mind and soul into a lifestyle linked and interrelated the human relationship with a…

  7. Effective Blocking of the White Enhancer Requires Cooperation between Two Main Mechanisms Suggested for the Insulator Function

    PubMed Central

    Stakhov, Viacheslav; Ivlieva, Tatyana; Parshikov, Alexander; Studitsky, Vasily M.; Georgiev, Pavel

    2013-01-01

    Chromatin insulators block the action of transcriptional enhancers when interposed between an enhancer and a promoter. In this study, we examined the role of chromatin loops formed by two unrelated insulators, gypsy and Fab-7, in their enhancer-blocking activity. To test for this activity, we selected the white reporter gene that is activated by the eye-specific enhancer. The results showed that one copy of the gypsy or Fab-7 insulator failed to block the eye enhancer in most of genomic sites, whereas a chromatin loop formed by two gypsy insulators flanking either the eye enhancer or the reporter completely blocked white stimulation by the enhancer. However, strong enhancer blocking was achieved due not only to chromatin loop formation but also to the direct interaction of the gypsy insulator with the eye enhancer, which was confirmed by the 3C assay. In particular, it was observed that Mod(mdg4)-67.2, a component of the gypsy insulator, interacted with the Zeste protein, which is critical for the eye enhancer–white promoter communication. These results suggest that efficient enhancer blocking depends on the combination of two factors: chromatin loop formation by paired insulators, which generates physical constraints for enhancer–promoter communication, and the direct interaction of proteins recruited to an insulator and to the enhancer–promoter pair. PMID:23861668

  8. Approaches to Measuring the Effects of Wake-Promoting Drugs: A Focus on Cognitive Function

    PubMed Central

    Edgar, Christopher J.; Pace-Schott, Edward F.; Wesnes, Keith A.

    2009-01-01

    Objectives In clinical drug development, wakefulness and wake-promotion maybe assessed by a large number of scales and questionnaires. Objective assessment of wakefulness is most commonly made using sleep latency/maintenance of wakefulness tests, polysomnography and/or behavioral measures. The purpose of the present review is to highlight the degree of overlap in the assessment of wakefulness and cognition, with consideration of assessment techniques and the underlying neurobiology of both concepts. Design Reviews of four key areas were conducted: commonly used techniques in the assessment of wakefulness; neurobiology of sleep/wake and cognition; targets of wake promoting and/or cognition enhancing drugs; and ongoing clinical trials investigating wake promoting effects. Results There is clear overlap between the assessment of wakefulness and cognition. There are common techniques which may be used to assess both concepts; aspects of the neurobiology of both concepts may be closely related; and wake promoting drugs may have nootropic properties (and vice-versa). Clinical trials of wake promoting drugs often, though not routinely, assess aspects of cognition. Conclusions Routine and broad assessment of cognition in the development of wake promoting drugs may reveal important nootropic effects, which are not secondary to alertness/wakefulness, whilst existing cognitive enhancers may have under explored or unknown wake promoting properties. PMID:19565524

  9. The Promotion and Marketing of OxyContin: Commercial Triumph, Public Health Tragedy

    PubMed Central

    2009-01-01

    I focus on issues surrounding the promotion and marketing of controlled drugs and their regulatory oversight. Compared with noncontrolled drugs, controlled drugs, with their potential for abuse and diversion, pose different public health risks when they are overpromoted and highly prescribed. An in-depth analysis of the promotion and marketing of OxyContin illustrates some of the associated issues. Modifications of the promotion and marketing of controlled drugs by the pharmaceutical industry and an enhanced capacity of the Food and Drug Administration to regulate and monitor such promotion can have a positive impact on the public health. PMID:18799767

  10. Effect of infection control strategy on knowledge, attitude and practice towards hepatitis B transmission and prevention in vulnerable populations.

    PubMed

    Al-Tawil, M M; El-Gohary, E E; El-Sayed, M H

    2013-01-01

    Health care workers (HCWs) and hematological patients needing blood/ blood product transfusion are particularly vulnerable to blood born infections (BBI) including viral hepatitis. To evaluate knowledge, attitude and practice (KAP) of these target groups regarding viral hepatitis B (HBV) transmission and its change with implementing infection control policy and procedures. An anonymous questionnaire with closed questions was used to evaluate KAP including vaccination status in 2 target groups, in Children Hospital, Ain Shams University, Cairo, Egypt: 184 nurses and 210 children and adolescents with blood diseases. One year after instituting infection control as a part of hospital procedures, the same questionnaire was reused to evaluate KAP towards HBV. Baseline knowledge regarding HBV transmission, sequelae and preventive measures, was poor in both groups. Among nurses, only 62% wore gloves on withdrawing or giving blood to patients, 43.5% routinely washed hands between patients and 37.5% reported exposure after sharp injury. Only 38% of patients and 40% of nurses received HBV vaccination. Targeted infection control policy and procedures significantly improved KAP regarding HBV in both groups. Vaccination coverage significantly increased and reached 88.7% for nurses and 72% for patients. Hospital based infection control units with established policy and procedures against BBI significantly improved KAP towards HBV including a significant increase in vaccination intake.

  11. Peroxiredoxin 5 promotes the epithelial-mesenchymal transition in colon cancer

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

    Ahn, Hye-Mi; Yoo, Jin-Woo; College of Natural Sciences, Kyungpook National University, Daegu

    Globally, colorectal cancer (CRC) is common cause of cancer-related deaths. The high mortality rate of patients with colon cancer is due to cancer cell invasion and metastasis. Initiation of the epithelial-to-mesenchymal transition (EMT) is essential for the tumorigenesis. Peroxiredoinxs (PRX1-6) have been reported to be overexpressed in various tumor tissues, and involved to be responsible for tumor progression. However, the exact role of PRX5 in colon cancer remains to be investigated enhancing proliferation and promoting EMT properties. In this study, we constructed stably overexpressing PRX5 and suppressed PRX5 expression in CRC cells. Our results revealed that PRX5 overexpression significantly enhancedmore » CRC cell proliferation, migration, and invasion. On the other hand, PRX5 suppression markedly inhibited these EMT properties. PRX5 was also demonstrated to regulate the expression of two hallmark EMT proteins, E-cadherin and Vimentin, and the EMT-inducing transcription factors, Snail and Slug. Moreover, in the xenograft mouse model, showed that PRX5 overexpression enhances tumor growth of CRC cells. Thus, our findings first provide evidence in CRC that PRX5 promotes EMT properties by inducing the expression of EMT-inducing transcription factors. Therefore, PRX5 can be used as a predictive biomarker and serves as a putative therapeutic target for the development of clinical treatments for human CRC. - Highlights: • PRX5 promoted colorectal cancer cell proliferation. • PRX5 enhanced EMT properties in colorectal cancer. • PRX5 mediated the EMT by inducing the expression of Snail and Slug. • PRX5 promoted tumor growth of colorectal cancer cells.« less

  12. Health promotion in Swedish schools: school managers' views.

    PubMed

    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.

  13. B29 Gene Silencing in Pituitary Cells is Regulated by Its 3′ Enhancer

    PubMed Central

    Malone, Cindy S.; Kuraishy, Ali I.; Fike, Francesca M.; Loya, Ruchika G.; Mikkili, Minil R.; Teitell, Michael A.; Wall, Randolph

    2007-01-01

    Summary B cell-specific B29 (Igβ, CD79b) genes in rat, mouse, and human are situated between the 5′ growth hormone (GH) locus control region (LCR) and the 3′ GH gene cluster. The entire GH genomic region is DNase1 hypersensitive in GH-expressing pituitary cells, which predicts an “open” chromatin configuration, and yet B29 is not expressed. The B29 promoter and enhancers exhibit histone deacetylation in pituitary cells, but histone deacetylase inhibition failed to activate B29 expression. The B29 promoter and a 3′ enhancer showed local dense DNA methylation in both pituitary and non-lymphoid cells consistent with gene silencing. However, DNA methyltransferase inhibition did not activate B29 expression either. B29 promoter constructs were minimally activated in transfected pituitary cells. Co-transfection of the B cell-specific octamer transcriptional co-activator Bob1 with the B29 promoter construct resulted in high level promoter activity in pituitary cells comparable to B29 promoter activity in transfected B cells. Unexpectedly, inclusion of the B29 3′ enhancer in B29 promoter constructs strongly inhibited B29 transcriptional activity even when pituitary cells were co-transfected with Bob1. Both Oct-1 and Pit-1 bind the B29 3′ enhancer in in vitro EMSA and in in vivo chromatin immunoprecipitation analyses. These data indicate that the GH locus-embedded, tissue-specific B29 gene is silenced in GH-expressing pituitary cells by epigenetic mechanisms, the lack of a B cell-specific transcription factor, and likely by the B29 3′ enhancer acting as a powerful silencer in a context and tissue-specific manner. PMID:16920149

  14. A Social-Ecological Approach to Promote Self-Determination

    ERIC Educational Resources Information Center

    Walker, Hill M.; Calkins, Carl; Wehmeyer, Michael L.; Walker, Laura; Bacon, Ansley; Palmer, Susan B.; Jesien, George S.; Nygren, Margaret A.; Heller, Tamar; Gotto, George S.; Abery, Brian H.; Johnson, David R.

    2011-01-01

    This article describes a social-ecological approach for promoting and enhancing self-determination among individuals with developmental disabilities. A five-level model is presented, based on the interaction of person and environmental factors, that identifies a series of social mediator variables (i.e., social effectiveness, social capital,…

  15. [Comparison of knowledge, attitude and practice of students left at home or not on schistosomiasis prevention and control].

    PubMed

    Zhang, Gang-Gang; Zhao, An; Tang, Qi-Qiang; Zhu, Jing; Huang, Chao-Qing

    2012-02-01

    The questionnaire survey on knowledge, attitude and practice (KAP)of students left at home or not about schistosomiasis prevention and control showed that there were no statistically significant differences of the scores of KAP between the two groups of students (all P values were above 0.05).

  16. Technical Advance: Transcription factor, promoter, and enhancer utilization in human myeloid cells.

    PubMed

    Joshi, Anagha; Pooley, Christopher; Freeman, Tom C; Lennartsson, Andreas; Babina, Magda; Schmidl, Christian; Geijtenbeek, Teunis; Michoel, Tom; Severin, Jessica; Itoh, Masayoshi; Lassmann, Timo; Kawaji, Hideya; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Rehli, Michael; Hume, David A

    2015-05-01

    The generation of myeloid cells from their progenitors is regulated at the level of transcription by combinatorial control of key transcription factors influencing cell-fate choice. To unravel the global dynamics of this process at the transcript level, we generated transcription profiles for 91 human cell types of myeloid origin by use of CAGE profiling. The CAGE sequencing of these samples has allowed us to investigate diverse aspects of transcription control during myelopoiesis, such as identification of novel transcription factors, miRNAs, and noncoding RNAs specific to the myeloid lineage. We further reconstructed a transcription regulatory network by clustering coexpressed transcripts and associating them with enriched cis-regulatory motifs. With the use of the bidirectional expression as a proxy for enhancers, we predicted over 2000 novel enhancers, including an enhancer 38 kb downstream of IRF8 and an intronic enhancer in the KIT gene locus. Finally, we highlighted relevance of these data to dissect transcription dynamics during progressive maturation of granulocyte precursors. A multifaceted analysis of the myeloid transcriptome is made available (www.myeloidome.roslin.ed.ac.uk). This high-quality dataset provides a powerful resource to study transcriptional regulation during myelopoiesis and to infer the likely functions of unannotated genes in human innate immunity. © The Author(s).

  17. Dual personality of Mad1: regulation of nuclear import by a spindle assembly checkpoint protein.

    PubMed

    Cairo, Lucas V; Ptak, Christopher; Wozniak, Richard W

    2013-01-01

    Nuclear transport is a dynamic process that can be modulated in response to changes in cellular physiology. We recently reported that the transport activity of yeast nuclear pore complexes (NPCs) is altered in response to kinetochore-microtubule (KT-MT) interaction defects. Specifically, KT detachment from MTs activates a signaling pathway that prevents the nuclear import of cargos by the nuclear transport factor Kap121p. This loss of Kap121p-mediated import is thought to influence the nuclear environment, including the phosphorylation state of nuclear proteins. A key regulator of this process is the spindle assembly checkpoint protein Mad1p. In response to unattached KTs, Mad1p dynamically cycles between NPCs and KTs. This cycling appears to induce NPC molecular rearrangements that prevent the nuclear import of Kap121p-cargo complexes. Here, we discuss the underlying mechanisms and the physiological relevance of Mad1p cycling and the inhibition of Kap121p-mediated nuclear import, focusing on outstanding questions within the pathway.

  18. Are There Differences in Antibiotic Use Between the Recent-Immigrants from Mainland China and the Local-Born in Hong Kong?

    PubMed

    Wun, Yuk Tsan; Lam, Tai Pong; Lam, Kwok Fai; Ho, Pak Leung; Yung, Wai Hung Raymond

    2015-08-01

    Immigrants, especially the first-generation, were thought to have different knowledge, attitudes and practice (KAP) with antibiotics. Doctors often perceived extra pressure from them to prescribe antibiotics. To test these perceptions, we studied the difference in KAP with antibiotics between the recent-immigrants from mainland China and the local-born of Hong Kong-places with significantly different healthcare and socio-economic systems. Focus groups (including one specific group of recent-immigrants) with 56 participants and territory-wide telephone questionnaire survey with 2,471 randomly selected respondents. Recent-immigrants shared similar KAP with the local-born. After adjustment for age, sex and education, the main significant difference was the new-immigrants' behaviour of acquiring antibiotics without prescription and keeping the leftover. They, like the local-born, preferred doctors who prescribed antibiotics cautiously. Immigration status could be the surrogate for age, sex and education in the KAP with antibiotics. For antibiotic use, health education and patient care could be similar between the recent-immigrants and the local-born.

  19. Knowledge, attitude and perception of medical and dental undergraduates about antimicrobial stewardship

    PubMed Central

    Sharma, Kopal; Jain, Pushpawati; Sharma, Amit

    2015-01-01

    Objectives: This study aimed to identify the current knowledge, attitude, and perception (KAP) of the future prescribers about antimicrobial (AM) education so that the identified lacunae in the training curriculum can be effectively addressed. Materials and Methods: A questionnaire-based survey was carried out in the 2nd year students of medical and the dental undergraduate (UG) courses at a tertiary care teaching center in Jaipur. Each respondent completed the given questionnaire independently in the allocated time. A scoring system was used to rate the KAP of the respondents as poor, average, or good. Results: Statistically significant differences were found in the KAP of the medical and dental future prescribers (P = 0.0086, 0.0002, and <0.0001 for the KAP, respectively). Conclusion: The attitude of the UG students towards AM education is good, but the deficiencies in the knowledge and perception need to be improved further. Suitable interventions to address these lacunae must be planned. PMID:26729963

  20. Mental Health Promotion as a New Goal in Public Mental Health Care: A Randomized Controlled Trial of an Intervention Enhancing Psychological Flexibility

    PubMed Central

    Bohlmeijer, Ernst T.; Smit, Filip; Westerhof, Gerben J.

