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Sample records for regulations enhanced treatment

  1. Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala.

    Science.gov (United States)

    Sawamura, Takehito; Klengel, Torsten; Armario, Antonio; Jovanovic, Tanja; Norrholm, Seth D; Ressler, Kerry J; Andero, Raül

    2016-02-01

    Posttraumatic stress disorder (PTSD) is both a prevalent and debilitating trauma-related disorder associated with dysregulated fear learning at the core of many of its signs and symptoms. Improvements in the currently available psychological and pharmacological treatments are needed in order to improve PTSD treatment outcomes and to prevent symptom relapse. In the present study, we used a putative animal model of PTSD that included presentation of immobilization stress (IMO) followed by fear conditioning (FC) a week later. We then investigated the acute effects of GR receptor activation on the extinction (EXT) of conditioned freezing, using dexamethasone administered systemically which is known to result in suppression of the HPA axis. In our previous work, IMO followed by tone-shock-mediated FC was associated with impaired fear EXT. In this study, we administered dexamethasone 4 h before EXT training and then examined EXT retention (RET) 24 h later to determine whether dexamethasone suppression rescued EXT deficits. Dexamethasone treatment produced dose-dependent enhancement of both EXT and RET. Dexamethasone was also associated with reduced amygdala Fkbp5 mRNA expression following EXT and after RET. Moreover, DNA methylation of the Fkbp5 gene occurred in a dose-dependent and time course-dependent manner within the amygdala. Additionally, we found dynamic changes in epigenetic regulation, including Dnmt and Tet gene pathways, as a function of both fear EXT and dexamethasone suppression of the HPA axis. Together, these data suggest that dexamethasone may serve to enhance EXT by altering Fkbp5-mediated glucocorticoid sensitivity via epigenetic regulation of Fkbp5 expression.

  2. Ultrasound Microbubble Treatment Enhances Clathrin-Mediated Endocytosis and Fluid-Phase Uptake through Distinct Mechanisms.

    Directory of Open Access Journals (Sweden)

    Farnaz Fekri

    Full Text Available Drug delivery to tumors is limited by several factors, including drug permeability of the target cell plasma membrane. Ultrasound in combination with microbubbles (USMB is a promising strategy to overcome these limitations. USMB treatment elicits enhanced cellular uptake of materials such as drugs, in part as a result of sheer stress and formation of transient membrane pores. Pores formed upon USMB treatment are rapidly resealed, suggesting that other processes such as enhanced endocytosis may contribute to the enhanced material uptake by cells upon USMB treatment. How USMB regulates endocytic processes remains incompletely understood. Cells constitutively utilize several distinct mechanisms of endocytosis, including clathrin-mediated endocytosis (CME for the internalization of receptor-bound macromolecules such as Transferrin Receptor (TfR, and distinct mechanism(s that mediate the majority of fluid-phase endocytosis. Tracking the abundance of TfR on the cell surface and the internalization of its ligand transferrin revealed that USMB acutely enhances the rate of CME. Total internal reflection fluorescence microscopy experiments revealed that USMB treatment altered the assembly of clathrin-coated pits, the basic structural units of CME. In addition, the rate of fluid-phase endocytosis was enhanced, but with delayed onset upon USMB treatment relative to the enhancement of CME, suggesting that the two processes are distinctly regulated by USMB. Indeed, vacuolin-1 or desipramine treatment prevented the enhancement of CME but not of fluid phase endocytosis upon USMB, suggesting that lysosome exocytosis and acid sphingomyelinase, respectively, are required for the regulation of CME but not fluid phase endocytosis upon USMB treatment. These results indicate that USMB enhances both CME and fluid phase endocytosis through distinct signaling mechanisms, and suggest that strategies for potentiating the enhancement of endocytosis upon USMB treatment may

  3. Memory Enhancement by Targeting Cdk5 Regulation of NR2B

    Science.gov (United States)

    Plattner, Florian; Hernandéz, Adan; Kistler, Tara M.; Pozo, Karine; Zhong, Ping; Yuen, Eunice Y.; Tan, Chunfeng; Hawasli, Ammar H.; Cooke, Sam F.; Nishi, Akinori; Guo, Ailan; Wiederhold, Thorsten; Yan, Zhen; Bibb, James A.

    2014-01-01

    SUMMARY Many psychiatric and neurological disorders are characterized by learning and memory deficits, for which cognitive enhancement is considered a valid treatment strategy. The N-methyl-D-aspartate receptor (NMDAR) is a prime target for the development of cognitive enhancers due to its fundamental role in learning and memory. In particular, the NMDAR subunit NR2B improves synaptic plasticity and memory when over-expressed in neurons. However, NR2B regulation is not well understood and no therapies potentiating NMDAR function have been developed. Here, we show that serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5). Cdk5-dependent NR2B phosphorylation is regulated by neuronal activity and controls the receptor’s cell surface expression. Disrupting NR2B-Cdk5 interaction using a small interfering peptide (siP) increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation in vivo. Our results reveal a novel regulatory mechanism critical to NR2B function that can be targeted for the development of cognitive enhancers. PMID:24607229

  4. Choosing to regulate: does choice enhance craving regulation?

    Science.gov (United States)

    Mobasser, Arian; Zeithamova, Dagmar; Pfeifer, Jennifer H

    2018-01-01

    Abstract Goal-directed behavior and lifelong well-being often depend on the ability to control appetitive motivations, such as cravings. Cognitive reappraisal is an effective way to modulate emotional states, including cravings, but is often studied under explicit instruction to regulate. Despite the strong prediction from Self-Determination Theory that choice should enhance task engagement and regulation success, little is known empirically about whether and how regulation is different when participants choose (vs are told) to exert control. To investigate how choice affects neural activity and regulation success, participants reappraised their responses to images of personally-craved foods while undergoing functional neuroimaging. Participants were either instructed to view or reappraise (‘no-choice’) or chose freely to view or reappraise (‘yes-choice’). Choice increased activity in the frontoparietal control network. We expected this activity would be associated with increased task engagement, resulting in better regulation success. However, contrary to this prediction, choice slightly reduced regulation success. Follow-up multivariate functional neuroimaging analyses indicated that choice likely disrupted allocation of limited cognitive resources during reappraisal. While unexpected, these results highlight the importance of studying upstream processes such as regulation choice, as they may affect the ability to regulate cravings and other emotional states. PMID:29462475

  5. ABT737 enhances cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics

    International Nuclear Information System (INIS)

    Fan, Zhongqi; Yu, Huimei; Cui, Ni; Kong, Xianggui; Liu, Xiaomin; Chang, Yulei; Wu, Yao; Sun, Liankun; Wang, Guangyi

    2015-01-01

    Cholangiocarcinoma responses weakly to cisplatin. Mitochondrial dynamics participate in the response to various stresses, and mainly involve mitophagy and mitochondrial fusion and fission. Bcl-2 family proteins play critical roles in orchestrating mitochondrial dynamics, and are involved in the resistance to cisplatin. Here we reported that ABT737, combined with cisplatin, can promote cholangiocarcinoma cells to undergo apoptosis. We found that the combined treatment decreased the Mcl-1 pro-survival form and increased Bak. Cells undergoing cisplatin treatment showed hyperfused mitochondria, whereas fragmentation was dominant in the mitochondria of cells exposed to the combined treatment, with higher Fis1 levels, decreased Mfn2 and OPA1 levels, increased ratio of Drp1 60 kD to 80 kD form, and more Drp1 located on mitochondria. More p62 aggregates were observed in cells with fragmented mitochondria, and they gradually translocated to mitochondria. Mitophagy was induced by the combined treatment. Knockdown p62 decreased the Drp1 ratio, increased Tom20, and increased cell viability. Our data indicated that mitochondrial dynamics play an important role in the response of cholangiocarcinoma to cisplatin. ABT737 might enhance cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics and the balance within Bcl-2 family proteins. Furthermore, p62 seems to be critical in the regulation of mitochondrial dynamics. - Highlights: • Cholangiocarcinoma may adapt to cisplatin through mitochondrial fusion. • ABT737 sensitizes cholangiocarcinoma to cisplatin by promoting fission and mitophagy. • p62 might participate in the regulation of mitochondrial fission and mitophagy

  6. Legal regulation of treatment of wild animals

    OpenAIRE

    Kolečkářová, Eliška

    2014-01-01

    The diploma thesis deals with the legal regulation of the treatment with wild animals. It compares different terms used in legal regulation of protection of animals. It specified differences between concept of an animal in private law and public law. The diploma thesis is focused on possibilities of gaining ownership to the wild animals, proving origin of animals bred in human care. It concerns with legal regulation of treatment with handicap animals. The diploma thesis analyzes preparation a...

  7. Synergism between the mTOR inhibitor rapamycin and FAK down-regulation in the treatment of acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Pei-Jie Shi

    2016-02-01

    Full Text Available Abstract Background Acute lymphoblastic leukemia (ALL is an aggressive malignant disorder of lymphoid progenitor cells in both children and adults. Although improvements in contemporary therapy and development of new treatment strategies have led to dramatic increases in the cure rate in children with ALL, the relapse rate remains high and the prognosis of relapsed childhood ALL is poor. Molecularly targeted therapies have emerged as the leading treatments in cancer therapy. Multi-cytotoxic drug regimens have achieved success, yet many studies addressing targeted therapies have focused on only one single agent. In this study, we attempted to investigate whether the effect of the mammalian target of rapamycin (mTOR inhibitor rapamycin is synergistic with the effect of focal adhesion kinase (FAK down-regulation in the treatment of ALL. Methods The effect of rapamycin combined with FAK down-regulation on cell proliferation, the cell cycle, and apoptosis was investigated in the human precursor B acute lymphoblastic leukemia cells REH and on survival time and leukemia progression in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID mouse model. Results When combined with FAK down-regulation, rapamycin-induced suppression of cell proliferation, G0/G1 cell cycle arrest, and apoptosis were significantly enhanced. In addition, REH cell-injected NOD/SCID mice treated with rapamycin and a short-hairpin RNA (shRNA to down-regulate FAK had significantly longer survival times and slower leukemia progression compared with mice injected with REH-empty vector cells and treated with rapamycin. Moreover, the B-cell CLL/lymphoma-2 (BCL-2 gene family was shown to be involved in the enhancement, by combined treatment, of REH cell apoptosis. Conclusions FAK down-regulation enhanced the in vitro and in vivo inhibitory effects of rapamycin on REH cell growth, indicating that the simultaneous targeting of mTOR- and FAK-related pathways might offer a novel

  8. Cognitive enhancement therapy improves fronto-limbic regulation of emotion in alcohol and/or cannabis misusing schizophrenia: a preliminary study

    Directory of Open Access Journals (Sweden)

    Jessica Ann Wojtalik

    2016-01-01

    Full Text Available Individuals with schizophrenia who misuse substances are burdened with impairments in emotion regulation. Cognitive Enhancement Therapy (CET may address these problems by enhancing prefrontal brain function. A small sample of outpatients with schizophrenia and alcohol and/or cannabis substance use problems participating in an 18-month randomized trial of CET (n = 10 or usual care (n = 4 completed post-treatment functional neuroimaging using an emotion regulation task. General linear models explored CET effects on brain activity in emotional neurocircuitry. Individuals treated with CET had significantly greater activation in broad regions of the prefrontal cortex, limbic and striatal systems implicated in emotion regulation compared to usual care. Differential activation favoring CET in prefrontal regions and the insula mediated behavioral improvements in emotional processing. Our data lend preliminary support of CET effects on neuroplasticity in fronto-limbic and striatal circuitries which mediate emotion regulation in people with schizophrenia and comorbid substance misuse problems.

  9. Environmental regulations handbook for enhanced oil recovery

    International Nuclear Information System (INIS)

    Madden, M.P.; Blatchford, R.P.; Spears, R.B.

    1991-12-01

    This handbook is intended to assist owners and operators of enhanced oil recovery (EOR) operations in acquiring some introductory knowledge of the various state agencies, the US Environmental Protection Agency, and the many environmental laws, rules and regulations which can have jurisdiction over their permitting and compliance activities. It is a compendium of summarizations of environmental rules. It is not intended to give readers specific working details of what is required from them, nor can it be used in that manner. Readers of this handbook are encouraged to contact environmental control offices nearest to locations of interest for current regulations affecting them

  10. Environmental regulations handbook for enhanced oil recovery

    Energy Technology Data Exchange (ETDEWEB)

    Madden, M.P. [National Inst. for Petroleum and Energy Research, Bartlesville, OK (United States); Blatchford, R.P.; Spears, R.B. [Spears and Associates, Inc., Tulsa, OK (United States)

    1991-12-01

    This handbook is intended to assist owners and operators of enhanced oil recovery (EOR) operations in acquiring some introductory knowledge of the various state agencies, the US Environmental Protection Agency, and the many environmental laws, rules and regulations which can have jurisdiction over their permitting and compliance activities. It is a compendium of summarizations of environmental rules. It is not intended to give readers specific working details of what is required from them, nor can it be used in that manner. Readers of this handbook are encouraged to contact environmental control offices nearest to locations of interest for current regulations affecting them.

  11. Behavioral Therapy, Incentives Enhance Addiction Treatment

    Science.gov (United States)

    ... Research News From NIH Behavioral Therapy, Incentives Enhance Addiction Treatment Past Issues / Summer 2006 Table of Contents ... that people who are trying to end their addiction to marijuana can benefit from a treatment program ...

  12. Intersect between self-esteem and emotion regulation in narcissistic personality disorder - implications for alliance building and treatment.

    Science.gov (United States)

    Ronningstam, Elsa

    2017-01-01

    Building an alliance with patients with pathological narcissism or narcissistic personality disorder, NPD, can be challenging and include avoidance, negative reactivity and disruptions. A main contributing factor can be the complex interaction between emotion and self-esteem regulation, which affects patients' ability to engage in a therapeutic alliance and treatment. Recent studies, especially in neuroscience have identified functional characteristic and compromises in self-esteem and emotion regulation related to NPD. Self-enhancement, hyper reactivity and need for control, which patients within the range of disordered narcissism often present, can have different roots and underpinnings that require thorough exploration in the process of building the therapeutic alliance and promote change in treatment. Clinical examples with treatment implications and strategies will be discussed to highlight both internal fluctuations and external features and shifts in narcissistic personality functioning.

  13. Environmental regulations handbook for enhanced oil recovery. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, T.D.

    1980-08-01

    A guide to environmental laws and regulations which have special significance for enhanced oil recovery (EOR) is presented. The Clean Air Act, the Clean Water Act, the Safe Drinking Water Act, Resource Conservation and Recovery Act, federal regulations, and state regulations are discussed. This handbook has been designed as a planning tool and a convenient reference source. The 16 states included comprise the major oil-producing states in various regions of the state. The major topics covered are: general guidelines for complying with environmental laws and regulations; air pollution control; water pollution control; protecting drinking water: underground injection control; hazardous waste management; and federal laws affecting siting or operation of EOR facilities. (DMC)

  14. Emotion regulation promotes persistence in a residential substance abuse treatment.

    Science.gov (United States)

    Hopwood, Christopher J; Schade, Nick; Matusiewicz, Alexis; Daughters, Stacey B; Lejuez, Carl W

    2015-01-01

    Emotion regulation at treatment entry was evaluated among 115 patients in an inner-city substance use residential facility who either persisted (N = 94) or discontinued treatment (N = 21). Emotion regulation capacity including emotional clarity and the ability to engage in goal-directed behavior despite emotional distress, as well as lower scores on a measure of trait-negative emotionality, were associated with treatment persistence, whereas motivational variables were not. Findings indicate the importance of regulating negative emotions for treatment engagement among substance abusers.

  15. Activating Transcription Factor 3 regulates in part the enhanced tumour cell cytotoxicity of the histone deacetylase inhibitor M344 and cisplatin in combination

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    St Germain Carly

    2010-09-01

    Full Text Available Abstract Background Activating Transcription Factor (ATF 3 is a key regulator of the cellular integrated stress response whose expression has also been correlated with pro-apoptotic activities in tumour cell models. Combination treatments with chemotherapeutic drugs, such as cisplatin, and histone deacetylase (HDAC inhibitors have been demonstrated to enhance tumour cell cytotoxicity. We recently demonstrated a role for ATF3 in regulating cisplatin-induced apoptosis and others have shown that HDAC inhibition can also induce cellular stress. In this study, we evaluated the role of ATF3 in regulating the co-operative cytotoxicity of cisplatin in combination with an HDAC inhibitor. Results The HDAC inhibitor M344 induced ATF3 expression at the protein and mRNA level in a panel of human derived cancer cell lines as determined by Western blot and quantitative RT-PCR analyses. Combination treatment with M344 and cisplatin lead to increased induction of ATF3 compared with cisplatin alone. Utilizing the MTT cell viability assay, M344 treatments also enhanced the cytotoxic effects of cisplatin in these cancer cell lines. The mechanism of ATF3 induction by M344 was found to be independent of MAPKinase pathways and dependent on ATF4, a known regulator of ATF3 expression. ATF4 heterozygote (+/- and knock out (-/- mouse embryonic fibroblast (MEF as well as chromatin immunoprecipitation (ChIP assays were utilized in determining the mechanistic induction of ATF3 by M344. We also demonstrated that ATF3 regulates the enhanced cytotoxicity of M344 in combination with cisplatin as evidenced by attenuation of cytotoxicity in shRNAs targeting ATF3 expressing cells. Conclusion This study identifies the pro-apoptotic factor, ATF3 as a novel target of M344, as well as a mediator of the co-operative effects of cisplatin and M344 induced tumour cell cytotoxicity.

  16. Enhanced integrated nonthermal treatment system study

    International Nuclear Information System (INIS)

    Biagi, C.; Schwinkendorf, B.; Teheranian, B.

    1997-02-01

    The purpose of the Enhanced Nonthermal Treatment Systems (ENTS) study is to evaluate alternative configurations of one of the five systems evaluated in the Integrated Nonthermal Treatment Systems (INTS) study. Five alternative configurations are evaluated. Each is designed to enhance the final waste form performance by replacing grout with improved stabilization technologies, or to improve system performance by improving the destruction efficiency for organic contaminants. AU enhanced systems are alternative configurations of System NT-5, which has the following characteristics: Nonthermal System NT-5: (1) catalytic wet oxidation (CWO) to treat organic material including organic liquids, sludges, and soft (or combustible) debris, (2) thermal desorption of inorganic sludge and process residue, (3) washing of soil and inorganic debris with treatment by CWO of removed organic material, (4) metal decontamination by abrasive blasting, (5) stabilization of treated sludge, soil, debris, and untreated debris with entrained contamination in grout, and (6) stabilization of inorganic sludge, salts and secondary waste in polymer. System NT-5 was chosen because it was designed to treat combustible debris thereby minimizing the final waste form volume, and because it uses grout for primary stabilization. The enhanced nonthermal systems were studied to determine the cost and performance impact of replacing grout (a commonly used stabilization agent in the DOE complex) with improved waste stabilization methods such as vitrification and polymer

  17. 76 FR 7522 - Federal Acquisition Regulation; Enhancing Contract Transparency

    Science.gov (United States)

    2011-02-10

    ... transparency while retaining the protection of information that should be considered in the contracting process... the need for transparency in Government contracting information and believe these recommendations... Regulation; Enhancing Contract Transparency AGENCY: Department of Defense (DoD), General Services...

  18. Cognitive emotion regulation enhances aversive prediction error activity while reducing emotional responses.

    Science.gov (United States)

    Mulej Bratec, Satja; Xie, Xiyao; Schmid, Gabriele; Doll, Anselm; Schilbach, Leonhard; Zimmer, Claus; Wohlschläger, Afra; Riedl, Valentin; Sorg, Christian

    2015-12-01

    Cognitive emotion regulation is a powerful way of modulating emotional responses. However, despite the vital role of emotions in learning, it is unknown whether the effect of cognitive emotion regulation also extends to the modulation of learning. Computational models indicate prediction error activity, typically observed in the striatum and ventral tegmental area, as a critical neural mechanism involved in associative learning. We used model-based fMRI during aversive conditioning with and without cognitive emotion regulation to test the hypothesis that emotion regulation would affect prediction error-related neural activity in the striatum and ventral tegmental area, reflecting an emotion regulation-related modulation of learning. Our results show that cognitive emotion regulation reduced emotion-related brain activity, but increased prediction error-related activity in a network involving ventral tegmental area, hippocampus, insula and ventral striatum. While the reduction of response activity was related to behavioral measures of emotion regulation success, the enhancement of prediction error-related neural activity was related to learning performance. Furthermore, functional connectivity between the ventral tegmental area and ventrolateral prefrontal cortex, an area involved in regulation, was specifically increased during emotion regulation and likewise related to learning performance. Our data, therefore, provide first-time evidence that beyond reducing emotional responses, cognitive emotion regulation affects learning by enhancing prediction error-related activity, potentially via tegmental dopaminergic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. CmWRKY1 Enhances the Dehydration Tolerance of Chrysanthemum through the Regulation of ABA-Associated Genes.

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    Qingqing Fan

    Full Text Available WRKY transcription factors serve as antagonistic or synergistic regulators in a variety of abiotic stress responses in plants. Here, we show that CmWRKY1, a member of the group IIb WRKY family isolated from Chrysanthemum morifolium, exhibits no transcriptional activation in yeast cells. The subcellular localization examination showed that CmWRKY1 localizes to the nucleus in vivo. Furthermore, CmWRKY1-overexpressing transgenic lines exhibit enhanced dehydration tolerance in response to polyethylene glycol (PEG treatment compared with wild-type plants. We further confirmed that the transgenic plants exhibit suppressed expression levels of genes negatively regulated by ABA, such as PP2C, ABI1 and ABI2, and activated expression levels of genes positively regulated by ABA, such as PYL2, SnRK2.2, ABF4, MYB2, RAB18, and DREB1A. Taken together, our results indicate that CmWRKY1 plays an important role in the response to drought in chrysanthemum through an ABA-mediated pathway.

  20. Enhancing composite durability : using thermal treatments

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    Jerrold E. Winandy; W. Ramsay Smith

    2007-01-01

    The use of thermal treatments to enhance the moisture resistance and aboveground durability of solid wood materials has been studied for years. Much work was done at the Forest Products Laboratory in the last 15 years on the fundamental process of both short-and long-term exposure to heat on wood materials and its interaction with various treatment chemicals. This work...

  1. Salinomycin enhances cisplatin-induced cytotoxicity in human lung cancer cells via down-regulation of AKT-dependent thymidylate synthase expression.

    Science.gov (United States)

    Ko, Jen-Chung; Zheng, Hao-Yu; Chen, Wen-Ching; Peng, Yi-Shuan; Wu, Chia-Hung; Wei, Chia-Li; Chen, Jyh-Cheng; Lin, Yun-Wei

    2016-12-15

    Salinomycin, a polyether antibiotic, acts as a highly selective potassium ionophore and has anticancer activity on various cancer cell lines. Cisplatin has been proved as chemotherapy drug for advanced human non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) is a key enzyme in the pyrimidine salvage pathway, and increased expression of TS is thought to be associated with resistance to cisplatin. In this study, we showed that salinomycin (0.5-2μg/mL) treatment down-regulating of TS expression in an AKT inactivation manner in two NSCLC cell lines, human lung adenocarcinoma A549 and squamous cell carcinoma H1703 cells. Knockdown of TS using small interfering RNA (siRNA) or inhibiting AKT activity with PI3K inhibitor LY294002 enhanced the cytotoxicity and cell growth inhibition of salinomycin. A combination of cisplatin and salinomycin resulted in synergistic enhancement of cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced activation of phospho-AKT, and TS expression. Overexpression of a constitutive active AKT (AKT-CA) expression vector reversed the salinomycin and cisplatin-induced synergistic cytotoxicity. In contrast, pretreatment with LY294002 further decreased the cell viability in salinomycin and cisplatin cotreated cells. Our findings suggested that the down-regulation of AKT-mediated TS expression by salinomycin enhanced the cisplatin-induced cytotoxicity in NSCLC cells. These results may provide a rationale to combine salinomycin with cisplatin for lung cancer treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Up-regulation of granzyme B and perforin by staphylococcal enterotoxin C2 mutant induces enhanced cytotoxicity in Hepa1–6 cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Guojun [Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning (China); University of Chinese Academy of Sciences, Beijing (China); Xu, Mingkai, E-mail: mkxu@iae.ac.cn [Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning (China); Zhang, Huiwen [Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning (China); Song, Yubo [Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning (China); University of Chinese Academy of Sciences, Beijing (China); Wang, Jian; Zhang, Chenggang [Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning (China)

    2016-12-15

    Staphylococcal enterotoxin C2 (SEC2), a member of bacterial superantigen, is one of the most potent known activators of T lymphocytes. With this property, SEC2 has already been used in clinic as a tumor immunotherapy agent in China. To increase the antitumor activity, a SEC2 mutant named ST-4 (GKVTG102-106WWH) with amino acid substitutions in T cell receptor (TCR)-binding domain was generated by site-directed mutagenesis, and the molecular mechanism of the enhanced antitumor activity was investigated. Results showed that ST-4 could activate much more Vβ 8.2 and 8.3 T cells and NK cells compared with SEC2, and exhibited significantly enhanced immunocyte stimulation and antitumor activity in vitro. The synthetic peptide sequencing the residues of mutant TCR-binding domain could competitively inhibit the immunocyte stimulation activity of ST-4. Most importantly, ST-4 up-regulated granzyme B and perforin at both mRNA and protein levels. We also found that expression of proapoptotic proteins cytochrome c, BAX and activation of caspase-3, 9 was up-regulated, and antiapoptotic protein Bcl-xL was down-regulated in the treatment with either ST-4 or SEC2. When granzyme B inhibitor or perforin inhibitor is presented, tumor cell viability was significantly rescued. Taken together, we demonstrate that increased ST-4-TCR recognition contributed to massive T cells and NK cells activation. These activated cells released up-regulated granzyme B and perforin, which induced the enhanced tumor cells apoptosis by mitochondrial apoptotic pathway, and ultimately led to enhanced tumor cell growth inhibition. ST-4 may be a promising candidate for antitumor clinic usage in future. - Highlights: • We obtained a SEC2 mutant ST-4 with enhanced superantigen and antitumor activity. • Increased ST-4-TCR recognition contributed to massive T cells and NK cells activation. • Up-regulated GzmB and PRF1 in T cell by ST-4 induced enhanced tumor cells apoptosis. • Enhanced tumor cell apoptosis

  3. 78 FR 60169 - Federal Acquisition Regulation; Pilot Program for Enhancement of Contractor Employee...

    Science.gov (United States)

    2013-09-30

    ... 9000-AM56 Federal Acquisition Regulation; Pilot Program for Enhancement of Contractor Employee... program enhancing whistleblower protections for contractor employees. DATES: Effective: September 30, 2013... contractor employees at FAR subpart 3.9. The pilot program is mandated by section 828, entitled ``Pilot...

  4. Manganese-Enhanced MRI for Preclinical Evaluation of Retinal Degeneration Treatments.

    Science.gov (United States)

    Schur, Rebecca M; Sheng, Li; Sahu, Bhubanananda; Yu, Guanping; Gao, Songqi; Yu, Xin; Maeda, Akiko; Palczewski, Krzysztof; Lu, Zheng-Rong

    2015-07-01

    Apply manganese-enhanced magnetic resonance imaging (MEMRI) to assess ion channel activity and structure of retinas from mice subject to light-induced retinal degeneration treated with prophylactic agents. Abca4(-/-)Rdh8(-/-) double knockout mice with and without prophylactic retinylamine (Ret-NH2) treatment were illuminated with strong light. Manganese-enhanced MRI was used to image the retina 2 hours after intravitreous injection of MnCl2 into one eye. Contrast-enhanced MRIs of the retina and vitreous humor in each experimental group were assessed and correlated with the treatment. Findings were compared with standard structural and functional assessments of the retina by optical coherence tomography (OCT), histology, and electroretinography (ERG). Manganese-enhanced MRI contrast in the retina was high in nonilluminated and illuminated Ret-NH2-treated mice, whereas no enhancement was evident in the retina of the light-illuminated mice without Ret-NH2 treatment (P treatment based on the measurement of ion channel activity. This approach could be used as a complementary tool in preclinical development of new prophylactic therapies for retinopathies.

  5. 76 FR 77115 - Amendments to the Export Administration Regulations: Facilitating Enhanced Public Understanding...

    Science.gov (United States)

    2011-12-12

    ..., and 774 [Docket No. 110627356-1475-01] RIN 0694-AF29 Amendments to the Export Administration Regulations: Facilitating Enhanced Public Understanding of the Provisions That Implement the Comprehensive U.S... rule, the Bureau of Industry and Security (BIS) amends the Export Administration Regulations (EAR) by...