    2010-01-01

    Objectives. We assessed whether an intervention based on acceptance and commitment therapy (ACT) and mindfulness was successful in promoting positive mental health by enhancing psychological flexibility. Methods. Participants were 93 adults with mild to moderate psychological distress. They were randomly assigned to the group intervention (n = 49) or to a waiting-list control group (n = 44). Participants completed measures before and after the intervention as well as 3 months later at follow-up to assess mental health in terms of emotional, psychological, and social well-being (Mental Health Continuum–Short Form) as well as psychological flexibility (i.e., acceptance of present experiences and value-based behavior, Acceptance and Action Questionnaire-II). Results. Regression analyses showed that compared with the participants on the waiting list, participants in the ACT and mindfulness intervention had greater emotional and psychological well-being after the intervention and also greater psychological flexibility at follow-up. Mediational analyses showed that the enhancement of psychological flexibility during the intervention mediated the effects of the intervention on positive mental health. Conclusions. The intervention is effective in improving positive mental health by stimulating skills of acceptance and value-based action. PMID:20966360

  1. Mental health promotion as a new goal in public mental health care: a randomized controlled trial of an intervention enhancing psychological flexibility.

    PubMed

    Fledderus, Martine; Bohlmeijer, Ernst T; Smit, Filip; Westerhof, Gerben J

    2010-12-01

    We assessed whether an intervention based on acceptance and commitment therapy (ACT) and mindfulness was successful in promoting positive mental health by enhancing psychological flexibility. Participants were 93 adults with mild to moderate psychological distress. They were randomly assigned to the group intervention (n = 49) or to a waiting-list control group (n = 44). Participants completed measures before and after the intervention as well as 3 months later at follow-up to assess mental health in terms of emotional, psychological, and social well-being (Mental Health Continuum-Short Form) as well as psychological flexibility (i.e., acceptance of present experiences and value-based behavior, Acceptance and Action Questionnaire-II). Regression analyses showed that compared with the participants on the waiting list, participants in the ACT and mindfulness intervention had greater emotional and psychological well-being after the intervention and also greater psychological flexibility at follow-up. Mediational analyses showed that the enhancement of psychological flexibility during the intervention mediated the effects of the intervention on positive mental health. The intervention is effective in improving positive mental health by stimulating skills of acceptance and value-based action.

  2. Viral Activation of MK2-hsp27-p115RhoGEF-RhoA Signaling Axis Causes Cytoskeletal Rearrangements, P-body Disruption and ARE-mRNA Stabilization

    PubMed Central

    Corcoran, Jennifer A.; Johnston, Benjamin P.; McCormick, Craig

    2015-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the infectious cause of several AIDS-related cancers, including the endothelial cell (EC) neoplasm Kaposi's sarcoma (KS). KSHV-infected ECs secrete abundant host-derived pro-inflammatory molecules and angiogenic factors that contribute to tumorigenesis. The precise contributions of viral gene products to this secretory phenotype remain to be elucidated, but there is emerging evidence for post-transcriptional regulation. The Kaposin B (KapB) protein is thought to contribute to the secretory phenotype in infected cells by binding and activating the stress-responsive kinase MK2, thereby selectively blocking decay of AU-rich mRNAs (ARE-mRNAs) encoding pro-inflammatory cytokines and angiogenic factors. Processing bodies (PBs) are cytoplasmic ribonucleoprotein foci in which ARE-mRNAs normally undergo rapid 5′ to 3′ decay. Here, we demonstrate that PB dispersion is a feature of latent KSHV infection, which is dependent on kaposin protein expression. KapB is sufficient to disperse PBs, and KapB-mediated ARE-mRNA stabilization could be partially reversed by treatments that restore PBs. Using a combination of genetic and chemical approaches we provide evidence that KapB-mediated PB dispersion is dependent on activation of a non-canonical Rho-GTPase signaling axis involving MK2, hsp27, p115RhoGEF and RhoA. PB dispersion in latently infected cells is likewise dependent on p115RhoGEF. In addition to PB dispersion, KapB-mediated RhoA activation in primary ECs caused actin stress fiber formation, increased cell motility and angiogenesis; these effects were dependent on the activity of the RhoA substrate kinases ROCK1/2. By contrast, KapB-mediated PB dispersion occurred in a ROCK1/2-independent manner. Taken together, these observations position KapB as a key contributor to viral reprogramming of ECs, capable of eliciting many of the phenotypes characteristic of KS tumor cells, and strongly contributing to the post

  3. Physician resilience: what it means, why it matters, and how to promote it.

    PubMed

    Epstein, Ronald M; Krasner, Michael S

    2013-03-01

    Resilience is the capacity to respond to stress in a healthy way such that goals are achieved at minimal psychological and physical cost; resilient individuals "bounce back" after challenges while also growing stronger. Resilience is a key to enhancing quality of care, quality of caring, and sustainability of the health care workforce. Yet, ways of identifying and promoting resilience have been elusive. Resilience depends on individual, community, and institutional factors. The study by Zwack and Schweitzer in this issue of Academic Medicine illustrates that individual factors of resilience include the capacity for mindfulness, self-monitoring, limit setting, and attitudes that promote constructive and healthy engagement with (rather than withdrawal from) the often-difficult challenges at work. Cultivating these specific skills, habits, and attitudes that promote resilience is possible for medical students and practicing clinicians alike. Resilience-promoting programs should also strive to build community among clinicians and other members of the health care workforce. Just as patient safety is the responsibility of communities of practice, so is clinician well-being and support. Finally, it is in the self-interest of health care institutions to support the efforts of all members of the health care workforce to enhance their capacity for resilience; it will increase quality of care while reducing errors, burnout, and attrition. Successful organizations outside of medicine offer insight about institutional structures and values that promote individual and collective resilience. This commentary proposes methods for enhancing individuals' resilience while building community, as well as directions for future interventions, research, and institutional involvement.

  4. Regulation of the syncytin-1 promoter in human astrocytes by multiple sclerosis-related cytokines

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

    Mameli, Giuseppe; Astone, Vito; Khalili, Kamel

    Syncytin-1 has a physiological role during early pregnancy, as mediator of trophoblast fusion into the syncytiotrophoblast layer, hence allowing embryo implantation. In addition, its expression in nerve tissue has been proposed to contribute to the pathogenesis of multiple sclerosis (MS). Syncytin-1 is the env glycoprotein of the ERVWE1 component of the W family of human endogenous retroviruses (HERV), located on chromosome 7q21-22, in a candidate region for genetic susceptibility to MS. The mechanisms of ERVWE1 regulation in nerve tissue remain to be identified. Since there are correlations between some cytokines and MS outcome, we examined the regulation of the syncytin-1more » promoter by MS-related cytokines in human U-87MG astrocytic cells. Using transient transfection assays, we observed that the MS-detrimental cytokines TNF{alpha}, interferon-{gamma}, interleukin-6, and interleukin-1 activate the ERVWE1 promoter, while the MS-protective interferon-{beta} is inhibitory. The effects of cytokines are reduced by the deletion of the cellular enhancer domain of the promoter that contains binding sites for several transcription factors. In particular, we found that TNF{alpha} had the ability to activate the ERVWE1 promoter through an NF-{kappa}B-responsive element located within the enhancer domain of the promoter. Electrophoretic mobility shift and ChIP assays showed that TNF{alpha} enhances the binding of the p65 subunit of NF-{kappa}B, to its cognate site within the promoter. The effect of TNF{alpha} is abolished by siRNA directed against p65. Taken together, these results illustrate a role for p65 in regulating the ERVWE1 promoter and in TNF{alpha}-mediated induction of syncytin-1 in multiple sclerosis.« less

  5. Single- and double-walled carbon nanotubes enhance atherosclerogenesis by promoting monocyte adhesion to endothelial cells and endothelial progenitor cell dysfunction.

    PubMed

    Suzuki, Yuka; Tada-Oikawa, Saeko; Hayashi, Yasuhiko; Izuoka, Kiyora; Kataoka, Misa; Ichikawa, Shunsuke; Wu, Wenting; Zong, Cai; Ichihara, Gaku; Ichihara, Sahoko

    2016-10-13

    The use of carbon nanotubes has increased lately. However, the cardiovascular effect of exposure to carbon nanotubes remains elusive. The present study investigated the effects of pulmonary exposure to single-walled carbon nanotubes (SWCNTs) and double-walled carbon nanotubes (DWCNTs) on atherosclerogenesis using normal human aortic endothelial cells (HAECs) and apolipoprotein E-deficient (ApoE -/- ) mice, a model of human atherosclerosis. HAECs were cultured and exposed to SWCNTs or DWCNTs for 16 h. ApoE -/- mice were exposed to SWCNTs or DWCNTs (10 or 40 μg/mouse) once every other week for 10 weeks by pharyngeal aspiration. Exposure to CNTs increased the expression level of adhesion molecule (ICAM-1) and enhanced THP-1 monocyte adhesion to HAECs. ApoE -/- mice exposed to CNTs showed increased plaque area in the aorta by oil red O staining and up-regulation of ICAM-1 expression in the aorta, compared with vehicle-treated ApoE -/- mice. Endothelial progenitor cells (EPCs) are mobilized from the bone marrow into the circulation and subsequently migrate to the site of endothelial damage and repair. Exposure of ApoE -/- mice to high-dose SWCNTs or DWCNTs reduced the colony-forming units of EPCs in the bone marrow and diminished their migration function. The results suggested that SWCNTs and DWCNTs enhanced atherosclerogenesis by promoting monocyte adhesion to endothelial cells and inducing EPC dysfunction.

  6. Analysis of Volatile Organic Compounds Emitted by Plant Growth-Promoting Fungus Phoma sp. GS8-3 for Growth Promotion Effects on Tobacco

    PubMed Central

    Naznin, Hushna Ara; Kimura, Minako; Miyazawa, Mitsuo; Hyakumachi, Mitsuro

    2013-01-01

    We extracted volatile organic compounds (VOCs) emitted by a plant growth-promoting fungus (PGPF) Phoma sp. GS8-3 by gas chromatography and identified them by mass spectrometry. All of the identified compounds belonged to C4-C8 hydrocarbons. Volatiles varied in number and quantity by the culture period of the fungus (in days). 2-Methyl-propanol and 3-methyl-butanol formed the main components of the volatile blends for all the culture periods of fungus. Growth-promoting effects of the identified synthetic compounds were analyzed individually and in blends using tobacco plants. We found that the mixture of volatiles extracted from 3-day-old culture showed significant growth promotion in tobacco in vitro. The volatile blend showed better growth promotion at lower than higher concentrations. Our results confirm the potential role of volatile organic compounds in the mechanism of growth enhancement by GS8-3. PMID:23080408

  7. Promoting Early Reading: Research, Resources, and Best Practices

    ERIC Educational Resources Information Center

    McKenna, Michael C., Ed.; Walpole, Sharon, Ed.; Conradi, Kristin, Ed.

    2010-01-01

    Bringing together leading scholars, this book describes proven ways to enhance early literacy skills in 3- and 4-year-olds, especially those from low-income families. Presented are scientifically based methods and approaches that are being applied in Early Reading First programs around the country. Important topics include promoting oral language…

  8. Enhancing Doctors' Competencies in Communication With and Activation of Older Patients: The Promoting Active Aging (PRACTA) Computer-Based Intervention Study.

    PubMed

    Wlodarczyk, Dorota; Chylińska, Joanna; Lazarewicz, Magdalena; Rzadkiewicz, Marta; Jaworski, Mariusz; Adamus, Miroslawa; Haugan, Gørill; Lillefjell, Monica; Espnes, Geir Arild

    2017-02-22

    Demographic changes over the past decades call for the promotion of health and disease prevention for older patients, as well as strategies to enhance their independence, productivity, and quality of life. Our objective was to examine the effects of a computer-based educational intervention designed for general practitioners (GPs) to promote active aging. The Promoting Active Aging (PRACTA) study consisted of a baseline questionnaire, implementation of an intervention, and a follow-up questionnaire that was administered 1 month after the intervention. A total of 151 primary care facilities (response rate 151/767, 19.7%) and 503 GPs (response rate 503/996, 50.5%) agreed to participate in the baseline assessment. At the follow-up, 393 GPs filled in the questionnaires (response rate, 393/503, 78.1%), but not all of them took part in the intervention. The final study group of 225 GPs participated in 3 study conditions: e-learning (knowledge plus skills modelling, n=42), a pdf article (knowledge only, n=89), and control (no intervention, n=94). We measured the outcome as scores on the Patients Expectations Scale, Communication Scale, Attitude Toward Treatment and Health Scale, and Self-Efficacy Scale. GPs participating in e-learning demonstrated a significant rise in their perception of older patients' expectations for disease explanation (Wald χ 2 =19.7, P<.001) and in perception of motivational aspect of older patients' attitude toward treatment and health (Wald χ 2 =8.9, P=.03) in comparison with both the control and pdf article groups. We observed additional between-group differences at the level of statistical trend. GPs participating in the pdf article intervention demonstrated a decline in self-assessed communication, both at the level of global scoring (Wald χ 2 =34.5, P<.001) and at the level of 20 of 26 specific behaviors (all P<.05). Factors moderating the effects of the intervention were the number of patients per GP and the facility's organizational

  9. Promotion of flu vaccination among healthcare workers in an Italian academic hospital: An experience with tailored web tools

    PubMed Central

    Conte, Alessandro; Quattrin, Rosanna; Filiputti, Elisa; Cocconi, Roberto; Arnoldo, Luca; Tricarico, Pierfrancesco; Delendi, Mauro; Brusaferro, Silvio

    2016-01-01

    ABSTRACT Background: Influenza causes significant mortality particularly among the elderly and high-risk groups. Healthcare workers (HCWs) are at risk of occupational exposure due to contact with patients. Aims of this study was to promote flu shot among HCWs through a multimedia campaign in a large North-Eastern Italian Hospital. Methods: The 2013/2014 flu vaccination multimedia campaign addressed to HCWs was developed by maintaining pre-existing tools (letters in pay slip and poster displayed in wards) and creating 4 on-line spots (30") delivered trough the hospital intranet. Campaign effectiveness was assessed in terms of changes in knowledge, attitude and practice comparing data of pre (10 items) and post test (20 items) survey on a randomized sample of HCWs. Results: Response rates were 92.6% (464/501) in pre-test and 83.2% (417/501) in post-test. 93.8% (391/417) of HCWs reported to awareness of the campaign to promote vaccination. Spots were seen by 59.6% (233/391) of HCWs. Some reasons for vaccine denial, “not believing in vaccine efficacy” (34.7% to 14.9%), “not considering flu as a serious problem” (from 24% to 12.6%), “thinking not to get sick” (28.7% to 18.2%) or “being against the vaccine” (32.7% to 21%), showed a statistically significant reduction after the exposure to the campaign. The “intention to get vaccinated in the next year” instead, raised effectively (13.1% to 36.6%). Vaccinated HCWs rate in 2013-2014 season was 7.6% (221/2910), and 5.6% (164/2910) in 2012-2013 (p<0.005). Conclusions: The multimedia campaign succeeded with regard to KAP outcomes, but the vaccination rate is still far from the goal of 90%. Due to their impact, especially on younger age groups, web tools deserve to be better studied as effective approach to convey health information among HCWs. PMID:27245587

  10. Managing to enhance soil health

    USDA-ARS?s Scientific Manuscript database

    Healthy soils are critical for meeting current and future societal demands. Management strategies that protect the soil against erosion, build soil organic matter and promote nutrient cycling are ways to enhance soil health. Keeping soils covered and judicious use of agrochemicals are akin to us “hu...

  11. MiR-21/PTEN Axis Promotes Skin Wound Healing by Dendritic Cells Enhancement.

    PubMed

    Han, Zhaofeng; Chen, Ya; Zhang, Yile; Wei, Aizhou; Zhou, Jian; Li, Qian; Guo, Lili

    2017-10-01

    A number of miRNAs associated with wound repair have been identified and characterized, but the mechanism has not been fully clarified. MiR-21 is one of wound-related lncRNAs, and the study aimed to explore the functional involvement of miR-21 and its concrete mechanism in wound healing. In this study, the rat model of skin wounds was established. The expression of miR-21, PTEN and related molecules of wound tissues or cells was determined by quantitative real-time PCR and Western blot, respectively. The regulatory role of miR-21 on PTEN was examined by luciferase reporter gene assay. Flow cytometry assay was applied to measure cell number changes. MiR-21 was upregulated at 6, 24, 48, 72 h after model establishment, and the increase reached a maximum at 24 h in wound tissues. MMP-9 expression presented the same tread as miR-21 and was significantly enhanced within 6 h of wound formation, and then remained to be increased to the maximum at 24 h. The increase of miR-21 was accompanied by the increase of cell total number and DCs ratio in wound fluids. MiR-21 overexpression significantly improved the healing of skin wounds and increased the ratio of DCs in rats. The results of using FL confirmed that miR-21 overexpression obviously promoted DCs differentiation. Additionally, miR-21 could activate AKT/PI3K signaling pathway via inhibition of PTEN. MiR-21 contributes to wound healing via inhibition of PTEN that activated AKT/PI3K signaling pathway to increase DCs. J. Cell. Biochem. 118: 3511-3519, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Biomedical enhancements as justice.

    PubMed

    Nam, Jeesoo

    2015-02-01

    Biomedical enhancements, the applications of medical technology to make better those who are neither ill nor deficient, have made great strides in the past few decades. Using Amartya Sen's capability approach as my framework, I argue in this article that far from being simply permissible, we have a prima facie moral obligation to use these new developments for the end goal of promoting social justice. In terms of both range and magnitude, the use of biomedical enhancements will mark a radical advance in how we compensate the most disadvantaged members of society. © 2013 John Wiley & Sons Ltd.

  13. Hetero-oligomerization among the TIF family of RBCC/TRIM domain-containing nuclear cofactors: a potential mechanism for regulating the switch between coactivation and corepression.

    PubMed

    Peng, Hongzhuang; Feldman, Irina; Rauscher, Frank J

    2002-07-12

    The RING-B box-coiled-coil (RBCC) motif (also re-named recently as the tripartite motif (TRIM)) is a widely distributed motif that is hypothesized to be a protein-protein interface. The RBCC/TRIM domain of the corepressor KAP-1 is both necessary and sufficient to interact directly with the transcription repressor KRAB domain. Each subdomain of the KAP-1-RBCC contributes directly to the oligomerization and/or ligand recognition. Little is known about the function or the natural binding ligands for the RBCC/TRIM domain of the other TIF family members. In order to investigate whether hetero-oligomerization might be a biological regulatory mechanism, we have evaluated the hetero-oligomerization potential of the TIF family members including KAP-1, TIF1alpha, TIF1gamma, and the RBCC/TRIM family members including PML1, and MID1. We have reconstituted and characterized the oligomerization for these proteins using baculovirus and mammalian expression systems by biochemical approaches. Our data indicate that the RBCC/TRIM domains of KAP-1, TIF1alpha and TIF1gamma exist in a homo-oligomeric state. However, there is little cross-talk between KAP-1 and other TIF family members, suggesting that a high degree of specificity for oligomerization interface and ligand recognition is intrinsically built into the RBCC/TRIM domain of KAP-1. Finally, we demonstrate that TIF1alpha interacts with TIF1gamma and the coiled-coil region of TIF1gamma is necessary for this interaction. The hetero-oligomerization between TIF1alpha and TIF1gamma implies a potential regulatory mechanism for transcriptional regulation. (c) 2002 Elsevier Science Ltd.

  14. Exosomes Derived from Mesenchymal Stromal Cells Promote Axonal Growth of Cortical Neurons.

    PubMed

    Zhang, Yi; Chopp, Michael; Liu, Xian Shuang; Katakowski, Mark; Wang, Xinli; Tian, Xinchu; Wu, David; Zhang, Zheng Gang

    2017-05-01

    Treatment of brain injury with exosomes derived from mesenchymal stromal cells (MSCs) enhances neurite growth. However, the direct effect of exosomes on axonal growth and molecular mechanisms underlying exosome-enhanced neurite growth are not known. Using primary cortical neurons cultured in a microfluidic device, we found that MSC-exosomes promoted axonal growth, whereas attenuation of argonaut 2 protein, one of the primary microRNA (miRNA) machinery proteins, in MSC-exosomes abolished their effect on axonal growth. Both neuronal cell bodies and axons internalized MSC-exosomes, which was blocked by botulinum neurotoxins (BoNTs) that cleave proteins of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Moreover, tailored MSC-exosomes carrying elevated miR-17-92 cluster further enhanced axonal growth compared to native MSC-exosomes. Quantitative RT-PCR and Western blot analysis showed that the tailored MSC-exosomes increased levels of individual members of this cluster and activated the PTEN/mTOR signaling pathway in recipient neurons, respectively. Together, our data demonstrate that native MSC-exosomes promote axonal growth while the tailored MSC-exosomes can further boost this effect and that tailored exosomes can deliver their selective cargo miRNAs into and activate their target signals in recipient neurons. Neuronal internalization of MSC-exosomes is mediated by the SNARE complex. This study reveals molecular mechanisms that contribute to MSC-exosome-promoted axonal growth, which provides a potential therapeutic strategy to enhance axonal growth.

  15. Decoy receptor 3 promotes cell adhesion and enhances endometriosis development.

    PubMed

    Tsai, Hsiao-Wen; Huang, Ming-Ting; Wang, Peng-Hui; Huang, Ben-Shian; Chen, Yi-Jen; Hsieh, Shie-Liang

    2018-02-01

    Endometriosis is a multifactorial inflammatory disease with persistent activation of the nuclear factor-κB (NF-κB) signalling pathway. Aberrant adhesion of endometrium is the essential step in the progression of endometriosis, but the molecular mechanism of ectopic growth of endometrium is still unclear. Decoy receptor 3 (DcR3)/TNFRSF6B, a pleiotropic immunomodulator regulated by oestrogen, is able to activate focal adhesion kinase to promote cell adhesion. We found that DcR3 is upregulated in human ectopic endometrial cells via activation of the Akt-NF-κB signalling pathway, and its expression level correlates positively with that of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and homing cell adhesion molecule (HCAM; CD44). In a multivariate regression model, DcR3 expression level was the most significant parameter associated with endometriosis severity. Knockdown of DcR3 not only downregulated the expression of ICAM-1 and HCAM, but also reduced cell adhesion and migration. In vivo investigation further showed that DcR3 promoted the growth and spread of endometrium, whereas knockdown of DcR3 by lentivirus-delivered short hairpin RNA inhibited ectopic adhesion of endometrium and abrogated endometriosis progression. These observations are in support of DcR3 playing a critical role in the pathogenesis of endometriosis, and the inhibition of DcR3 expression being a promising approach for the treatment of endometriosis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  16. Negative modulation of the chicken infectious anemia virus promoter by COUP-TF1 and an E box-like element at the transcription start site binding deltaEF1.

    PubMed

    Miller, Myrna M; Jarosinski, Keith W; Schat, Karel A

    2008-12-01

    Expression of enhanced green fluorescent protein (EGFP) under control of the promoter-enhancer of chicken infectious anemia virus (CAV) is increased in an oestrogen receptor-enhanced cell line when treated with oestrogen and the promoter-enhancer binds unidentified proteins that recognize a consensus oestrogen response element (ERE). Co-transfection assays with the CAV promoter and the nuclear receptor chicken ovalbumin upstream promoter transcription factor 1 (COUP-TF1) showed that expression of EGFP was decreased by 50 to 60 % in DF-1 and LMH cells. The CAV promoter that included sequences at and downstream of the transcription start point had less expression than a short promoter construct. Mutation of a putative E box at this site restored expression levels. Electromobility shift assays showed that the transcription regulator delta-EF1 (deltaEF1) binds to this E box region. These findings indicate that the CAV promoter activity can be affected directly or indirectly by COUP-TF1 and deltaEF1.

  17. Investigation of smallholder farmer biosecurity and implications for sustainable foot-and-mouth disease control in Cambodia.

    PubMed

    Young, J R; Suon, S; Olmo, L; Bun, C; Hok, C; Ashley, K; Bush, R D; Windsor, P A

    2017-12-01

    In Cambodia, the majority of the population is rural and reliant on subsistence agriculture, with cattle raised by smallholder farmers using traditional practices, resulting in low productivity and vulnerability to foot-and-mouth disease (FMD). As FMD causes deleterious impacts on rural livelihoods, known FMD risk factors were reviewed, using knowledge, attitudes and practice (KAP) surveys of smallholders (n = 240) from four regions. The study aimed to understand current biosecurity threats to smallholder livelihoods and investigate the hypothesis that smallholder farmers practising FMD risk management should be associated with higher incomes from cattle. Descriptive data were examined to demonstrate trends in KAP and a multivariable linear regression model developed to identify cattle income predictors. Results showed that baseline mean knowledge scores were low at 28.4% across all regions and basic biosecurity practices, including quarantine of new cattle, isolation of sick cattle and FMD vaccination, were lacking. As farmers purchase and sell cattle from and to various administration levels (including export), there is high risk of FMD transmission into and from smallholder communities. The final multivariable linear regression model identified significant explanatory parameters for annual cattle income, including region, number of calves born, forage plot size (ha), vaccination of cattle and the number of cattle purchased (F pr. < 0.001, R 2  = 29.9). Individual biosecurity practices including FMD vaccination were not significant predictors of income. With the current focus of farmers on treatment of FMD with inappropriate antibiotics leading to potential anti-microbial residue issues, yet receptivity to payment for vaccine in most regions, there is an urgent need for a coordinated national biosecurity and FMD management public awareness campaign. Further, to enhance the association between improved cattle health and rural livelihoods, it is recommended

  18. Narciclasine attenuates diet-induced obesity by promoting oxidative metabolism in skeletal muscle

    PubMed Central

    Sinnakannu, Joanna R.; Ge, Xiaojia; Ma, Wei; Velan, Sendhil S.; Röder, Pia V.; Zhang, Qiongyi; Sim, Choon Kiat; Wu, Jingyi; Garcia-Miralles, Marta; Xie, Wei; McFarlane, Craig

    2017-01-01

    Obesity develops when caloric intake exceeds metabolic needs. Promoting energy expenditure represents an attractive approach in the prevention of this fast-spreading epidemic. Here, we report a novel pharmacological strategy in which a natural compound, narciclasine (ncls), attenuates diet-induced obesity (DIO) in mice by promoting energy expenditure. Moreover, ncls promotes fat clearance from peripheral metabolic tissues, improves blood metabolic parameters in DIO mice, and protects these mice from the loss of voluntary physical activity. Further investigation suggested that ncls achieves these beneficial effects by promoting a shift from glycolytic to oxidative muscle fibers in the DIO mice thereby enhancing mitochondrial respiration and fatty acid oxidation (FAO) in the skeletal muscle. Moreover, ncls strongly activates AMPK signaling specifically in the skeletal muscle. The beneficial effects of ncls treatment in fat clearance and AMPK activation were faithfully reproduced in vitro in cultured murine and human primary myotubes. Mechanistically, ncls increases cellular cAMP concentration and ADP/ATP ratio, which further lead to the activation of AMPK signaling. Blocking AMPK signaling through a specific inhibitor significantly reduces FAO in myotubes. Finally, ncls also enhances mitochondrial membrane potential and reduces the formation of reactive oxygen species in cultured myotubes. PMID:28207742

  19. Developing Trainee School Teachers' Expertise as Health Promoters

    ERIC Educational Resources Information Center

    Speller, Viv; Byrne, Jenny; Dewhirst, Sue; Almond, Palo; Mohebati, Lisa; Norman, Melanie; Polack, Sarah; Memon, Anjum; Grace, Marcus; Margetts, Barrie; Roderick, Paul

    2010-01-01

    Purpose: The purpose of this paper is to report the outcome of an education and public health collaboration investigating the impact of adapted training to enhance teachers' potential role to promote child health and wellbeing. Design/methodology/approach: The study was conducted in three phases: a survey of the health education content in…

  20. Using Prediction to Promote Mathematical Understanding and Reasoning

    ERIC Educational Resources Information Center

    Kasmer, Lisa; Kim, Ok-Kyeong

    2011-01-01

    Research has shown that prediction has the potential to promote the teaching and learning of mathematics because it can be used to enhance students' thinking and reasoning at all grade levels in various topics. This article addresses the effectiveness of using prediction on students' understanding and reasoning of mathematical concepts in a middle…

  1. Artistic Representation: Promoting Student Creativity and Self-Reflection

    ERIC Educational Resources Information Center

    Autry, Linda L.; Walker, Mary E.

    2011-01-01

    The authors conducted a qualitative study on the use of artistic representation to promote students' creativity and enhance their ability to self-reflect. The researchers used self-reflection articles about artistic representation and responses to a questionnaire at the end of the semester. Three overarching themes, as seen through the lens of the…

  2. Enhancing Access to Journal Literature.

    ERIC Educational Resources Information Center

    Maine Univ., Orono. Raymond H. Fogler Library.

    The libraries of the University of Maine System, Bates, Bowdoin, and Colby Colleges have installed integrated systems which are being linked electronically and are designed to promote the maximum sharing of library resources, thereby significantly enhancing the teaching and research capabilities of each institution. The institutions propose to…

  3. Promotion and resignation in employee networks

    NASA Astrophysics Data System (ADS)

    Yuan, Jia; Zhang, Qian-Ming; Gao, Jian; Zhang, Linyan; Wan, Xue-Song; Yu, Xiao-Jun; Zhou, Tao

    2016-02-01

    Enterprises have put more and more emphasis on data analysis so as to obtain effective management advices. Managers and researchers are trying to dig out the major factors that lead to employees' promotion and resignation. Most previous analyses are based on questionnaire survey, which usually consists of a small fraction of samples and contains biases caused by psychological defense. In this paper, we successfully collect a data set consisting of all the employees' work-related interactions (action network, AN for short) and online social connections (social network, SN for short) of a company, which inspires us to reveal the correlations between structural features and employees' career development, namely promotion and resignation. Through statistical analysis, we show that the structural features of both AN and SN are correlated and predictive to employees' promotion and resignation, and the AN has higher correlation and predictability. More specifically, the in-degree in AN is the most relevant indicator for promotion, while the k-shell index in AN and in-degree in SN are both very predictive to resignation. Our results provide a novel and actionable understanding of enterprise management and suggest that to enhance the interplays among employees, no matter work-related or social interplays, can be helpful to reduce staffs' turnover risk.

  4. FBI-1 promotes cell proliferation and enhances resistance to chemotherapy of hepatocellular carcinoma in vitro and in vivo.