  6. The effects of psychotherapy treatment on outcome in bulimia nervosa: Examining indirect effects through emotion regulation, self-directed behavior, and self-discrepancy within the mediation model.

    Science.gov (United States)

    Peterson, Carol B; Berg, Kelly C; Crosby, Ross D; Lavender, Jason M; Accurso, Erin C; Ciao, Anna C; Smith, Tracey L; Klein, Marjorie; Mitchell, James E; Crow, Scott J; Wonderlich, Stephen A

    2017-06-01

    The purpose of this investigation was to examine the indirect effects of Integrative Cognitive-Affective Therapy (ICAT-BN) and Cognitive-Behavioral Therapy-Enhanced (CBT-E) on bulimia nervosa (BN) treatment outcome through three hypothesized maintenance variables: emotion regulation, self-directed behavior, and self-discrepancy. Eighty adults with BN were randomized to 21 sessions of ICAT-BN or CBT-E. A regression-based bootstrapping approach was used to test the indirect effects of treatment on outcome at end of treatment through emotion regulation and self-directed behavior measured at mid-treatment, as well as the indirect effects of treatment at follow-up through emotion regulation, self-directed behavior, and self-discrepancy measured at end of treatment. No significant differences in outcome between treatment conditions were observed, and no significant direct or indirect effects were found. Examination of the individual paths within the indirect effects models revealed comparable treatment effects. Across treatments, improvements in emotion regulation and self-directed behavior between baseline and mid-treatment predicted improvements in global eating disorder scores but not binge eating and purging frequency at end of treatment. Baseline to end of treatment improvements in emotion regulation and self-directed behavior also predicted improvements in global eating disorder scores at follow-up. Baseline to end of treatment improvements in emotion regulation predicted improvements in binge eating and baseline to end of treatment increases in positive self-directed behavior predicted improvements in purging at follow-up. These findings suggest that emotion regulation and self-directed behavior are important treatment targets and that ICAT-BN and CBT-E are comparable in modifying these psychological processes among individuals with BN. © 2017 Wiley Periodicals, Inc.

  7. Multinuclear giant cell formation is enhanced by down-regulation of Wnt signaling in gastric cancer cell line, AGS

    International Nuclear Information System (INIS)

    Kim, Shi-Mun; Kim, Rockki; Ryu, Jae-Hyun; Jho, Eek-Hoon; Song, Ki-Joon; Jang, Shyh-Ing; Kee, Sun-Ho

    2005-01-01

    AGS cells, which were derived from malignant gastric adenocarcinoma tissue, lack E-cadherin-mediated cell adhesion but have a high level of nuclear β-catenin, which suggests altered Wnt signal. In addition, approximately 5% of AGS cells form multinuclear giant cells in the routine culture conditions, while taxol treatment causes most AGS cells to become giant cells. The observation of reduced nuclear β-catenin levels in giant cells induced by taxol treatment prompted us to investigate the relationship between Wnt signaling and giant cell formation. After overnight serum starvation, the shape of AGS cells became flattened, and this morphological change was accompanied by decrease in Myc expression and an increase in the giant cell population. Lithium chloride treatment, which inhibits GSK3β activity, reversed these serum starvation effects, which suggests an inverse relationship between Wnt signaling and giant cell formation. Furthermore, the down-regulation of Wnt signaling caused by the over-expression of ICAT, E-cadherin, and Axin enhanced giant cell formation. Therefore, down-regulation of Wnt signaling may be related to giant cell formation, which is considered to be a survival mechanism against induced cell death

  8. Regulation of hepatitis B virus ENI enhancer activity by hepatocyte-enriched transcription factor HNF3.

    Science.gov (United States)

    Chen, M; Hieng, S; Qian, X; Costa, R; Ou, J H

    1994-11-15

    Hepatitis B virus (HBV) ENI enhancer can activate the expression of HBV and non-HBV genes in a liver-specific manner. By performing the electrophoretic mobility-shift assays, we demonstrated that the three related, liver-enriched, transcription factors, HNF3 alpha, HNF3 beta, and HNF3 gamma could all bind to the 2c site of HBV ENI enhancer. Mutations introduced in the 2c site to abolish the binding by HNF3 reduced the enhancer activity approximately 15-fold. Moreover, expression of HNF3 antisense sequences to suppress the expression of HNF3 in Huh-7 hepatoma cells led to reduction of the ENI enhancer activity. These results indicate that HNF3 positively regulates the ENI enhancer activity and this regulation is most likely mediated through the 2c site. The requirement of HNF3 for the ENI enhancer activity could explain the liver specificity of this enhancer element.

  9. Regulation of Vapor Pressure Deficit by Greenhouse Micro-Fog Systems Improved Growth and Productivity of Tomato via Enhancing Photosynthesis during Summer Season.

    Science.gov (United States)

    Zhang, Dalong; Zhang, Zhongdian; Li, Jianming; Chang, Yibo; Du, Qingjie; Pan, Tonghua

    2015-01-01

    The role of a proposed micro-fog system in regulating greenhouse environments and enhancing tomato (Solanum lycopersicum L.) productivity during summer season was studied. Experiments were carried out in a multi-span glass greenhouse, which was divided into two identical compartments involving different environments: (1) without environment control and (2) with a micro-fog system operating when the air vapor pressure deficit (VPD) of greenhouse was higher than 0.5 KPa. The micro-fog system effectively alleviated heat stress and evaporative demand in the greenhouse during summer season. The physiologically favourable environment maintained by micro-fog treatment significantly enhanced elongation of leaf and stem, which contributed to a substantial elevation of final leaf area and shoot biomass. These improvements in physiological and morphological traits resulted in around 12.3% increase of marketable tomato yield per plant. Relative growth rate (RGR) of micro-fog treatment was also significantly higher than control plants, which was mainly determined by the substantial elevation in net assimilation rate (NAR), and to a lesser extent caused by leaf area ratio (LAR). Measurement of leaf gas exchange parameters also demonstrated that micro-fog treatment significantly enhanced leaf photosynthesis capacity. Taken together, manipulation of VPD in greenhouses by micro-fog systems effectively enhanced tomato growth and productivity via improving photosynthesis during summer season.

  10. Study on influence over approaching a market in the international trade by enhancing the international environmental regulation

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Sang In; Park, Joon Young [Korea Environment Institute, Seoul (Korea)

    1999-12-01

    The focal point of connecting trade and environment is what kind of influence over a national competitiveness of a national economy can be brought by enhancing environmental regulations. Traditionally it was accepted that the enhancement of environmental policy had a negative impact on competitiveness. However, recent study results show that the enhancement of environmental policy can strengthen industrial competitiveness for a long term. This study analyzes the significance of enhancing the international environmental regulation from a developing country's standpoint in association with this. 27 refs., 8 tabs.

  11. Study on influence over approaching a market in the international trade by enhancing the international environmental regulation

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Sang In; Park, Joon Young [Korea Environment Institute, Seoul (Korea)

    1999-12-01

    The focal point of connecting trade and environment is what kind of influence over a national competitiveness of a national economy can be brought by enhancing environmental regulations. Traditionally it was accepted that the enhancement of environmental policy had a negative impact on competitiveness. However, recent study results show that the enhancement of environmental policy can strengthen industrial competitiveness for a long term. This study analyzes the significance of enhancing the international environmental regulation from a developing country's standpoint in association with this. 27 refs., 8 tabs.

  12. A transient-enhanced NMOS low dropout voltage regulator with parallel feedback compensation

    International Nuclear Information System (INIS)

    Wang Han; Tan Lin

    2016-01-01

    This paper presents a transient-enhanced NMOS low-dropout regulator (LDO) for portable applications with parallel feedback compensation. The parallel feedback structure adds a dynamic zero to get an adequate phase margin with a load current variation from 0 to 1 A. A class-AB error amplifier and a fast charging/discharging unit are adopted to enhance the transient performance. The proposed LDO has been implemented in a 0.35 μm BCD process. From experimental results, the regulator can operate with a minimum dropout voltage of 150 mV at a maximum 1 A load and I Q of 165 μA. Under the full range load current step, the voltage undershoot and overshoot of the proposed LDO are reduced to 38 mV and 27 mV respectively. (paper)

  13. Future directions in water quality regulations

    International Nuclear Information System (INIS)

    Pontius, F.W.

    1997-01-01

    The Safe Drinking Water Act amendments of 1996 have imposed new requirements on the US Environmental Protection Agency (USEPA) to establish drinking water regulations. The regulatory process has been revised and now requires the use of sound science. Costs, benefits, and competing risks may also be considered. Current regulations for fluoride, volatile organic chemicals, total coliforms, surface water treatment, Phase 2 and Phase 5 synthetic organic and inorganic contaminants, and lead and copper remain basically unchanged. New deadlines are established for the regulation of arsenic, sulfate, radon, disinfectants and disinfection by-products, enhanced surface water treatment, and groundwater disinfection

  14. Ribavirin enhances IFN-α signalling and MxA expression: a novel immune modulation mechanism during treatment of HCV.

    Directory of Open Access Journals (Sweden)

    Nigel J Stevenson

    Full Text Available The nucleoside analogue Ribavirin significantly increases patient response to IFN-α treatment of HCV, by directly inhibiting viral replication. Recent studies indicate that Ribavirin also regulates immunity and we propose that Ribavirin enhances specific interferon sensitive gene (ISG expression by amplifying the IFN-α-JAK/STAT pathway. We found that IFN-α-induced STAT1 and STAT3 phosphorylation was increased in hepatocytes co-treated with Ribavirin and IFN-α, compared to IFN-α alone. Ribavirin specifically enhanced IFN-α induced mRNA and protein of the anti-viral mediator MxA, which co-localised with HCV core protein. These novel findings indicate for the first time that Ribavirin, in addition to its viral incorporation, also enhances IFN-α-JAK/STAT signalling, leading to a novel MxA-mediated immuno-modulatory mechanism that may enhance IFN-α anti-viral activity against HCV.

  15. Regulation of Vapor Pressure Deficit by Greenhouse Micro-Fog Systems Improved Growth and Productivity of Tomato via Enhancing Photosynthesis during Summer Season.

    Directory of Open Access Journals (Sweden)

    Dalong Zhang

    Full Text Available The role of a proposed micro-fog system in regulating greenhouse environments and enhancing tomato (Solanum lycopersicum L. productivity during summer season was studied. Experiments were carried out in a multi-span glass greenhouse, which was divided into two identical compartments involving different environments: (1 without environment control and (2 with a micro-fog system operating when the air vapor pressure deficit (VPD of greenhouse was higher than 0.5 KPa. The micro-fog system effectively alleviated heat stress and evaporative demand in the greenhouse during summer season. The physiologically favourable environment maintained by micro-fog treatment significantly enhanced elongation of leaf and stem, which contributed to a substantial elevation of final leaf area and shoot biomass. These improvements in physiological and morphological traits resulted in around 12.3% increase of marketable tomato yield per plant. Relative growth rate (RGR of micro-fog treatment was also significantly higher than control plants, which was mainly determined by the substantial elevation in net assimilation rate (NAR, and to a lesser extent caused by leaf area ratio (LAR. Measurement of leaf gas exchange parameters also demonstrated that micro-fog treatment significantly enhanced leaf photosynthesis capacity. Taken together, manipulation of VPD in greenhouses by micro-fog systems effectively enhanced tomato growth and productivity via improving photosynthesis during summer season.

  16. FK506 Binding Protein Mediates Glioma Cell Growth and Sensitivity to Rapamycin Treatment by Regulating NF-κB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Wei Jiang

    2008-03-01

    Full Text Available FK506 binding protein 5 (FKBP5 belongs to a family of immunophilins named for their ability to bind immunosuppressive drugs, also known as peptidyl-prolyl cis-trans isomerases, and also with chaperones to help protein folding. Using glioma cDNA microarray analysis, we found that FKBP5 was overexpressed in glioma tumors. This finding was further validated by real-time reverse transcription-polymerase chain reaction and Western blot analysis. The roles of FKBP5 in glioma cells were then examined. We found that cell growth was suppressed after FKBP5 expression was inhibited by short interfering RNA transfection and enhanced by FKBP5 overexpression. Electrophoretic mobility shift assay showed that nuclear factor-kappa B (NF-κB and DNA binding was enhanced by FKBP5 overexpression. The expression level of I-kappa B alpha and phosphorylated NF-κB was regulated by the expression of FKBP5. These data suggest that FKBP5 is involved in NF-κB pathway activation in glioma cells. In addition, FKBP5 overexpression in rapamycin-sensitive U87 cells blocked the cells' response to rapamycin treatment, whereas rapamycin-resistant glioma cells, both PTEN-positive and -negative, were synergistically sensitive to rapamycin after FKBP5 was knocked down, suggesting that the FKBP5 regulates glioma cell response to rapamycin treatment. In conclusion, our study demonstrates that FKBP5 plays an important role in glioma growth and chemoresistance through regulating signal transduction of the NF-κB pathway.

  17. Measuring ability to enhance and suppress emotional expression: The Flexible Regulation of Emotional Expression (FREE) Scale.

    Science.gov (United States)

    Burton, Charles L; Bonanno, George A

    2016-08-01

    Flexibility in self-regulatory behaviors has proved to be an important quality for adjusting to stressful life events and requires individuals to have a diverse repertoire of emotion regulation abilities. However, the most commonly used emotion regulation questionnaires assess frequency of behavior rather than ability, with little evidence linking these measures to observable capacity to enact a behavior. The aim of the current investigation was to develop and validate a Flexible Regulation of Emotional Expression (FREE) Scale that measures a person's ability to enhance and suppress displayed emotion across an array of hypothetical contexts. In Studies 1 and 2, a series of confirmatory factor analyses revealed that the FREE Scale consists of 4 first-order factors divided by regulation and emotional valence type that can contribute to 2 higher order factors: expressive enhancement ability and suppression ability. In Study 1, we also compared the FREE Scale to other commonly used emotion regulation measures, which revealed that suppression ability is conceptually distinct from suppression frequency. In Study 3, we compared the FREE Scale with a composite of traditional frequency-based indices of expressive regulation to predict performance in a previously validated emotional modulation paradigm. Participants' enhancement and suppression ability scores on the FREE Scale predicted their corresponding performance on the laboratory task, even when controlling for baseline expressiveness. These studies suggest that the FREE Scale is a valid and flexible measure of expressive regulation ability. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  18. 78 FR 59851 - Defense Federal Acquisition Regulation Supplement: Enhancement of Contractor Employee...

    Science.gov (United States)

    2013-09-30

    ...-AH97 Defense Federal Acquisition Regulation Supplement: Enhancement of Contractor Employee... contractor and subcontractor employees. DATES: Effective date: September 30, 2013. In accordance with FAR 1... Whistleblower Protections for Contractor Employees) made extensive changes to 10 U.S.C. 2409, entitled...

  19. Implication of mGlu5 receptor in the enhancement of morphine-induced hyperlocomotion under chronic treatment with zolpidem.

    Science.gov (United States)

    Shibasaki, Masahiro; Ishii, Kazunori; Masukawa, Daiki; Ando, Koji; Ikekubo, Yuiko; Ishikawa, Yutori; Shibasaki, Yumiko; Mori, Tomohisa; Suzuki, Tsutomu

    2014-09-05

    Long-term exposure to zolpidem induces drug dependence, and it is well known that the balance between the GABAergic and glutamatergic systems plays a critical role in maintaining the neuronal network. In the present study, we investigated the interaction between GABAA receptor α1 subunit and mGlu5 receptor in the limbic forebrain including the N.Acc. after treatment with zolpidem for 7 days. mGlu5 receptor protein levels were significantly increased after treatment with zolpidem for 7 days, and this change was accompanied by the up-regulation of phospholipase Cβ1 and calcium/calmodulin-dependent protein kinase IIα, which are downstream of mGlu5 receptor in the limbic forebrain. To confirm that mGlu5 receptor is directly involved in dopamine-related behavior in mice following chronic treatment with zolpidem, we measured morphine-induced hyperlocomotion after chronic treatment with zolpidem in the presence or absence of an mGlu5 receptor antagonist. Although chronic treatment with zolpidem significantly enhanced morphine-induced hyperlocomotion, this enhancement of morphine-induced hyperlocomotion was suppressed by treating it with the mGlu5 receptor antagonist MPEP. These results suggest that chronic treatment with zolpidem caused neural plasticity in response to activation of the mesolimbic dopaminergic system accompanied by an increase in mGlu5 receptor. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review

    Directory of Open Access Journals (Sweden)

    Rianne A. de Kleine

    2013-10-01

    Full Text Available There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD. Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: D-cycloserine, MDMA, hydrocortisone, and propranolol.

  1. Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review.

    Science.gov (United States)

    de Kleine, Rianne A; Rothbaum, Barbara O; van Minnen, Agnes

    2013-10-17

    There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD). Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. The current review aims to give an overview of clinical studies on pharmacological enhancement of exposure-based treatment for PTSD. The working mechanisms, efficacy studies in PTSD patients, and clinical utility of four different pharmacological enhancers will be discussed: d-cycloserine, MDMA, hydrocortisone, and propranolol.

  2. miR-133b down-regulates ABCC1 and enhances the sensitivity of CRC to anti-tumor drugs.

    Science.gov (United States)

    Chen, Miao; Li, Daojiang; Gong, Ni; Wu, Hao; Su, Chen; Xie, Canbin; Xiang, Hong; Lin, Changwei; Li, Xiaorong

    2017-08-08

    Multidrug resistance (MDR) is the main cause of failed chemotherapy treatments. Therefore, preventing MDR is pivotal in treating colorectal cancer (CRC). In a previous study miR-133b was shown to be a tumor suppressor. Additionally, in CRC cells transfected with miR-133b, ATP-binding cassette (ABC) subfamily C member 1(ABCC1) was shown to be significantly down regulated. Whether miR-133b also enhances the chemosensitivity of drugs used to treat CRC by targeting ABCC1 is still unclear. Here, we utilized flow cytometry and high-performance liquid chromatography (HPLC) analysis to identify the ability of miR-133b to reserve MDR in CRC. We then used a dual-luciferase reporter assay to validate that miR-133b targets ABCC1. Further in vivo experiments were designed to validate the method in which miR-133b reversed MDR in CRC cells. The results demonstrated that the level of miR-133b was down-regulated and the expression of ABCC1 was up-regulated in drug-resistant CRC cells compared to non-drug-resistant CRC cells. The restoration of miR-133b expression in CRC drug-resistant cells in vitro resulted in reduced IC50s to chemotherapeutic drugs, significantly induced G1 accumulation, inhibited growth and promoted necrosis in combination with either 5-fluorouracil (5-FU) or vincristine (VCR), and decreased the expression of ABCC1. The dual-luciferase assay demonstrated that miR-133b directly targets ABCC1. The combination of agomiRNA-133b with chemotherapeutic drugs in vivo inhibited tumor growth induced by CRC drug-resistant cells. A xenograft from the in vivo model resulted in up-regulated levels of miR-133b and down-regulated levels of ABCC1. Therefore, miR-133b enhances the chemosensitivity of CRC cells to anti-tumor drugs by directly down-regulating ABCC1. This discovery provides a therapeutic strategy in which miR-133b is used as a potential sensitizer for drug-resistant CRC.

  3. Mediastinal lymphoma: quantitative changes in gadolinium enhancement at MR imaging after treatment.

    Science.gov (United States)

    Rahmouni, A; Divine, M; Lepage, E; Jazaerli, N; Belhadj, K; Gaulard, P; Golli, M; Reyes, F; Vasile, N

    2001-06-01

    To compare changes in gadolinium enhancement at magnetic resonance (MR) imaging with outcome in mediastinal lymphoma after treatment. Thirty-one patients with bulky mediastinal lymphoma (17 with Hodgkin disease, 14 with non-Hodgkin lymphoma) underwent serial MR imaging before and up to 50 months after treatment, with routine follow-up (including computed tomography). Signal intensity ratios between masses and muscle were calculated on T1-weighted, T2-weighted, and contrast material-enhanced T1-weighted spin-echo MR images. The percentage enhancement and signal intensity ratios of mediastinal masses on T2-weighted MR images were calculated at diagnosis and during and after treatment. Twenty-one patients with persistent complete remission had a mean percentage enhancement of residual masses (4%; range, -26% to 40%) that was significantly lower than that of initial masses (78%; range, 41%-124%). Although the mean signal intensity ratio of residual masses on T2-weighted images was significantly lower than that of initial masses, an increase in this ratio was observed in four patients after treatment. In seven patients with relapse, the percentage enhancement value of the residual mass was as high as that of the initial mass. Gadolinium enhancement of lymphomatous masses of the mediastinum decreased markedly after treatment in patients in continuous complete remission but not in patients with relapse.

  4. Technically enhanced naturally occurring radioactive materials; identification, characterization and treatment

    International Nuclear Information System (INIS)

    Aly, H.F.

    2001-01-01

    Radioactive materials (TENORM) is produced in a relatively large amount with relatively small radioactivity, however in many instances the radioactivity levels exceeds that permissible. In this presentation, the different industries where enhanced levels of natural radioactivity is identified and characterized will be given. The different approaches for treatment of this enhanced radioactivity will be addressed. Finally, our research and development activities in characterization and treatment of TENORM produced from the oil fields in Egypt will be presented. (authors)

  5. Enhancing well-being at work: The role of emotion regulation skills as personal resources.

    Science.gov (United States)

    Buruck, Gabriele; Dörfel, Denise; Kugler, Joachim; Brom, Sarah Susanne

    2016-10-01

    Dealing with negative emotions is a crucial work demand, particularly for employees in health care. Job resources (e.g., autonomy, social support, or reward) but also personal resources (such as emotion regulation strategies) might reduce job stress and support well-being. Following this, the present study focused on strengthening emotion regulation as 1 way of dealing with high job demands. The aim of this study was to evaluate the impact of a standardized emotion regulation training (Affect Regulation Training [ART]; Berking, 2010) to improve emotion regulation skills and well-being of employees in elderly health care. Therefore, 96 elderly care workers filled out an established questionnaire of emotion regulation skills as well as a measure of well-being at pretreatment, posttreatment and at 6-month follow-up. The findings show that the ART fosters emotion regulation skills. In particularly, acceptance, tolerance, and modification of negative emotions was enhanced in the training groups in comparison to a control-group. Modification, meaning the ability to actively change emotions, improved even more over the follow-up-period. Simultaneously, well-being of participants increased over all measurement time points in the ART-group compared with the control-group. Additionally, the improvement in emotion regulation skills from pre to posttreatment was related to well-being at follow-up. In summary, our results support the ART as an effective intervention for dealing with negative emotions and to enhance well-being among employees in elderly care. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  6. Aneurysmal wall enhancement and perianeurysmal edema after endovascular treatment of unruptured cerebral aneurysms

    International Nuclear Information System (INIS)

    Su, I. Chang; Willinsky, Robert A.; Agid, Ronit; Fanning, Noel F.

    2014-01-01

    Perianeurysmal edema and aneurysm wall enhancement are previously described phenomenon after coil embolization attributed to inflammatory reaction. We aimed to demonstrate the prevalence and natural course of these phenomena in unruptured aneurysms after endovascular treatment and to identify factors that contributed to their development. We performed a retrospective analysis of consecutively treated unruptured aneurysms between January 2000 and December 2011. The presence and evolution of wall enhancement and perianeurysmal edema on MRI after endovascular treatment were analyzed. Variable factors were compared among aneurysms with and without edema. One hundred thirty-two unruptured aneurysms in 124 patients underwent endovascular treatment. Eighty-five (64.4 %) aneurysms had wall enhancement, and 9 (6.8 %) aneurysms had perianeurysmal brain edema. Wall enhancement tends to persist for years with two patterns identified. Larger aneurysms and brain-embedded aneurysms were significantly associated with wall enhancement. In all edema cases, the aneurysms were embedded within the brain and had wall enhancement. Progressive thickening of wall enhancement was significantly associated with edema. Edema can be symptomatic when in eloquent brain and stabilizes or resolves over the years. Our study demonstrates the prevalence and some appreciation of the natural history of aneurysmal wall enhancement and perianeurysmal brain edema following endovascular treatment of unruptured aneurysms. Aneurysmal wall enhancement is a common phenomenon while perianeurysmal edema is rare. These phenomena are likely related to the presence of inflammatory reaction near the aneurysmal wall. Both phenomena are usually asymptomatic and self-limited, and prophylactic treatment is not recommended. (orig.)

  7. MiR-155 Enhances Insulin Sensitivity by Coordinated Regulation of Multiple Genes in Mice

    Science.gov (United States)

    Lin, Taoyan; Lin, Xia; Chen, Li; Zeng, Hui; Han, Yanjiang; Wu, Lihong; Huang, Shun; Wang, Meng; Huang, Shenhao; Xie, Raoying; Liang, Liqi; Liu, Yu; Liu, Ruiyu; Zhang, Tingting; Li, Jing; Wang, Shengchun; Sun, Penghui; Huang, Wenhua; Yao, Kaitai; Xu, Kang; Du, Tao; Xiao, Dong

    2016-01-01

    miR-155 plays critical roles in numerous physiological and pathological processes, however, its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal that miR-155 levels are downregulated in serum from type 2 diabetes (T2D) patients, suggesting that miR-155 might be involved in blood glucose control and diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that miR-155 has no effects on the pancreatic β-cell proliferation and function. Global transgenic overexpression of miR-155 in mice leads to hypoglycaemia, improved glucose tolerance and insulin sensitivity. Conversely, miR-155 deficiency in mice causes hyperglycemia, impaired glucose tolerance and insulin resistance. In addition, consistent with a positive regulatory role of miR-155 in glucose metabolism, miR-155 positively modulates glucose uptake in all cell types examined, while mice overexpressing miR-155 transgene show enhanced glycolysis, and insulin-stimulated AKT and IRS-1 phosphorylation in liver, adipose tissue or skeletal muscle. Furthermore, we reveal these aforementioned phenomena occur, at least partially, through miR-155-mediated repression of important negative regulators (i.e. C/EBPβ, HDAC4 and SOCS1) of insulin signaling. Taken together, these findings demonstrate, for the first time, that miR-155 is a positive regulator of insulin sensitivity with potential applications for diabetes treatment. PMID:27711113

  8. Hormonal changes in spring barley after triazine herbicide treatment and its mixtures of regulators of polyamine biosynthesis

    Directory of Open Access Journals (Sweden)

    Pavol Trebichalský

    2017-01-01

    Full Text Available Plants adapt to abiotic stress by undergoing diverse biochemical and physiological changes that involve hormone-dependent signalling pathways. The effects of regulators of polyamine biosynthesis can be mimicked by exogenous chemical regulators such as herbicide safeners, which not only enhance stress tolerance but also confer hormetic benefits such as increased vigor and yield. The phytohormones, abscisic acid (ABA and auxin (IAA play key roles in regulating stress responses in plants. Two years pot trials at Slovak University of agriculture Nitra were carried out with analyses of contents of plant hormones in spring barley grain of variety Kompakt: indolyl-acetic acid (IAA and abscisic acid (ABA, after exposing of tested plants to herbicide stress, as well as the possible decrease of these stress factors with application of regulators of polyamine synthesis was evaluated. At 1st year in spring barley grain after application of solo triazine herbicide treatment in dose 0,5 L.ha-1 an increase of all analyzed plant hormones was observed and contrary, at 2nd year there was the decrease of their contents. From our work there is an obvious influence of herbicide stress induced by application of certain dose of triazine herbicide at 1st year. Expect of the variant with mixture of triazine herbicide (in amount of 0,5 L.ha-1 and 29,6 g.ha-1 DAB, at this year all by us applied regulators of polyamine synthesis reduced the level of both plant hormones. Higher affect of stress caused by enhanced content of soluble macroelements in soil where the plants of barley were grown was observed next year. Soil with increased contents of macronutrients (mg.kg-1: N30.7 + P108.3 + K261.5 + Mg604.2 had reducing effect on contents of plant hormones in barley grain at variant treated with solo triazine herbicide (in dose at 0,5 L.ha-1 in comparison to control variant. The mixtures of regulators of polyamine synthesis reduced the contents of IAA only in comparison to

  9. Solution scanning as a key policy tool: identifying management interventions to help maintain and enhance regulating ecosystem services

    Directory of Open Access Journals (Sweden)

    William J. Sutherland

    2014-06-01

    Full Text Available The major task of policy makers and practitioners when confronted with a resource management problem is to decide on the potential solution(s to adopt from a range of available options. However, this process is unlikely to be successful and cost effective without access to an independently verified and comprehensive available list of options. There is currently burgeoning interest in ecosystem services and quantitative assessments of their importance and value. Recognition of the value of ecosystem services to human well-being represents an increasingly important argument for protecting and restoring the natural environment, alongside the moral and ethical justifications for conservation. As well as understanding the benefits of ecosystem services, it is also important to synthesize the practical interventions that are capable of maintaining and/or enhancing these services. Apart from pest regulation, pollination, and global climate regulation, this type of exercise has attracted relatively little attention. Through a systematic consultation exercise, we identify a candidate list of 296 possible interventions across the main regulating services of air quality regulation, climate regulation, water flow regulation, erosion regulation, water purification and waste treatment, disease regulation, pest regulation, pollination and natural hazard regulation. The range of interventions differs greatly between habitats and services depending upon the ease of manipulation and the level of research intensity. Some interventions have the potential to deliver benefits across a range of regulating services, especially those that reduce soil loss and maintain forest cover. Synthesis and applications: Solution scanning is important for questioning existing knowledge and identifying the range of options available to researchers and practitioners, as well as serving as the necessary basis for assessing cost effectiveness and guiding implementation strategies. We

  10. 75 FR 26916 - Federal Acquisition Regulation: FAR Case 2009-004, Enhancing Contract Transparency

    Science.gov (United States)

    2010-05-13

    ... Regulation: FAR Case 2009-004, Enhancing Contract Transparency AGENCY: Department of Defense (DoD), General... commercial or financial information. This transparency effort is intended to promote efficiency in Government... the Administration's memorandum entitled Transparency and Open Government (January 21, 2009...