    PubMed

    Fang, Feng; Yang, Lianyue; Tao, Yiming; Qin, Wei

    2012-01-01

    The so-called factor that binds to inducer of short transcripts-1 (FBI-1) purportedly plays an important role in tumorigenesis; however, its role in hepatocellular carcinoma (HCC) remains unknown. The objective of this study was to investigate the expression level, clinical relevance, and biologic function of FBI-1 in HCC. Real-time quantitative reverse transcriptase-polymerase chain reaction analysis, Western blot analysis, and immunohistochemical staining were used to detect expression levels of FBI-1 and to analyze its relation to clinicopathologic parameters and to the prognosis of patients with HCC. In addition, the biologic functions of FBI-1 in regulating cell proliferation, migration, and reaction to chemotherapy were detected by using HepG2 cells and SMMC-7721 cells; subsequently, the molecular mechanism of FBI-1 also was investigated. Finally, a xenograft mouse model was used to validate the observations obtained from in vitro studies. Expression levels of FBI-1 messenger RNA and protein were elevated significantly in HCC tissues compared with adjacent nontumorous liver tissues (ANLTs). Increased FBI-1 expression was correlated with multiple tumor nodes, Edmondson-Steiner grade, and a poor prognosis in patients with HCC (P < .05). In vitro studies revealed that FBI-1 was capable of promoting cell proliferation (but not cell migration) by regulating the cell cycle regulation proteins p53, p21, and p27. In addition, FBI-1 could inhibit cell death induced by 5-fluorouracil or doxorubicin through suppressing the activation of p53. Consistent with the in vitro data, FBI-1 was capable of promoting cell proliferation and enhancing chemotherapy resistance of HCC in vivo. The current findings indicated that FBI-1 plays an important role in HCC carcinogenesis and chemotherapy tolerance, and FBI-1 may served as a novel prognostic marker and therapeutic target for HCC. Copyright © 2011 American Cancer Society.

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

    PubMed

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

    2013-06-01

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

  6. Enhancing Graduate Education: Promoting a Scholarship of Teaching and Learning through Mentoring

    ERIC Educational Resources Information Center

    Trask, Bahira Sherif; Marotz-Baden, Ramona; Settles, Barbara; Gentry, Deborah; Berke, Debra

    2008-01-01

    This article highlights the importance of mentoring processes in the education of future scholars. The purpose is to recommend that scholars link the process of mentoring graduate students with promoting a scholarship of teaching and learning (SoTL). It suggests that through this process graduate students will acquire some of the skills they need…

  7. Genetic enhancement, human nature, and rights.

    PubMed

    McConnell, Terrance

    2010-08-01

    Authors such as Francis Fukuyama, the President's Council on Bioethics, and George Annas have argued that biotechnological interventions that aim to promote genetic enhancement pose a threat to human nature. This paper clarifies what conclusions these critics seek to establish, and then shows that there is no plausible account of human nature that will meet the conditions necessary to support this position. Appeals to human nature cannot establish a prohibition against the pursuit of genetic enhancement.

  8. Enhanced Expression of Fibroblast Growth Factor Receptor 3 IIIc Promotes Human Esophageal Carcinoma Cell Proliferation

    PubMed Central

    Ueno, Nobuhiro; Shimizu, Akio; Kanai, Michiyuki; Iwaya, Yugo; Ueda, Shugo; Nakayama, Jun; Seo, Misuzu Kurokawa

    2015-01-01

    Deregulated expression of fibroblast growth factor receptors (FGFRs) and their ligands plays critical roles in tumorigenesis. The gene expression of an alternatively spliced isoforms of FGFR3, FGFR3IIIc, was analyzed by RT-PCR in samples from patients with esophageal carcinoma (EC), including esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). The incidence of FGFR3IIIc was higher in EC [12/16 (75%); p=0.073] than in non-cancerous mucosa (NCM) [6/16 (38%)]. Indeed, an immunohistochemical analysis of early-stage ESCC showed that carcinoma cells expressing FGFR3IIIc stained positively with SCC-112, a tumor marker, and Ki67, a cell proliferation marker, suggesting that the expression of FGFR3IIIc promotes cell proliferation. We used EC-GI-10 cells endogenously expressing FGFR3IIIc as a model of ESCC to provide mechanistic insight into the role of FGFR3IIIc in ESCC. The knockdown of endogenous FGFR3 using siRNA treatment significantly abrogated cell proliferation and the overexpression of FGFR3IIIc in cells with enhanced cell proliferation. EC-GI-10 cells and ESCC from patients with EC showed endogenous expression of FGF2, a specific ligand for FGFR3IIIc, suggesting that the upregulated expression of FGFR3IIIc may create autocrine FGF signaling in ESCC. Taken together, FGFR3IIIc may have the potential to be an early-stage tumor marker and a molecular target for ESCC therapy. PMID:26487184

  9. Yeast Nucleoporins Involved in Passive Nuclear Envelope Permeability

    PubMed Central

    Shulga, Nataliya; Mosammaparast, Nima; Wozniak, Richard; Goldfarb, David S.

    2000-01-01

    The vertebrate nuclear pore complex (NPC) harbors an ∼10-nm diameter diffusion channel that is large enough to admit 50-kD polypeptides. We have analyzed the permeability properties of the Saccharomyces cerevisiae nuclear envelope (NE) using import (NLS) and export (NES) signal-containing green fluorescent protein (GFP) reporters. Compared with wild-type, passive export rates of a classical karyopherin/importin (Kap) Kap60p/Kap95p-targeted NLS-GFP reporter (cNLS-GFP) were significantly faster in nup188-Δ and nup170-Δ cells. Similar results were obtained using two other NLS-GFP reporters, containing either the Kap104p-targeted Nab2p NLS (rgNLS) or the Kap121p-targeted Pho4p NLS (pNLS). Elevated levels of Hsp70 stimulated cNLS-GFP import, but had no effect on the import of rgNLS-GFP. Thus, the role of Hsp70 in NLS-directed import may be NLS- or targeting pathway-specific. Equilibrium sieving limits for the diffusion channel were assessed in vivo using NES-GFP reporters of 36–126 kD and were found to be greater than wild-type in nup188-Δ and nup170-Δ cells. We propose that Nup170p and Nup188p are involved in establishing the functional resting diameter of the NPC's central transport channel. PMID:10831607

  10. CDKL2 promotes epithelial-mesenchymal transition and breast cancer progression

    PubMed Central

    Li, Linna; Liu, Chunping; Amato, Robert J.; Chang, Jeffrey T.; Du, Guangwei; Li, Wenliang

    2014-01-01

    The epithelial–mesenchymal transition (EMT) confers mesenchymal properties on epithelial cells and has been closely associated with the acquisition of aggressive traits by epithelial cancer cells. To identify novel regulators of EMT, we carried out cDNA screens that covered 500 human kinases. Subsequent characterization of candidate kinases led us to uncover cyclin-dependent kinase-like 2 (CDKL2) as a novel potent promoter for EMT and breast cancer progression. CDKL2-expressing human mammary gland epithelial cells displayed enhanced mesenchymal traits and stem cell-like phenotypes, which was acquired through activating a ZEB1/E-cadherin/β-catenin positive feedback loop and regulating CD44 mRNA alternative splicing to promote conversion of CD24high cells to CD44high cells. Furthermore, CDKL2 enhanced primary tumor formation and metastasis in a breast cancer xenograft model. Notably, CDKL2 is expressed significantly higher in mesenchymal human breast cancer cell lines than in epithelial lines, and its over-expression/amplification in human breast cancers is associated with shorter disease-free survival. Taken together, our study uncovered a major role for CDKL2 in promoting EMT and breast cancer progression. PMID:25333262

  11. Tetramethylpyrazine-Inducible Promoter Region from Rhodococcus jostii TMP1.

    PubMed

    Stanislauskienė, Rūta; Kutanovas, Simonas; Kalinienė, Laura; Bratchikov, Maksim; Meškys, Rolandas

    2018-06-25

    An inducible promoter region, P TTMP (tetramethylpyrazine [TTMP]), has been identified upstream of the tpdABC operon, which contains the genes required for the initial degradation of 2,3,5,6-tetramethylpyrazine in Rhodococcus jostii TMP1 bacteria. In this work, the promoter region was fused with the gene for the enhanced green fluorescent protein (EGFP) to investigate the activity of P TTMP by measuring the fluorescence of bacteria. The highest promoter activity was observed when bacteria were grown in a nutrient broth (NB) medium supplemented with 5 mM 2,3,5,6-tetramethylpyrazine for 48 h. Using a primer extension reaction, two transcriptional start sites for tpdA were identified, and the putative −35 and −10 promoter motifs were determined. The minimal promoter along with two 15 bp long direct repeats and two 7 bp inverted sequences were identified. Also, the influence of the promoter elements on the activity of P TTMP were determined using site-directed mutagenesis. Furthermore, P TTMP was shown to be induced by pyrazine derivatives containing methyl groups in the 2- and 5-positions of the heterocyclic ring, in the presence of the LuxR family transcriptional activator TpdR.

  12. mTORC2 Promotes Tumorigenesis via Lipid Synthesis.

    PubMed

    Guri, Yakir; Colombi, Marco; Dazert, Eva; Hindupur, Sravanth K; Roszik, Jason; Moes, Suzette; Jenoe, Paul; Heim, Markus H; Riezman, Isabelle; Riezman, Howard; Hall, Michael N

    2017-12-11

    Dysregulated mammalian target of rapamycin (mTOR) promotes cancer, but underlying mechanisms are poorly understood. We describe an mTOR-driven mouse model that displays hepatosteatosis progressing to hepatocellular carcinoma (HCC). Longitudinal proteomic, lipidomics, and metabolomic analyses revealed that hepatic mTORC2 promotes de novo fatty acid and lipid synthesis, leading to steatosis and tumor development. In particular, mTORC2 stimulated sphingolipid (glucosylceramide) and glycerophospholipid (cardiolipin) synthesis. Inhibition of fatty acid or sphingolipid synthesis prevented tumor development, indicating a causal effect in tumorigenesis. Increased levels of cardiolipin were associated with tubular mitochondria and enhanced oxidative phosphorylation. Furthermore, increased lipogenesis correlated with elevated mTORC2 activity and HCC in human patients. Thus, mTORC2 promotes cancer via formation of lipids essential for growth and energy production. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Health promoting attitudes and behaviors of emergency physicians: exploring gender differences.

    PubMed

    Rondeau, Kent V; Francescutti, Louis H; Cummings, Garnet E

    2006-01-01

    The purpose of this paper is to report on gender differences in emergency physicians with respect to their attitudes, knowledge, and practices concerning health promotion and disease prevention. A mail survey of 325 male and 97 female Canadian emergency physicians. Results suggest female emergency physicians report having greater knowledge of health promotion topics, spend more time with each of their patients in the emergency setting, and engage in more health promotion counseling in the emergency setting than do their male counterparts. The paper argues that in the future, educating and socializing emergency physicians, both male and female, in the practice of health promotion will enhance the potential of the emergency department to be a more effective resource for their community.

  14. Far infrared promotes wound healing through activation of Notch1 signaling.

    PubMed

    Hsu, Yung-Ho; Lin, Yuan-Feng; Chen, Cheng-Hsien; Chiu, Yu-Jhe; Chiu, Hui-Wen

    2017-11-01

    The Notch signaling pathway is critically involved in cell proliferation, differentiation, development, and homeostasis. Far infrared (FIR) has an effect that promotes wound healing. However, the underlying molecular mechanisms are unclear. In the present study, we employed in vivo and HaCaT (a human skin keratinocyte cell line) models to elucidate the role of Notch1 signaling in FIR-promoted wound healing. We found that FIR enhanced keratinocyte migration and proliferation. FIR induced the Notch1 signaling pathway in HaCaT cells and in a microarray dataset from the Gene Expression Omnibus database. We next determined the mRNA levels of NOTCH1 in paired normal and wound skin tissues derived from clinical patients using the microarray dataset and Ingenuity Pathway Analysis software. The result indicated that the Notch1/Twist1 axis plays important roles in wound healing and tissue repair. In addition, inhibiting Notch1 signaling decreased the FIR-enhanced proliferation and migration. In a full-thickness wound model in rats, the wounds healed more rapidly and the scar size was smaller in the FIR group than in the light group. Moreover, FIR could increase Notch1 and Delta1 in skin tissues. The activation of Notch1 signaling may be considered as a possible mechanism for the promoting effect of FIR on wound healing. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model.

  15. Enhanced photocatalytic activity of wool-ball-like TiO2 microspheres on carbon fabric and FTO substrates

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Gu, Jian; Zhang, Mengqi

    2018-06-01

    The wool-ball-like TiO2 microspheres on carbon fabric (TiO2-CF) and FTO substrates (TiO2-FTO) have been synthesized by a facile hydrothermal method in alkali environment, using commercial TiO2 (P25) as precursors. The XRD results indicate that the as-prepared TiO2 have good crystallinity. And the SEM images show that the wool-ball-like TiO2 microspheres with a diameter of 2-3 μm are composed of TiO2 nanowires, which have a diameter of 50 nm. The photocatalytic behavior of the wool-ball-like TiO2 microspheres, TiO2-CF and TiO2-FTO under ultraviolet light was investigated by a pseudo first-order kinetic model, using methyl orange (MO) as pollutant. The wool-ball-like TiO2 microspheres obtained a degradation rate constant (Kap) of 6.91×10-3 min-1 . The Kap values of TiO2-FTO and TiO2-CF reach 13.97×10-3 min-1 and 11.80×10-3 min-1, which are 2.0 and 1.7 times higher than that of pristine wool-ball-like TiO2 microspheres due to the "sum effect" between TiO2 and substrates. This study offers a facile hydrothermal method to prepare wool-ball-like TiO2 microspheres on CF and FTO substrates, which will improve the recyclability of phtocatalysts and can be extended to other fields.

  16. Role of Arachidonic Acid in Promoting Hair Growth

    PubMed Central

    Munkhbayar, Semchin; Jang, Sunhyae; Cho, A-Ri; Choi, Soon-Jin; Shin, Chang Yup; Eun, Hee Chul; Kim, Kyu Han

    2016-01-01

    Background Arachidonic acid (AA) is an omega-6 polyunsaturated fatty acid present in all mammalian cell membranes, and involved in the regulation of many cellular processes, including cell survival, angiogenesis, and mitogenesis. The dermal papilla, composed of specialized fibroblasts located in the bulb of the hair follicle, contributes to the control of hair growth and the hair cycle. Objective This study investigated the effect of AA on hair growth by using in vivo and in vitro models. Methods The effect of AA on human dermal papilla cells (hDPCs) and hair shaft elongation was evaluated by MTT assay and hair follicle organ culture, respectively. The expression of various growth and survival factors in hDPCs were investigated by western blot or immunohistochemistry. The ability of AA to induce and prolong anagen phase in C57BL/6 mice was analyzed. Results AA was found to enhance the viability of hDPCs and promote the expression of several factors responsible for hair growth, including fibroblast growth factor-7 (FGF-7) and FGF-10. Western blotting identified the role of AA in the phosphorylation of various transcription factors (ERK, CREB, and AKT) and increased expression of Bcl-2 in hDPCs. In addition, AA significantly promoted hair shaft elongation, with increased proliferation of matrix keratinocytes, during ex vivo hair follicle culture. It was also found to promote hair growth by induction and prolongation of anagen phase in telogen-stage C57BL/6 mice. Conclusion This study concludes that AA plays a role in promoting hair growth by increasing the expression of growth factors in hDPCs and enhancing follicle proliferation and survival. PMID:26848219

  17. Forensics: Enhancing Civic Literacy & Democracy

    ERIC Educational Resources Information Center

    Briscoe, Shawn F.

    2009-01-01

    Forensics--interpretation, speech, and debate--can and should be a meaningful part of every school's curriculum. To put it simply, the course of study, alongside cocurricular competition, promotes civic education and enhances the standard curriculum by helping students explore myriad topics from multiple angles and find the truth in each,…

  18. Effect of applying an arsenic-resistant and plant growth-promoting rhizobacterium to enhance soil arsenic phytoremediation by Populus deltoides LH05-17.

    PubMed

    Wang, Q; Xiong, D; Zhao, P; Yu, X; Tu, B; Wang, G

    2011-11-01

    Bioremediation of highly arsenic (As)-contaminated soil is difficult because As is very toxic for plants and micro-organisms. The aim of this study was to investigate soil arsenic removal effects using poplar in combination with the inoculation of a plant growth-promoting rhizobacterium (PGPR). A rhizobacterium D14 was isolated and identified within Agrobacterium radiobacter. This strain was highly resistant to arsenic and produced indole acetic acid and siderophore. Greenhouse pot bioremediation experiments were performed for 5 months using poplar (Populus deltoides LH05-17) grown on As-amended soils, inoculated with strain D14. The results showed that P. deltoides was an efficient arsenic accumulator; however, high As concentrations (150 and 300 mg kg(-1)) inhibited its growth. With the bacterial inoculation, in the 300 mg kg(-1) As-amended soils, 54% As in the soil was removed, which was higher than the uninoculated treatments (43%), and As concentrations in roots, stems and leaves were significantly increased by 229, 113 and 291%, respectively. In addition, the As translocation ratio [(stems + leaves)/roots = 0·8] was significantly higher than the uninoculated treatments (0·5). About 45% As was translocated from roots to the above-ground tissues. The plant height and dry weight of roots, stems and leaves were all enhanced; the contents of chlorophyll and soluble sugar, and the activities of superoxide dismutase and catalase were all increased; and the content of a toxic compound malondialdehyde was decreased. The results indicated that the inoculation of strain D14 could contribute to the increase in the As tolerance of P. deltoides, promotion of the growth, increase in the uptake efficiency and enhancement of As translocation. The use of P. deltoides in combination with the inoculation of strain D14 provides a potential application for efficient soil arsenic bioremediation. © 2011 The Authors. Journal of Applied Microbiology ©2011 The Society for Applied

  19. RSPOs facilitated HSC activation and promoted hepatic fibrogenesis

    PubMed Central

    Yin, Xinguang; Yi, Huixing; Wang, Linlin; Wu, Wanxin; Wu, Xiaojun; Yu, Linghua

    2016-01-01

    Roof plate-specific spondin (RSPO) proteins are potent Wnt pathway agonists and involve in a broad range of developmental and physiological processes. This study investigated the activities and mechanisms of RSPOs in liver fibrogenesis, especially in hepatic stellate cell (HSC) activation. HSC activation was assessed by fibrosis biomarker (α-smooth muscle actin and Collagen-I), phenotypic change (accumulation of lipid droplets), and increased proliferation. Similarly, Wnt pathway activity was evaluated by the expression of nuclear β-catenin and T cell-specific transcription factors (TCF) activity. We found RSPOs were overexpressed in human fibrotic liver tissue and the expressions were correlated with liver fibrosis stages. In vitro studies showed RSPOs level increased during HSC activation, and stimuli with RSPOs enhanced Wnt pathway activity and promoted HSC activation subsequently. Furthermore, in vivo experiments demonstrated that the knockdown of RSPOs suppressed both Wnt pathway activity and HSC activation. Interestingly, the inhibitor of the Wnt signaling pathway Dickkopf1 impairs RSPOs effects on HSCs. Taken together, our results revealed that RSPOs facilitated HSC activation and promote liver fibrogenesis by enhancing the Wnt pathway. PMID:27572318

  20. RSPOs facilitated HSC activation and promoted hepatic fibrogenesis.

    PubMed

    Yin, Xinguang; Yi, Huixing; Wang, Linlin; Wu, Wanxin; Wu, Xiaojun; Yu, Linghua

    2016-09-27

    Roof plate-specific spondin (RSPO) proteins are potent Wnt pathway agonists and involve in a broad range of developmental and physiological processes. This study investigated the activities and mechanisms of RSPOs in liver fibrogenesis, especially in hepatic stellate cell (HSC) activation. HSC activation was assessed by fibrosis biomarker (α-smooth muscle actin and Collagen-I), phenotypic change (accumulation of lipid droplets), and increased proliferation. Similarly, Wnt pathway activity was evaluated by the expression of nuclear β-catenin and T cell-specific transcription factors (TCF) activity. We found RSPOs were overexpressed in human fibrotic liver tissue and the expressions were correlated with liver fibrosis stages. In vitro studies showed RSPOs level increased during HSC activation, and stimuli with RSPOs enhanced Wnt pathway activity and promoted HSC activation subsequently. Furthermore, in vivo experiments demonstrated that the knockdown of RSPOs suppressed both Wnt pathway activity and HSC activation. Interestingly, the inhibitor of the Wnt signaling pathway Dickkopf1 impairs RSPOs effects on HSCs. Taken together, our results revealed that RSPOs facilitated HSC activation and promote liver fibrogenesis by enhancing the Wnt pathway.

  1. Predictors of the Health-Promoting Behaviors of Nepalese Migrant Workers.

    PubMed

    Bhandari, Pratibha; Kim, MiYoung

    2016-09-01

    Health-promoting behaviors assist individuals to prevent disease, promote health, increase longevity, and enjoy a better quality of life. A number of interpersonal, social, and environmental factors have been shown to influence health-promoting behaviors. Little empirical evidence exists about the predictors of health-promoting behaviors among migrant workers. This study uses Pender's health promotion model to describe and identify the predictors of health-promoting behaviors in Nepalese migrant workers in Korea. A cross-sectional research design was used. Nepalese migrants who had been working in South Korea (n = 169) for over 6 months were surveyed between July and December 2012. Self-efficacy was measured using the Perceived Health Competence Scale, the Health-Promoting Lifestyle Profile II was used to measure health-promoting lifestyle behaviors, and perceived health status was measured using a single-item question. Descriptive statistics, correlation analysis, and multiple regression analysis were used to analyze data. Spiritual activity was the highest reported health-promoting behavior, whereas physical activity was the least practiced behavior. Self-efficacy was the only significant predictor of health-promoting behavior. The results of this study suggest that future health-promoting interventions should enhance the self-efficacy of target populations for individual health behaviors. Factors such as working conditions, culture, and economic background that may affect the health-promoting behaviors of migrant workers must be considered when planning nursing interventions. Multicultural nursing structures and policies are needed to reach out proactively to all adult migrant groups.

  2. Staff's perceptions of the use of evidence-based physical activity promotion strategies for promoting girls' physical activity at afterschool programs: a qualitative study.

    PubMed

    Dinkel, Danae; Huberty, Jennifer; Beets, Michael; Tibbits, Melissa

    2014-08-01

    There is a need to improve girls' physical activity (PA) in afterschool programs as girls' PA levels are consistently lower than boys'. An evidence-based professional development framework, the 5 Ms, has been effective in helping staff to improve PA in both girls and boys but further improvements in girls' PA are needed. Little is known about staff's perceptions of using PA promotion strategies to promote girls' PA. Therefore, the purpose of this study was to explore staff perceptions of the use of evidence-based PA promotion strategies for promoting PA in girls. Semi-structured interviews were conducted with staff from three community-based afterschool programs located within a school setting (n=18). Data were analyzed using the process of immersion/crystallization. A majority of staff had some knowledge of PA promotion strategies but few staff consistently utilized these strategies and a majority felt several strategies were unnecessary (i.e., having a PA policy). Newer staff reported depending on senior staff to promote PA in girls. Overall, findings suggest that staff's perceptions may impact their use of PA promotions strategies. The results of this study will contribute to the enhancement of an existing staff training framework (the 5 Ms) to improve girls' PA in afterschool programs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. PTEN inhibition enhances angiogenesis in an in vitro model of ischemic injury by promoting Akt phosphorylation and subsequent hypoxia inducible factor-1α upregulation.

    PubMed

    Xue, Lixia; Huang, Jiankang; Zhang, Ting; Wang, Xiuzhe; Fu, Jianliang; Geng, Zhi; Zhao, Yuwu; Chen, Hao

    2018-06-24

    Angiogenesis is an important pathophysiological response to cerebral ischemia. PTEN is a lipid phosphatase whose loss activates PI3K/Akt signaling, which is related to HIF-1α upregulation and enhanced angiogenesis in human cancer cells. However, the specific roles of PTEN in endothelial cell functions and angiogenesis after cerebral ischemia remain unknown. Therefore, we sought to examine the potential effects of PTEN inhibition on post-ischemic angiogenesis in human blood vessel cells and to determine the underlying mechanism. In this present study, human umbilical vein endothelial cells (HUVECs) were exposed to oxygen-glucose deprivation (OGD), cell proliferation, migration and apoptosis, in vitro tube formation and expression of PTEN/Akt pathway and angiogenic factors were examined in HUVECs after treatment with PTEN inhibitor bisperoxovanadium (bpV) at different doses. The results showed that bpV significantly increased the cell proliferation and reduced cell apoptosis indicating that the drug exerts a cytoprotective effect on HUVECs with OGD exposure. bpV also enhanced cell migration and tube formation in HUVECs following OGD, and upregulated HIF-1α and VEGF expressions, but attenuated endostatin expression. Additionally, western blotting analysis demonstrated that Akt phosphorylation in HUVECs was significantly increased after bpV treatment. These findings suggest that PTEN inhibition promotes post-ischemic angiogenesis in HUVECs after exposure to OGD and this enhancing effect might be achieved through activation of the Akt signal cascade.

  4. Enhancing CO2 Electroreduction with the Metal-Oxide Interface.

    PubMed

    Gao, Dunfeng; Zhang, Yi; Zhou, Zhiwen; Cai, Fan; Zhao, Xinfei; Huang, Wugen; Li, Yangsheng; Zhu, Junfa; Liu, Ping; Yang, Fan; Wang, Guoxiong; Bao, Xinhe

    2017-04-26

    The electrochemical CO 2 reduction reaction (CO 2 RR) typically uses transition metals as the catalysts. To improve the efficiency, tremendous efforts have been dedicated to tuning the morphology, size, and structure of metal catalysts and employing electrolytes that enhance the adsorption of CO 2 . We report here a strategy to enhance CO 2 RR by constructing the metal-oxide interface. We demonstrate that Au-CeO x shows much higher activity and Faradaic efficiency than Au or CeO x alone for CO 2 RR. In situ scanning tunneling microscopy and synchrotron-radiation photoemission spectroscopy show that the Au-CeO x interface is dominant in enhancing CO 2 adsorption and activation, which can be further promoted by the presence of hydroxyl groups. Density functional theory calculations indicate that the Au-CeO x interface is the active site for CO 2 activation and the reduction to CO, where the synergy between Au and CeO x promotes the stability of key carboxyl intermediate (*COOH) and thus facilitates CO 2 RR. Similar interface-enhanced CO 2 RR is further observed on Ag-CeO x , demonstrating the generality of the strategy for enhancing CO 2 RR.

  5. Arabidopsis ENHANCED DISEASE SUSCEPTIBILITY1 promotes systemic acquired resistance via azelaic acid and its precursor 9-oxo nonanoic acid

    PubMed Central

    Wittek, Finni; Hoffmann, Thomas; Kanawati, Basem; Bichlmeier, Marlies; Knappe, Claudia; Wenig, Marion; Schmitt-Kopplin, Philippe; Parker, Jane E.; Schwab, Wilfried; Vlot, A. Corina

    2014-01-01

    Systemic acquired resistance (SAR) is a form of inducible disease resistance that depends on salicylic acid and its upstream regulator ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). Although local Arabidopsis thaliana defence responses activated by the Pseudomonas syringae effector protein AvrRpm1 are intact in eds1 mutant plants, SAR signal generation is abolished. Here, the SAR-specific phenotype of the eds1 mutant is utilized to identify metabolites that contribute to SAR. To this end, SAR bioassay-assisted fractionation of extracts from the wild type compared with eds1 mutant plants that conditionally express AvrRpm1 was performed. Using high-performance liquid chromatography followed by mass spectrometry, systemic immunity was associated with the accumulation of 60 metabolites, including the putative SAR signal azelaic acid (AzA) and its precursors 9-hydroperoxy octadecadienoic acid (9-HPOD) and 9-oxo nonanoic acid (ONA). Exogenous ONA induced SAR in systemic untreated leaves when applied at a 4-fold lower concentration than AzA. The data suggest that in planta oxidation of ONA to AzA might be partially responsible for this response and provide further evidence that AzA mobilizes Arabidopsis immunity in a concentration-dependent manner. The AzA fragmentation product pimelic acid did not induce SAR. The results link the C9 lipid peroxidation products ONA and AzA with systemic rather than local resistance and suggest that EDS1 directly or indirectly promotes the accumulation of ONA, AzA, or one or more of their common precursors possibly by activating one or more pathways that either result in the release of these compounds from galactolipids or promote lipid peroxidation. PMID:25114016

  6. Polyandry promotes enhanced offspring survival in decorated crickets.

    PubMed

    Ivy, Tracie M; Sakaluk, Scott K

    2005-01-01

    Although female multiple mating is ubiquitous in insects, its adaptive significance remains poorly understood. Benefits to multiple mating can accrue via direct material benefits, indirect genetic benefits, or both. We investigated the effects of multiple mating in the decorated cricket, Gryllodes sigillatus, by simultaneously varying the number of times that females mated and the number of different males with which they mated, measuring aspects of female fecundity and elements of offspring performance and viability. Multiple matings resulted in enhanced female fitness relative to single matings when females mated with different partners, but not when females mated repeatedly with the same male. Specifically, polyandrous females produced significantly more offspring surviving to reproductive maturity than did monogamous females mating once or mating repeatedly with the same male. These results suggest that the benefit females gain from multiple mating is influenced primarily by genetic and not material benefits.

  7. First Pass Annotation of Promoters on Human Chromosome 22

    PubMed Central

    Scherf, Matthias; Klingenhoff, Andreas; Frech, Kornelie; Quandt, Kerstin; Schneider, Ralf; Grote, Korbinian; Frisch, Matthias; Gailus-Durner, Valérie; Seidel, Alexander; Brack-Werner, Ruth; Werner, Thomas

    2001-01-01

    The publication of the first almost complete sequence of a human chromosome (chromosome 22) is a major milestone in human genomics. Together with the sequence, an excellent annotation of genes was published which certainly will serve as an information resource for numerous future projects. We noted that the annotation did not cover regulatory regions; in particular, no promoter annotation has been provided. Here we present an analysis of the complete published chromosome 22 sequence for promoters. A recent breakthrough in specific in silico prediction of promoter regions enabled us to attempt large-scale prediction of promoter regions on chromosome 22. Scanning of sequence databases revealed only 20 experimentally verified promoters, of which 10 were correctly predicted by our approach. Nearly 40% of our 465 predicted promoter regions are supported by the currently available gene annotation. Promoter finding also provides a biologically meaningful method for “chromosomal scaffolding”, by which long genomic sequences can be divided into segments starting with a gene. As one example, the combination of promoter region prediction with exon/intron structure predictions greatly enhances the specificity of de novo gene finding. The present study demonstrates that it is possible to identify promoters in silico on the chromosomal level with sufficient reliability for experimental planning and indicates that a wealth of information about regulatory regions can be extracted from current large-scale (megabase) sequencing projects. Results are available on-line at http://genomatix.gsf.de/chr22/. PMID:11230158

  8. Both the constitutive Cauliflower Mosaic Virus 35S and tissue-specific AGAMOUS enhancers activate transcription autonomously in Arabidopsis thaliana

    USDA-ARS?s Scientific Manuscript database

    The presence of multiple enhancers and promoters within a single vector often provokes complicated mutual interaction and crosstalk, thereby, altering promoter specificity, which causes serious problems for precisely engineering gene function and agronomic traits in transgenic plants. Enhancer elem...