  11. Enhancement of the Electrocatalytic Activity of Gold Nanoparticles via Anodic Treatment and the Decrease of the Enhanced Activity with Aging

    International Nuclear Information System (INIS)

    Jo, Kyung Min; Kang, Hyun Ju; Yang, Hae Sik

    2011-01-01

    We have recently shown that the electrocatalytic activity of Au nanoparticles (AuNPs) can be enhanced via NaBH 4 treatment and cathodic treatment and that the enhanced activity slowly decreases with aging. We have also demonstrated that the electrocatalytic activity of the AuNPs freshly prepared by electrochemical or chemical reduction slowly decreases with aging in both air and solution. Likewise, the electrocatalytic activity of anodically treated Au electrodes or AuNPs might change with aging. Herein, we report that the electrocatalytic activity of long-aged AuNPs can be enhanced via anodic treatment and that the enhanced electrocatalytic activity decreases with aging in air. The change in the electrocatalytic activity of AuNPs was evaluated by comparing cyclic voltammograms for the electrooxi-dation of hydrogen peroxide (H 2 O 2 ) and formic acid

  12. Enhancement of radioresponse by combined treatment with flavopiridol, a cycline dependent kinase (CDK) inhibitor, in oral cancer cells

    International Nuclear Information System (INIS)

    Mihara, Mariko; Mano, Takamitsu; Ueyama, Yoshiya; Shintani, Satoru; Li, Syunnann; Klosek, S.; Hamakawa, Hiroyuki

    2005-01-01

    Cyclin dependent kinases (CDKs) play a pivotal role in cell cycle regulation. Flavopiridol is known to potently inhibit such CDKs as CDK1, CDK2, CDK4, CDK7. We already reported that flavopiridol inhibited the growth of oral squamous cell carcinoma (OSCC) cells and induced apoptosis in OSCC cells. In the present study, we investigated whether the treatment with flavopiridol improves the response to radiosensitivity in OSCC cell lines. In an in vitro study, there was a cooperative antiproliferative effect of combined treatment with flavopiridol and radiation in OSCC cell lines. Tumor xenograft studies demonstrated that the combination of flavopiridol and radiation caused growth inhibition and tumor regression of well-established OSCC tumor in athymic mice. Overall, we concluded that flavopiridol enhances tumor radioresponse and it is considered a suitable candidate drug in the treatment of oral cancer. (author)

  13. Arctigenin enhances swimming endurance of sedentary rats partially by regulation of antioxidant pathways.

    Science.gov (United States)

    Wu, Ruo-ming; Sun, Yan-yan; Zhou, Ting-ting; Zhu, Zhi-yuan; Zhuang, Jing-jing; Tang, Xuan; Chen, Jing; Hu, Li-hong; Shen, Xu

    2014-10-01

    Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan found in traditional Chinese herbs, has been determined to exhibit a variety of pharmacological activities, including anti-tumor, anti-inflammation, neuroprotection, and endurance enhancement. In the present study, we investigated the antioxidation and anti-fatigue effects of arctigenin in rats. Rat L6 skeletal muscle cell line was exposed to H2O2 (700 μmol/L), and ROS level was assayed using DCFH-DA as a probe. Male SD rats were injected with arctigenin (15 mg·kg(-1)·d(-1), ip) for 6 weeks, and then the weight-loaded forced swimming test (WFST) was performed to evaluate their endurance. The levels of antioxidant-related genes in L6 cells and the skeletal muscles of rats were analyzed using real-time RT-PCR and Western blotting. Incubation of L6 cells with arctigenin (1, 5, 20 μmol/L) dose-dependently decreased the H2O2-induced ROS production. WFST results demonstrated that chronic administration of arctigenin significantly enhanced the endurance of rats. Furthermore, molecular biology studies on L6 cells and skeletal muscles of the rats showed that arctigenin effectively increased the expression of the antioxidant-related genes, including superoxide dismutase (SOD), glutathione reductase (Gsr), glutathione peroxidase (GPX1), thioredoxin (Txn) and uncoupling protein 2 (UCP2), through regulation of two potential antioxidant pathways: AMPK/PGC-1α/PPARα in mitochondria and AMPK/p53/Nrf2 in the cell nucleus. Arctigenin efficiently enhances rat swimming endurance by elevation of the antioxidant capacity of the skeletal muscles, which has thereby highlighted the potential of this natural product as an antioxidant in the treatment of fatigue and related diseases.

  14. Enhancing nitrogen removal in stormwater treatment facilities for transportation.

    Science.gov (United States)

    2015-01-01

    Stormwater from roadways is a point source of pollution. State DOTs must comply with Total Maximum : Daily Load (TMDL) regulations for nutrients such as nitrogen, which causes water quality impairment. Existing stormwater treatment technologies, such...

  15. Enhanced Performance of Thin Film Composite Forward Osmosis Membrane by Chemical Post-Treatment

    Science.gov (United States)

    Liu, Zheng; Chen, Jiangrong; Cao, Zhen; Wang, Jian; Guo, Chungang

    2018-01-01

    Forward osmosis is an attractive technique in water purification and desalination fields. Enhancement of the forward osmosis membrane performance is essential to the application of this technique. In this study, an optimized chemical post-treatment approach which was used to improve RO membrane performance was employed for enhancing water flux of thin film composite forward osmosis membrane. Home-made polysulfide-based forward osmosis membrane was prepared and nitric acid, sulfuric acid, ethanol, 2-propanol were employed as post-treatment solutions. After a short-term treatment, all the membrane samples manifested water flux enhancement compared with their untreated counterparts. Over 50% increase of water flux had been obtained by ethanol solution treatment. The swelling, changes of hydrophobicity and solvency in both active layer and substrate were verified as the major causes for the enhancement of the water flux. It is noted that the treatment time and solution concentration should be controlled to get both appropriate water flux and reverse salt flux. The results obtained in this study will be useful for further FO membrane development and application.

  16. Long-time treatment by low-dose N-acetyl-L-cysteine enhances proinflammatory cytokine expressions in LPS-stimulated macrophages.

    Directory of Open Access Journals (Sweden)

    Tomokazu Ohnishi

    Full Text Available N-acetyl-L-cysteine is known to act as a reactive oxygen species scavenger and used in clinical applications. Previous reports have shown that high-dose N-acetyl-L-cysteine treatment inhibits the expression of proinflammatory cytokines in activated macrophages. Here, we have found that long-time N-acetyl-L-cysteine treatment at low-concentration increases phosphorylation of extracellular signal-regulated kinase 1/2 and AKT, which are essential for the induction of proinflammatory cytokines including interleukin 1β and interleukin 6 in lipopolysaccharide-stimulated RAW264.7 cells. Furthermore, long-time N-acetyl-L-cysteine treatment decreases expressions of protein phosphatases, catalytic subunit of protein phosphatase-2A and dual specificity phosphatase 1. On the other hand, we have found that short-time N-acetyl-L-cysteine treatment at low dose increases p53 expression, which inhibits expressions of proinflammatory cytokines. These observations suggest that long-time low-dose N-acetyl-L-cysteine treatment increases expressions of proinflammatory cytokines through enhancement of kinase phosphorylation.

  17. Spatial diversification of agroecosystems to enhance biological control and other regulating services: An agroecological perspective.

    Science.gov (United States)

    Hatt, Séverin; Boeraeve, Fanny; Artru, Sidonie; Dufrêne, Marc; Francis, Frédéric

    2018-04-15

    Spatial diversification of crop and non-crop habitats in farming systems is promising for enhancing natural regulation of insect pests. Nevertheless, results from recent syntheses show variable effects. One explanation is that the abundance and diversity of pests and natural enemies are affected by the composition, design and management of crop and non-crop habitats. Moreover, interactions between both local and landscape elements and practices carried out at different spatial scales may affect the regulation of insect pests. Hence, research is being conducted to understand these interdependencies. However, insects are not the only pests and pests are not the only elements to regulate in agroecosystems. Broadening the scope could allow addressing multiple issues simultaneously, but also solving them together by enhancing synergies. Indeed, spatial diversification of crop and non-crop habitats can allow addressing the issues of weeds and pathogens, along with being beneficial to several other regulating services like pollination, soil conservation and nutrient cycling. Although calls rise to develop multifunctional landscapes that optimize the delivery of multiple ecosystem services, it still represents a scientific challenge today. Enhancing interdisciplinarity in research institutions and building interrelations between scientists and stakeholders may help reach this goal. Despite obstacles, positive results from research based on such innovative approaches are encouraging for engaging science in this path. Hence, the aim of the present paper is to offer an update on these issues by exploring the most recent findings and discussing these results to highlight needs for future research. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Arctigenin enhances swimming endurance of sedentary rats partially by regulation of antioxidant pathways

    Science.gov (United States)

    Wu, Ruo-ming; Sun, Yan-yan; Zhou, Ting-ting; Zhu, Zhi-yuan; Zhuang, Jing-jing; Tang, Xuan; Chen, Jing; Hu, Li-hong; Shen, Xu

    2014-01-01

    Aim: Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan found in traditional Chinese herbs, has been determined to exhibit a variety of pharmacological activities, including anti-tumor, anti-inflammation, neuroprotection, and endurance enhancement. In the present study, we investigated the antioxidation and anti-fatigue effects of arctigenin in rats. Methods: Rat L6 skeletal muscle cell line was exposed to H2O2 (700 μmol/L), and ROS level was assayed using DCFH-DA as a probe. Male SD rats were injected with arctigenin (15 mg·kg−1·d−1, ip) for 6 weeks, and then the weight-loaded forced swimming test (WFST) was performed to evaluate their endurance. The levels of antioxidant-related genes in L6 cells and the skeletal muscles of rats were analyzed using real-time RT-PCR and Western blotting. Results: Incubation of L6 cells with arctigenin (1, 5, 20 μmol/L) dose-dependently decreased the H2O2-induced ROS production. WFST results demonstrated that chronic administration of arctigenin significantly enhanced the endurance of rats. Furthermore, molecular biology studies on L6 cells and skeletal muscles of the rats showed that arctigenin effectively increased the expression of the antioxidant-related genes, including superoxide dismutase (SOD), glutathione reductase (Gsr), glutathione peroxidase (GPX1), thioredoxin (Txn) and uncoupling protein 2 (UCP2), through regulation of two potential antioxidant pathways: AMPK/PGC-1α/PPARα in mitochondria and AMPK/p53/Nrf2 in the cell nucleus. Conclusion: Arctigenin efficiently enhances rat swimming endurance by elevation of the antioxidant capacity of the skeletal muscles, which has thereby highlighted the potential of this natural product as an antioxidant in the treatment of fatigue and related diseases. PMID:25152028

  19. CCAAT/enhancer-binding proteins regulate expression of the human steroidogenic acute regulatory protein (StAR) gene.

    Science.gov (United States)

    Christenson, L K; Johnson, P F; McAllister, J M; Strauss, J F

    1999-09-10

    Two putative CCAAT/enhancer-binding protein (C/EBP) response elements were identified in the proximal promoter of the human steroidogenic acute regulatory protein (StAR) gene, which encodes a key protein-regulating steroid hormone synthesis. Expression of C/EBPalpha and -beta increased StAR promoter activity in COS-1 and HepG2 cells. Cotransfection of C/EBPalpha or -beta and steroidogenic factor 1, a transcription factor required for cAMP regulation of StAR expression, into COS-1 augmented 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP)-stimulated promoter activity. When the putative C/EBP response elements were mutated, individually or together, a pronounced decline in basal StAR promoter activity in human granulosa-lutein cells resulted, but the fold stimulation of promoter activity by 8-Br-cAMP was unaffected. Recombinant C/EBPalpha and -beta bound to the two identified sequences but not the mutated elements. Human granulosa-lutein cell nuclear extracts also bound these elements but not the mutated sequences. An antibody to C/EBPbeta, but not C/EBPalpha, supershifted the nuclear protein complex associated with the more distal element. The complex formed by nuclear extracts with the proximal element was not supershifted by either antibody. Western blot analysis revealed the presence of C/EBPalpha and C/EBPbeta in human granulosa-lutein cell nuclear extracts. C/EBPbeta levels were up-regulated 3-fold by 8-Br-cAMP treatment. Our studies demonstrate a role for C/EBPbeta as well as yet to be identified proteins, which can bind to C/EBP response elements, in the regulation of StAR gene expression and suggest a mechanism by which C/EBPbeta participates in the cAMP regulation of StAR gene transcription.

  20. Enhancing E. coli tolerance towards oxidative stress via engineering its global regulator cAMP receptor protein (CRP.

    Directory of Open Access Journals (Sweden)

    Souvik Basak

    Full Text Available Oxidative damage to microbial hosts often occurs under stressful conditions during bioprocessing. Classical strain engineering approaches are usually both time-consuming and labor intensive. Here, we aim to improve E. coli performance under oxidative stress via engineering its global regulator cAMP receptor protein (CRP, which can directly or indirectly regulate redox-sensing regulators SoxR and OxyR, and other ~400 genes in E. coli. Error-prone PCR technique was employed to introduce modifications to CRP, and three mutants (OM1~OM3 were identified with improved tolerance via H(2O(2 enrichment selection. The best mutant OM3 could grow in 12 mM H(2O(2 with the growth rate of 0.6 h(-1, whereas the growth of wild type was completely inhibited at this H(2O(2 concentration. OM3 also elicited enhanced thermotolerance at 48°C as well as resistance against cumene hydroperoxide. The investigation about intracellular reactive oxygen species (ROS, which determines cell viability, indicated that the accumulation of ROS in OM3 was always lower than in WT with or without H(2O(2 treatment. Genome-wide DNA microarray analysis has shown not only CRP-regulated genes have demonstrated great transcriptional level changes (up to 8.9-fold, but also RpoS- and OxyR-regulated genes (up to 7.7-fold. qRT-PCR data and enzyme activity assay suggested that catalase (katE could be a major antioxidant enzyme in OM3 instead of alkyl hydroperoxide reductase or superoxide dismutase. To our knowledge, this is the first work on improving E. coli oxidative stress resistance by reframing its transcription machinery through its native global regulator. The positive outcome of this approach may suggest that engineering CRP can be successfully implemented as an efficient strain engineering alternative for E. coli.

  1. Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation

    Directory of Open Access Journals (Sweden)

    Charlotte Proudhon

    2016-06-01

    Full Text Available V(DJ recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR loci in a lineage- and stage-specific manner. Unexpectedly, we find that both active and inactive AgR enhancers cooperate to disseminate their effects in a localized and long-range manner. Here, we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. Furthermore, we establish that, in T cells, long-range contact and cooperation between the inactive Igk enhancer MiEκ and the active Tcrb enhancer Eβ alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage- and stage-specific control.

  2. Molecular and functional analysis of anchorage independent, treatment-evasive neuroblastoma tumorspheres with enhanced malignant properties: A possible explanation for radio-therapy resistance.

    Science.gov (United States)

    Abou-Antoun, Tamara J; Nazarian, Javad; Ghanem, Anthony; Vukmanovic, Stanislav; Sandler, Anthony D

    2018-01-01

    Despite significant advances in cancer treatment and management, more than 60% of patients with neuroblastoma present with very poor prognosis in the form of metastatic and aggressive disease. Solid tumors including neuroblastoma are thought to be heterogeneous with a sub-population of stem-like cells that are treatment-evasive with highly malignant characteristics. We previously identified a phenomenon of reversible adaptive plasticity (RAP) between anchorage dependent (AD) cells and anchorage independent (AI) tumorspheres in neuroblastoma cell cultures. To expand our molecular characterization of the AI tumorspheres, we sought to define the comprehensive proteomic profile of murine AD and AI neuroblastoma cells. The proteomic profiles of the two phenotypic cell populations were compared to each other to determine the differential protein expression and molecular pathways of interest. We report exclusive or significant up-regulation of tumorigenic pathways expressed by the AI tumorspheres compared to the AD cancer cells. These pathways govern metastatic potential, enhanced malignancy and epithelial to mesenchymal transition. Furthermore, radio-therapy induced significant up-regulation of specific tumorigenic and proliferative proteins, namely survivin, CDC2 and the enzyme Poly [ADP-ribose] polymerase 1. Bio-functional characteristics of the AI tumorspheres were resistant to sutent inhibition of receptor tyrosine kinases (RTKs) as well as to 2.5 Gy radio-therapy as assessed by cell survival, proliferation, apoptosis and migration. Interestingly, PDGF-BB stimulation of the PDGFRβ led to transactivation of EGFR and VEGFR in AI tumorspheres more potently than in AD cells. Sutent inhibition of PDGFRβ abrogated this transactivation in both cell types. In addition, 48 h sutent treatment significantly down-regulated the protein expression of PDGFRβ, MYCN, SOX2 and Survivin in the AI tumorspheres and inhibited tumorsphere self-renewal. Radio-sensitivity in AI

  3. Efficient in vitro delivery of Noggin siRNA enhances osteoblastogenesis

    Directory of Open Access Journals (Sweden)

    S. Ghadakzadeh

    2017-11-01

    Full Text Available Several types of serious bone defects would not heal without invasive clinical intervention. One approach to such defects is to enhance the capacity of bone-formation cells. Exogenous bone morphogenetic proteins (BMP have been utilized to positively regulate matrix mineralization and osteoblastogenesis, however, numerous adverse effects are associated with this approach. Noggin, a potent antagonist of BMPs, is an ideal candidate to target and decrease the need for supraphysiological doses of BMPs. In the current research we report a novel siRNA-mediated gene knock-down strategy to down-regulate Noggin. We utilized a lipid nanoparticle (LNP delivery strategy in pre-osteoblastic rat cells. In vitro LNP-siRNA treatment caused inconsequential cell toxicity and transfection was achieved in over 85% of cells. Noggin siRNA treatment successfully down-regulated cellular Noggin protein levels and enhanced BMP signal activity which in turn resulted in significantly increased osteoblast differentiation and extracellular matrix mineralization evidenced by histological assessments. Gene expression analysis showed that targeting Noggin specifically in bone cells would not lead to a compensatory effect from other BMP negative regulators such as Gremlin and Chordin. The results from this study support the notion that novel therapeutics targeting Noggin have the clinically relevant potential to enhance bone formation without the need for toxic doses of exogenous BMPs. Such treatments will undeniably provide safe and economical treatments for individuals whose poor bone repair results in permanent morbidity and disability. Keywords: Biological sciences, Biomedical engineering, Bioengineering, Biotechnology, Cell biology, Genetics

  4. Inhalable Andrographolide-β-cyclodextrin Inclusion Complexes for Treatment of Staphylococcus aureus Pneumonia by Regulating Immune Responses.

    Science.gov (United States)

    Zhang, Tongtong; Zhu, Lifei; Li, Miao; Hu, Yuzhen; Zhang, Erfeng; Jiang, Qingcheng; Han, Guang; Jin, Yiguang

    2017-05-01

    Bacterial pneumonia is a serious disease with high mortality if no appropriate and immediate therapy is available. Andrographolide (AG) is an anti-inflammatory agent extracted from a traditional Chinese herb andrographis paniculata. Oral AG tablets and pills are clinically applied for treatment of upper respiratory tract infections. However, the low solubility and bioavailability of AG lead to high doses and long-term therapy. Here we developed an andrographolide-β-cyclodextrin inclusion complex (AG-β-CD) for inhalation therapy of Staphylococcus aureus pneumonia. AG-β-CD was identified with X-ray diffraction and FT-IR. Surprisingly, both AG-β-CD and AG showed little in vitro anti-S. aureus activity. However, pulmonary delivery of AG, AG-β-CD, or penicillin had significant anti-S. aureus pneumonia effects. Leukocytes, neutrophils, white blood cells, total proteins, TNF-α, IL-6, NF-κB p65 expression, and bacterial colonies in the bronchoalveolar lavage fluids were detected. Pulmonary delivery of AG and AG-β-CD led to bacterial inhibition and inflammation alleviation by regulating immune responses, while penicillin only killed bacteria without significant immune regulation. Moreover, the antipneumonia activity of AG-β-CD was much higher than that of AG, probably resulting from locally accelerated AG dissolution due to β-CD inclusion. The aerodynamic diameter of AG-β-CD powders was 2.03 μm, suitable for pulmonary delivery. Inhalable AG-β-CD is a promising antibacterial and anti-inflammatory medicine for the treatment of S. aureus pneumonia by regulating immune responses, and the effect is enhanced by β-CD inclusion. AG and its formulations might be potent weapons against the resistant bacterial pneumonia due to their specific mechanism in the future.

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

    Science.gov (United States)

    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.

  6. Enhancing treatment of osteoarthritis knee pain by boosting expectancy: A functional neuroimaging study

    Directory of Open Access Journals (Sweden)

    Jian Kong

    Full Text Available Objectives: Expectation can significantly modulate pain and treatment effects. This study aims to investigate if boosting patients' expectancy can enhance the treatment of knee osteoarthritis (KOA, and its underlying brain mechanism. Methods: Seventy-four KOA patients were recruited and randomized to three groups: boosted acupuncture (with a manipulation to enhance expectation, standard acupuncture, or treatment as usual (TAU. Each patient underwent six treatments before being debriefed, and four additional treatments after being debriefed. The fMRI scans were applied during the first and sixth treatment sessions. Results: We found significantly decreased knee pain in the boosted acupuncture group compared to the standard acupuncture or TAU groups after both six and ten treatments. Resting state functional connectivity (rsFC analyses using the nucleus accumbens (NAc as the seed showed rsFC increases between the NAc and the medial prefrontal cortex (MPFC/rostral anterior cingulate cortex (rACC and dorsolateral prefrontal cortex in the boosted group as compared to the standard acupuncture group after multiple treatments. Expectancy scores after the first treatment were significantly associated with increased NAc-rACC/MPFC rsFC and decreased knee pain following treatment. Conclusions: Our study provides a novel method and mechanism for boosting the treatment of pain in patients with KOA. Our findings may shed light on enhancing outcomes of pharmacological and integrative medicines in clinical settings. Keywords: Knee osteoarthritis, Expectancy, Acupuncture, Reward, Resting state functional connectivity

  7. Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation.

    Science.gov (United States)

    Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

    2016-06-07

    V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage- and stage-specific manner. Unexpectedly, we find that both active and inactive AgR enhancers cooperate to disseminate their effects in a localized and long-range manner. Here, we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. Furthermore, we establish that, in T cells, long-range contact and cooperation between the inactive Igk enhancer MiEκ and the active Tcrb enhancer Eβ alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage- and stage-specific control. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Down-regulation of LncRNA TUG1 enhances radiosensitivity in bladder cancer via suppressing HMGB1 expression.

    Science.gov (United States)

    Jiang, Huijuan; Hu, Xigang; Zhang, Hongzhi; Li, Wenbo

    2017-04-04

    Long non-coding RNAs (lncRNAs) have been reported to regulate the sensitivity of different cancer cells to chemoradiotherapy. Aberrant expression of lncRNA Taurine-upregulated gene 1 (TUG1) has been found to be involved in the development of bladder cancer, however, its function and underlying mechanism in the radioresistance of bladder cancer remains unclear. Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of TUG1 and HMGB1 mRNA in bladder cancer tissues and cell lines. HMGB1 protein levels were tested by western blot assays. Different doses of X-ray were used for radiation treatment of bladder cancer cells. Colony survival and cell viability were detected by clonogenic assay and CCK-8 Kit, respectively. Cell apoptosis was determined by flow cytometry. A xenograft mouse model was constructed to observe the effect of TUG1 on tumor growth in vivo. The levels of TUG1 and HMGB1 were remarkably increased in bladder cancer tissues and cell lines. Radiation treatment markedly elevated the expression of TUG1 and HMGB1. TUG1 knockdown inhibited cell proliferation, promoted cell apoptosis and decreased colony survival in SW780 and BIU87 cells under radiation. Moreover, TUG1 depletion suppressed the HMGB1 mRNA and protein levels. Furthermore, overexpression of HMGB1 reversed TUG1 knockdown-induced effect in bladder cancer cells. Radiation treatment dramatically reduced the tumor volume and weight in xenograft model, and this effect was more obvious when combined with TUG1 silencing. LncRNA TUG1 knockdown enhances radiosensitivity of bladder cancer by suppressing HMGB1 expression. TUG1 acts as a potential regulator of radioresistance of bladder cancer, and it may represent a promising therapeutic target for bladder cancer patients.

  9. Effects of sulekang capsule in enhancement of resistance to radiation and regulating immunological function in mice

    International Nuclear Information System (INIS)

    Zhao Naikun; Zhou Ouliang; Du Weixia

    1990-01-01

    The effects of Sulekang capsule in enhancing the resistance to radiation and regulating the immunological function in mice were described. The results show that Sulekang capsule may lengthen the survival time (p 60 Co gamma rays. The experimental results of ANAE reaction show that the activety of T cells of normal or exposed mice may be enhanced by Sulekang capsule, which can control the decrease of both ANAE-positive cells and T cells in exposed mice. So it may enhance the immunological function on exposed animals

  10. Bixin regulates mRNA expression involved in adipogenesis and enhances insulin sensitivity in 3T3-L1 adipocytes through PPAR{gamma} activation

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Nobuyuki; Goto, Tsuyoshi; Taimatsu, Aki; Egawa, Kahori; Katoh, Sota; Kusudo, Tatsuya; Sakamoto, Tomoya; Ohyane, Chie; Lee, Joo-Young; Kim, Young-il; Uemura, Taku; Hirai, Shizuka [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011 (Japan); Kawada, Teruo, E-mail: fat@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011 (Japan)

    2009-12-25

    Insulin resistance is partly due to suppression of insulin-induced glucose uptake into adipocytes. The uptake is dependent on adipocyte differentiation, which is controlled at mRNA transcription level. The peroxisome proliferator-activated receptor (PPAR), a ligand-regulated nuclear receptor, is involved in the differentiation. Many food-derived compounds serve as ligands to activate or inactivate PPAR. In this study, we demonstrated that bixin and norbixin (annatto extracts) activate PPAR{gamma} by luciferase reporter assay using GAL4-PPAR chimera proteins. To examine the effects of bixin on adipocytes, 3T3-L1 adipocytes were treated with bixin or norbixin. The treatment induced mRNA expression of PPAR{gamma} target genes such as adipocyte-specific fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and adiponectin in differentiated 3T3-L1 adipocytes and enhanced insulin-dependent glucose uptake. The observations indicate that bixin acts as an agonist of PPAR{gamma} and enhances insulin sensitivity in 3T3-L1 adipocytes, suggesting that bixin is a valuable food-derived compound as a PPAR ligand to regulate lipid metabolism and to ameliorate metabolic syndrome.

  11. Resveratrol strongly enhances the retinoic acid-induced superoxide generating activity via up-regulation of gp91-phox gene expression in U937 cells.

    Science.gov (United States)

    Kikuchi, Hidehiko; Mimuro, Hitomi; Kuribayashi, Futoshi

    2018-01-01

    The membrane bound cytochrome b 558 composed of gp91-phox and p22-phox proteins, and cytosolic proteins p40-, p47-and p67-phox are important components of superoxide (O 2 - )-generating system in phagocytes. Here, we describe that resveratrol, a pleiotropic phytochemical belonging to the stilbenoids, dramatically activates the O 2 - -generating system during retinoic acid (RA)-induced differentiation of human monoblastic leukemia U937 cells to macrophage-like cells. When U937 cells were cultured in the presence of RA and resveratrol, the O 2 - -generating activity increased more than 5-fold compared with that in the absence of the latter. Semiquantitative RT-PCR showed that co-treatment with RA and resveratrol strongly enhanced transcription of the gp91-phox compared with those of the RA-treatment only. On the other hand, immunoblot analysis revealed that co-treatment with RA and resveratrol caused remarkable accumulation of protein levels of gp91-phox (to 4-fold), p22-phox (to 5-fold) and p47-phox (to 4-fold) compared with those of the RA-treatment alone. In addition, ChIP assay suggested that resveratrol participates in enhancing the gene expression of gp91-phox via promoting acetylation of Lys-9 residues and Lys-14 residues of histone H3 within chromatin around the promoter regions of the gene. These results suggested that resveratrol strongly enhances the RA-induced O 2 - -generating activity via up-regulation of gp91-phox gene expression in U937 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Effects of low dose treatment of tributyltin on the regulation of estrogen receptor functions in MCF-7 cells.

    Science.gov (United States)

    Sharan, Shruti; Nikhil, Kumar; Roy, Partha

    2013-06-01

    Endocrine disrupting chemicals are the natural/synthetic compounds which mimic or inhibit the actions of endogenous hormones. Organotin compounds, such as tributyltin (TBT) are typical environmental contaminants and suspected endocrine-disrupting chemical. The present study evaluates the estrogenic potential of this compound in vitro in ER (+) breast adenocarcinoma, MCF-7 cell line. Our data showed that tributyltin chloride (TBTCl) had agonistic activities for estrogen receptor-α (ER-α). Its estrogenic potential was checked using cell proliferation assay, aromatase assay, transactivation assay, and protein expression analysis. Low dose treatment of TBTCl had a proliferative effect on MCF-7 cells and resulted in up-regulation of aromatase enzyme activity and enhanced estradiol production in MCF-7 cells. Immunofluorescence staining showed translocation of ER-α from cytoplasm to nucleus and increased expression of ER-α, 3β-HSD and aromatase on treatment with increasing doses of TBTCl. Further, to decipher the probable signaling pathways involved in its action, the MCF-7 cells were transfected with different pathway dependent luciferase reporter plasmids (CRE, SRE, NF-κB and AP1). A significant increase in CRE and SRE and decrease in NF-κB regulated pathway were observed (ptributyltin genomically and non-genomically augmented estrogen dependent signaling by targeting various pathways. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Pharmacological enhancement of treatment for amblyopia

    Science.gov (United States)

    Rashad, Mohammad A

    2012-01-01

    Background The purpose of this study was to compare a weight-adjusted dose of carbidopa- levodopa as treatment adjunctive to occlusion therapy with occlusion therapy alone in children and adults with different types of amblyopia. Methods This prospective study included 63 patients with amblyopia classified into two groups, ie, an occlusion group which included 35 patients who received occlusion therapy only and a pharmacological enhancement group which included 28 patients who received oral carbidopa-levodopa together with occlusion therapy for 6 weeks. Results The mean logarithm of the minimal angle of resolution (logMAR) of the eyes with amblyopia was not significantly different in the occlusion group (0.52, 0.52, and 0.51) than in the pharmacological enhancement group (0.58, 0.49, and 0.56) at three follow-up visits (at months 1, 3, and 12, respectively). There was a highly significant improvement in mean logMAR of amblyopic eyes compared with baseline in both occlusion groups (from 0.68 to 0.52, from 0.68 to 0.52, and from 0.68 to 0.51) and in the pharmacological enhancement group (from 0.81 to 0.58, from 0.81 to 0.49, and from 0.81 to 0.56) at the month 1, 3, and 12 visits (P = 0.01, P = 0.01, and P = 0.001, respectively). The improvement of mean logMAR in the subgroup of patients older than 12 years was greater in the pharmacological enhancement group (42.5%) than in the occlusion group (30%). The improvement of mean logMAR in the subgroup of patients with severe amblyopia was greater in the pharmacological enhancement group (34.3%) than in the occlusion group (22%). Conclusion Significant improvement was reported in both groups at all follow-up visits over 1 year. Regardless of the etiology of amblyopia, levodopa-carbidopa may be added to part-time occlusion in older patients as a means of increasing the plasticity of the visual cortex. Levodopa may add to the effect of occlusion in severe amblyopia and bilateral amblyopia. PMID:22536029

  14. Active and inactive enhancers co-operate to exert localized and long-range control of gene regulation

    Science.gov (United States)

    Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

    2016-01-01

    V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage and stage specific manner. Unexpectedly we find that both active and inactive AgR enhancers co-operate to disseminate their effects in a localized and long-range manner. Here we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. We further establish that in T cells long-range contact and co-operation between the inactive Igk enhancer, MiEκ and the active Tcrb enhancer, Eβ, alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage and stage specific control. PMID:27239026

  15. Does Using E-Portfolios for Reflective Writing Enhance High School Students' Self-Regulated Learning?

    Science.gov (United States)

    Chang, Chi-Cheng; Liang, Chaoyun; Shu, Kuen-Ming; Tseng, Kuo-Hung; Lin, Chun-Yu

    2016-01-01

    The study aims to examine whether reflective writing using e-portfolios enhances high school students' self-regulated learning. Participants included two classes of eighth-graders majoring in Information Processing and taking a course called "Website Design" at a vocational high school in Taiwan. There were 41 students, with 18 males and…

  16. Degradation of chloramphenicol by UV/chlorine treatment: Kinetics, mechanism and enhanced formation of halonitromethanes.

    Science.gov (United States)

    Dong, Huiyu; Qiang, Zhimin; Hu, Jun; Qu, Jiuhui

    2017-09-15

    Ultraviolet (UV)/chlorine process is considered as an emerging advanced oxidation process for the degradation of micropollutants. This study investigated the degradation of chloramphenicol (CAP) and formation of disinfection by-products (DBPs) during the UV/chlorine treatment. It was found that CAP degradation was enhanced by combined UV/chlorine treatment compared to that of UV and chlorination treatment alone. The pseudo-first-order rate constant of the UV/chlorine process at pH 7.0 reached 0.016 s -1 , which was 10.0 and 2.0 folds that observed from UV and chlorination alone, respectively. The enhancement can be attributed to the formation of diverse radicals (HO and reactive chlorine species (RCSs)), and the contribution of RCSs maintained more stable than that of HO at pH 5.5-8.5. Meanwhile, enhanced DBPs formation during the UV/chlorine treatment was observed. Both the simultaneous formation and 24-h halonitromethanes formation potential (HNMsFP) were positively correlated with the UV/chlorine treatment time. Although the simultaneous trichloronitromethane (TCNM) formation decreased with the prolonged UV irradiation, TCNM dominated the formation of HNMs after 24 h (>97.0%). According to structural analysis of transformation by-products, both the accelerated CAP degradation and enhanced HNMs formation steps were proposed. Overall, the formation of diverse radicals during the UV/chlorine treatment accelerated the degradation of CAP, while also enhanced the formation of DBPs simultaneously, indicating the need for DBPs evaluation before the application of combined UV/chlorine process. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Cationic polyacrylamide enhancing cellulase treatment efficiency of hardwood kraft-based dissolving pulp.

    Science.gov (United States)

    Wang, Qiang; Liu, Shanshan; Yang, Guihua; Chen, Jiachuan; Ni, Yonghao

    2015-05-01

    Cellulase treatment for decreasing viscosity and increasing Fock reactivity of dissolving pulp is a promising approach to reduce the use of toxic chemicals, such as hypochlorite in the dissolving pulp manufacturing process in the industry. Improving the cellulase treatment efficiency during the process is of practical interest. In the present study, the concept of using cationic polyacrylamide (CPAM) to enhance the cellulase treatment efficiency was demonstrated. This was mainly attributed to the increased cellulase adsorption onto cellulose fibers based on the patching/bridging mechanism. Results showed that the cellulase adsorption was increased by about 20% with the addition of 250 ppm of CPAM under the same conditions as those of the control. It was found that the viscosity decrease and Fock reactivity increase for the cellulase treatment was enhanced from using CPAM. The CPAM-assisted cellulase treatment concept may provide a practical alternative to the present hypochlorite-based technology for viscosity control in the industry. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Enhancing offspring hypothalamic-pituitary-adrenal (HPA regulation via systematic neonatal novelty exposure: the influence of maternal HPA function

    Directory of Open Access Journals (Sweden)

    Sarah M. Dinces

    2014-06-01

    Full Text Available In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother’s ability to mount a rapid corticosterone (CORT response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring HPA regulation. Using a 2x2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel daily during infancy (PND1-21 and the other half of the litter remained in the home cage (Neo_Home; we further exposed half of these two groups to early adulthood (PND54-63 novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB and the ability to mount a large rapid CORT response (CORTE to the onset of an acute stressor. Assessment of adult offspring’s ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring’s ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the context of maternal

  19. Electron beam treatment with radical scavengers/enhancers

    International Nuclear Information System (INIS)

    Gehringer, P.

    1994-08-01

    E-beam treatment of low level contaminated groundwater is best apt to demonstrate the role of scavengers and enhancers, respectively because groundwater already contains some scavengers as natural solutes. The action of ionizing radiation to water is known to result in the formation of ions, molecular and free radical species. For low level contaminations of groundwater (pollutant concentration aqu - and H are of interest for pollutant decomposition. The pollutants have to compete for the free radical species with the natural solutes. 10 figures are discussed. (author)

  20. An ultra-low power output capacitor-less low-dropout regulator with slew-rate-enhanced circuit

    Science.gov (United States)

    Cheng, Xin; Zhang, Yu; Xie, Guangjun; Yang, Yizhong; Zhang, Zhang

    2018-03-01

    An ultra-low power output-capacitorless low-dropout (LDO) regulator with a slew-rate-enhanced (SRE) circuit is introduced. The increased slew rate is achieved by sensing the transient output voltage of the LDO and then charging (or discharging) the gate capacitor quickly. In addition, a buffer with ultra-low output impedance is presented to improve line and load regulations. This design is fabricated by SMIC 0.18 μm CMOS technology. Experimental results show that, the proposed LDO regulator only consumes an ultra-low quiescent current of 1.2 μA. The output current range is from 10 μA to 200 mA and the corresponding variation of output voltage is less than 40 mV. Moreover, the measured line regulation and load regulation are 15.38 mV/V and 0.4 mV/mA respectively. Project supported by the National Natural Science Foundation of China (Nos. 61401137, 61404043, 61674049).

  1. Pharmacological enhancement of treatment for amblyopia

    Directory of Open Access Journals (Sweden)

    Rashad MA

    2012-03-01

    Full Text Available Mohammad A RashadOphthalmology Department, Faculty of Medicine, Ain Shams University, Cairo, EgyptBackground: The purpose of this study was to compare a weight-adjusted dose of carbidopa-levodopa as treatment adjunctive to occlusion therapy with occlusion therapy alone in children and adults with different types of amblyopia.Methods: This prospective study included 63 patients with amblyopia classified into two groups, ie, an occlusion group which included 35 patients who received occlusion therapy only and a pharmacological enhancement group which included 28 patients who received oral carbidopa-levodopa together with occlusion therapy for 6 weeks.Results: The mean logarithm of the minimal angle of resolution (logMAR of the eyes with amblyopia was not significantly different in the occlusion group (0.52, 0.52, and 0.51 than in the pharmacological enhancement group (0.58, 0.49, and 0.56 at three follow-up visits (at months 1, 3, and 12, respectively. There was a highly significant improvement in mean logMAR of amblyopic eyes compared with baseline in both occlusion groups (from 0.68 to 0.52, from 0.68 to 0.52, and from 0.68 to 0.51 and in the pharmacological enhancement group (from 0.81 to 0.58, from 0.81 to 0.49, and from 0.81 to 0.56 at the month 1, 3, and 12 visits (P = 0.01, P = 0.01, and P = 0.001, respectively. The improvement of mean logMAR in the subgroup of patients older than 12 years was greater in the pharmacological enhancement group (42.5% than in the occlusion group (30%. The improvement of mean logMAR in the subgroup of patients with severe amblyopia was greater in the pharmacological enhancement group (34.3% than in the occlusion group (22%.Conclusion: Significant improvement was reported in both groups at all follow-up visits over 1 year. Regardless of the etiology of amblyopia, levodopa-carbidopa may be added to part-time occlusion in older patients as a means of increasing the plasticity of the visual cortex. Levodopa may add

  2. Integrating stormwater and greywater treatment for thermal regulation and the enhancement of biological diversity using mass balance of water as a design criteria

    Energy Technology Data Exchange (ETDEWEB)

    Mankiewicz, P.S.; Simon, D.B. [Gaia Inst., Bronx, NY (United States)

    2007-07-01

    This paper presented green roof projects scheduled for construction in New York City in 2007 which will test the hypothesis that green roof water budgets can favorably impact energy consumption in buildings and in their immediate surroundings. It presented specific methods and applications to move water and partition heat through vegetation to reach complementary goals in both ecology and economics of increasing plant coverage, decreasing urban summer temperature, and eliminating the expense of treating stormwater and greywater through evaporative cooling. A commercial facility will be retrofitted with a green roof and photovoltaic (PV) array as well as a below grade stormwater capture and recycle system. The overall energy efficiency, as well as PV performance, will be enhanced by coupling a green roof with water treatment with photovoltaic energy capture. Condensers for this building will be situated beneath a green roof and next to a vegetated landscape, resulting in cool air that is expected to increase air conditioning efficiencies. The objective is zero stormwater discharge into the combined sewer. The density of plant coverage, the quantity of available water, and the output of crops were studied in detail. The interdependent criteria of thermal partitioning, water loss, leaf area index, and green roof energetics have begun to receive attention because green roof evaluation has begun to focus on the ability of plants to discharge quantities of water into the atmosphere, and because this water movement pathway has large physical chemical impacts on the thermal environment. This paper revealed that green roofs contribute to thermal regulation and energy savings, with a kilowatt usage difference of 20 per cent or greater for black versus green roofs. 26 refs., 2 figs.

  3. Self-regulation strategies may enhance the acute effect of exercise on smoking delay.

    Science.gov (United States)

    Hatzigeorgiadis, Antonis; Pappa, Vassiliki; Tsiami, Anastasia; Tzatzaki, Theodora; Georgakouli, Kalliopi; Zourbanos, Nikos; Goudas, Marios; Chatzisarantis, Nikos; Theodorakis, Yannis

    2016-06-01

    The present study examined the acute effect of a moderate intensity aerobic exercise session combined with self-regulation on smoking delay in physically inactive smokers. Participants were 11 adults (5 males and 6 females) that completed three experimental conditions: control, exercise, and exercise using self-regulation strategies (SR). Following the experimental treatment smoking for the two exercise conditions delayed significantly more than for the control condition; in addition exercise SR delayed smoking marginally more that the plain exercise condition. Findings supported previous research that acute exercise reduces cravings to smoke, and suggests that the use of self-regulation strategies may strengthen exercise for smoking cessation interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Effect of thermal, chemical and thermo-chemical pre-treatments to enhance methane production

    Energy Technology Data Exchange (ETDEWEB)

    Rafique, Rashad; Nizami, Abdul-Sattar; Murphy, Jerry D.; Kiely, Gerard [Department of Civil and Environmental Engineering, University College Cork (Ireland); Poulsen, Tjalfe Gorm [Department of Biotechnology, Chemistry and Environmental Engineering, Aalborg University (Denmark); Asam, Zaki-ul-Zaman [Department of Civil Engineering, National University of Ireland Galway (Ireland)

    2010-12-15

    The rise in oil price triggered the exploration and enhancement of various renewable energy sources. Producing biogas from organic waste is not only providing a clean sustainable indigenous fuel to the number of on-farm digesters in Europe, but also reducing the ecological and environmental deterioration. The lignocellulosic substrates are not completely biodegraded in anaerobic digesters operating at commercial scale due to their complex physical and chemical structure, which result in meager energy recovery in terms of methane yield. The focus of this study is to investigate the effect of pre-treatments: thermal, thermo-chemical and chemical pre-treatments on the biogas and methane potential of dewatered pig manure. A laboratory scale batch digester is used for these pre-treatments at different temperature range (25 C-150 C). Results showed that thermo-chemical pretreatment has high effect on biogas and methane potential in the temperature range (25-100 C). Maximum enhancement is observed at 70 C with increase of 78% biogas and 60% methane production. Thermal pretreatment also showed enhancement in the temperature range (50-10 C), with maximum enhancement at 100 C having 28% biogas and 25% methane increase. (author)

  5. Dynamic contrast-enhanced MR imaging in predicting progression of enhancing lesions persisting after standard treatment in glioblastoma patients: a prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Roh-Eul; Choi, Hye Jeong; You, Sung-Hye; Kang, Koung Mi; Yun, Tae Jin; Kim, Ji-Hoon; Sohn, Chul-Ho [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Choi, Seung Hong [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University, Center for Nanoparticle Research, Institute for Basic Science, and School of Chemical and Biological Engineering, Seoul (Korea, Republic of); Seoul National University, School of Chemical and Biological Engineering, Seoul (Korea, Republic of); Kim, Tae Min [Seoul National University College of Medicine, Department of Internal Medicine, Cancer Research Institute, Seoul (Korea, Republic of); Park, Chul-Kee [Seoul National University College of Medicine, Department of Neurosurgery, Biomedical Research Institute, Seoul (Korea, Republic of); Park, Sung-Hye; Won, Jae-Kyung [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Kim, Il Han [Seoul National University College of Medicine, Department of Radiation Oncology, Cancer Research Institute, Seoul (Korea, Republic of); Lee, Soon Tae [Seoul National University College of Medicine, Department of Neurology, Seoul (Korea, Republic of)

    2017-08-15

    To prospectively explore the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the progression of enhancing lesions persisting after standard treatment in patients with surgically resected glioblastoma (GBM). Forty-seven GBM patients, who underwent near-total tumorectomy followed by concurrent chemoradiation therapy (CCRT) with temozolomide (TMZ) between May 2014 and February 2016, were enrolled. Twenty-four patients were finally analyzed for measurable enhancing lesions persisting after standard treatment. DCE-MRI parameters were calculated at enhancing lesions. Mann-Whitney U tests and multivariable stepwise logistic regression were used to compare parameters between progression (n = 16) and non-progression (n = 8) groups. Mean K{sup trans} and v{sub e} were significantly lower in progression than in non-progression (P = 0.037 and P = 0.037, respectively). The 5th percentile of the cumulative K{sup trans} histogram was also significantly lower in the progression than in non-progression group (P = 0.017). Mean v{sub e} was the only independent predictor of progression (P = 0.007), with a sensitivity of 100%, specificity of 63%, and an overall accuracy of 88% at a cut-off value of 0.873. DCE-MRI may help predict the progression of enhancing lesions persisting after the completion of standard treatment in patients with surgically resected GBM, with mean v{sub e} serving as an independent predictor of progression. (orig.)

  6. Dynamic contrast-enhanced MR imaging in predicting progression of enhancing lesions persisting after standard treatment in glioblastoma patients: a prospective study

    International Nuclear Information System (INIS)

    Yoo, Roh-Eul; Choi, Hye Jeong; You, Sung-Hye; Kang, Koung Mi; Yun, Tae Jin; Kim, Ji-Hoon; Sohn, Chul-Ho; Choi, Seung Hong; Kim, Tae Min; Park, Chul-Kee; Park, Sung-Hye; Won, Jae-Kyung; Kim, Il Han; Lee, Soon Tae

    2017-01-01

    To prospectively explore the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the progression of enhancing lesions persisting after standard treatment in patients with surgically resected glioblastoma (GBM). Forty-seven GBM patients, who underwent near-total tumorectomy followed by concurrent chemoradiation therapy (CCRT) with temozolomide (TMZ) between May 2014 and February 2016, were enrolled. Twenty-four patients were finally analyzed for measurable enhancing lesions persisting after standard treatment. DCE-MRI parameters were calculated at enhancing lesions. Mann-Whitney U tests and multivariable stepwise logistic regression were used to compare parameters between progression (n = 16) and non-progression (n = 8) groups. Mean K trans and v e were significantly lower in progression than in non-progression (P = 0.037 and P = 0.037, respectively). The 5th percentile of the cumulative K trans histogram was also significantly lower in the progression than in non-progression group (P = 0.017). Mean v e was the only independent predictor of progression (P = 0.007), with a sensitivity of 100%, specificity of 63%, and an overall accuracy of 88% at a cut-off value of 0.873. DCE-MRI may help predict the progression of enhancing lesions persisting after the completion of standard treatment in patients with surgically resected GBM, with mean v e serving as an independent predictor of progression. (orig.)

  7. Enhanced field emission from carbon nanotubes by hydrogen plasma treatment

    International Nuclear Information System (INIS)

    Zhi, C.Y.; Bai, X.D.; Wang, E.G.

    2002-01-01

    The field emission capability of the carbon nanotubes (CNTs) has been improved by hydrogen plasma treatment, and the enhanced emission mechanism has been studied systematically using Fourier-transform infrared spectroscopy, Raman, and transmission electron microscopy. The hydrogen concentration in the samples increases with increasing plasma treatment duration. A C δ- -H δ+ dipole layer may form on CNTs' surface and a high density of defects results from the plasma treatment, which is likely to make the external surface of CNTs more active to emit electrons after treatment. In addition, the sharp edge of CNTs' top, after removal of the catalyst particles, may increase the local electronic field more effectively. The present study suggests that hydrogen plasma treatment is a useful method for improving the field electron emission property of CNTs

  8. Combination Treatments with Luteolin and Fisetin Enhance Anti-Inflammatory Effects in High Glucose-Treated THP-1 Cells Through Histone Acetyltransferase/Histone Deacetylase Regulation.

    Science.gov (United States)

    Kim, Arang; Yun, Jung-Mi

    2017-08-01

    Hyperglycemia leads to diabetes and its diabetic complications. In this study, we investigated the synergistic effects of luteolin and fisetin on proinflammatory cytokine secretion and its underlying epigenetic regulation in human monocytes exposed to hyperglycemic (HG) concentrations. Human monocytic cells (THP-1) were cultured under controlled (14.5 mM mannitol), normoglycemic (5.5 mM glucose), or HG (20 mM glucose) conditions in the absence or presence of the two phytochemicals for 48 h. Whereas HG conditions significantly induced histone acetylation, nuclear factor-kappa B (NF-κB) activation, interleukin 6, and tumor necrosis factor-α release from THP-1 cells; combination treatments with the two phytochemicals (500 nM fisetin, and l μM and 500 nM luteolin) suppressed NF-κB activity and inflammatory cytokine release. Fisetin, luteolin, and their combination treatments also significantly decreased the activity of histone acetyltransferase, a known NF-κB coactivator; inhibited reactive oxygen species production; and activated sirtuin (SIRT)1 and forkhead box O3a (FOXO3a) expressions (P < .05). Thus, combination treatments with the two phytochemicals inhibited HG condition-induced cytokine production in monocytes, through epigenetic changes involving NF-κB activation. We, therefore, suggest that combination treatments with luteolin and fisetin may be a potential candidate for the treatment and prevention of diabetes and its complications.

  9. Microwave enhanced oxidation treatment of organic fertilizers.

    Science.gov (United States)

    More, Abhilasha; Srinivasan, Asha; Liao, Ping Huang; Lo, Kwang Victor

    2017-08-01

    Liquid organic fertilizers (LOFs) are relatively easier to degrade than those of solid organic fertilizers, and the nutrients are readily available for plant uptake. Microwave enhanced advanced oxidation treatment (MW/H 2 O 2 -AOP) was used to convert solid organic fertilizers (insoluble blood meal, bone meal, feather meal, sunflower ash and a mixture) into LOF. After the MW/H 2 O 2 -AOP treatment, high soluble nitrogen (11-29%), soluble phosphorus (64%) and potassium (92%), as well as low total suspended solids content could be obtained. The resulting LOF would make the nutrients more bioavailable, and would provide some of them for the plant uptake immediately. Temperature and hydrogen peroxide dosage were found to be significant factors affecting nitrogen release from blood meal and feather meal, while temperature and pH were found to be significant factors for solubilizing phosphorus and potassium from bone meal and ash, respectively. The MW/H 2 O 2 -AOP reduced suspended solids, and released nutrients into solution; therefore, it was an effective treatment method to make LOFs. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  10. Selective Regulation of Oocyte Meiotic Events Enhances Progress in Fertility Preservation Methods

    Directory of Open Access Journals (Sweden)

    Onder Celik

    2015-01-01

    Full Text Available Following early embryonic germ cell migration, oocytes are surrounded by somatic cells and remain arrested at diplotene stage until luteinizing hormone (LH surge. Strict regulation of both meiotic arrest and meiotic resumption during dormant stage are critical for future fertility. Intercellular signaling system between the somatic compartment and oocyte regulates these meiotic events and determines the follicle quality. As well as the collected number of eggs, their qualities are also important for in vitro fertilization (IVF outcome. In spontaneous and IVF cycles, germinal vesicle (GV–stage oocytes, premature GV breakdown, and persistence of first meiotic arrest limit the reproductive performance. Likewise, both women with premature ovarian aging and young cancer women are undergoing chemoradiotherapy under the risk of follicle loss because of unregulated meiotic events. Understanding of oocyte meiotic events is therefore critical for the prevention of functional ovarian reserve. High levels of cyclic guanosine monophophate (cGMP, cyclic adenosine monophophate (cAMP and low phosphodiesterase (PDE 3A enzyme activity inside the oocyte are responsible for maintaining of meiotic arrest before the LH surge. cGMP is produced in the somatic compartment, and natriuretic peptide precursor C (Nppc and natriuretic peptide receptor 2 (Npr2 regulate its production. cGMP diffuses into the oocyte and reduces the PDE3A activity, which inhibits the conversion of cAMP to the 5′AMP, and cAMP levels are enhanced. In addition, oocyte itself has the ability to produce cAMP. Taken together, accumulation of cAMP inside the oocyte induces protein kinase activity, which leads to the inhibition of maturation-promoting factor and meiotic arrest also continues. By stimulating the expression of epidermal growth factor, LH inhibits the Nppc/Npr2 system, blocks cGMP synthesis, and initiates meiotic resumption. Oocytes lacking the functional of this pathway may lead to

  11. Enhanced induction of apoptosis by combined treatment of human carcinoma cells with X rays and death receptor agonists

    International Nuclear Information System (INIS)

    Hamasu, Taku; Inanami, Osamu; Asanuma, Taketoshi; Kuwabara, Mikinori

    2005-01-01

    The death receptors Fas and DR5 are known to be expressed not only in immune cells but also in various tumor cells. The aim of the present study was to determine whether X irradiation enhanced induction of apoptosis in Tp53 wild type and Tp53-mutated tumor cell lines treated with agonists against these death receptors. We showed that 5 Gy of X irradiation significantly up-regulated the expression of death receptors Fas and DR5 on the plasma membrane in gastric cancer cell lines MKN45 and MKN28, lung cancer cell line A549, and prostate cancer cell line DU145, and that subsequent treatments with agonistic molecules for these death receptors, Fas antibody CHl1 and TRAIL, increased the formation of active fragment p20 of caspase 3 followed by the induction of apoptosis. This death-receptor-mediated apoptosis was independent of Tp53 status since MKN28 and DU145 were Tp53-mutated. The post-irradiation treatment of the cells with N-acetyl-L-cysteine (NAC) abolished the up-regulation of the expression of Fas and DR5 on the plasma membrane. NAC also attenuated the increase in the formation of p20 and the induction of apoptosis by agonistic molecules. These results suggested that the increase in the induction of apoptosis by combined treatment with X irradiation and CHl1 or TRAIL occurred through a change of the intracellular redox state independent of Tp53 status in human carcinoma cell lines. (author)

  12. Regulation of the neuropathy-associated Pmp22 gene by a distal super-enhancer.

    Science.gov (United States)

    Pantera, Harrison; Moran, John J; Hung, Holly A; Pak, Evgenia; Dutra, Amalia; Svaren, John

    2018-05-16

    Peripheral nerve myelination is adversely affected in the most common form of the hereditary peripheral neuropathy called Charcot-Marie-Tooth Disease. This form, classified as CMT1A, is caused by a 1.4 Mb duplication on chromosome 17, which includes the abundantly expressed Schwann cell myelin gene, Peripheral Myelin Protein 22 (PMP22). This is one of the most common copy number variants causing neurological disease. Overexpression of Pmp22 in rodent models recapitulates several aspects of neuropathy, and reduction of Pmp22 in such models results in amelioration of the neuropathy phenotype. Recently we identified a potential super-enhancer approximately 90-130 kb upstream of the Pmp22 transcription start sites. This super-enhancer encompasses a cluster of individual enhancers that have the acetylated histone H3K27 active enhancer mark, and coincides with smaller duplications identified in patients with milder CMT1A-like symptoms, where the PMP22 coding region itself was not part of the duplication. In this study, we have utilized genome editing to create a deletion of this super-enhancer to determine its role in Pmp22 regulation. Our data show a significant decrease in Pmp22 transcript expression using allele-specific internal controls. Moreover, the P2 promoter of the Pmp22 gene, which is used in other cell types, is affected, but we find that the Schwann cell-specific P1 promoter is disproportionately more sensitive to loss of the super-enhancer. These data show for the first time the requirement of these upstream enhancers for full Pmp22 expression.