  9. Enhancing the Emotional and Social Skills of the Youth to Promote their Wellbeing and Positive Development: A Systematic Review of Universal School-based Randomized Controlled Trials.

    PubMed

    Sancassiani, Federica; Pintus, Elisa; Holte, Arne; Paulus, Peter; Moro, Maria Francesca; Cossu, Giulia; Angermeyer, Matthias C; Carta, Mauro Giovanni; Lindert, Jutta

    2015-01-01

    The acquisition of social and emotional skills is associated with positive youth development, character education, healthy lifestyle behaviours, reduction in depression and anxiety, conduct disorders, violence, bullying, conflict, and anger. School-based interventions aimed to enhance these skills go beyond a problem-focused approach to embrace a more positive view of health; they could also improve the youth's wellbeing. To describe the main features and to establish the effectiveness of universal school-based RCTs for children and the youth, aimed to promote their psychosocial wellbeing, positive development, healthy lifestyle behaviours and/or academic performance by improving their emotional and social skills. Systematic review by searching for relevant papers in PubMed/Medline with the following key words: "mental health" OR "wellbeing" OR "health promotion" OR "emotional learning" OR "social learning" OR "emotional and social learning" OR "positive youth development" OR "life skills" OR "life skills training" AND "school". Interval was set from January 2000 to April 2014. 1,984 papers were identified through the search. Out of them 22 RCTs were included. While most interventions were characterized by a whole-school approach and SAFE practices, few studies only used standardized measures to assess outcomes, or had collected follow-up data after ≥ 6 months. The results of all these trials were examined and discussed. Universal school-based RCTs to enhance emotional and social skills showed controversial findings, due to some methodological issues mainly. Nevertheless they show promising outcomes that are relatively far-reaching for children and youth wellbeing and therefore are important in the real world.

  10. The hTERT Promoter Enhances the Antitumor Activity of an Oncolytic Adenovirus under a Hypoxic Microenvironment

    PubMed Central

    Hashimoto, Yuuri; Tazawa, Hiroshi; Teraishi, Fuminori; Kojima, Toru; Watanabe, Yuichi; Uno, Futoshi; Yano, Shuya; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi

    2012-01-01

    Hypoxia is a microenvironmental factor that contributes to the invasion, progression and metastasis of tumor cells. Hypoxic tumor cells often show more resistance to conventional chemoradiotherapy than normoxic tumor cells, suggesting the requirement of novel antitumor therapies to efficiently eliminate the hypoxic tumor cells. We previously generated a tumor-specific replication-competent oncolytic adenovirus (OBP-301: Telomelysin), in which the human telomerase reverse transcriptase (hTERT) promoter drives viral E1 expression. Since the promoter activity of the hTERT gene has been shown to be upregulated by hypoxia, we hypothesized that, under hypoxic conditions, the antitumor effect of OBP-301 with the hTERT promoter would be more efficient than that of the wild-type adenovirus 5 (Ad5). In this study, we investigated the antitumor effects of OBP-301 and Ad5 against human cancer cells under a normoxic (20% oxygen) or a hypoxic (1% oxygen) condition. Hypoxic condition induced nuclear accumulation of the hypoxia-inducible factor-1α and upregulation of hTERT promoter activity in human cancer cells. The cytopathic activity of OBP-301 was significantly higher than that of Ad5 under hypoxic condition. Consistent with their cytopathic activity, the replication of OBP-301 was significantly higher than that of Ad5 under the hypoxic condition. OBP-301-mediated E1A was expressed within hypoxic areas of human xenograft tumors in mice. These results suggest that the cytopathic activity of OBP-301 against hypoxic tumor cells is mediated through hypoxia-mediated activation of the hTERT promoter. Regulation of oncolytic adenoviruses by the hTERT promoter is a promising antitumor strategy, not only for induction of tumor-specific oncolysis, but also for efficient elimination of hypoxic tumor cells. PMID:22720091

  11. Molecular cloning and functional characterization of the promoter region of the human uncoupling protein-2 gene.

    PubMed

    Tu, N; Chen, H; Winnikes, U; Reinert, I; Marmann, G; Pirke, K M; Lentes, K U

    1999-11-19

    As a member of the uncoupling protein family, UCP2 is ubiquitously expressed in rodents and humans, implicating a major role in thermogenesis. To analyze promoter function and regulatory motifs involved in the transcriptional regulation of UCP2 gene expression, 3.3 kb of 5'-flanking region of the human UCP2 (hUCP2) gene have been cloned. Sequence analysis showed that the promoter region of hUCP2 lacks a classical TATA or CAAT box, however, appeared GC-rich resulting in the presence of several Sp-1 motifs and Ap-1/-2 binding sites near the transcription initiation site. Functional characterization of human UCP2 promoter-CAT fusion constructs in transient expression assays showed that minimal promoter activity was observed within 65 bp upstream of the transcriptional start site (+1). 75 bp further upstream (from nt -141 to -66) a strong cis-acting regulatory element (or enhancer) was identified, which significantly enhanced basal promoter activity. The regulation of human UCP2 gene expression involves complex interactions among positive and negative regulatory elements distributed over a minimum of 3.3 kb of the promoter region. Copyright 1999 Academic Press.

  12. Monoclonal antibody Zt/g4 targeting RON receptor tyrosine kinase enhances chemosensitivity of bladder cancer cells to Epirubicin by promoting G1/S arrest and apoptosis.

    PubMed

    Chen, Jun-Feng; Yu, Bi-Xia; Yu, Rui; Ma, Liang; Lv, Xiu-Yi; Cheng, Yue; Ma, Qi

    2017-02-01

    Epirubicin (EPI) is one of the most used intravesical chemotherapy agents after transurethral resection to non-muscle invasive bladder tumors (NMIBC) to prevent cancer recurrence and progression. However, even after resection of bladder tumors and intravesical chemotherapy, half of them will recur and progress. RON is a membrane tyrosine kinase receptor usually overexpressed in bladder cancer cells and associated with poor pathological features. This study aims to investigate the effects of anti-RON monoclonal antibody Zt/g4 on the chemosensitivity of bladder cells to EPI. After Zt/g4 treatment, cell cytotoxicity was significantly increased and cell invasion was markedly suppressed in EPI-treated bladder cancer cells. Further investigation indicated that combing Zt/g4 with EPI promoted cell G1/S-phase arrest and apoptosis, which are the potential mechanisms that RON signaling inhibition enhances chemosensitivity of EPI. Thus, combing antibody-based RON targeted therapy enhances the therapeutic effects of intravesical chemotherapy, which provides new strategy for further improvement of NMIBC patient outcomes.

  13. Health promotion for people with intellectual disabilities - A concept analysis.

    PubMed

    Roll, Anne E

    2018-03-01

    Whereas 'health promotion' is a well-known concept for healthcare professionals, the concept of 'health promotion for people with intellectual disabilities' and its unique associated challenges are not well understood. This article provides a systematic analysis of how health promotion is being conceptualised for people with intellectual disabilities and how health promotion can work best in the light of this group's specific needs and limitations. Rodgers' evolutionary concept analysis. MEDLINE, PsycINFO, CINAHL and SocINDEX were searched using the search terms 'health promotion', 'people with intellectual disabilities' and 'developmental disabilities'. This review includes studies published between 1992 and 2014. A total of 52 articles were included. Health promotion for people intellectual disabilities, as discussed in the literature, focuses on four aspects, namely supporting a healthy lifestyle, providing health education, involving supporters and being person-centred. Antecedents of the concept 'health promotion for people with intellectual disabilities' were healthcare access and sensitised healthcare providers. The outcomes were improved health, being empowered, enhanced quality of life and reduced health disparities. This analysis provides a solid foundation for healthcare stakeholders' planning, implementing and evaluating health-promotion activities for people with intellectual disabilities at the policy level and in the community. © 2017 Nordic College of Caring Science.

  14. Initial Investigation of Factors Influencing Radiation Dose to Patients Undergoing Barium-Based Fluoroscopy Procedures in Tanzania.

    PubMed

    Ngaile, J E; Msaki, P K; Kazema, R R; Schreiner, L J

    2017-04-25

    The aim of this study was to investigate the nature and causes of radiation dose imparted to patients undergoing barium-based X-ray fluoroscopy procedures in Tanzania and to compare these doses to those reported in the literature from other regions worldwide. The air kerma area product (KAP) to patient undergoing barium investigations of gastrointestinal tract system was obtained from four consultant hospitals. The KAP was determined using a flat transparent transmission ionization chamber. Mean values of KAP for barium swallow (BS), barium meal (BM) and barium enema (BE) were 2.79, 2.62 and 15.04 Gy cm2, respectively. The mean values of KAP per hospital for the BS, BM and BE procedures varied by factors of up to 7.3, 1.6 and 2.0, respectively. The overall difference between individual patient doses across the four consultant hospitals investigated differed by factors of up to 53, 29.5 and 12 for the BS, BM and BE procedures, respectively. The majority of the mean values of KAP was lower than the reported values for Ghana, Greece, Spain and the UK, while slightly higher than those reported for India. The observed wide variation of KAP values for the same fluoroscopy procedure within and among the hospitals was largely attributed to the dynamic nature of the procedures, the patient characteristics, the skills and experience of personnel, and the different examination protocols employed among hospitals. The observed great variations of procedural protocols and patient doses within and across the hospitals call for the need to standardize examination protocols and optimize barium-based fluoroscopy procedures. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Knowledge, attitude, and practice of people toward epilepsy in a South Indian village

    PubMed Central

    Krishnaiah, Balaji; Alwar, Seenivasan P.; Ranganathan, Lakshmi N.

    2016-01-01

    Introduction: People living with epilepsy continue to suffer from enacted or perceived stigma that is based on myths, misconceptions, and misunderstandings that have persisted for many years. In the last decade, there has been an increase in individual literacy rate and increased access to technology in rural population. However, it is unclear if this has any effect on knowledge, attitude, and practice (KAP) attitude toward epilepsy. Objective: Our primary aim is to evaluate KAP toward epilepsy. In addition, we also estimated the prevalence of stroke and epilepsy in rural South India. Materials and Methods: Using a 14-item questionnaire, we assessed KAP toward epilepsy and identified determinants of inappropriate attitudes toward people with epilepsy and 10-item questionnaires to assess the prevalence of epilepsy and stroke among 500 randomly selected populations in a Pattaravakkam village (Tamil Nadu, India). Results: About 87.7% of the people had heard or read about epilepsy. Negative attitudes appeared to be reinforced by beliefs that epilepsy is hereditary (23.1%), kind of insanity (22.6%), or as contagious (12.0%). The knowledge about the clinical characteristics and first aid to a person during a seizure was 25.8%. About 36.5% of people think that society discriminates people with epilepsy. Moreover, our prevalence study showed that 8.7% people are suffering from epilepsy and 3.7% had stroke previously and at the day of survey, the stroke prevalence is 3.3%. Conclusion: Even with increased literacy, technology, and communication devices, the KAP of people toward epilepsy is relatively low. General public education campaigns and specific school education campaigns children should be encouraged to increase the KAP toward epilepsy. The prevalence and pattern of epilepsy and stroke is on the higher side in the village of Pattaravakkam. Future research regarding the value of targeted education in improving KAP will be worthwhile. PMID:27365954

  16. Knowledge, attitude, and practice of people toward epilepsy in a South Indian village.

    PubMed

    Krishnaiah, Balaji; Alwar, Seenivasan P; Ranganathan, Lakshmi N

    2016-01-01

    People living with epilepsy continue to suffer from enacted or perceived stigma that is based on myths, misconceptions, and misunderstandings that have persisted for many years. In the last decade, there has been an increase in individual literacy rate and increased access to technology in rural population. However, it is unclear if this has any effect on knowledge, attitude, and practice (KAP) attitude toward epilepsy. Our primary aim is to evaluate KAP toward epilepsy. In addition, we also estimated the prevalence of stroke and epilepsy in rural South India. Using a 14-item questionnaire, we assessed KAP toward epilepsy and identified determinants of inappropriate attitudes toward people with epilepsy and 10-item questionnaires to assess the prevalence of epilepsy and stroke among 500 randomly selected populations in a Pattaravakkam village (Tamil Nadu, India). About 87.7% of the people had heard or read about epilepsy. Negative attitudes appeared to be reinforced by beliefs that epilepsy is hereditary (23.1%), kind of insanity (22.6%), or as contagious (12.0%). The knowledge about the clinical characteristics and first aid to a person during a seizure was 25.8%. About 36.5% of people think that society discriminates people with epilepsy. Moreover, our prevalence study showed that 8.7% people are suffering from epilepsy and 3.7% had stroke previously and at the day of survey, the stroke prevalence is 3.3%. Even with increased literacy, technology, and communication devices, the KAP of people toward epilepsy is relatively low. General public education campaigns and specific school education campaigns children should be encouraged to increase the KAP toward epilepsy. The prevalence and pattern of epilepsy and stroke is on the higher side in the village of Pattaravakkam. Future research regarding the value of targeted education in improving KAP will be worthwhile.

  17. Knowledge, attitude and practice of hygiene and sanitation in a Burundian refugee camp: implications for control of a Salmonella typhi outbreak

    PubMed Central

    Nahimana, Marie-Rosette; Ngoc, Candide Tran; Olu, Olushayo; Nyamusore, Jose; Isiaka, Ayodeji; Ndahindwa, Vedaste; Dassanayake, Lakruwan; Rusanganwa, André

    2017-01-01

    Introduction A Salmonella typhi outbreak was reported in a Burundian refugee camp in Rwanda in October 2015. Transmission persisted despite increased hygiene promotion activities and hand-washing facilities instituted to prevent and control the outbreak. A knowledge, attitude and practice (KAP) study was carried out to assess the effectiveness of ongoing typhoid fever preventive interventions. Methods A cross-sectional survey was conducted in Mahama Refugee Camp of Kirehe District, Rwanda from January to February 2016. Data were obtained through administration of a structured KAP questionnaire. Descriptive, bivariate and multivariate analysis was performed using STATA software. Results A total of 671 respondents comprising 264 (39.3%) males and 407 (60.7%) females were enrolled in the study. A comparison of hand washing practices before and after institution of prevention and control measures showed a 37% increase in the proportion of respondents who washed their hands before eating and after using the toilet (p < 0.001). About 52.8% of participants reported having heard about typhoid fever, however 25.9% had received health education. Only 34.6% and 38.6% of the respondents respectively knew how typhoid fever spreads and is prevented. Most respondents (98.2%) used pit latrines for disposal of feces. Long duration of stay in the camp, age over 35 years and being unemployed were statistically associated with poor hand washing practices. Conclusion The findings of this study underline the need for bolstering up health education and hygiene promotion activities in Mahama and other refugee camp settings. PMID:29184606

  18. Knowledge, Attitude and Practice of Iranian Pharmacists, Body Builders, and Their Coaches Regarding Sports Supplements

    PubMed Central

    Bastani, Peivand; Nia, Ali Amjad; Shabanpoor, Mohammadreza; Mehravar, Safoora; Kashefian, Sara

    2017-01-01

    Objective: This study is conducted on Iranian pharmacists, coaches, and athletes regarding sports supplements to assess their knowledge, attitude, and practice (KAP) regarding sports supplements. Methods: This was a cross-sectional study conducted in 2015. The study population consisted of all community pharmacists, bodybuilders, and bodybuilding coaches. The questionnaire was applied consisting some demographic questions and 25 questions for assessing KAP (6, 9, and 10, respectively). The collected data were analyzed with independent t-test, ANOVA, and Pearson correlation. Findings: In all three studied groups, the mean of KAP was upper than intermediate level 3 (P < 0.05) except the pharmacists' knowledge. A statistically significant difference appears between knowledge and age of pharmacists (P = 0.007). In addition, there was a significant relationship between coaches' practice and age (P = 0.04). Conclusion: According to the results although the studied groups have the intermediate level of KAP, organized and regular education courses are highly recommended along with paying more attention to the curriculum taught in the pharmacy schools according to the community current needs. PMID:29026842

  19. Knowledge, Attitude and Practice of Iranian Pharmacists, Body Builders, and Their Coaches Regarding Sports Supplements.