  13. Regulation of the Drosophila Enhancer of split and invected-engrailed gene complexes by sister chromatid cohesion proteins.

    Directory of Open Access Journals (Sweden)

    Cheri A Schaaf

    2009-07-01

    Full Text Available The cohesin protein complex was first recognized for holding sister chromatids together and ensuring proper chromosome segregation. Cohesin also regulates gene expression, but the mechanisms are unknown. Cohesin associates preferentially with active genes, and is generally absent from regions in which histone H3 is methylated by the Enhancer of zeste [E(z] Polycomb group silencing protein. Here we show that transcription is hypersensitive to cohesin levels in two exceptional cases where cohesin and the E(z-mediated histone methylation simultaneously coat the entire Enhancer of split and invected-engrailed gene complexes in cells derived from Drosophila central nervous system. These gene complexes are modestly transcribed, and produce seven of the twelve transcripts that increase the most with cohesin knockdown genome-wide. Cohesin mutations alter eye development in the same manner as increased Enhancer of split activity, suggesting that similar regulation occurs in vivo. We propose that cohesin helps restrain transcription of these gene complexes, and that deregulation of similarly cohesin-hypersensitive genes may underlie developmental deficits in Cornelia de Lange syndrome.

  14. Enhancement of nucleation during hanging drop protein crystallization using HF treatment of cover glasses

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Yun-Zhu; Yin, Da-Chuan; Lu, Qin-Qin; Wang, Xi-Kai; Liu, Jun [Key Laboratory for Space Bioscience and Biotechnology, Faculty of Life Sciences, Northwestern Polytechnical University, Xi' an 710072, Shaanxi (China)

    2010-02-15

    We examined a simple approach, i.e., etching cover glasses using hydrofluoric acid (HF), to determine whether cover glass treatment enhances nucleation in hanging drop protein crystallization. Hen egg white lysozyme and proteinase K were used as the model proteins. We found that the treatment increased the success rate of crystallization. The results indicated that the simple treatment, which is easy to adopt without changing much in the hanging drop method, can be utilized as an alternative method to enhance protein crystallization screens (copyright 2010 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  15. Performance enhancement of microbial fuel cell by applying transient-state regulation

    International Nuclear Information System (INIS)

    Liang, Peng; Zhang, Changyong; Jiang, Yong; Bian, Yanhong; Zhang, Helan; Sun, Xueliang; Yang, Xufei; Zhang, Xiaoyuan; Huang, Xia

    2017-01-01

    Highlights: • MFC was operated with transient-state regulation to enhance its performance. • Effects of the TSR parameters on MFC performance were thoroughly investigated. • Long-term operation of MFC in TSR mode allowed 32.7% higher power production. • Anode capacitance helped reduce the MFC’s internal impedance in the TSR mode. - Abstract: A binder-free, pseudocapacitive anode was fabricated by coating reduced graphene oxide (rGO) and manganese oxide (MnO_2) nanoparticles on stainless steel fibre felt (SS). Microbial fuel cell (MFC) equipped with this novel anode yielded a maximum power density of 1045 mW m"−"2, 20 times higher than that of a similar MFC with a bare SS anode (46 mW m"−"2). Transient-state regulation (TSR) was implemented to further improve the MFC’s power generation. The optimal TSR duty cycle ranged from 67% to 95%, and the MFC’s power density increased with TSR frequency. A maximum power density output of 1238 mW m"−"2 was achieved at the TSR duty cycle of 75% and the frequency of 1 Hz, 18.4% greater than that obtained from the steady state operation. The TSR mode delivered better MFC performance especially when the external resistance was small. Long-term operation tests revealed that the current density and power density yielded in the TSR mode were on average 15.0% and 32.7% greater than those in the steady state mode, respectively. The TSR mode was believed to reduce the internal resistance of the MFC while enhance substrate mass transfer and electron transfer within the anode matrix, thereby improving the MFC performance.

  16. Graphene quantum dots as enhanced plant growth regulators: effects on coriander and garlic plants.

    Science.gov (United States)

    Chakravarty, Disha; Erande, Manisha B; Late, Dattatray J

    2015-10-01

    We report investigations on the use of graphene quantum dots for growth enhancement in coriander (Coriandrum sativam L.) and garlic (Allium sativum) plants. The as-received seeds of coriander and garlic were treated with 0.2 mg mL(-1) of graphene quantum dots for 3 h before planting. Graphene quantum dots enhanced the growth rate in coriander and garlic plants, including leaves, roots, shoots, flowers and fruits, when the seeds were treated with graphene quantum dots. Our investigations open up the opportunity to use graphene quantum dots as plant growth regulators that can be used in a variety of other food plants for high yield. © 2015 Society of Chemical Industry.

  17. Application of ceramic membranes to SAGD produced water treatment for enhanced recycle and reuse

    Energy Technology Data Exchange (ETDEWEB)

    Minnich, K. [Veolia Water Solutions and Technologies, Mississauga, ON (Canada)

    2009-07-01

    Drivers for using ceramic membranes in steam assisted gravity drainage (SAGD) include reduced investment cost; alternative treatment technologies that reduce energy and greenhouse gas emissions; and ceramic membranes can be chemically and steam cleaned. This presentation discussed the application of ceramic membranes to SAGD produced water treatment for enhanced recycle and reuse. The presentation illustrated conventional ceramic membranes as well as surface enhanced membranes and provided background information on oil separation. Other topics that were discussed included issues regarding desalter bottoms de-oiling; challenges in de-oiling oil sands produced water; CeraMem surface enhanced membranes; surface facilities and ceramic membrane opportunities; and water treatment using ceramic membranes. The presentation concluded with a discussion of the application of ceramic membranes to SAGD next steps such as a demonstration test of industrial prototype membranes for de-oiling, and pilot testing of ceramic desilication. tabs., figs.

  18. Day treatment versus enhanced standard methadone services for opioid-dependent patients: a comparison of clinical efficacy and cost.

    Science.gov (United States)

    Avants, S K; Margolin, A; Sindelar, J L; Rounsaville, B J; Schottenfeld, R; Stine, S; Cooney, N L; Rosenheck, R A; Li, S H; Kosten, T R

    1999-01-01

    This study examined the differential efficacy and relative costs of two intensities of adjunctive psychosocial services--a day treatment program and enhanced standard care--for the treatment of opioid-dependent patients maintained on methadone hydrochloride. A 12-week randomized clinical trial with 6-month follow-up was conducted in a community-based methadone maintenance program. Of the 308 patients who met inclusion criteria, 291 began treatment (day treatment program: N=145; enhanced standard care: N=146), and 237 completed treatment (82% of those assigned to the day treatment program and 81% of those receiving enhanced standard care). Two hundred twenty of the patients participated in the 6-month follow-up (75% of those in the day treatment program and 73% of those in enhanced standard care provided a follow-up urine sample for screening). Both interventions were 12 weeks in duration, manual-guided, and provided by master's-level clinicians. The day treatment was an intensive, 25-hour-per-week program. The enhanced standard care was standard methadone maintenance plus a weekly skills training group and referral to on- and off-site services. Outcome measures included twice weekly urine toxicology screens, severity of addiction-related problems, prevalence of HIV risk behaviors, and program costs. Although the cost of the day treatment program was significantly higher, there was no significant difference in the two groups' use of either opiates or cocaine. Over the course of treatment, drug use, drug-related problems, and HIV risk behaviors decreased significantly for patients assigned to both treatment intensities. Improvements were maintained at follow-up. Providing an intensive day treatment program to unemployed, inner-city methadone patients was not cost-effective relative to a program of enhanced methadone maintenance services, which produced comparable outcomes at less than half the cost.

  19. Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer

    Science.gov (United States)

    Charité, Jeroen; McFadden, David G.; Merlo, Giorgio; Levi, Giovanni; Clouthier, David E.; Yanagisawa, Masashi; Richardson, James A.; Olson, Eric N.

    2001-01-01

    Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix–loop–helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, Dlx6 was down-regulated in branchial arches from EdnrA mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis. PMID:11711438

  20. A dynamical systems model for combinatorial cancer therapy enhances oncolytic adenovirus efficacy by MEK-inhibition.

    Science.gov (United States)

    Bagheri, Neda; Shiina, Marisa; Lauffenburger, Douglas A; Korn, W Michael

    2011-02-01

    Oncolytic adenoviruses, such as ONYX-015, have been tested in clinical trials for currently untreatable tumors, but have yet to demonstrate adequate therapeutic efficacy. The extent to which viruses infect targeted cells determines the efficacy of this approach but many tumors down-regulate the Coxsackievirus and Adenovirus Receptor (CAR), rendering them less susceptible to infection. Disrupting MAPK pathway signaling by pharmacological inhibition of MEK up-regulates CAR expression, offering possible enhanced adenovirus infection. MEK inhibition, however, interferes with adenovirus replication due to resulting G1-phase cell cycle arrest. Therefore, enhanced efficacy will depend on treatment protocols that productively balance these competing effects. Predictive understanding of how to attain and enhance therapeutic efficacy of combinatorial treatment is difficult since the effects of MEK inhibitors, in conjunction with adenovirus/cell interactions, are complex nonlinear dynamic processes. We investigated combinatorial treatment strategies using a mathematical model that predicts the impact of MEK inhibition on tumor cell proliferation, ONYX-015 infection, and oncolysis. Specifically, we fit a nonlinear differential equation system to dedicated experimental data and analyzed the resulting simulations for favorable treatment strategies. Simulations predicted enhanced combinatorial therapy when both treatments were applied simultaneously; we successfully validated these predictions in an ensuing explicit test study. Further analysis revealed that a CAR-independent mechanism may be responsible for amplified virus production and cell death. We conclude that integrated computational and experimental analysis of combinatorial therapy provides a useful means to identify treatment/infection protocols that yield clinically significant oncolysis. Enhanced oncolytic therapy has the potential to dramatically improve non-surgical cancer treatment, especially in locally advanced

  1. Alcohol Treatment and Cognitive-Behavioral Therapy: Enhancing Effectiveness by Incorporating Spirituality and Religion

    Science.gov (United States)

    Hodge, David R.

    2011-01-01

    Cognitive-behavioral therapy (CBT) is an effective modality for the treatment of alcoholism. Given widespread interest in incorporating spirituality into professional treatment, this article orients practitioners to spiritually modified CBT, an approach that may enhance outcomes with some spiritually motivated clients. More specifically, by…

  2. Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review

    OpenAIRE

    de Kleine, Rianne A.; Rothbaum, Barbara O.; van Minnen, Agnes

    2013-01-01

    There is a good amount of evidence that exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD). Notwithstanding its efficacy, there is room for improvement, since a large proportion of patients does not benefit from treatment. Recently, an interesting new direction in the improvement of exposure therapy efficacy for PTSD emerged. Basic research found evidence of the pharmacological enhancement of the underlying learning and memory processes of exposure therapy. Th...

  3. Rapid improvements in emotion regulation predict intensive treatment outcome for patients with bulimia nervosa and purging disorder.

    Science.gov (United States)

    MacDonald, Danielle E; Trottier, Kathryn; Olmsted, Marion P

    2017-10-01

    Rapid and substantial behavior change (RSBC) early in cognitive behavior therapy (CBT) for eating disorders is the strongest known predictor of treatment outcome. Rapid change in other clinically relevant variables may also be important. This study examined whether rapid change in emotion regulation predicted treatment outcomes, beyond the effects of RSBC. Participants were diagnosed with bulimia nervosa or purging disorder (N = 104) and completed ≥6 weeks of CBT-based intensive treatment. Hierarchical regression models were used to test whether rapid change in emotion regulation variables predicted posttreatment outcomes, defined in three ways: (a) binge/purge abstinence; (b) cognitive eating disorder psychopathology; and (c) depression symptoms. Baseline psychopathology and emotion regulation difficulties and RSBC were controlled for. After controlling for baseline variables and RSBC, rapid improvement in access to emotion regulation strategies made significant unique contributions to the prediction of posttreatment binge/purge abstinence, cognitive psychopathology of eating disorders, and depression symptoms. Individuals with eating disorders who rapidly improve their belief that they can effectively modulate negative emotions are more likely to achieve a variety of good treatment outcomes. This supports the formal inclusion of emotion regulation skills early in CBT, and encouraging patient beliefs that these strategies are helpful. © 2017 Wiley Periodicals, Inc.

  4. Microwave enhanced Fenton-like process for the treatment of high concentration pharmaceutical wastewater

    International Nuclear Information System (INIS)

    Yang Yu; Wang Peng; Shi Shujie; Liu Yuan

    2009-01-01

    This paper explored a novel process for wastewater treatment, i.e. microwave enhanced Fenton-like process. This novel process was introduced to treat high concentration pharmaceutical wastewater with initial COD loading of 49,912.5 mg L -1 . Operating parameters were investigated and the optimal condition included as follows: microwave power was 300 W, radiation time was 6 min, initial pH was 4.42, H 2 O 2 dosage was 1300 mg L -1 and Fe 2 (SO 4 ) 3 dosage was 4900 mg L -1 , respectively. Within the present experimental condition used, the COD removal and UV 254 removal reached to 57.53% and 55.06%, respectively, and BOD 5 /COD was enhanced from 0.165 to 0.470. The variation of molecular weight distribution indicated that both macromolecular substances and micromolecular substances were eliminated quite well. The structure of flocs revealed that one ferric hydrated ion seemed to connect with another ferric hydrated ion and/or organic compound molecule to form large-scale particles by means of van der waals force and/or hydrogen bond. Subsequently, these particles aggregated to form flocs and settled down. Comparing with traditional Fenton-like reaction and conventional heating assisted Fenton-like reaction, microwave enhanced Fenton-like process displayed superior treatment efficiency. Microwave was in favor of improving the degradation efficiency, the settling quality of sludge, as well as reducing the yield of sludge and enhancing the biodegradability of effluent. Microwave enhanced Fenton-like process is believed to be a promising treatment technology for high concentration and biorefractory wastewater.

  5. Effects of low dose treatment of tributyltin on the regulation of estrogen receptor functions in MCF-7 cells

    International Nuclear Information System (INIS)

    Sharan, Shruti; Nikhil, Kumar; Roy, Partha

    2013-01-01

    Endocrine disrupting chemicals are the natural/synthetic compounds which mimic or inhibit the actions of endogenous hormones. Organotin compounds, such as tributyltin (TBT) are typical environmental contaminants and suspected endocrine-disrupting chemical. The present study evaluates the estrogenic potential of this compound in vitro in ER (+) breast adenocarcinoma, MCF-7 cell line. Our data showed that tributyltin chloride (TBTCl) had agonistic activities for estrogen receptor-α (ER-α). Its estrogenic potential was checked using cell proliferation assay, aromatase assay, transactivation assay, and protein expression analysis. Low dose treatment of TBTCl had a proliferative effect on MCF-7 cells and resulted in up-regulation of aromatase enzyme activity and enhanced estradiol production in MCF-7 cells. Immunofluorescence staining showed translocation of ER-α from cytoplasm to nucleus and increased expression of ER-α, 3β-HSD and aromatase on treatment with increasing doses of TBTCl. Further, to decipher the probable signaling pathways involved in its action, the MCF-7 cells were transfected with different pathway dependent luciferase reporter plasmids (CRE, SRE, NF-κB and AP1). A significant increase in CRE and SRE and decrease in NF-κB regulated pathway were observed (p < 0.05). Our results thus showed that the activation of SRE by TBTCl may be due to ligand dependent ER-α activation of the MAPK pathway and increased phosphorylation of ERK. In summary, the present data suggests that low dose of tributyltin genomically and non-genomically augmented estrogen dependent signaling by targeting various pathways. - Highlights: • Tributyltin chloride is agonistic to ER-α in MCF-7 cell line at low doses. • Tributyltin chloride up regulated aromatase activity and estradiol production. • Tributyltin chloride also activates MAPK pathway inducing ERK activation

  6. Effects of low dose treatment of tributyltin on the regulation of estrogen receptor functions in MCF-7 cells

    Energy Technology Data Exchange (ETDEWEB)

    Sharan, Shruti; Nikhil, Kumar; Roy, Partha, E-mail: paroyfbs@iitr.ernet.in

    2013-06-01

    Endocrine disrupting chemicals are the natural/synthetic compounds which mimic or inhibit the actions of endogenous hormones. Organotin compounds, such as tributyltin (TBT) are typical environmental contaminants and suspected endocrine-disrupting chemical. The present study evaluates the estrogenic potential of this compound in vitro in ER (+) breast adenocarcinoma, MCF-7 cell line. Our data showed that tributyltin chloride (TBTCl) had agonistic activities for estrogen receptor-α (ER-α). Its estrogenic potential was checked using cell proliferation assay, aromatase assay, transactivation assay, and protein expression analysis. Low dose treatment of TBTCl had a proliferative effect on MCF-7 cells and resulted in up-regulation of aromatase enzyme activity and enhanced estradiol production in MCF-7 cells. Immunofluorescence staining showed translocation of ER-α from cytoplasm to nucleus and increased expression of ER-α, 3β-HSD and aromatase on treatment with increasing doses of TBTCl. Further, to decipher the probable signaling pathways involved in its action, the MCF-7 cells were transfected with different pathway dependent luciferase reporter plasmids (CRE, SRE, NF-κB and AP1). A significant increase in CRE and SRE and decrease in NF-κB regulated pathway were observed (p < 0.05). Our results thus showed that the activation of SRE by TBTCl may be due to ligand dependent ER-α activation of the MAPK pathway and increased phosphorylation of ERK. In summary, the present data suggests that low dose of tributyltin genomically and non-genomically augmented estrogen dependent signaling by targeting various pathways. - Highlights: • Tributyltin chloride is agonistic to ER-α in MCF-7 cell line at low doses. • Tributyltin chloride up regulated aromatase activity and estradiol production. • Tributyltin chloride also activates MAPK pathway inducing ERK activation.

  7. Prostaglandin E2 regulates hematopoietic stem cell

    International Nuclear Information System (INIS)

    Wang Yingying; Zhou Daohong; Meng Aimin

    2013-01-01

    Prostaglandin E2 (PGE2) is a bioactive lipid molecule produced by cyclooxygenase (COX), which plays an important role on hematopoiesis. While it can block differentiation of myeloid progenitors but enhance proliferation of erythroid progenitors. Recent research found that PGE2 have the effects on hematopoietic stem cell (HSC) function and these effects were independent from effects on progenitor cells. Exposure of HSC cells to PGE2 in vitro can increase homing efficiency of HSC to the murine bone marrow compartment and decrease HSC apoptosis, meanwhile increase long-term stem cell engraftment. In-vivo treatment with PGE2 expands short-term HSC and engraftment in murine bone marrow but not long-term HSC.In addition, PGE2 increases HSC survival after radiation injury and enhance hematopoietic recovery, resulting maintains hematopoietic homeostasis. PGE2 regulates HSC homeostasis by reactive oxygen species and Wnt pathway. Clinical beneficial of 16, 16-dimethyl-prostaglandin E2 treatment to enhance engraftment of umbilical cord blood suggest important improvements to therapeutic strategies. (authors)

  8. SU-E-T-56: Brain Metastasis Treatment Plans for Contrast-Enhanced Synchrotron Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Obeid, L; Adam, J [Grenoble Institut des Neurosciences, La Tronche, Rhone-Alpes (France); Tessier, A [Centre Hospitalier Universitaire, La Tronche, Rhone-Alpes (France); Vautrin, M; Benkebil, M [DOSIsoft, Cachan, Ile de France (France); Sihanath, R [Centre Hospitalier Universitaire, La Tronche, Rhone- Alpes (France)

    2014-06-01

    Purpose: Iodine-enhanced radiotherapy is an innovative treatment combining the selective accumulation of an iodinated contrast agent in brain tumors with irradiations using monochromatic medium energy x-rays. The aim of this study is to compare dynamic stereotactic arc-therapy and iodineenhanced SSRT. Methods: Five patients bearing brain metastasis received a standard helical 3D-scan without iodine. A second scan was acquired 13 min after an 80 g iodine infusion. Two SSRT treatment plans (with/without iodine) were performed for each patient using a dedicated Monte Carlo (MC) treatment planning system (TPS) based on the ISOgray TPS. Ten coplanar beams (6×6 cm2, shaped with collimator) were simulated. MC statistical error objective was less than 5% in the 50% isodose. The dynamic arc-therapy plan was achieved on the Iplan Brainlab TPS. The treatment plan validation criteria were fixed such that 100% of the prescribed dose is delivered at the beam isocentre and the 70% isodose contains the whole target volume. The comparison elements were the 70% isodose volume, the average and maximum doses delivered to organs at risk (OAR): brainstem, optical nerves, chiasma, eyes, skull bone and healthy brain parenchyma. Results: The stereotactic dynamic arc-therapy remains the best technique in terms of dose conformation. Iodine-enhanced SSRT presents similar performances to dynamic arc-therapy with increased brainstem and brain parenchyma sparing. One disadvantage of SSRT is the high dose to the skull bone. Iodine accumulation in metastasis may increase the dose by 20–30%, allowing a normal tissue sparing effect at constant prescribed dose. Treatment without any iodine enhancement (medium-energy stereotactic radiotherapy) is not relevant with degraded HDVs (brain, parenchyma and skull bone) comparing to stereotactic dynamic arc-therapy. Conclusion: Iodine-enhanced SSRT exhibits a good potential for brain metastasis treatment regarding the dose distribution and OAR criteria.

  9. Hypoxia regulates the expression and localization of CCAAT/enhancer binding protein α by hypoxia inducible factor-1α in bladder transitional carcinoma cells.

    Science.gov (United States)

    Xue, Mei; Li, Xu; Chen, Wei

    2015-08-01

    Hypoxia inducible factor-1α (HIF-1α) is overexpressed in various types of solid tumor in humans, including bladder cancer. HIF-1α regulates the expression of a series of genes, which are involved in cell proliferation, differentiation, apoptosis, angiogenesis, migration and invasion and represents a potential therapeutic target for the treatment of human cancer. Despite extensive investigation of the effects of HIF-1α in the progression and metastasis of bladder cancer, the possible regulatory mechanisms underlying the effects of HIF-1α on bladder cancer cell proliferation and differentiation remain to be elucidated. It has been suggested that the transcription factor CCAAT/enhancer binding protein α (C/EBPα) acts as a tumor suppressor in several types of cancer cell, which are involved in regulating cell differentiation, proliferation and apoptosis. The present study confirmed that, in bladder cancer cells, the expression and localization of C/EBPα was regulated by hypoxia through an HIF-1α -dependent mechanism, which may be significant in bladder cancer cell proliferation and differentiation. The 5637 and T24 bladder cancer cell lines were incubated under normoxic and hypoxic conditions. The expression levels of HIF-1α and C/EBPα were detected by reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence analysis. The results revealed that, under hypoxic conditions, the protein expression levels of HIF-1α were markedly upregulated, but the mRNA levels were not altered. However, the mRNA and protein levels of C/EBPα were significantly reduced. The present study further analyzed the subcellular localization of C/EBPα, which was markedly decreased in the nuclei under hypoxic conditions. Following HIF-1α small interference RNA silencing of HIF-1α, downregulation of C/EBPα was prevented in the bladder cancer cells cultured under hypoxic conditions. In addition, groups of cells treated with 3-(5'-hydroxymethyl

  10. Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy

    International Nuclear Information System (INIS)

    Kiso, Hironori; Ohba, Takayoshi; Iino, Kenji; Sato, Kazuhiro; Terata, Yutaka; Murakami, Manabu; Ono, Kyoichi; Watanabe, Hiroyuki; Ito, Hiroshi

    2013-01-01

    Highlights: •Transient receptor potential canonical (TRPC1, 3 and 6) are up-regulated by ET-1. •Sildenafil inhibited hypertrophic responses (BNP, Ca entry, NFAT activation). •Sildenafil suppressed TRPC1, 3 and 6 expression. -- Abstract: Background: Transient receptor potential canonical (TRPCs) channels are up-regulated in the development of cardiac hypertrophy. Sildenafil inhibits TRPC6 activation and expression, leading to the prevention of cardiac hypertrophy. However, the effects of sildenafil on the expression of other TRPCs remain unknown. We hypothesized that in addition to its effects of TRPC6, sildenafil blocks the up-regulation of other TRPC channels to suppress cardiomyocyte hypertrophy. Methods and results: In cultured neonatal rat cardiomyocytes, a 48 h treatment with 10 nM endothelin (ET)-1 induced hypertrophic responses characterized by nuclear factor of activated T cells activation and enhancement of brain natriuretic peptide expression and cell surface area. Co-treatment with sildenafil (1 μM, 48 h) inhibited these ET-1-induced hypertrophic responses. Although ET-1 enhanced the gene expression of TRPCs, sildenafil inhibited the enhanced gene expression of TRPC1, C3 and C6. Moreover, co-treatment with sildenafil abolished the augmentation of SOCE in the hypertrophied cardiomyocytes. Conclusions: These results suggest that sildenafil inhibits cardiomyocyte hypertrophy by suppressing the up-regulation of TRPC expression

  11. Dual-specificity phosphatase 6 (Dusp6), a negative regulator of FGF2/ERK1/2 signaling, enhances 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell.

    Science.gov (United States)

    Zhang, Hui; Guo, Qiufen; Wang, Chong; Yan, Lei; Fu, Yibing; Fan, Mingjun; Zhao, Xingbo; Li, Mingjiang

    2013-08-25

    Dual-specificity phosphatase 6 (Dusp6) is a negative feedback mechanism of fibroblast growth factors (FGFs)/mitogen-activated protein kinase (MAPK)/ERK1/2 signaling. The aim of this study was to explore the expression of Dusp6 in human endometrial adenocarcinomas and the role of Dusp6 expression in the growth regulation of endometrial adenocarcinoma cell. We found that Dusp6 was over-expressed in human endometrial adenocarcinomas. In Ishikawa cells, plasmid-driven Dusp6 expression efficiently blocked the activity of FGF2-induced MAPK/ERK1/2 signaling. Unexpectedly, Dusp6 expression significantly enhanced the growth of Ishikawa cells. In Dusp6 forced-expression cells, 17β-estradiol stimulation increased the cell growth by all most threefolds. In addition, progesterone treatment reduced the cell growth to about half both in Ishikawa cells with and without forced-Dusp6-expression. Dusp6 over-expression is involved in the pathogenesis and development of human endometrial adenocarcinomas. Dusp6 functions as a negative regulator of FGF2/ERK1/2 signaling but enhances the growth and 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell. Copyright © 2013. Published by Elsevier Ireland Ltd.

  12. Changes in emotion regulation in adults with and without a history of childhood abuse following posttraumatic stress disorder treatment.

    Science.gov (United States)

    Jerud, Alissa B; Zoellner, Lori A; Pruitt, Larry D; Feeny, Norah C

    2014-08-01

    This study compared changes in emotion regulation and trait affect over the course of PTSD treatment with either prolonged exposure (PE) therapy or sertraline in adults with and without a history of childhood abuse (CA). Two hundred adults with PTSD received 10 weeks of PE or sertraline. Emotion regulation and trait affect were assessed pre- and posttreatment and at 6-month follow-up with the Emotion Regulation Questionnaire (Gross & John, 2003), the Negative Mood Regulation Scale (Catanzaro & Mearns, 1990), and the Positive and Negative Affect Schedule (Watson, Clark, & Tellegen, 1988). Individuals with and without a history of CA did not differ from one another at pretreatment on PTSD severity, emotion regulation, or positive/negative affect. In addition, treatment was effective at improving emotion regulation and trait affect in those with and without a history of CA, and no significant differences in emotion regulation or trait affect emerged posttreatment or at 6-month follow-up between adults with and without a history of CA. Furthermore, noninferiority analyses indicated that the emotion regulation and trait affect outcomes of individuals with a history of CA were no worse than those of individuals without a history of CA. These findings cast doubt on the assumption that CA is associated with worse emotion regulation following PTSD treatment, arguing against assertions that a history of CA itself is a contraindication for traditional PTSD treatment, and that there is a clear necessity for additional interventions designed to target assumed emotion regulation deficits. [Corrected] PsycINFO Database Record (c) 2014 APA, all rights reserved.