    PubMed

    Bastani, Peivand; Nia, Ali Amjad; Shabanpoor, Mohammadreza; Mehravar, Safoora; Kashefian, Sara

    2017-01-01

    This study is conducted on Iranian pharmacists, coaches, and athletes regarding sports supplements to assess their knowledge, attitude, and practice (KAP) regarding sports supplements. This was a cross-sectional study conducted in 2015. The study population consisted of all community pharmacists, bodybuilders, and bodybuilding coaches. The questionnaire was applied consisting some demographic questions and 25 questions for assessing KAP (6, 9, and 10, respectively). The collected data were analyzed with independent t -test, ANOVA, and Pearson correlation. In all three studied groups, the mean of KAP was upper than intermediate level 3 ( P < 0.05) except the pharmacists' knowledge. A statistically significant difference appears between knowledge and age of pharmacists ( P = 0.007). In addition, there was a significant relationship between coaches' practice and age ( P = 0.04). According to the results although the studied groups have the intermediate level of KAP, organized and regular education courses are highly recommended along with paying more attention to the curriculum taught in the pharmacy schools according to the community current needs.

  20. Hpa1 harpin needs nitroxyl terminus to promote vegetative growth and leaf photosynthesis in Arabidopsis.

    PubMed

    Li, Xiaojie; Han, Liping; Zhao, Yanying; You, Zhenzhen; Dong, Hansong; Zhang, Chunling

    2014-03-01

    Hpa1 is a harpin protein produced by Xanthomonas oryzae, an important bacterial pathogen of rice, and has the growth-promoting activity in plants. To understand the molecular basis for the function of Hpa1, we generated an inactive variant protein, Hpa1 delta NT, by deleting the nitroxyl-terminal region of the Hpa1 sequence and compared Hpa1 delta NT with the full-length protein in terms of the effects on vegetative growth and related physiological responses in Arabidopsis. When Hpa1 was applied to plants, it acted to enhance the vegetative growth but did not affect the floral development. Enhanced plant growth was accompanied by induced expression of growth-promoting genes in plant leaves. The growth-promoting activity of Hpa1 was further correlated with a physiological consequence shown as promoted leaf photosynthesis as a result of facilitated CO2 conduction through leaf stomata and mesophyll cells. On the contrary, plant growth, growth-promoting gene expression, and the physiological consequence changed little in response to the Hpa1 delta NT treatment. These analyses suggest that Hpa1 requires the nitroxyl-terminus to facilitate CO2 transport inside leaf cells and promote leaf photosynthesis and vegetative growth of the plant.

  1. Health and nutrition knowledge, attitudes and practices of pregnant women attending and not-attending ANC clinics in Western Kenya: a cross-sectional analysis.

    PubMed

    Perumal, Nandita; Cole, Donald C; Ouédraogo, Hermann Z; Sindi, Kirimi; Loechl, Cornelia; Low, Jan; Levin, Carol; Kiria, Christine; Kurji, Jaameeta; Oyunga, Mary

    2013-07-11

    Antenatal care (ANC) is a key strategy to decreasing maternal mortality in low-resource settings. ANC clinics provide resources to improve nutrition and health knowledge and promote preventive health practices. We sought to compare the knowledge, attitude and practices (KAP) among women seeking and not-seeking ANC in rural Kenya. Data from a community-based cross-sectional survey conducted in Western Province, Kenya were used. Nutrition knowledge (NKS), health knowledge (HKS), attitude score (AS), and dietary diversity score (DDS) were constructed indices. χ2 test and Student's t-test were used to compare proportions and means, respectively, to assess the difference in KAP among pregnant women attending and not-attending ANC clinics. Multiple regression analyses were used to assess the impact of the number of ANC visits (none, <4, ≥4) on knowledge and practice scores, adjusting for maternal socio-demographic confounders, such as age, gestational age, education level and household wealth index. Among the 979 pregnant women in the survey, 59% had attended ANC clinics while 39% had not. The mean (±SD) NKS was 4.6 (1.9) out of 11, HKS was 6.2 (1.7) out of 12, DDS was 4.9 (1.4) out of 12, and AS was 7.4 (2.2) out of 10. Nutrition knowledge, attitudes, and DDS were not significantly different between ANC clinic attending and non-attending women. Among women who attended ANC clinics, 82.6% received malaria and/or antihelmintic treatment, compared to 29.6% of ANC clinic non-attendees. Higher number of ANC clinic visits and higher maternal education level were significantly positively associated with maternal health knowledge. Substantial opportunities exist for antenatal KAP improvement among women in Western Kenya, some of which could occur with greater ANC attendance. Further research is needed to understand multi-level factors that may affect maternal knowledge and practices.

  2. Transcriptional reprogramming underpins enhanced plant growth promotion by the biocontrol fungus Trichoderma hamatum GD12 during antagonistic interactions with Sclerotinia sclerotiorum in soil.

    PubMed

    Shaw, Sophie; Le Cocq, Kate; Paszkiewicz, Konrad; Moore, Karen; Winsbury, Rebecca; de Torres Zabala, Marta; Studholme, David J; Salmon, Deborah; Thornton, Christopher R; Grant, Murray R

    2016-12-01

    The free-living soil fungus Trichoderma hamatum strain GD12 is notable amongst Trichoderma strains in both controlling plant diseases and stimulating plant growth, a property enhanced during its antagonistic interactions with pathogens in soil. These attributes, alongside its markedly expanded genome and proteome compared with other biocontrol and plant growth-promoting Trichoderma strains, imply a rich potential for sustainable alternatives to synthetic pesticides and fertilizers for the control of plant disease and for increasing yields. The purpose of this study was to investigate the transcriptional responses of GD12 underpinning its biocontrol and plant growth promotion capabilities during antagonistic interactions with the pathogen Sclerotinia sclerotiorum in soil. Using an extensive mRNA-seq study capturing different time points during the pathogen-antagonist interaction in soil, we show that dynamic and biphasic signatures in the GD12 transcriptome underpin its biocontrol and plant (lettuce) growth-promoting activities. Functional predictions of differentially expressed genes demonstrate the enrichment of transcripts encoding proteins involved in transportation and oxidation-reduction reactions during both processes and an over-representation of siderophores. We identify a biphasic response during biocontrol characterized by a significant induction of transcripts encoding small-secreted cysteine-rich proteins, secondary metabolite-producing gene clusters and genes unique to GD12. These data support the hypothesis that Sclerotinia biocontrol is mediated by the synthesis and secretion of antifungal compounds and that GD12's unique reservoir of uncharacterized genes is actively recruited during the effective biological control of a plurivorous plant pathogen. © 2016 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.

  3. MDM2 Associates with Polycomb Repressor Complex 2 and Enhances Stemness-Promoting Chromatin Modifications Independent of p53.

    PubMed

    Wienken, Magdalena; Dickmanns, Antje; Nemajerova, Alice; Kramer, Daniela; Najafova, Zeynab; Weiss, Miriam; Karpiuk, Oleksandra; Kassem, Moustapha; Zhang, Yanping; Lozano, Guillermina; Johnsen, Steven A; Moll, Ute M; Zhang, Xin; Dobbelstein, Matthias

    2016-01-07

    The MDM2 oncoprotein ubiquitinates and antagonizes p53 but may also carry out p53-independent functions. Here we report that MDM2 is required for the efficient generation of induced pluripotent stem cells (iPSCs) from murine embryonic fibroblasts, in the absence of p53. Similarly, MDM2 depletion in the context of p53 deficiency also promoted the differentiation of human mesenchymal stem cells and diminished clonogenic survival of cancer cells. Most of the MDM2-controlled genes also responded to the inactivation of the Polycomb Repressor Complex 2 (PRC2) and its catalytic component EZH2. MDM2 physically associated with EZH2 on chromatin, enhancing the trimethylation of histone 3 at lysine 27 and the ubiquitination of histone 2A at lysine 119 (H2AK119) at its target genes. Removing MDM2 simultaneously with the H2AK119 E3 ligase Ring1B/RNF2 further induced these genes and synthetically arrested cell proliferation. In conclusion, MDM2 supports the Polycomb-mediated repression of lineage-specific genes, independent of p53. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Unforgettable Ultimatums? Expectation Violations Promote Enhanced Social Memory Following Economic Bargaining

    PubMed Central

    Chang, Luke J.; Sanfey, Alan G.

    2009-01-01

    Recent work in the field of neuroeconomics has examined how people make decisions in interactive settings. However, less is currently known about how these social decisions influence subsequent memory for these interactions. We investigated this question by using functional magnetic resonance imaging to scan participants as they viewed photographs of people they had either recently played an Ultimatum Game with in the role of Responder, or that they had never seen before. Based on previous work that has investigated “cheater detection”, we were interested in whether participants demonstrated a relative enhanced memory for partners that made either fair or unfair proposals. We found no evidence, either behaviorally or neurally, supporting enhanced memory based on the amount of money offered by the Proposer. However, we did find that participants’ initial expectations about the offers they would experience in the game influenced their memory. Participants demonstrated relatively enhanced subjective memory for partners that made proposals that were contradictory to their initial expectations. In addition, we observed two distinct brain systems that were associated with partners that either offered more or less than the participants’ expectations. Viewing pictures of partners that exceeded initial expectations was associated with the bilateral anterior insula, anterior cingulate cortex/premotor area, striatum, and bilateral posterior hippocampi, while viewing partners that offered less than initial expectations was associated with bilateral temporal-parietal junction, right STS, bilateral posterior insula, and precuneus. These results suggest that memory for social interaction may not be guided by a specific cheater detection system, but rather a more general expectation violation system. PMID:19876405

  5. Reprogramming Enhancers to Drive Metastasis.

    PubMed

    Mostoslavsky, Raul; Bardeesy, Nabeel

    2017-08-24

    Acquired molecular changes can promote the spreading of primary tumor cells to distant tissues. In this issue of Cell, Roe et al. show that metastatic progression of pancreatic cancer involves large-scale enhancer reprogramming by Foxa1, which activates transcriptional program specifying early endodermal stem cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Enhanced Osteogenesis by Reduced Graphene Oxide/Hydroxyapatite Nanocomposites

    PubMed Central

    Lee, Jong Ho; Shin, Yong Cheol; Lee, Sang-Min; Jin, Oh Seong; Kang, Seok Hee; Hong, Suck Won; Jeong, Chang-Mo; Huh, Jung Bo; Han, Dong-Wook

    2015-01-01

    Recently, graphene-based nanomaterials, in the form of two dimensional substrates or three dimensional foams, have attracted considerable attention as bioactive scaffolds to promote the differentiation of various stem cells towards specific lineages. On the other hand, the potential advantages of using graphene-based hybrid composites directly as factors inducing cellular differentiation as well as tissue regeneration are unclear. This study examined whether nanocomposites of reduced graphene oxide (rGO) and hydroxyapatite (HAp) (rGO/HAp NCs) could enhance the osteogenesis of MC3T3-E1 preosteoblasts and promote new bone formation. When combined with HAp, rGO synergistically promoted the spontaneous osteodifferentiation of MC3T3-E1 cells without hindering their proliferation. This enhanced osteogenesis was corroborated from determination of alkaline phosphatase activity as early stage markers of osteodifferentiation and mineralization of calcium and phosphate as late stage markers. Immunoblot analysis showed that rGO/HAp NCs increase the expression levels of osteopontin and osteocalcin significantly. Furthermore, rGO/HAp grafts were found to significantly enhance new bone formation in full-thickness calvarial defects without inflammatory responses. These results suggest that rGO/HAp NCs can be exploited to craft a range of strategies for the development of novel dental and orthopedic bone grafts to accelerate bone regeneration because these graphene-based composite materials have potentials to stimulate osteogenesis. PMID:26685901

  7. LDB1-mediated enhancer looping can be established independent of mediator and cohesin.

    PubMed

    Krivega, Ivan; Dean, Ann

    2017-08-21

    Mechanistic studies in erythroid cells indicate that LDB1, as part of a GATA1/TAL1/LMO2 complex, brings erythroid-expressed genes into proximity with enhancers for transcription activation. The role of co-activators in establishing this long-range interaction is poorly understood. Here we tested the contributions of the RNA Pol II pre-initiation complex (PIC), mediator and cohesin to establishment of locus control region (LCR)/β-globin proximity. CRISPR/Cas9 editing of the β-globin promoter to eliminate the RNA Pol II PIC by deleting the TATA-box resulted in loss of transcription, but enhancer-promoter interaction was unaffected. Additional deletion of the promoter GATA1 site eliminated LDB1 complex and mediator occupancy and resulted in loss of LCR/β-globin proximity. To separate the roles of LDB1 and mediator in LCR looping, we expressed a looping-competent but transcription-activation deficient form of LDB1 in LDB1 knock down cells: LCR/β-globin proximity was restored without mediator core occupancy. Further, Cas9-directed tethering of mutant LDB1 to the β-globin promoter forced LCR loop formation in the absence of mediator or cohesin occupancy. Moreover, ENCODE data and our chromatin immunoprecipitation results indicate that cohesin is almost completely absent from validated and predicted LDB1-regulated erythroid enhancer-gene pairs. Thus, lineage specific factors largely mediate enhancer-promoter looping in erythroid cells independent of mediator and cohesin. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

  8. Mental health promotion in comprehensive schools.

    PubMed

    Onnela, A M; Vuokila-Oikkonen, P; Hurtig, T; Ebeling, H

    2014-09-01

    The purpose of this paper is to describe a participatory action research process on the development of a professional practice model of mental health nurses in mental health promotion in a comprehensive school environment in the city of Oulu, Finland. The developed model is a new method of mental health promotion for mental health nurses working in comprehensive schools. The professional practice model has been developed in workshops together with school staff, interest groups, parents and students. Information gathered from the workshops was analysed using action research methods. Mental health promotion interventions are delivered at three levels: universal, which is an intervention that affects the whole school or community; selective, which is an intervention focusing on a certain group of students; and indicated, which is an individually focused intervention. All interventions are delivered within the school setting, which is a universal setting for all school-aged children. The interventions share the goal of promoting mental health. The purposes of the interventions are enhancing protective factors, reducing risk factors relating to mental health problems and early identification of mental health problems as well as rapid delivery of support or referral to specialized services. The common effect of the interventions on all levels is the increase in the experience of positive mental health. © 2014 John Wiley & Sons Ltd.