  13. Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

    Science.gov (United States)

    Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Zhou, Zhanmei

    2014-01-01

    In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II), angiotensin type II receptor 1 (ATR1) were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the interstitial fibrosis

  14. Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

    Directory of Open Access Journals (Sweden)

    Xiaoyan Bai

    Full Text Available In view of increased vascular endothelial growth factor-A (VEGF-A expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM. In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II, angiotensin type II receptor 1 (ATR1 were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR, Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the

  15. Emotion Regulation through Movement: Unique Sets of Movement Characteristics are Associated with and Enhance Basic Emotions.

    Science.gov (United States)

    Shafir, Tal; Tsachor, Rachelle P; Welch, Kathleen B

    2015-01-01

    We have recently demonstrated that motor execution, observation, and imagery of movements expressing certain emotions can enhance corresponding affective states and therefore could be used for emotion regulation. But which specific movement(s) should one use in order to enhance each emotion? This study aimed to identify, using Laban Movement Analysis (LMA), the Laban motor elements (motor characteristics) that characterize movements whose execution enhances each of the basic emotions: anger, fear, happiness, and sadness. LMA provides a system of symbols describing its motor elements, which gives a written instruction (motif) for the execution of a movement or movement-sequence over time. Six senior LMA experts analyzed a validated set of video clips showing whole body dynamic expressions of anger, fear, happiness and sadness, and identified the motor elements that were common to (appeared in) all clips expressing the same emotion. For each emotion, we created motifs of different combinations of the motor elements common to all clips of the same emotion. Eighty subjects from around the world read and moved those motifs, to identify the emotion evoked when moving each motif and to rate the intensity of the evoked emotion. All subjects together moved and rated 1241 motifs, which were produced from 29 different motor elements. Using logistic regression, we found a set of motor elements associated with each emotion which, when moved, predicted the feeling of that emotion. Each emotion was predicted by a unique set of motor elements and each motor element predicted only one emotion. Knowledge of which specific motor elements enhance specific emotions can enable emotional self-regulation through adding some desired motor qualities to one's personal everyday movements (rather than mimicking others' specific movements) and through decreasing motor behaviors which include elements that enhance negative emotions.

  16. Emotion regulation through movement: Unique sets of movement characteristics are associated with and enhance basic emotions

    Directory of Open Access Journals (Sweden)

    Tal eShafir

    2016-01-01

    Full Text Available We have recently demonstrated that motor execution, observation and imagery of movements expressing certain emotions can enhance corresponding affective states and therefore could be used for emotion regulation. But which specific movement(s should one use in order to enhance each emotion? This study aimed to identify, using Laban Movement Analysis (LMA, the Laban motor elements (motor characteristics that characterize movements whose execution enhances each of the basic emotions: anger, fear happiness, and sadness. LMA provides a system of symbols describing its motor elements, which gives a written instruction (motif for the execution of a movement or movement-sequence over time. Six senior LMA experts analyzed a validated set of video clips showing whole body dynamic expressions of anger, fear, happiness and sadness, and identified the motor elements that were common to (appeared in all clips expressing the same emotion. For each emotion, we created motifs of different combinations of the motor elements common to all clips of the same emotion. Eighty subjects from around the world read and moved those motifs, to identify the emotion evoked when moving each motif and to rate the intensity of the evoked emotion. All subjects together moved and rated 1241 motifs, which were produced from 29 different motor elements. Using logistic regression, we found a set of motor elements associated with each emotion which, when moved, predicted the feeling of that emotion. Each emotion was predicted by a unique set of motor elements and each motor element predicted only one emotion. Knowledge of which specific motor elements enhance specific emotions can enable emotional self-regulation through adding some desired motor qualities to one’s personal everyday movements (rather than mimicking others’ specific movements and through decreasing motor behaviors which include elements that enhance negative emotions.

  17. Regulable process for sawage electrochemical treatment from heavy metals

    International Nuclear Information System (INIS)

    Covaliov, V.; Covaliova, O.

    2004-01-01

    The invention relates to a process for sewage treatment and may be used in the protection for metal working, in particular, for electroplating. The disperse magnetic particle are obtaining in the comminution of the sintered spheric particle into a magnetilique faction block at the electrolyser at the outlet from the electrolyzer it is determined the suspension magnetization value concentration of the solid phase and the redox potential of the values it is automatically regulated the feed of magnetic particles and the current intensity correspondingly

  18. Responses of wild husk tomato, Physalis angulata L. to growth regulators and gamma rays on chlorophyll content and fruit yield

    International Nuclear Information System (INIS)

    Raghava, R.P.; Raghava, Nisha

    1994-01-01

    Effect of different growth regulators and gamma rays on the total chlorophyll content and fruit yield were studied in wild species of husk tomato and concluded that indole-3-acetic acid (IAA) 200 and kinetin (KIN) 10 ppm showed remarkable enhancement in both total chlorophyll content and fruit yield, while maleic hydrazide (MH) 100, 200 ppm and coumarin (COU) in all the treatments enhanced total chlorophyll content. Gamma ray treatments significantly enhanced both the parameters. Amongst all the treatments maximum fruit yield was in 20 kR of gamma rays. (author). 31 refs., 1 tab

  19. Activated Integrin-Linked Kinase Negatively Regulates Muscle Cell Enhancement Factor 2C in C2C12 Cells

    Directory of Open Access Journals (Sweden)

    Zhenguo Dong

    2015-01-01

    Full Text Available Our previous study reported that muscle cell enhancement factor 2C (MEF2C was fully activated after inhibition of the phosphorylation activity of integrin-linked kinase (ILK in the skeletal muscle cells of goats. It enhanced the binding of promoter or enhancer of transcription factor related to proliferation of muscle cells and then regulated the expression of these genes. In the present investigation, we explored whether ILK activation depended on PI3K to regulate the phosphorylation and transcriptional activity of MEF2C during C2C12 cell proliferation. We inhibited PI3K activity in C2C12 with LY294002 and then found that ILK phosphorylation levels and MEF2C phosphorylation were decreased and that MCK mRNA expression was suppressed significantly. After inhibiting ILK phosphorylation activity with Cpd22 and ILK-shRNA, we found MEF2C phosphorylation activity and MCK mRNA expression were increased extremely significantly. In the presence of Cpd22, PI3K activity inhibition increased MEF2C phosphorylation and MCK mRNA expression indistinctively. We conclude that ILK negatively and independently of PI3K regulated MEF2C phosphorylation activity and MCK mRNA expression in C2C12 cells. The results provide new ideas for the study of classical signaling pathway of PI3K-ILK-related proteins and transcription factors.

  20. Emotion Regulation Enhancement of Cognitive Behavior Therapy for College Student Problem Drinkers: A Pilot Randomized Controlled Trial

    Science.gov (United States)

    Ford, Julian D.; Grasso, Damion J.; Levine, Joan; Tennen, Howard

    2018-01-01

    This pilot randomized clinical trial tested an emotion regulation enhancement to cognitive behavior therapy (CBT) with 29 college student problem drinkers with histories of complex trauma and current clinically significant traumatic stress symptoms. Participants received eight face-to-face sessions of manualized Internet-supported CBT for problem…

  1. Pyrolytic Treatment and Fertility Enhancement of Soils Contaminated with Heavy Hydrocarbons.

    Science.gov (United States)

    Vidonish, Julia E; Zygourakis, Kyriacos; Masiello, Caroline A; Gao, Xiaodong; Mathieu, Jacques; Alvarez, Pedro J J

    2016-03-01

    Pyrolysis of contaminated soils at 420 °C converted recalcitrant heavy hydrocarbons into "char" (a carbonaceous material similar to petroleum coke) and enhanced soil fertility. Pyrolytic treatment reduced total petroleum hydrocarbons (TPH) to below regulatory standards (typically hydrocarbons (PAHs) was not observed, with post-pyrolysis levels well below applicable standards. Plant growth studies showed a higher biomass production of Arabidopsis thaliana and Lactuca sativa (Simpson black-seeded lettuce) (80-900% heavier) in pyrolyzed soils than in contaminated or incinerated soils. Elemental analysis showed that pyrolyzed soils contained more carbon than incinerated soils (1.4-3.2% versus 0.3-0.4%). The stark color differences between pyrolyzed and incinerated soils suggest that the carbonaceous material produced via pyrolysis was dispersed in the form of a layer coating the soil particles. Overall, these results suggest that soil pyrolysis could be a viable thermal treatment to quickly remediate soils impacted by weathered oil while improving soil fertility, potentially enhancing revegetation.

  2. Enhanced skin delivery of vismodegib by microneedle treatment.

    Science.gov (United States)

    Nguyen, Hiep X; Banga, Ajay K

    2015-08-01

    The present study investigated the effects of microneedle treatment (maltose microneedles, Admin Pen™ 1200, and Admin Pen™ 1500) on in vitro transdermal delivery of vismodegib with different needle lengths, skin equilibration times, and microneedle insertion durations. The influence of microneedle treatment on the dimensions of microchannels (dye binding, calcein imaging, histology, and confocal microscopy studies), transepidermal water loss, and skin permeability of vismodegib was also evaluated. Skin viscoelasticity was assessed using a rheometer, and microneedle geometry was characterized by scanning electron microscopy. Permeation studies of vismodegib through dermatomed porcine ear skin were conducted using vertical Franz diffusion cells. Skin irritation potential of vismodegib formulation was assessed using an in vitro reconstructed human epidermis model. Results of the in vitro permeation studies revealed significant enhancement in permeation of vismodegib through microneedle-treated skin. As the needle length increased from 500 to 1100 and 1400 μm, drug delivery increased from 14.50 ± 2.35 to 32.38 ± 3.33 and 74.40 ± 15.86 μg/cm(2), respectively. Positive correlation between drug permeability and microneedle treatment duration was observed. The equilibration time was also found to affect the delivery of vismodegib. Thus, changes in microneedle length, equilibration time, and duration of treatment altered transdermal delivery of vismodegib.

  3. Analysis of mining-medicinal waters regulation. Possible treatments

    Directory of Open Access Journals (Sweden)

    María del Mar Corral Lledó

    2006-12-01

    Full Text Available The mineral waters have been a part of our lives for many centuries, since they are believe to be beneficial and to have therapeutic properties for the human health. This fact makes a key issue to provide an analyses od the current legislation on this issue ( Royal Decree-Law 743/1928, April 25th, that aproves the statute on exploitation of spring of mineral and medicinal water; Mining Law of 1973 and its regulations, in order to determine the treatments that may be applied to these watersm meanly in the case of Legionella appearance, or as preventive maesure of it. The results of this analysis shows that there is no limitation or prohibition in the treatments to what they may be subjected, as long as their physico-chemical characteristic remains altered. Contamination by Legionella bacterium, is nowadays an issue of concern, and that is reason why Public Health Authority has established the quidelines to apply for spas in order to avoid or fight a possible outbreak.

  4. Enhancing Social Responsibility within Global Supply Chains: Is Legal Regulation the Optimal Solution?

    Directory of Open Access Journals (Sweden)

    Katerina Peterková

    2011-03-01

    Full Text Available This paper was presented at the first meeting of the NSU study group “Conceptions of ethical and social values in post-secular society: Towards a new ethical imagination in a cosmopolitan world society”, held on January 28-30, 2011 at Copenhagen Business School. First, this paper examines the voluntary (ethical v. mandatory (legal basis of corporate social responsibility (CSR. Second, it examines the relationship between CSR, law and business ethics. Third, it tries to answer the question if there is a need for a hard[2] legal regulation of CSR within international supply relationships or if ethical norms, e.g. expressed in the form of self-regulation, may better serve the purpose. And finally, it suggests possible ways for the future development of suitable regulatory methods for enhancing social standards within international supply chains. The questions are approached solely from the perspectives of legal theory and socio-legal analysis.

  5. Comparison of TALE designer transcription factors and the CRISPR/dCas9 in regulation of gene expression by targeting enhancers

    Science.gov (United States)

    Gao, Xuefei; Tsang, Jason C.H.; Gaba, Fortis; Wu, Donghai; Lu, Liming; Liu, Pentao

    2014-01-01

    The transcription activator–like effectors (TALEs) and the RNA-guided clustered regularly interspaced short palindromic repeat (CRISPR) associated protein (Cas9) utlilize distinct molecular mechanisms in targeting site recognition. The two proteins can be modified to carry additional functional domains to regulate expression of genomic loci in mammalian cells. In this study, we have compared the two systems in activation and suppression of the Oct4 and Nanog loci by targeting their enhancers. Although both are able to efficiently activate the luciferase reporters, the CRISPR/dCas9 system is much less potent in activating the endogenous loci and in the application of reprogramming somatic cells to iPS cells. Nevertheless, repression by CRISPR/dCas9 is comparable to or even better than TALE repressors. We demonstrated that dCas9 protein binding results in significant physical interference to binding of native transcription factors at enhancer, less efficient active histone markers induction or recruitment of activating complexes in gene activation. This study thus highlighted the merits and drawbacks of transcription regulation by each system. A combined approach of TALEs and CRISPR/dCas9 should provide an optimized solution to regulate genomic loci and to study genetic elements such as enhancers in biological processes including somatic cell reprogramming and guided differentiation. PMID:25223790

  6. DNA breaks and chromatin structural changes enhance the transcription of autoimmune regulator target genes.

    Science.gov (United States)

    Guha, Mithu; Saare, Mario; Maslovskaja, Julia; Kisand, Kai; Liiv, Ingrid; Haljasorg, Uku; Tasa, Tõnis; Metspalu, Andres; Milani, Lili; Peterson, Pärt

    2017-04-21

    The autoimmune regulator (AIRE) protein is the key factor in thymic negative selection of autoreactive T cells by promoting the ectopic expression of tissue-specific genes in the thymic medullary epithelium. Mutations in AIRE cause a monogenic autoimmune disease called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. AIRE has been shown to promote DNA breaks via its interaction with topoisomerase 2 (TOP2). In this study, we investigated topoisomerase-induced DNA breaks and chromatin structural alterations in conjunction with AIRE-dependent gene expression. Using RNA sequencing, we found that inhibition of TOP2 religation activity by etoposide in AIRE-expressing cells had a synergistic effect on genes with low expression levels. AIRE-mediated transcription was not only enhanced by TOP2 inhibition but also by the TOP1 inhibitor camptothecin. The transcriptional activation was associated with structural rearrangements in chromatin, notably the accumulation of γH2AX and the exchange of histone H1 with HMGB1 at AIRE target gene promoters. In addition, we found the transcriptional up-regulation to co-occur with the chromatin structural changes within the genomic cluster of carcinoembryonic antigen-like cellular adhesion molecule genes. Overall, our results suggest that the presence of AIRE can trigger molecular events leading to an altered chromatin landscape and the enhanced transcription of low-expressed genes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Enhancement of the Laser Transmission Weldability between Polyethylene and Polyoxymethylene by Plasma Surface Treatment

    Directory of Open Access Journals (Sweden)

    Huixia Liu

    2017-12-01

    Full Text Available Due to their large compatibility difference, polyethylene (PE and polyoxymethylene (POM cannot be welded together by laser transmission welding. In this study, PE and POM are pretreated using plasma that significantly enhances their laser transmission welding strength. To understand the mechanism underlying the laser welding strength enhancement, surface modification is analyzed using contact angle measurements, atomic force microscopy (AFM, optical microscopy, and X-ray photoelectron spectroscopy (XPS. Characterization results show that the plasma surface treatment improves the surface free energy, significantly enhancing the wettability of the materials. The increase in surface roughness and the generation of homogeneous bubbles contribute to the formation of mechanical micro-interlocking. The oxygen-containing groups introduced by the oxygen plasma treatment improve the compatibility of PE and POM, and facilitate the diffusion and entanglement of molecular chains and the formation of van der Waals force.

  8. Motivational interviewing to enhance treatment attendance in mental health settings: A systematic review and meta-analysis.

    Science.gov (United States)

    Lawrence, P; Fulbrook, P; Somerset, S; Schulz, P

    2017-11-01

    WHAT IS KNOWN ON THE SUBJECT?: Despite differences between samples, some literature reviews have suggested that MI is effective in enhancing treatment attendance for individuals with mental health issues. Little is known regarding the effects of MI as a pre-treatment on individuals who are not seeking treatment for mental health issues. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This systematic review of the literature and meta-analysis demonstrates that MI is most beneficial for individuals who are not seeking mental health treatment. MI represents an opportunity for health promotion when patients are unmotivated but may otherwise be amenable to an intervention. MI is effective as a pre-treatment intervention to motivate individuals to attend further post-MI treatment and counselling. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: MI is a process and a useful tool for clinicians in all therapeutic interactions, to motivate their patients to seek further assistance for mental heath issues. Health promotion and encouragement to attend further treatment sessions can be facilitated through telephone contact. Introduction The stages of change model suggests that individuals seeking treatment are in the "preparation" or the "action" stage of change, which is the desired outcome of successful Motivational Interviewing (MI) interventions. MI is known to enhance treatment attendance among individuals with mental health problems. Aim This study examined the published research on MI as a pre-treatment to enhance attendance among individuals treatment-seeking and non-treatment-seeking for mental health issues. Methods Fourteen randomized controlled trials were identified, and MI efficacy was examined dichotomously: attendance or non-attendance for post-MI therapy. Subgroup analysis investigated treatment-seeking and non-treatment-seeking groups. Results Despite wide variations in sample sizes, blinding and monitoring, intervention fidelity was absent in the majority of published

  9. CRP-Mediated Carbon Catabolite Regulation of Yersinia pestis Biofilm Formation Is Enhanced by the Carbon Storage Regulator Protein, CsrA.

    Directory of Open Access Journals (Sweden)

    Stephan P Willias

    Full Text Available The natural transmission of Yersinia pestis is reliant upon biofilm blockage of the flea vector. However, the environmentally-responsive adaptive regulators which facilitate Y. pestis biofilm production in accordance with the flea midgut milieu are not well understood. We seek to establish the impact of available carbon source metabolism and storage upon Y. pestis biofilm production. Our findings demonstrate that Y. pestis biofilm production is subject to carbon catabolite regulation in which the presence of glucose impairs biofilm production; whereas, the sole metabolism of alternate carbon sources promotes robust biofilm formation. This observation is facilitated by the cAMP receptor protein, CRP. In accordance with a stark growth defect, deletion of crp in both CO92 and KIM6+ Y. pestis strains significantly impaired biofilm production when solely utilizing alternate carbon sources. Media supplementation with cAMP, a small-molecule activator of CRP, did not significantly alter Y. pestis biofilm production. Furthermore, CRP did not alter mRNA abundance of previously-characterized hms biofilm synthesis and regulation factors. Therefore, our findings indicate CRP does not confer a direct stimulatory effect, but may indirectly promote Y. pestis biofilm production by facilitating the alternate carbon source expression profile. Additionally, we assessed the impact of the carbon storage regulator protein, CsrA, upon Y. pestis biofilm production. Contrary to what has been described for E. coli, Y. pestis biofilm formation was found to be enhanced by CsrA. Regardless of media composition and available carbon source, deletion of csrA significantly impaired Y. pestis biofilm production. CsrA was found to promote Y. pestis biofilm production independent of glycogen regulation. Loss of csrA did not significantly alter relative hmsH, hmsP, or hmsT mRNA abundance. However, deletion of hmsP in the csrA-deficient mutant enabled excessive biofilm production

  10. From assistive to enhancing technology: should the treatment-enhancement distinction apply to future assistive and augmenting technologies?

    Science.gov (United States)

    Minerva, Francesca; Giubilini, Alberto

    2018-04-01

    The treatment-enhancement distinction is often used to delineate acceptable and unacceptable medical interventions. It is likely that future assistive and augmenting technologies will also soon develop to a level that they might be considered to provide users, in particular those with disabilities, with abilities that go beyond natural human limits, and become in effect an enhancing technology. In this paper, we describe how this process might take place, and discuss the moral implications of such developments. We argue that such developments are morally acceptable and indeed desirable. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Self-Regulated Learning Strategies of Engineering College Students While Learning Electric Circuit Concepts with Enhanced Guided Notes

    Science.gov (United States)

    Lawanto, Oenardi; Santoso, Harry

    2013-01-01

    The current study evaluated engineering college students' self-regulated learning (SRL) strategies while learning electric circuit concepts using enhanced guided notes (EGN). Our goal was to describe how students exercise SRL strategies and how their grade performance changes after using EGN. Two research questions guided the study: (1) To what…

  12. Cystic fibrosis transmembrane conductance regulator intracellular processing, trafficking, and opportunities for mutation-specific treatment.

    LENUS (Irish Health Repository)

    Rogan, Mark P

    2012-02-01

    Recent advances in basic science have greatly expanded our understanding of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), the chloride and bicarbonate channel that is encoded by the gene, which is mutated in patients with CF. We review the structure, function, biosynthetic processing, and intracellular trafficking of CFTR and discuss the five classes of mutations and their impact on the CF phenotype. The therapeutic discussion is focused on the significant progress toward CFTR mutation-specific therapies. We review the results of encouraging clinical trials examining orally administered therapeutics, including agents that promote read-through of class I mutations (premature termination codons); correctors, which overcome the CFTR misfolding that characterizes the common class II mutation F508del; and potentiators, which enhance the function of class III or IV mutated CFTR at the plasma membrane. Long-term outcomes from successful mutation-specific treatments could finally answer the question that has been lingering since and even before the CFTR gene discovery: Will therapies that specifically restore CFTR-mediated chloride secretion slow or arrest the deleterious cascade of events leading to chronic infection, bronchiectasis, and end-stage lung disease?

  13. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity

    International Nuclear Information System (INIS)

    Mullins, Dana; Proulx, Denise; Saoudi, A.; Ng, Cheng E.

    2005-01-01

    Purpose: Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. Methods: We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 AM or 3 HALO [hours after light onset]), late rest period (3 PM or 9 HALO), early active period (9 PM or 15 HALO), and late active period (3 AM or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Results: Treatment with either TPT or XR at 3 AM demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 PM, in particular, showed increased toxicity without any enhanced efficacy. Conclusions: Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial

  14. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity.

    Science.gov (United States)

    Mullins, Dana; Proulx, Denise; Saoudi, A; Ng, Cheng E

    2005-05-01

    Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 am or 3 HALO [hours after light onset]), late rest period (3 pm or 9 HALO), early active period (9 pm or 15 HALO), and late active period (3 am or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Treatment with either TPT or XR at 3 am demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 pm, in particular, showed increased toxicity without any enhanced efficacy. Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial.

  15. Hydrogen peroxide-enhanced iron-mediated aeration for the treatment of mature landfill leachate.

    Science.gov (United States)

    Deng, Yang; Englehardt, James D

    2008-05-01

    Municipal landfill leachate is being disallowed for biological treatment by some sewer authorities due to its recalcitrance and corrosiveness, and therefore physicochemical treatment may be needed. In this paper, hydrogen peroxide-enhanced iron (Fe(0))-mediated aeration (IMA) was studied as an alternative for the treatment of mature landfill leachate. Bench-scale Taguchi array screening tests and full factorial tests were conducted. Iron grade, initial pH, H(2)O(2) addition rate, and aeration rate significantly influenced both overall chemical oxygen demand (COD) removal and iron consumption. In the enhanced IMA-treated leachate at an initial pH of 8.2, COD was reduced by 50% due to oxidation and coagulation, a level almost equivalent to those obtained by Fenton treatment. Meanwhile, the 5-day biochemical oxygen demand (BOD(5))/COD ratio was increased from 0.02 to 0.17. In particular, the effect of initial pH became minor at H(2)O(2) addition rate greater than the theoretical demand for complete oxidation of organics by H(2)O(2). In addition, 83% of 300 mg/L ammonia nitrogen and 38% of 8.30 mS/cm electrical conductivity were removed when the initial pH was not adjusted. Based on these results, the process appears suitable for treatment of mature leachate.

  16. Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression

    Science.gov (United States)

    Grether-Beck, Susanne; Felsner, Ingo; Brenden, Heidi; Kohne, Zippora; Majora, Marc; Marini, Alessandra; Jaenicke, Thomas; Rodriguez-Martin, Marina; Trullas, Carles; Hupe, Melanie; Elias, Peter M.; Krutmann, Jean

    2012-01-01

    Urea is an endogenous metabolite, known to enhance stratum corneum hydration. Yet, topical urea anecdotally also improves permeability barrier function, and it appears to exhibit antimicrobial activity. Hence, we hypothesized that urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. In 21 human volunteers, topical urea improved barrier function in parallel with enhanced antimicrobial peptide (LL-37 and β-defensin-2) expression. Urea both stimulates expression of, and is transported into keratinocytes by two urea transporters, UT-A1 and UT-A2, and by aquaporin 3, 7 and 9. Inhibitors of these urea transporters block the downstream biological effects of urea, which include increased mRNA and protein levels for: (i) transglutaminase-1, involucrin, loricrin and filaggrin; (ii) epidermal lipid synthetic enzymes, and (iii) cathelicidin/LL-37 and β-defensin-2. Finally, we explored the potential clinical utility of urea, showing that topical urea applications normalized both barrier function and antimicrobial peptide expression in a murine model of atopic dermatitis (AD). Together, these results show that urea is a small-molecule regulator of epidermal permeability barrier function and antimicrobial peptide expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with potential therapeutic applications in diseased skin. PMID:22418868

  17. Enhancement of Self-Regulation, Assertiveness, and Empathy.

    Science.gov (United States)

    Sanz de Acedo Lizarraga, M. Luisa; Ugarte, M. Dolores; Cardelle-Elawar, Maria; Iriarte, M. Dolores; Sanz de Acedo Baquedano, M. Teresa

    2003-01-01

    Examined the effects of teaching self-regulation strategies and social skills to 40 middle school students who presented difficulties in self-reflection, self-inquiry, assertiveness, and empathy. Significant gains were observed in the experimental group in self-regulation of learning, self-control of behavior, assertiveness, empathy, and…

  18. Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer’s Disease Treatment

    Science.gov (United States)

    Peron, Rafaela; Vatanabe, Izabela Pereira; Manzine, Patricia Regina; Camins, Antoni

    2018-01-01

    ADAM (a disintegrin and metalloproteinase) is a family of widely expressed, transmembrane and secreted proteins of approximately 750 amino acids in length with functions in cell adhesion and proteolytic processing of the ectodomains of diverse cell-surface receptors and signaling molecules. ADAM10 is the main α-secretase that cleaves APP (amyloid precursor protein) in the non-amyloidogenic pathway inhibiting the formation of β-amyloid peptide, whose accumulation and aggregation leads to neuronal degeneration in Alzheimer’s disease (AD). ADAM10 is a membrane-anchored metalloprotease that sheds, besides APP, the ectodomain of a large variety of cell-surface proteins including cytokines, adhesion molecules and notch. APP cleavage by ADAM10 results in the production of an APP-derived fragment, sAPPα, which is neuroprotective. As increased ADAM10 activity protects the brain from β-amyloid deposition in AD, this strategy has been proved to be effective in treating neurodegenerative diseases, including AD. Here, we describe the physiological mechanisms regulating ADAM10 expression at different levels, aiming to propose strategies for AD treatment. We report in this review on the physiological regulation of ADAM10 at the transcriptional level, by epigenetic factors, miRNAs and/or translational and post-translational levels. In addition, we describe the conditions that can change ADAM10 expression in vitro and in vivo, and discuss how this knowledge may help in AD treatment. Regulation of ADAM10 is achieved by multiple mechanisms that include transcriptional, translational and post-translational strategies, which we will summarize in this review. PMID:29382156

  19. Variations in criteria regulating treatment with reimbursed biologic DMARDs across European countries. Are differences related to country's wealth?

    DEFF Research Database (Denmark)

    Putrik, Polina; Ramiro, Sofia; Kvien, Tore K

    2014-01-01

    To explore criteria regulating treatment with reimbursed biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) across Europe and to relate criteria to indicators of national socioeconomic welfare.......To explore criteria regulating treatment with reimbursed biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) across Europe and to relate criteria to indicators of national socioeconomic welfare....

  20. Social exclusion, personal control, self-regulation, and stress among substance abuse treatment clients.

    Science.gov (United States)

    Cole, Jennifer; Logan, T K; Walker, Robert

    2011-01-01

    The purpose of this study was to examine the relationship of social exclusion, personal control, and self-regulation to perceived stress among individuals who participated in publicly funded substance abuse treatment. Participants entered treatment between June 2006 and July 2007 and completed a 12-month follow-up survey by telephone (n=787). The results of the OLS regression analysis indicate that individuals with greater social exclusion factors (e.g. greater economic hardship, lower subjective social standing, greater perceived discrimination), lower perceived control of one's life, and lower self-regulation had higher perceived stress. Furthermore, a significant interaction was found suggesting a stress-buffering effect of personal control between subjective social standing and perceived stress. Interestingly, income status was not significantly related to perceived stress, while economic hardship, which assesses participants' inability to meet basic expenses, was significantly associated with perceived stress. Future research should examine how to integrate the AA/NA teaching about powerlessness and its role in recovery with the importance of increased personal control and self-control in decreasing perceived stress. Implications for future research and substance abuse treatment are discussed. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  1. Enhancing electronic and optoelectronic performances of tungsten diselenide by plasma treatment.

    Science.gov (United States)

    Xie, Yuan; Wu, Enxiu; Hu, Ruixue; Qian, Shuangbei; Feng, Zhihong; Chen, Xuejiao; Zhang, Hao; Xu, Linyan; Hu, Xiaodong; Liu, Jing; Zhang, Daihua

    2018-06-21

    Transition metal dichalcogenides (TMDCs) have recently become spotlighted as nanomaterials for future electronic and optoelectronic devices. In this work, we develop an effective approach to enhance the electronic and optoelectronic performances of WSe2-based devices by N2O plasma treatment. The hole mobility and sheet density increase by 2 and 5 orders of magnitude, reaching 110 cm2 V-1 s-1 and 2.2 × 1012 cm-2, respectively, after the treatment. At the same time, the contact resistance (Rc) between WSe2 and its metal electrode drop by 5 orders of magnitude from 1.0 GΩ μm to 28.4 kΩ μm. The WSe2 photoconductor exhibits superior performance with high responsivity (1.5 × 105 A W-1), short response time (106). We have also built a lateral p-n junction on a single piece of WSe2 flake by selective plasma exposure. The junction reaches an exceedingly high rectifying ratio of 106, an excellent photoresponsivity of 2.49 A W-1 and a fast response of 8 ms. The enhanced optoelectronic performance is attributed to band-engineering through the N2O plasma treatment, which can potentially serve as an effective and versatile approach for device engineering and optimization in a wide range of electronic and optoelectronic devices based on 2D materials.

  2. Delignification and Enhanced Gas Release from Soil Containing Lignocellulose by Treatment with Bacterial Lignin Degraders.

    Science.gov (United States)

    Rashid, Goran M M; Duran-Pena, Maria Jesus; Rahmanpour, Rahman; Sapsford, Devin; Bugg, Timothy D H

    2017-04-10

    The aim of the study was to isolate bacterial lignin-degrading bacteria from municipal solid waste soil, and to investigate whether they could be used to delignify lignocellulose-containing soil, and enhance methane release. A set of 20 bacterial lignin degraders, including 11 new isolates from municipal solid waste soil, were tested for delignification and phenol release in soil containing 1% pine lignocellulose. A group of 7 strains were then tested for enhancement of gas release from soil containing 1% lignocellulose in small-scale column tests. Using an aerobic pre-treatment, aerobic strains such as Pseudomonas putida showed enhanced gas release from the treated sample, but four bacterial isolates showed 5-10 fold enhancement in gas release in an in situ experiment under microanaerobic conditions: Agrobacterium sp., Lysinibacillus sphaericus, Comamonas testosteroni, and Enterobacter sp.. The results show that facultative anaerobic bacterial lignin degraders found in landfill soil can be used for in situ delignification and enhanced gas release in soil containing lignocellulose. The study demonstrates the feasibility of using an in situ bacterial treatment to enhance gas release and resource recovery from landfill soil containing lignocellulosic waste. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  3. Bias-enhanced post-treatment process for enhancing the electron field emission properties of ultrananocrystalline diamond films

    International Nuclear Information System (INIS)

    Saravanan, A.; Huang, B. R.; Sankaran, K. J.; Tai, N. H.; Dong, C. L.; Lin, I. N.

    2015-01-01

    The electron field emission (EFE) properties of ultrananocrystalline diamond films were markedly improved via the bias-enhanced plasma post-treatment (bep) process. The bep-process induced the formation of hybrid-granular structure of the diamond (bep-HiD) films with abundant nano-graphitic phase along the grain boundaries that increased the conductivity of the films. Moreover, the utilization of Au-interlayer can effectively suppress the formation of resistive amorphous-carbon (a-C) layer, thereby enhancing the transport of electrons crossing the diamond-to-Si interface. Therefore, bep-HiD/Au/Si films exhibit superior EFE properties with low turn-on field of E 0  = 2.6 V/μm and large EFE current density of J e  = 3.2 mA/cm 2 (at 5.3 V/μm)

  4. CyberKnife SRS: new technologies that enhance the treatment of cancer

    International Nuclear Information System (INIS)

    Cohen, A.

    2008-01-01

    The CyberKnife Robotic Radiosurgery System (Accuracy Incorporated, Sunnyvale, CA, USA) is used worldwide to treat tumors and neurological disorders anywhere in the body with sub-millimetre beam delivery accuracy. Accuracy has developed a number of new technologies in recent years to enhance the treatment of cancer patients. Such new technologies include a fast Monte Carlo Dose Calculation algorithm, Sequential Optimization dose planning, the Iris TM Variable Aperture Collimator, an 800 MU/min Linear Accelerator, and Optimized Path Traversal. These technologies enable physicists and physicians to plan treatments quickly and easily and deliver them with unrivalled accuracy and precision

  5. Passive flow regulators for drug delivery and hydrocephalus treatment

    Science.gov (United States)

    Chappel, E.; Dumont-Fillon, D.; Mefti, S.

    2014-03-01

    Passive flow regulators are usually intended to deliver or drain a fluid at a constant rate independently from pressure variations. New designs of passive flow regulators made of a stack of a silicon membrane anodically bonded to a Pyrex substrate are proposed. A first design has been built for the derivation of cerebrospinal fluid (CSF) towards peritoneum for hydrocephalus treatment. The device allows draining CSF at the patient production rate independently from postural changes. The flow rate is regulated at 20 ml/h in the range 10 to 40 mbar. Specific features to adjust in vivo the nominal flow rate are shown. A second design including high pressure shut-off feature has been made. The intended use is drug delivery with pressurized reservoir of typically 100 to 300 mbar. In both cases, the membrane comprises several holes facing pillars in the Pyrex substrate. These pillars are machined in a cavity which ensures a gap between the membrane and the pillars at rest. The fluid in the pressurized reservoir is directly in contact with the top surface of the membrane, inducing its deflection towards Pyrex substrate and closing progressively the fluidic pathway through each hole of the membrane. Since the membrane deflection is highly non-linear, FEM simulations have been performed to determine both radial position and diameter of the membrane holes that ensure a constant flow rate for a given range of pressure.

  6. Vitamin K2-enhanced liver regeneration is associated with oval cell expansion and up-regulation of matrilin-2 expression in 2-AAF/PH rat model.

    Science.gov (United States)

    Lin, M; Sun, P; Zhang, G; Xu, X; Liu, G; Miao, H; Yang, Y; Xu, H; Zhang, L; Wu, P; Li, M

    2014-03-01

    Normal liver has a great potential of regenerative capacity after partial hepatectomy. In clinic, however, most patients receiving partial hepatectomy are usually suffering from chronic liver diseases with severely damaged hepatocyte population. Under these conditions, activation of hepatic progenitor cell (oval cell in rodents) population might be considered as an alternative mean to enhance liver functional recovery. Vitamin K2 has been shown to promote liver functional recovery in patients with liver cirrhosis. In this study, we explored the possibility of vitamin K2 treatment in activating hepatic oval cell for liver regeneration with the classic 2-acetamido-fluorene/partial hepatectomy (2-AAF/PH) model in Sprague-Dawley rats. In 2-AAF/PH animals, vitamin K2 treatment induced a dose-dependent increase of liver regeneration as assessed by the weight ratio of remnant liver versus whole body and by measuring serum albumin level. In parallel, a drastic expansion of oval cell population as assessed by anti-OV6 and anti-CK19 immunostaining was noticed in the periportal zone of the remnant liver. Since matrilin-2 was linked to oval cell proliferation and liver regeneration after partial hepatectomy, we assessed its expression at both the mRNA and protein levels. The results revealed a significant increase after vitamin K2 treatment in parallel with the expansion of oval cell population. Consistently, knocking down matrilin-2 expression in vivo largely reduced vitamin K2-induced liver regeneration and oval cell proliferation in 2-AAF/PH animals. In conclusion, these data suggest that vitamin K2 treatment enhances liver regeneration after partial hepatectomy, which is associated with oval cell expansion and matrilin-2 up-regulation.

  7. Combinatorial treatment with lithium chloride enhances recombinant antibody production in transiently transfected CHO and HEK293E cells

    DEFF Research Database (Denmark)

    Kim, Che Lin; Kwang Ha, Tae; Min Lee, Gyun

    2016-01-01

    Lithium chloride (LiCl), which induces cell cycle arrest at G2/M phase, is known as a specific production rate (qp)-enhancing additive in recombinant Chinese hamster ovary (CHO) cell culture. To determine the potential of LiCl as a chemical additive that enhances transient gene expression (TGE), Li......Cl was added to the CHO-NK and human embryonic kidney 293E (HEK293E) cell cultures before and/or after transfection with polyethylenimine as a transfection reagent. The effect of this addition on transfection efficiency (pre-treatment) and qp enhancement during TGE (post-treatment) was examined. For the TGE...... of monoclonal antibody (mAb) in CHO-NK cells, pretreatment alone with 10 mM LiCl and post-treatment alone with 5 mM LiCl resulted in 1.2- and 3.4-fold increase of maximum mAb concentration (MMC), respectively, compared with the TGE without LiCl treatment. Furthermore, combinatorial treatment with LiCl (10 m...

  8. Interventions for enhancing medication compliance/adherence with benefits in treatment outcomes

    Directory of Open Access Journals (Sweden)

    Hagen, Anja

    2007-01-01

    Full Text Available Scientific background: Poor compliance or adherence in drug therapy can cause increased morbidity, mortality and enormous costs in the healthcare system (in Germany annually approximately 10 billion euros. Different methods are used for enhancing the compliance or adherence. Research questions: The evaluation addresses the questions about existence, efficacy, cost-benefit relation as well as ethical-social and juridical implications of strategies for enhancing compliance or adherence in drug therapy with concomitant improvements in treatment outcomes. Methods: A systematic literature search was conducted in the medical, also health economic relevant, literature databases in January 2007, beginning from 2002. Systematic reviews on the basis of (randomised controlled trials (RCT concerning interventions to enhance compliance or adherence with regard to treatment outcomes as well as systematic reviews of health economic analyses were included in the evaluation. Additionally, it was also searched for publications which primarily considered ethical-social and juridical aspects of these interventions for the German context. Results: One systematic review with data for 57 RCT was included in the medical evaluation and one systematic review with data for six studies into the health economic evaluation. No publication primary concerning ethical-social or juridical implications could be identified. A significant positive effect on the treatment outcome was reported for 22 evaluated interventions. For many interventions the results can be classified as reliable: counseling with providing an information leaflet and compliance diary chart followed by phone consultation for helicobacter pylori positive patients, repeated counseling for patients with acute asthma symptoms, telephone calls to establish the level of compliance and to make recommendations based on that for the therapy of cardiovascular diseases, calls of an automated telephone system with phone

  9. Enhanced Biocide Treatments with D-amino Acid Mixtures against a Biofilm Consortium from a Water Cooling Tower.

    Science.gov (United States)

    Jia, Ru; Li, Yingchao; Al-Mahamedh, Hussain H; Gu, Tingyue

    2017-01-01

    Different species of microbes form mixed-culture biofilms in cooling water systems. They cause microbiologically influenced corrosion (MIC) and biofouling, leading to increased operational and maintenance costs. In this work, two D-amino acid mixtures were found to enhance two non-oxidizing biocides [tetrakis hydroxymethyl phosphonium sulfate (THPS) and NALCO 7330 (isothiazoline derivatives)] and one oxidizing biocide [bleach (NaClO)] against a biofilm consortium from a water cooling tower in lab tests. Fifty ppm (w/w) of an equimass mixture of D-methionine, D-leucine, D-tyrosine, D-tryptophan, D-serine, D-threonine, D-phenylalanine, and D-valine (D8) enhanced 15 ppm THPS and 15 ppm NALCO 7330 with similar efficacies achieved by the 30 ppm THPS alone treatment and the 30 ppm NALCO 7330 alone treatment, respectively in the single-batch 3-h biofilm removal test. A sequential treatment method was used to enhance bleach because D-amino acids react with bleach. After a 4-h biofilm removal test, the sequential treatment of 5 ppm bleach followed by 50 ppm D8 achieved extra 1-log reduction in sessile cell counts of acid producing bacteria, sulfate reducing bacteria, and general heterotrophic bacteria compared with the 5 ppm bleach alone treatment. The 10 ppm bleach alone treatment showed a similar efficacy with the sequential treatment of 5 ppm bleach followed by 50 ppm D8. The efficacy of D8 was found better than that of D4 (an equimass mixture of D-methionine, D-leucine, D-tyrosine, and D-tryptophan) in the enhancement of the three individual biocides against the biofilm consortium.

  10. Enhanced Biocide Treatments with D-amino Acid Mixtures against a Biofilm Consortium from a Water Cooling Tower

    Directory of Open Access Journals (Sweden)

    Ru Jia

    2017-08-01

    Full Text Available Different species of microbes form mixed-culture biofilms in cooling water systems. They cause microbiologically influenced corrosion (MIC and biofouling, leading to increased operational and maintenance costs. In this work, two D-amino acid mixtures were found to enhance two non-oxidizing biocides [tetrakis hydroxymethyl phosphonium sulfate (THPS and NALCO 7330 (isothiazoline derivatives] and one oxidizing biocide [bleach (NaClO] against a biofilm consortium from a water cooling tower in lab tests. Fifty ppm (w/w of an equimass mixture of D-methionine, D-leucine, D-tyrosine, D-tryptophan, D-serine, D-threonine, D-phenylalanine, and D-valine (D8 enhanced 15 ppm THPS and 15 ppm NALCO 7330 with similar efficacies achieved by the 30 ppm THPS alone treatment and the 30 ppm NALCO 7330 alone treatment, respectively in the single-batch 3-h biofilm removal test. A sequential treatment method was used to enhance bleach because D-amino acids react with bleach. After a 4-h biofilm removal test, the sequential treatment of 5 ppm bleach followed by 50 ppm D8 achieved extra 1-log reduction in sessile cell counts of acid producing bacteria, sulfate reducing bacteria, and general heterotrophic bacteria compared with the 5 ppm bleach alone treatment. The 10 ppm bleach alone treatment showed a similar efficacy with the sequential treatment of 5 ppm bleach followed by 50 ppm D8. The efficacy of D8 was found better than that of D4 (an equimass mixture of D-methionine, D-leucine, D-tyrosine, and D-tryptophan in the enhancement of the three individual biocides against the biofilm consortium.

  11. Sphingosine-1-Phosphate Is a Novel Regulator of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR Activity.

    Directory of Open Access Journals (Sweden)

    Firhan A Malik

    Full Text Available The cystic fibrosis transmembrane conductance regulator (CFTR attenuates sphingosine-1-phosphate (S1P signaling in resistance arteries and has emerged as a prominent regulator of myogenic vasoconstriction. This investigation demonstrates that S1P inhibits CFTR activity via adenosine monophosphate-activated kinase (AMPK, establishing a potential feedback link. In Baby Hamster Kidney (BHK cells expressing wild-type human CFTR, S1P (1μmol/L attenuates forskolin-stimulated, CFTR-dependent iodide efflux. S1P's inhibitory effect is rapid (within 30 seconds, transient and correlates with CFTR serine residue 737 (S737 phosphorylation. Both S1P receptor antagonism (4μmol/L VPC 23019 and AMPK inhibition (80μmol/L Compound C or AMPK siRNA attenuate S1P-stimluated (i AMPK phosphorylation, (ii CFTR S737 phosphorylation and (iii CFTR activity inhibition. In BHK cells expressing the ΔF508 CFTR mutant (CFTRΔF508, the most common mutation causing cystic fibrosis, both S1P receptor antagonism and AMPK inhibition enhance CFTR activity, without instigating discernable correction. In summary, we demonstrate that S1P/AMPK signaling transiently attenuates CFTR activity. Since our previous work positions CFTR as a negative S1P signaling regulator, this signaling link may positively reinforce S1P signals. This discovery has clinical ramifications for the treatment of disease states associated with enhanced S1P signaling and/or deficient CFTR activity (e.g. cystic fibrosis, heart failure. S1P receptor/AMPK inhibition could synergistically enhance the efficacy of therapeutic strategies aiming to correct aberrant CFTR trafficking.

  12. The H3K27 demethylase, Utx, regulates adipogenesis in a differentiation stage-dependent manner.

    Directory of Open Access Journals (Sweden)

    Kazushige Ota

    Full Text Available Understanding the molecular mechanisms that drive adipogenesis is important in developing new treatments for obesity and diabetes. Epigenetic regulations determine the capacity of adipogenesis. In this study, we examined the role of a histone H3 lysine 27 demethylase, the ubiquitously transcribed tetratricopeptide repeat protein on the X chromosome (Utx, in the differentiation of mouse embryonic stem cells (mESCs to adipocytes. Using gene trapping, we examined Utx-deficient male mESCs to determine whether loss of Utx would enhance or inhibit the differentiation of mESCs to adipocytes. Utx-deficient mESCs showed diminished potential to differentiate to adipocytes compared to that of controls. In contrast, Utx-deficient preadipocytes showed enhanced differentiation to adipocytes. Microarray analyses indicated that the β-catenin/c-Myc signaling pathway was differentially regulated in Utx-deficient cells during adipocyte differentiation. Therefore, our data suggest that Utx governs adipogenesis by regulating c-Myc in a differentiation stage-specific manner and that targeting the Utx signaling pathway could be beneficial for the treatment of obesity, diabetes, and congenital utx-deficiency disorders.

  13. Using Pretreatment and Posttreatment Assessments To Enhance and Evaluate Existing Treatment Packages.

    Science.gov (United States)

    Richman, David M.; Berg, Wendy K.; Wacker, David P.; Stephens, Tracy; Rankin, Barbara; Kilroy, Jennette

    1997-01-01

    Pretreatment assessment data were used to enhance an existing treatment package to reduce aggression and to increase the positive social interactions of a 9-year-old boy with moderate mental retardation and Hunter's syndrome. Additional reinforcements and punishment components were added and resulted in positive social interactions and suppressed…

  14. Coordinated risk informed regulation: a conceptual approach illustrated by the industry of phytosanitary radiation treatment

    International Nuclear Information System (INIS)

    Wieland, Patricia

    2012-01-01

    Regulatory bodies control areas such as health, environment, safety, transportation, finance or any other area of strategic importance to the national sustainable development, where the free activity of economic agents will not lead to socially desirable results. In Brazil, industrial activities impacting on different social and economic segments may be subject to regulation by several governmental agencies, with different cultures, requirements, procedures, and deadlines. To approve an industrial undertaking, most often each regulator analyzes in isolation the aspect of its concern. Also in monitoring and enforcement, the agencies usually act individually. The proliferation and fragmentation of regulation have, in some cases, delayed or even inhibited the development of industrial activities, and thus, working against the very purpose of regulation. This thesis illustrates the current situation with the regulation on food irradiation services, proposes and justifies an organizational structure to enhance coordination among regulatory agencies by aligning their activities and avoiding inconsistencies, overlaps and omissions. This structure comprises, among other mechanisms, a single Internet portal on Federal Regulation, an integrated and dynamic risk analysis and the harmonization of decision-making. The purpose is to promote regulation predictability, regulatory action consistency, optimization of public resources, transparency in the agencies' decision making, and to bring benefits to the entrepreneurs by offering them real-time monitoring and more agile processes. (author)

  15. Enhancing Decision-Making in STSE Education by Inducing Reflection and Self-Regulated Learning

    Science.gov (United States)

    Gresch, Helge; Hasselhorn, Marcus; Bögeholz, Susanne

    2017-02-01

    Thoughtful decision-making to resolve socioscientific issues is central to science, technology, society, and environment (STSE) education. One approach for attaining this goal involves fostering students' decision-making processes. Thus, the present study explores whether the application of decision-making strategies, combined with reflections on the decision-making processes of others, enhances decision-making competence. In addition, this study examines whether this process is supported by elements of self-regulated learning, i.e., self-reflection regarding one's own performance and the setting of goals for subsequent tasks. A computer-based training program which involves the resolution of socioscientific issues related to sustainable development was developed in two versions: with and without elements of self-regulated learning. Its effects on decision-making competence were analyzed using a pre test-post test follow-up control-group design ( N = 242 high school students). Decision-making competence was assessed using an open-ended questionnaire that focused on three facets: consideration of advantages and disadvantages, metadecision aspects, and reflection on the decision-making processes of others. The findings suggest that students in both training groups incorporated aspects of metadecision into their statements more often than students in the control group. Furthermore, both training groups were more successful in reflecting on the decision-making processes of others. The students who received additional training in self-regulated learning showed greater benefits in terms of metadecision aspects and reflection, and these effects remained significant two months later. Overall, our findings demonstrate that the application of decision-making strategies, combined with reflections on the decision-making process and elements of self-regulated learning, is a fruitful approach in STSE education.

  16. An Approach to Regulation on Financial Derivatives in the Spanish Law

    Directory of Open Access Journals (Sweden)

    Pablo Sanz Bayón

    2013-07-01

    Full Text Available This review examines the major reforms implemented in the regulations governing the trading of financial derivatives in Spain. This new regulation is intended to harmonize the treatment of derivative products with the legal standards of international markets in the European area as well as improving their competitiveness by enhancing the trading of new products and business lines in the Spanish markets while reducing the systemic risk associated to the clearing and settlement of derivatives contracts. Including measures regarding the conversion of OTC derivatives into assets quoted on organized markets into Spanish law has made an important contribution to a better regulation, security and transparency of the financial system.

  17. Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

    International Nuclear Information System (INIS)

    Seong, Jin Sil; Kim, Sung Hee; Suh, Chang Ok

    2000-01-01

    The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-l, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, 8c1-2, Sax, Bel-XL, Bd-XS, and p21 WAF1/CIP1 . Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gerncitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21 WAF1/CIP1 . Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21 WAF1/CIP1

  18. Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Jin Sil; Kim, Sung Hee; Suh, Chang Ok [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    2000-12-01

    The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-l, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, 8c1-2, Sax, Bel-XL, Bd-XS, and p21{sup WAF1/CIP1}. Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gerncitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21 {sup WAF1/CIP1}. Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21{sup WAF1/CIP1}.

  19. Enhancing dye-sensitized solar cell efficiency by anode surface treatments

    International Nuclear Information System (INIS)

    Chang, Chao-Hsuan; Lin, Hsin-Han; Chen, Chin-Cheng; Hong, Franklin C.-N.

    2014-01-01

    In this study, titanium substrates treated with HF solution and KOH solution sequentially forming micro- and nano-structures were used for the fabrication of flexible dye-sensitized solar cells (DSSCs). After wet etching treatments, the titanium substrates were then exposed to the O 2 plasma treatment and further immersed in titanium tetrachloride (TiCl 4 ) solution. The process conditions for producing a very thin TiO 2 blocking layer were studied, in order to avoid solar cell current leakage for increasing the solar cell efficiency. Subsequently, TiO 2 nanoparticles were spin-coated on Ti substrates with varied thickness. The dye-sensitized solar cells on the titanium substrates were subjected to simulate AM 1.5 G irradiation of 100 mW/cm 2 using backside illumination mode. Surface treatments of Ti substrate and TiO 2 anode were found to play a significant role in improving the efficiency of DSSC. The efficiencies of the backside illumination solar cells were raised from 4.6% to 7.8% by integrating these surface treatments. - Highlights: • The flexible dye-sensitized solar cell (DSSC) device can be fabricated. • Many effective surface treatment methods to improve DSSC efficiency are elucidated. • The efficiency is dramatically enhanced by integrating surface treatment methods. • The back-illuminated DSSC efficiency was raised from 4.6% to 7.8%

  20. [Sinusotrabeculectomy with regulated filtration in the treatment of secondary glaucoma].

    Science.gov (United States)

    Barashkov, V I; Dushin, N V; Beliaev, V S; Kravchinina, V V; Gonchar, P A; Frolov, M A; Semin, S B

    1999-01-01

    A new method for surgical treatment of secondary glaucoma (neovascular, postuveal, traumatic, and aphakic) is described. The aims of the new method are as follows: regulation of ophthalmic tone in the postoperative period, pain relief, organ preservation, stabilization of the process, and creation of reliable routes of intraocular fluid discharge with formation of a stable diffuse functional pad. Seven patients (8 eyes) aged 13-70 years were operated on and followed up for up to 6 months. Preliminary results are presented. Positive shifts were observed in all cases.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xiao-cai; Xiao, Cui-cui; Li, Hua [Department of Hepatic Surgery, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou (China); Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou (China); Tai, Yan; Zhang, Qi [Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou (China); Yang, Yang, E-mail: yysysu2@163.com [Department of Hepatic Surgery, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou (China)

    2016-08-19

    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 to 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.

  2. Down-regulation of ABCG2, a urate exporter, by parathyroid hormone enhances urate accumulation in secondary hyperparathyroidism.

    Science.gov (United States)

    Sugimoto, Ryusei; Watanabe, Hiroshi; Ikegami, Komei; Enoki, Yuki; Imafuku, Tadashi; Sakaguchi, Yoshiaki; Murata, Michiya; Nishida, Kento; Miyamura, Shigeyuki; Ishima, Yu; Tanaka, Motoko; Matsushita, Kazutaka; Komaba, Hirotaka; Fukagawa, Masafumi; Otagiri, Masaki; Maruyama, Toru

    2017-03-01

    Hyperuricemia occurs with increasing frequency among patients with hyperparathyroidism. However, the molecular mechanism by which the serum parathyroid hormone (PTH) affects serum urate levels remains unknown. This was studied in uremic rats with secondary hyperparathyroidism where serum urate levels were found to be increased and urate excretion in the intestine and kidney decreased, presumably due to down-regulation of the expression of the urate exporter ABCG2 in intestinal and renal epithelial membranes. These effects were prevented by administration of the calcimimetic cinacalcet, a PTH suppressor, suggesting that PTH may down-regulate ABCG2 expression. This was directly tested in intestinal Caco-2 cells where the expression of ABCG2 on the plasma membrane was down-regulated by PTH (1-34) while its mRNA level remained unchanged. Interestingly, an inactive PTH derivative (13-34) had no effect, suggesting that a posttranscriptional regulatory system acts through the PTH receptor to regulate ABCG2 plasma membrane expression. As found in an animal study, additional clinical investigations showed that treatment with cinacalcet resulted in significant reductions in serum urate levels together with decreases in PTH levels in patients with secondary hyperparathyroidism undergoing dialysis. Thus, PTH down-regulates ABCG2 expression on the plasma membrane to suppress intestinal and renal urate excretion, and the effects of PTH can be prevented by cinacalcet treatment. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  3. [Review for treatment effect and signaling pathway regulation of kidney-tonifying traditional Chinese medicine on osteoporosis].

    Science.gov (United States)

    Xiao, Ya-Ping; Zeng, Jie; Jiao, Lin-Na; Xu, Xiao-Yu

    2018-01-01

    The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/ β -catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus and Psoraleae Fructus up-regulated the expression of key proteins and genes of BMP-Smads and Wnt/ β -catenin signaling pathways to promote bone formation. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix inhibited the bone resorption by mediating the OPG/RANKL/RANK signaling pathway. ②Kidney-tonifying traditional Chinese medicine prevented and treated osteoporosis through a variety of ways: icariin in Epimedii Folium, naringin in Drynariae Rhizoma, osthole in Cnidii Fructus and psoralen in Psoraleae Fructus can regulate BMP-Smads, Wnt/ β -catenin signaling pathway to promote bone formation, but also activate OPG/RANKL/RANK, CTSK and other signaling pathways to inhibit bone resorption. ③The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification. Copyright© by the Chinese Pharmaceutical Association.