  9. 77 FR 47820 - Invention Promoters/Promotion Firms Complaints

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-10

    ... DEPARTMENT OF COMMERCE United States Patent and Trademark Office Invention Promoters/Promotion... investigate these complaints or participate in any legal proceedings against invention promoters or promotion... invention promoter or promotion firm, explain the basis for the complaint, and include the signature of the...

  10. Oxytocin Enhances Social Persuasion during Hypnosis

    PubMed Central

    Bryant, Richard A.; Hung, Lynette

    2013-01-01

    It has long been argued that hypnosis cannot promote behaviors that people will not otherwise engage in. Oxytocin can enhance trust in others, and may promote the extent to which a hypnotized person complies with the suggestion of a hypnotist. This double-blind placebo study administered oxytocin or placebo to high hypnotizable participants (N = 28), who were then administered hypnotic suggestions for socially unorthodox behaviors, including swearing during the experiment, singing out loud, and dancing in response to a posthypnotic cue. Participants who received oxytocin were significantly more likely to swear and dance than those who received the placebo. This finding may be interpreted in terms of oxytocin increasing social compliance in response as a function of (a) increased trust in the hypnotist, (b) reduced social anxiety, or (c) enhanced sensitivity to cues to respond to experimental expectations. These results point to the potential role of oxytocin in social persuasion. PMID:23577153

  11. Using quality improvement to promote breast-feeding in a local health department.

    PubMed

    Wright, Sarah S; Lea, C Suzanne; Holloman, Roxanne; Cornett, Amanda; Harrison, Lisa Macon; Randolph, Greg D

    2012-01-01

    In 2008, breast-feeding initiation and continuation rates in Beaufort County, North Carolina, were lower than statewide rates. A quality improvement (QI) project was initiated to increase breast-feeding rates by enhancing the overall environment that supports breast-feeding at the Beaufort County Health Department. This case study describes one of the first QI initiatives implemented through the North Carolina Center for Public Health Quality QI training program, conducted in 2009. The aim of this project was to improve the health and wellness of mothers and infants in Beaufort County by promoting breast-feeding among Beaufort County Health Department Women, Infants and Children (WIC) clients. Using QI tools, 4 new approaches to breast-feeding promotion were tested and implemented: creating a nurturing location to breast-feed while at the health department, actively telephoning new mothers to provide breast-feeding support, incentivizing adoption of educational messages by providing a breast-feeding tote bag, and promoting new WIC food packages. These enhancements involved staff in QI planning and implementation and correlated with improved breast-feeding initiation for WIC clients during the year following project completion.

  12. The promotional effects of cesium promoter on higher alcohol synthesis from syngas over cesium-promoted Cu/ZnO/Al2O3 catalysts

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

    Sun, Jie; Cai, Qiuxia; Wan, Yan

    In this study, the promotional effects of cesium promoter on higher alcohol (C2+OH) synthesis from syngas over Cs-Cu/ZnO/Al2O3 catalysts were investigated using a combined experimental and theoretical density functional theory (DFT) calculation method. In the presence of cesium, the C2+OH productivity increases from 77.1 g•kgcat-1•h-1 to 157.3 g•kgcat-1•h-1 at 583 K due to the enhancement of the initial C–C bond formation. Detailed analysis of chain growth probabilities (CGPs) confirms that initial C–C bond formation is the rate-determining step in the temperature range of 543-583 K. Addition of cesium promoter significantly increases the productivities of 2-methyl-1-propanol, while the CGPs values (C3*more » to 2-methyl-C3*) is almost unaffected. With the assistance of cesium promoter, the CGPs of the initial C–C bond formation step (C1* to C2*) could be increased from 0.13 to 0.25 at 583 K. DFT calculations indicate that the initial C–C bond formation is mainly contributed by the HCO+HCO coupling reaction over the ZnCu(211) model surface. In the presence of the Cs2O, the stabilities of key reaction intermediates such as HCO and H2CO are enhanced which facilitates both HCO+HCO and HCO+H2CO coupling reaction steps with lower activation barriers over the Cs2O-ZnCu(211) surface. The promotional effects of cesium on the C2+OH productivity are also benefited from the competitive CH+HCO coupling reaction over CH hydrogenation that leads to lower alkane formation. In addition, Bader charge analysis suggests that the presence of cesium ions would facilitate the nucleophilic reaction between HCO and H2CO for initial C–C bond formation. This work was supported by the National Natural Science Foundation of China (No. 91545114 and No. 91545203). We appreciate the joint PhD scholarship support from the China Scholarship Council. The authors would also like to thank the support from Collaborative Innovation Center of Chemistry for Energy Materials (2011-i

  13. Sulphur responsiveness of the Chlamydomonas reinhardtii LHCBM9 promoter.

    PubMed

    Sawyer, Anne L; Hankamer, Ben D; Ross, Ian L

    2015-05-01

    A 44-base-pair region in the Chlamydomonas reinhardtii LHCBM9 promoter is essential for sulphur responsiveness. The photosynthetic light-harvesting complex (LHC) proteins play essential roles both in light capture, the first step of photosynthesis, and in photoprotective mechanisms. In contrast to the other LHC proteins and the majority of photosynthesis proteins, the Chlamydomonas reinhardtii photosystem II-associated LHC protein, LHCBM9, was recently reported to be up-regulated under sulphur deprivation conditions, which also induce hydrogen production. Here, we examined the sulphur responsiveness of the LHCBM9 gene at the transcriptional level, through promoter deletion analysis. The LHCBM9 promoter was found to be responsive to sulphur deprivation, with a 44-base-pair region between nucleotide positions -136 and -180 relative to the translation start site identified as essential for this response. Anaerobiosis was found to enhance promoter activity under sulphur deprivation conditions, however, alone was unable to induce promoter activity. The study of LHCBM9 is of biological and biotechnological importance, as its expression is linked to photobiological hydrogen production, theoretically the most efficient process for biofuel production, while the simplicity of using an S-deprivation trigger enables the development of a novel C. reinhardtii-inducible promoter system based on LHCBM9.

  14. Promoting Higher Order Thinking Skills Using Inquiry-Based Learning

    ERIC Educational Resources Information Center

    Madhuri, G. V.; Kantamreddi, V. S. S. N; Prakash Goteti, L. N. S.

    2012-01-01

    Active learning pedagogies play an important role in enhancing higher order cognitive skills among the student community. In this work, a laboratory course for first year engineering chemistry is designed and executed using an inquiry-based learning pedagogical approach. The goal of this module is to promote higher order thinking skills in…

  15. The tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting.

    PubMed

    Elattar, Sawsan; Dimri, Manali; Satyanarayana, Ande

    2018-03-23

    Cachexia is a complex tissue-wasting syndrome characterized by inflammation, hypermetabolism, increased energy expenditure, and anorexia. Browning of white adipose tissue (WAT) is one of the significant factors that contribute to energy wasting in cachexia. By utilizing a cell implantation model, we demonstrate here that the lipid mobilizing factor zinc-α 2 -glycoprotein (ZAG) induces WAT browning in mice. Increased circulating levels of ZAG not only induced lipolysis in adipose tissues but also caused robust browning in WAT. Stimulating WAT progenitors with ZAG recombinant protein or expression of ZAG in mouse embryonic fibroblasts (MEFs) strongly enhanced brown-like differentiation. At the molecular level, ZAG stimulated peroxisome proliferator-activated receptor γ (PPARγ) and early B cell factor 2 expression and promoted their recruitment to the PR/SET domain 16 (Prdm16) promoter, leading to enhanced expression of Prdm16, which determines brown cell fate. In brown adipose tissue, ZAG stimulated the expression of PPARγ and PPARγ coactivator 1α and promoted recruitment of PPARγ to the uncoupling protein 1 (Ucp1) promoter, leading to increased expression of Ucp1. Overall, our results reveal a novel function of ZAG in WAT browning and highlight the targeting of ZAG as a potential therapeutic application in humans with cachexia.-Elattar, S., Dimri, M., Satyanarayana, A. The tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting.

  16. Direct Lentiviral-Cyclooxygenase 2 Application to the Tendon-Bone Interface Promotes Osteointegration and Enhances Return of the Pull-Out Tensile Strength of the Tendon Graft in a Rat Model of Biceps Tenodesis

    PubMed Central

    Wergedal, Jon E.; Stiffel, Virginia; Lau, Kin-Hing William

    2014-01-01

    This study sought to determine if direct application of the lentiviral (LV)-cyclooxygenase 2 (COX2) vector to the tendon-bone interface would promote osteointegration of the tendon graft in a rat model of biceps tenodesis. The LV-COX2 gene transfer strategy was chosen for investigation because a similar COX2 gene transfer strategy promoted bony bridging of the fracture gap during bone repair, which involves similar histologic transitions that occur in osteointegration. Briefly, a 1.14-mm diameter tunnel was drilled in the mid-groove of the humerus of adult Fischer 344 rats. The LV-COX2 or βgal control vector was applied directly into the bone tunnel and onto the end of the tendon graft, which was then pulled into the bone tunnel. A poly-L-lactide pin was press-fitted into the tunnel as interference fixation. Animals were sacrificed at 3, 5, or 8 weeks for histology analysis of osteointegration. The LV-COX2 gene transfer strategy enhanced neo-chondrogenesis at the tendon-bone interface but with only marginal effect on de novo bone formation. The tendon-bone interface of the LV-COX2-treated tenodesis showed the well-defined tendon-to-fibrocartilage-to-bone histologic transitions that are indicative of osteointegration of the tendon graft. The LV-COX2 in vivo gene transfer strategy also significantly enhanced angiogenesis at the tendon-bone interface. To determine if the increased osteointegration was translated into an improved pull-out mechanical strength property, the pull-out tensile strength of the LV-COX2-treated tendon grafts was determined with a pull-out mechanical testing assay. The LV-COX2 strategy yielded a significant improvement in the return of the pull-out strength of the tendon graft after 8 weeks. In conclusion, the COX2-based in vivo gene transfer strategy enhanced angiogenesis, osteointegration and improved return of the pull-out strength of the tendon graft. Thus, this strategy has great potential to be developed into an effective therapy to

  17. Health-Promoting Properties of Lactobacillus helveticus

    PubMed Central

    Taverniti, Valentina; Guglielmetti, Simone

    2012-01-01

    Lactobacillus helveticus is an important industrial thermophilic starter that is predominantly employed in the fermentation of milk for the manufacture of several cheeses. In addition to its technological importance, a growing body of scientific evidence shows that strains belonging to the L. helveticus species have health-promoting properties. In this review, we synthesize the results of numerous primary literature papers concerning the ability of L. helveticus strains to positively influence human health. Several in vitro studies showed that L. helveticus possesses many common probiotic properties, such as the ability to survive gastrointestinal transit, adhere to epithelial cells, and antagonize pathogens. In vivo studies in murine models showed that L. helveticus could prevent gastrointestinal infections, enhance protection against pathogens, modulate host immune responses, and affect the composition of the intestinal microbiota. Interventional studies and clinical trials have also demonstrated a number of health-promoting properties of L. helveticus. Finally, several studies suggested that specific enzymatic activities of L. helveticus could indirectly benefit the human host by enhancing the bioavailability of nutrients, removing allergens and other undesired molecules from food, and producing bioactive peptides through the digestion of food proteins. In conclusion, this review demonstrates that in light of the scientific literature presented, L. helveticus can be included among the bacterial species that are generally considered to be probiotic. PMID:23181058

  18. A Cross-Sectional Study of Heat Wave-Related Knowledge, Attitude, and Practice among the Public in the Licheng District of Jinan City, China

    PubMed Central

    Li, Jing; Xu, Xin; Ding, Guoyong; Zhao, Yun; Zhao, Ruixia; Xue, Fuzhong; Li, Jing; Gao, Jinghong; Yang, Jun; Jiang, Baofa; Liu, Qiyong

    2016-01-01

    Knowledge, attitude, and practice (KAP) are three key components for reducing the adverse health impacts of heat waves. However, research in eastern China regarding this is scarce. The present study aimed to evaluate the heat wave-related KAP of a population in Licheng in northeast China. This cross-sectional study included 2241 participants. Data regarding demographic characteristics, KAP, and heat illnesses were collected using a structured questionnaire. Univariate analysis and unconditional logistic regression models were used to analyze the data. Most residents had high KAP scores, with a mean score of 12.23 (standard deviation = 2.23) on a 17-point scale. Urban women and participants aged 35–44 years had relatively high total scores, and those with high education levels had the highest total score. There was an increased risk of heat-related illness among those with knowledge scores of 3–5 on an 8-point scale with mean score of 5.40 (standard deviation = 1.45). Having a positive attitude toward sunstroke prevention and engaging in more preventive practices to avoid heat exposure had a protective interaction effect on reducing the prevalence of heat-related illnesses. Although the KAP scores were relatively high, knowledge and practice were lacking to some extent. Therefore, governments should further develop risk-awareness strategies that increase awareness and knowledge regarding the adverse health impact of heat and help in planning response strategies to improve the ability of individuals to cope with heat waves. PMID:27367715

  19. Enhancer competition between H19 and Igf2 does not mediate their imprinting

    PubMed Central

    Schmidt, Jennifer V.; Levorse, John M.; Tilghman, Shirley M.

    1999-01-01

    The linked H19 and Igf2 genes on mouse distal chromosome 7 are subject to genomic imprinting. Competition between the promoters of the genes for transcription from shared enhancers has been proposed as an explanation for the coordinate expression and reciprocal imprinting of these two genes. To test this model, we have used Cre-loxP technology to generate in mice a conditional deletion of the H19 promoter and structural gene that leaves no transcription unit in the locus. Contrary to the prediction of enhancer competition we find that transcriptional activity from the H19 promoter is not required for the imprinted silencing of the Igf2 gene. PMID:10449763

  20. Functional Role of Bacteria from Invasive Phragmites australis in Promotion of Host Growth.

    PubMed

    Soares, M A; Li, H-Y; Kowalski, K P; Bergen, M; Torres, M S; White, J F

    2016-08-01

    We hypothesize that bacterial endophytes may enhance the competitiveness and invasiveness of Phragmites australis. To evaluate this hypothesis, endophytic bacteria were isolated from P. australis. The majority of the shoot meristem isolates represent species from phyla Firmicutes, Proteobacteria, and Actinobacteria. We chose one species from each phylum to characterize further and to conduct growth promotion experiments in Phragmites. Bacteria tested include Bacillus amyloliquefaciens A9a, Achromobacter spanius B1, and Microbacterium oxydans B2. Isolates were characterized for known growth promotional traits, including indole acetic acid (IAA) production, secretion of hydrolytic enzymes, phosphate solubilization, and antibiosis activity. Potentially defensive antimicrobial lipopeptides were assayed for through application of co-culturing experiments and mass spectrometer analysis. B. amyloliquefaciens A9a and M. oxydans B2 produced IAA. B. amyloliquefaciens A9a secreted antifungal lipopeptides. Capability to promote growth of P. australis under low nitrogen conditions was evaluated in greenhouse experiments. All three isolates were found to increase the growth of P. australis under low soil nitrogen conditions and showed increased absorption of isotopic nitrogen into plants. This suggests that the Phragmites microbes we evaluated most likely promote growth of Phragmites by enhanced scavenging of nitrogenous compounds from the rhizosphere and transfer to host roots. Collectively, our results support the hypothesis that endophytic bacteria play a role in enhancing growth of P. australis in natural populations. Gaining a better understanding of the precise contributions and mechanisms of endophytes in enabling P. australis to develop high densities rapidly could lead to new symbiosis-based strategies for management and control of the host.