  4. BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice.

    Science.gov (United States)

    Pereyra, Andrea S; Wang, Zhong-Min; Messi, Maria Laura; Zhang, Tan; Wu, Hanzhi; Register, Thomas C; Forbes, Elizabeth; Devarie-Baez, Nelmi O; Files, Daniel Clark; Abba, Martin C; Furdui, Cristina; Delbono, Osvaldo

    2017-08-01

    Loss of muscle mass and force with age leads to fall risk, mobility impairment, and reduced quality of life. This article shows that BDA-410, a calpain inhibitor, induced loss of body weight and fat but not lean mass or skeletal muscle proteins in a cohort of sedentary 23-month-old mice. Food and water intake and locomotor activity were not modified, whereas BDA-410 treatment decreased intramyocellular lipid and perigonadal fat, increased serum nonesterified fatty acids, and upregulated the genes mediating lipolysis and oxidation, lean phenotype, muscle contraction, muscle transcription regulation, and oxidative stress response. This finding is consistent with our recent report that lipid accumulation in skeletal myofibers is significantly correlated with slower fiber-contraction kinetics and diminished power in obese older adult mice. A proteomic analysis and immunoblot showed downregulation of the phosphatase PPP1R12B, which increases phosphorylated myosin half-life and modulates the calcium sensitivity of the contractile apparatus. This study demonstrates that BDA-410 exerts a beneficial effect on skeletal muscle contractility through new, alternative mechanisms, including enhanced lipolysis, upregulation of "lean phenotype-related genes," downregulation of the PP1R12B phosphatase, and enhanced excitation-contraction coupling. This single compound holds promise for treating age-dependent decline in muscle composition and strength. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. N-myc downstream-regulated gene 1 promotes oxaliplatin-triggered apoptosis in colorectal cancer cells via enhancing the ubiquitination of Bcl-2.

    Science.gov (United States)

    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.

  6. Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase.

    Science.gov (United States)

    Xiao, Ran; Li, Shan; Cao, Qian; Wang, Xiuling; Yan, Qiujin; Tu, Xiaoning; Zhu, Ying; Zhu, Fan

    2017-06-01

    Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS). These diseases are accompanied by immunological reactions in the central nervous system (CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter-nitric oxide (NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.

  7. Dioscin enhances methotrexate absorption by down-regulating MDR1 in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lijuan, E-mail: jlwang1979@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Wang, Changyuan, E-mail: wangcyuan@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Peng, Jinyong, E-mail: jinyongpeng2005@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Liu, Qi, E-mail: llaqii@yahoo.com.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Meng, Qiang, E-mail: mengq531@yahoo.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Sun, Huijun, E-mail: sunhuijun@hotmail.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); Huo, Xiaokui, E-mail: huoxiaokui@163.com [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning (China); and others

    2014-06-01

    The purpose of this study was to investigate the enhancing effect of dioscin on the absorption of methotrexate (MTX) and clarify the molecular mechanism involved in vivo and in vitro. Dioscin increased MTX chemosensitivity and transepithelial flux in the absorptive direction, significantly inhibiting multidrug resistance 1 (MDR1) mRNA and protein expression and MDR1 promoter and nuclear factor κ-B (NF-κB) activities in Caco-2 cells. Moreover, inhibitor κB-α (IκB-α) degradation was inhibited by dioscin. Dioscin enhanced the intracellular concentration of MTX by down-regulating MDR1 expression through a mechanism that involves NF-κB signaling pathway inhibition in Caco-2 cells. Dioscin strengthened MTX absorption by inhibiting MDR1 expression in rat intestine. In addition, even though MTX is absorbed into the enterocytes, there was no increase in toxicity observed, and that, in fact, decreased toxicity was seen. - Highlights: • Dioscin raised MTX concentration by inhibiting MDR1 in Caco-2 cells. • Dioscin suppresses MDR1 by inhibiting NF-κB signaling pathway in Caco-2 cells. • Dioscin can enhance MTX absorption via inhibiting MDR1 in vivo and in vitro. • Dioscin did not increase MTX-induced gastrointestinal mucosal toxicity.

  8. Enhancing forest tenure reforms through more responsive regulations

    Directory of Open Access Journals (Sweden)

    Anne M Larson

    2012-01-01

    Full Text Available Forest tenure reforms have offered new opportunities for communities to obtain formal rights to forests and forest benefits, but at the same time a variety of limitations are placed on livelihood options. This article draws on several case studies of reforms in Africa, Asia and Latin America to analyse the regulations accompanying reforms. It identifies three types of regulations, namely rules that limit areas available to local communities; rules that delineate conservation areas and impose related limits on use; and bureaucratic requirements for permits and management plans, which restrict the commercial use and marketing of valuable forest products. It discusses problems with these regulations, and proposes a simple framework for identifying ways to promote regulations that work for forest conservation but are more responsive to the needs of communities and forests.

  9. Daidzein enhances immune function in late lactation cows under heat stress.

    Science.gov (United States)

    Liu, De-Yi; He, Shao-Jun; Liu, Shi-Qing; Tang, Yi-Guo; Jin, Er-Hui; Chen, Hui-Liang; Li, Sheng-He; Zhong, Liang-Ting

    2014-01-01

    Heat stress decreases natural immunity making cows more vulnerable to diseases. A previous study reported that daidzein can enhance animal resistance to heat stress and regulate animal immunocompetence. However, it is unclear whether daidzein regulates the immune performance of late lactation cows under heat stress. In this study, late lactation cows in four groups were raised in hot weather and fed with basic diet, basic diet plus 200, 300, 400 mg/day daidzein, respectively, and the experimental period was 60 days. Blood was collected to examine the changes of serum total protein (TP), albumin (ALB), immunoglobulin G (IgG), interferon alpha (IFN-α), and interleukin-2 (IL-2). We found the levels of serum IgG and INF-α were significantly higher in late lactation cows after 300 and 400 mg/day daidzein treatment compared to those in the control group and 200 mg/day daidzein treatment (P 0.05). Daidzein can enhance the immunocompetence of late lactation cows and strengthen cow resistance to heat stress. © 2013 Japanese Society of Animal Science.

  10. Enhancing Cold Atmospheric Plasma Treatment Efficiency for Cancer Therapy

    Science.gov (United States)

    Cheng, Xiaoqian

    To improve efficiency and safety of anti-cancer therapies the researchers and clinicians alike are prompted to develop targeted combined therapies that especially minimize damage to healthy tissues while eradicating the body of cancerous tissues. Previous research in cold atmospheric plasma (CAP) and cancer cell interaction has repeatedly proven that cold plasma induced cell death. In this study, we seek to integrate the medical application of CAP. We proposed and implemented 3 novel ideas to enhance efficacy and selectivity of cancer therapy. It is postulated that the reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a major role in the CAP cancer therapy. We determined a mechanism of CAP therapy on glioblastoma cells (U87) through an understanding of the composition of CAP, including output voltage, treatment time, and gas flow-rate. We varied the characteristics of the cold plasma in order to obtain different major species (such as O, OH, N2+, and N2 lines). "plasma dosage" D ~ Q * V * t. is defined, where D is the entire "plasma dosage"; Q is the flow rate of feeding gas; V is output voltage; t is treatment time. The proper CAP dosage caused 3-fold cell death in the U87 cells compared to the normal human astrocytes E6/E7 cells. We demonstrated there is a synergy between AuNPS and CAP in cancer therapy. Specifically, the concentration of AuNPs plays an important role on plasma therapy. At an optimal concentration, gold nanoparticles can significantly induce U87 cell death up to a 30% overall increase compared to the control group with the same plasma dosage but no AuNPs applied. The ROS intensity of the corresponding conditions has a reversed trend compared to cell viability. This matches with the theory that intracellular ROS accumulation results in oxidative stress, which further changes the intracellular pathways, causing damage to the proteins, lipids and DNA. Our results show that this synergy has great potential in improving the

  11. Strategies and techniques to enhance constructed wetland performance for sustainable wastewater treatment.

    Science.gov (United States)

    Wu, Haiming; Fan, Jinlin; Zhang, Jian; Ngo, Huu Hao; Guo, Wenshan; Liang, Shuang; Hu, Zhen; Liu, Hai

    2015-10-01

    Constructed wetlands (CWs) have been used as an alternative to conventional technologies for wastewater treatment for more than five decades. Recently, the use of various modified CWs to improve treatment performance has also been reported in the literature. However, the available knowledge on various CW technologies considering the intensified and reliable removal of pollutants is still limited. Hence, this paper aims to provide an overview of the current development of CW strategies and techniques for enhanced wastewater treatment. Basic information on configurations and characteristics of different innovations was summarized. Then, overall treatment performance of those systems and their shortcomings were further discussed. Lastly, future perspectives were also identified for specialists to design more effective and sustainable CWs. This information is used to inspire some novel intensifying methodologies, and benefit the successful applications of potential CW technologies.

  12. Resveratrol treatment reveals a novel role for HMGB1 in regulation of the type 1 interferon response in dengue virus infection.

    Science.gov (United States)

    Zainal, Nurhafiza; Chang, Chih-Peng; Cheng, Yi-Lin; Wu, Yan-Wei; Anderson, Robert; Wan, Shu-Wen; Chen, Chia-Ling; Ho, Tzong-Shiann; AbuBakar, Sazaly; Lin, Yee-Shin

    2017-02-20

    Dengue is one of the most significant mosquito-borne virus diseases worldwide, particularly in tropical and subtropical regions. This study sought to examine the antiviral activity of resveratrol (RESV), a phytoalexin secreted naturally by plants, against dengue virus (DENV) infection. Our data showed that RESV inhibits the translocation of high mobility group box 1 (HMGB1), a DNA binding protein that normally resides in the nucleus, into the cytoplasm and extracellular milieu. HMGB1 migrates out of the nucleus during DENV infection. This migration is inhibited by RESV treatment and is mediated by induction of Sirt1 which leads to the retention of HMGB1 in the nucleus and consequently helps in the increased production of interferon-stimulated genes (ISGs). Nuclear HMGB1 was found to bind to the promoter region of the ISG and positively regulated the expression of ISG. The enhanced transcription of ISGs by nuclear HMGB1 thus contributes to the antiviral activity of RESV against DENV. To the best of our knowledge, this is the first report to demonstrate that RESV antagonizes DENV replication and that nuclear HMGB1 plays a role in regulating ISG production.

  13. Exogenously applied plant growth regulators enhance the morpho-physiological growth and yield of rice under high temperature

    Directory of Open Access Journals (Sweden)

    Shah Fahad

    2016-08-01

    Full Text Available A two-year experiment was conducted to ascertain the effects of exogenously applied plant growth regulators (PGR on rice growth and yield attributes under high day (HDT and high night temperature (HNT. Two rice cultivars (IR-64 and Huanghuazhan were subjected to temperature treatments in controlled growth chambers and four different combinations of ascorbic acid (Vc, alpha-tocopherol (Ve, brassinosteroids (Br, methyl jasmonates (MeJA and triazoles (Tr were applied. High temperature severely affected rice morphology, and also reduced leaf area, above- and below-ground biomass, photosynthesis, and water use efficiency, while increased the leaf water potential of both rice cultivars. Grain yield and its related attributes except number of panicles, were reduced under high temperature. The HDT posed more negative effects on rice physiological attributes, while HNT was more detrimental for grain formation and yield. The Huanghuazhan performed better than IR-64 under high temperature stress with better growth and higher grain yield. Exogenous application of PGRs was helpful in alleviating the adverse effects of high temperature. Among PGR combinations, the Vc+Ve+MejA+Br was the most effective treatment for both cultivars under high temperature stress. The highest grain production by Vc+Ve+MejA+Br treated plants was due to enhanced photosynthesis, spikelet fertility and grain filling, which compensated the adversities of high temperature stress. Taken together, these results will be of worth for further understanding the adaptation and survival mechanisms of rice to high temperature and will assist in developing heat-resistant rice germplasm in future.

  14. Interactive, technology-enhanced self-regulated learning tools in healthcare education: a literature review.

    Science.gov (United States)

    Petty, Julia

    2013-01-01

    Learning technology is increasingly being implemented for programmes of blended learning within nurse education. With a growing emphasis on self-directed study particularly in post-basic education, there is a need for learners to be guided in their learning away from practice and limited classroom time. Technology-enabled (TE) tools which engage learners actively can play a part in this. The effectiveness and value of interactive TE learning strategies within healthcare is the focus of this paper. To identify literature that explores the effectiveness of interactive, TE tools on knowledge acquisition and learner satisfaction within healthcare with a view to evaluating their use for post-basic nurse education. A Literature Review was performed focusing on papers exploring the comparative value and perceived benefit of TE tools compared to traditional modes of learning within healthcare. The Databases identified as most suitable due to their relevance to healthcare were accessed through EBSCOhost. Primary, Boolean and advanced searches on key terms were undertaken. Inclusion and exclusion criteria were applied which resulted in a final selection of 11 studies for critique. Analysis of the literature found that knowledge acquisition in most cases was enhanced and measured learner satisfaction was generally positive for interactive, self-regulated TE tools. However, TE education may not suit all learners and this is critiqued in the light of the identified limitations. Interactive self regulation and/or testing can be a valuable learning strategy that can be incorporated into self-directed programmes of study for post-registration learners. Whilst acknowledging the learning styles not suited to such tools, the concurrent use of self-directed TE tools with those learning strategies necessitating a more social presence can work together to support enhancement of knowledge required to deliver rationale for nursing practice. Copyright © 2012 Elsevier Ltd. All rights

  15. Enhancement of enzymatic saccharification of Eucalyptus globulus: steam explosion versus steam treatment.

    Science.gov (United States)

    Martin-Sampedro, Raquel; Revilla, Esteban; Villar, Juan C; Eugenio, Maria E

    2014-09-01

    Steam explosion and steam pre-treatment have proved capable of enhancing enzymatic saccharification of lignocellulosic materials. However, until now, these methods had not been compared under the same operational conditions and using the same raw material. Both pre-treatments lead to increased yields in the saccharification of Eucalyptus globulus; but results have been better with steam pre-treatments, despite the more accessible surface of exploded samples. The reason for this finding could be enzymatic inhibition: steam explosion causes a more extensive extraction of hemicelluloses and releases a greater amount of degradation products which can inhibit enzymatic action. Enzymatic inhibition is also dependent on the amount and chemical structure of lignin, which was also a contributing factor to the lower enzymatic yields obtained with the most severe pre-treatment. Thus, the highest yields (46.7% glucose and 73.4% xylose yields) were obtained after two cycle of steam treatment, of 5 and 3 min, at 183°C. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Enhanced age-strengthening by two-step progressive solution treatment in an Mg–Zn–Al–Re alloy

    International Nuclear Information System (INIS)

    Zhang, Jing; Yuan, Fuqing; Du, Yong

    2013-01-01

    Highlights: • A two-step progressive solution treatment schedule was proposed. • The treatment enhanced dissolution of ternary eutectic phases in Mg–Zn–Al alloy. • Solution temperature could break the limit of the ternary eutectic temperature. • There was no microstructural over-heating defect during the progressive heating. • The τ precipitates have a remarkable dispersion strengthening effect. - Abstract: A two-step progressive solution treatment was designed and performed on an as-extruded Mg–7Zn–3Al–0.7Er alloy. The resultant microstructure and mechanical properties were examined by means of scanning electron microscopy, X-ray diffractometer, differential scanning calorimetry and hardness testing. The results showed that the two-step progressive solution treatment could enhance the dissolution of the ternary eutectic phases in the Mg–Zn–Al system without the formation of microstructure over-heating defects. After homogenization for 50 h at 325 °C, the volume fraction of the undissolved particles in the Mg–7Zn–3Al–0.7Er alloy ingot was ∼4.1%. Two-step progressive solution treatment performed on the as-extruded alloy could further dissolve the particles. Only 1.5% undissolved particles remained after the treatment. The supersaturated degree of both the dissolved solute atoms and vacancies in the α-Mg matrix was expected to be increased, resulting in an enhanced age-strengthening, compared with normal solution and aging treatments. Moreover, the processed alloy exhibited a homogenous and stable fine grain structure. Remarkable dispersion strengthening effect of ternary τ (Mg 32 (Al,Zn) 49 ) precipitates occurred in Mg–Zn–Al alloy was also identified

  17. Aneurysmal wall enhancement and perianeurysmal edema after endovascular treatment of unruptured cerebral aneurysms.

    LENUS (Irish Health Repository)

    Su, I-Chang

    2014-06-01

    Perianeurysmal edema and aneurysm wall enhancement are previously described phenomenon after coil embolization attributed to inflammatory reaction. We aimed to demonstrate the prevalence and natural course of these phenomena in unruptured aneurysms after endovascular treatment and to identify factors that contributed to their development.

  18. Enhanced Hydrophilicity and Biocompatibility of Dental Zirconia Ceramics by Oxygen Plasma Treatment

    Directory of Open Access Journals (Sweden)

    Ching-Chou Wu

    2015-02-01

    Full Text Available Surface properties play a critical role in influencing cell responses to a biomaterial. The objectives of this study were (1 to characterize changes in surface properties of zirconia (ZrO2 ceramic after oxygen plasma treatment; and (2 to determine the effect of such changes on biological responses of human osteoblast-like cells (MG63. The results indicated that the surface morphology was not changed by oxygen plasma treatment. In contrast, oxygen plasma treatment to ZrO2 not only resulted in an increase in hydrophilicity, but also it retained surface hydrophilicity after 5-min treatment time. More importantly, surface properties of ZrO2 modified by oxygen plasma treatment were beneficial for cell growth, whereas the surface roughness of the materials did not have a significant efficacy. It is concluded that oxygen plasma treatment was certified to be effective in modifying the surface state of ZrO2 and has the potential in the creation and maintenance of hydrophilic surfaces and the enhancement of cell proliferation and differentiation.

  19. Amagnetic field-enhanced filtration/sorption Device and its potential for inexpensive water and wastewater treatment

    International Nuclear Information System (INIS)

    Navratil, J.D.

    2000-01-01

    A magnetic field-enhanced filtration/sorption device is described for removal of radioactive and heavy metals from water and wastewater. The device consists of a column of supported magnetite surrounded by a movable permanent magnet. The mineral magnetite, or synthetically prepared iron ferrite (Fe O Fe 2 O 3 ), is typically supported on various materials to permit adequate water passage through the column. In the presence of the external magnetic field, enhanced capacity was observed in using supported magnetite for removal of actinides and heavy metals from wastewater. The enhanced capacity is primarily due to magnetic filtration of colloidal and submicron particles along with some complex and ion exchange sorption mechanisms. The loaded magnetite can easily be regenerated by the removal of the magnetic field and use of a regenerating solution. This paper will review previous work on the use of iron oxides for wastewater treatment and discuss the development and potential of the magnetic filtration/sorption process for water and wastewater treatment

  20. Reducing symptoms of major depressive disorder through a systematic training of general emotion regulation skills: protocol of a randomized controlled trial.

    Science.gov (United States)

    Ehret, Anna M; Kowalsky, Judith; Rief, Winfried; Hiller, Wolfgang; Berking, Matthias

    2014-01-27

    Major Depressive Disorder is one of the most challenging mental health problems of our time. Although effective psychotherapeutic treatments are available, many patients fail to demonstrate clinically significant improvements. Difficulties in emotion regulation have been identified as putative risk and maintaining factors for Major Depressive Disorder. Systematically enhancing adaptive emotion regulation skills should thus help reduce depressive symptom severity. However, at this point, no study has systematically evaluated effects of increasing adaptive emotion regulation skills application on symptoms of Major Depressive Disorder. In the intended study, we aim to evaluate stand-alone effects of a group-based training explicitly and exclusively targeting general emotion regulation skills on depressive symptom severity and assess whether this training augments the outcome of subsequent individual cognitive behavioral therapy for depression. In the evaluation of the Affect Regulation Training, we will conduct a prospective randomized-controlled trial. Effects of the Affect Regulation Training on depressive symptom severity and outcomes of subsequent individual therapy for depression will be compared with an active, common factor based treatment and a waitlist control condition. The study sample will include 120 outpatients meeting criteria for Major Depressive Disorder. Depressive symptom severity as assessed by the Hamilton Rating Scale will serve as our primary study outcome. Secondary outcomes will include further indicators of mental health and changes in adaptive emotion regulation skills application. All outcomes will be assessed at intake and at 10 points in time over the course of the 15-month study period. Measures will include self-reports, observer ratings, momentary ecological assessments, and will be complemented in subsamples by experimental investigations and the analysis of hair steroids. If findings should support the hypothesis that enhancing

  1. Regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor

    International Nuclear Information System (INIS)

    Savkur, Rajesh S.; Bramlett, Kelli S.; Michael, Laura F.; Burris, Thomas P.

    2005-01-01

    The pyruvate dehydrogenase complex (PDC) functions as an important junction in intermediary metabolism by influencing the utilization of fat versus carbohydrate as a source of fuel. Activation of PDC is achieved by phosphatases, whereas, inactivation is catalyzed by pyruvate dehydrogenase kinases (PDKs). The expression of PDK4 is highly regulated by the glucocorticoid and peroxisome proliferator-activated receptors. We demonstrate that the farnesoid X receptor (FXR; NR1H4), which regulates a variety of genes involved in lipoprotein metabolism, also regulates the expression of PDK4. Treatment of rat hepatoma cells as well as human primary hepatocytes with FXR agonists stimulates the expression of PDK4 to levels comparable to those obtained with glucocorticoids. In addition, treatment of mice with an FXR agonist significantly increased hepatic PDK4 expression, while concomitantly decreasing plasma triglyceride levels. Thus, activation of FXR may suppress glycolysis and enhance oxidation of fatty acids via inactivation of the PDC by increasing PDK4 expression

  2. A late embryogenesis abundant protein HVA1 regulated by an inducible promoter enhances root growth and abiotic stress tolerance in rice without yield penalty.

    Science.gov (United States)

    Chen, Yi-Shih; Lo, Shuen-Fang; Sun, Peng-Kai; Lu, Chung-An; Ho, Tuan-Hua D; Yu, Su-May

    2015-01-01

    Regulation of root architecture is essential for maintaining plant growth under adverse environment. A synthetic abscisic acid (ABA)/stress-inducible promoter was designed to control the expression of a late embryogenesis abundant protein (HVA1) in transgenic rice. The background of HVA1 is low but highly inducible by ABA, salt, dehydration and cold. HVA1 was highly accumulated in root apical meristem (RAM) and lateral root primordia (LRP) after ABA/stress treatments, leading to enhanced root system expansion. Water-use efficiency (WUE) and biomass also increased in transgenic rice, likely due to the maintenance of normal cell functions and metabolic activities conferred by HVA1 which is capable of stabilizing proteins, under osmotic stress. HVA1 promotes lateral root (LR) initiation, elongation and emergence and primary root (PR) elongation via an auxin-dependent process, particularly by intensifying asymmetrical accumulation of auxin in LRP founder cells and RAM, even under ABA/stress-suppressive conditions. We demonstrate a successful application of an inducible promoter in regulating the spatial and temporal expression of HVA1 for improving root architecture and multiple stress tolerance without yield penalty. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  3. Tumor Therapeutics Work as Stress Inducers to Enhance Tumor Sensitivity to Natural Killer (NK) Cell Cytolysis by Up-regulating NKp30 Ligand B7-H6.

    Science.gov (United States)

    Cao, Guoshuai; Wang, Jian; Zheng, Xiaodong; Wei, Haiming; Tian, Zhigang; Sun, Rui

    2015-12-11

    Immune cells are believed to participate in initiating anti-tumor effects during regular tumor therapy such as chemotherapy, radiation, hyperthermia, and cytokine injection. One of the mechanisms underlying this process is the expression of so-called stress-inducible immunostimulating ligands. Although the activating receptor NKG2D has been proven to play roles in tumor therapy through targeting its ligands, the role of NKp30, another key activating receptor, is seldom addressed. In this study, we found that the NKp30 ligand B7-H6 was widely expressed in tumor cells and closely correlated to their susceptibility to NK cell lysis. Further studies showed that treatment of tumor cells with almost all standard tumor therapeutics, including chemotherapy (cisplatin, 5-fluorouracil), radiation therapy, non-lethal heat shock, and cytokine therapy (TNF-α), could up-regulate the expression of B7-H6 in tumor cells and enhance tumor sensitivity to NK cell cytolysis. B7-H6 shRNA treatment effectively dampened sensitization of tumor cells to NK-mediated lysis. Our study not only reveals the possibility that tumor therapeutics work as stress inducers to enhance tumor sensitivity to NK cell cytolysis but also suggests that B7-H6 could be a potential target for tumor therapy in the future. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Influence of DNA-methylation on zinc homeostasis in myeloid cells: Regulation of zinc transporters and zinc binding proteins.

    Science.gov (United States)

    Kessels, Jana Elena; Wessels, Inga; Haase, Hajo; Rink, Lothar; Uciechowski, Peter

    2016-09-01

    The distribution of intracellular zinc, predominantly regulated through zinc transporters and zinc binding proteins, is required to support an efficient immune response. Epigenetic mechanisms such as DNA methylation are involved in the expression of these genes. In demethylation experiments using 5-Aza-2'-deoxycytidine (AZA) increased intracellular (after 24 and 48h) and total cellular zinc levels (after 48h) were observed in the myeloid cell line HL-60. To uncover the mechanisms that cause the disturbed zinc homeostasis after DNA demethylation, the expression of human zinc transporters and zinc binding proteins were investigated. Real time PCR analyses of 14 ZIP (solute-linked carrier (SLC) SLC39A; Zrt/IRT-like protein), and 9 ZnT (SLC30A) zinc transporters revealed significantly enhanced mRNA expression of the zinc importer ZIP1 after AZA treatment. Because ZIP1 protein was also enhanced after AZA treatment, ZIP1 up-regulation might be the mediator of enhanced intracellular zinc levels. The mRNA expression of ZIP14 was decreased, whereas zinc exporter ZnT3 mRNA was also significantly increased; which might be a cellular reaction to compensate elevated zinc levels. An enhanced but not significant chromatin accessibility of ZIP1 promoter region I was detected by chromatin accessibility by real-time PCR (CHART) assays after demethylation. Additionally, DNA demethylation resulted in increased mRNA accumulation of zinc binding proteins metallothionein (MT) and S100A8/S100A9 after 48h. MT mRNA was significantly enhanced after 24h of AZA treatment also suggesting a reaction of the cell to restore zinc homeostasis. These data indicate that DNA methylation is an important epigenetic mechanism affecting zinc binding proteins and transporters, and, therefore, regulating zinc homeostasis in myeloid cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. Dynamic contrast-enhanced CT in advanced lung cancer after chemotherapy with/within radiation therapy: Can it predict treatment responsiveness of the tumor?

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Mi Ri; Whang, Sung Ho; Park, Chul Hwan; Kim, Sang Jin; Kim, Tae Hoon [Dept. of Radiology and Research Institute of Radiological Science, Yonsei University Health System, Seoul (Korea, Republic of)

    2013-08-15

    To evaluate the contrast enhancement patterns of lung cancer after chemotherapy using a dynamic contrast-enhanced (DCE) CT and to determine whether the enhancement patterns of tumors at early stages of treatment can predict treatment responses. Forty-two patients with advanced lung cancers underwent DCE-CT and follow-up CT after chemotherapy. We evaluated peak and net enhancement (PE and NE, respectively) and time-density curves (TDCs) (type A, B, C, and D) on DCE-CT images. Treatment responses were evaluated using revised Response Evaluation Criteria in Solid Tumor criteria. NE and PE values were significantly higher in the progressive disease (PD) groups than in the stable disease (SD) or partial response (PR) groups (p < 0.05). Types B, C, and D on TDCs were observed mostly in the PR and SD groups (96.0%), whereas type A was most frequent in the SD and PD groups (97.2%), which were significantly different in terms of PE and NE. Contrast enhancement pattern regarding the response of treatment on DCE-CT images could be helpful in predicting treatment response of advanced lung cancer after treatment.

  6. Differential regulation of fatty acid biosynthesis in two Chlorella species in response to nitrate treatments and the potential of binary blending microalgae oils for biodiesel application.

    Science.gov (United States)

    Cha, Thye San; Chen, Jian Woon; Goh, Eng Giap; Aziz, Ahmad; Loh, Saw Hong

    2011-11-01

    This study was undertaken to investigate the effects of different nitrate concentrations in culture medium on oil content and fatty acid composition of Chlorella vulgaris (UMT-M1) and Chlorella sorokiniana (KS-MB2). Results showed that both species produced significant higher (pdifferentially regulated fatty acid accumulation patterns in response to nitrate treatments at early stationary growth phase. Their potential use for biodiesel application could be enhanced by exploring the concept of binary blending of the two microalgae oils using developed mathematical equations to calculate the oil mass blending ratio and simultaneously estimated the weight percentage (wt.%) of desirable fatty acid compositions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Pharmacotherapy and group cognitive behavioral therapy enhance follow-up treatment duration in gambling disorder patients.

    Science.gov (United States)

    Choi, Sam-Wook; Shin, Young-Chul; Youn, HyunChul; Lim, Se-Won; Ha, Juwon

    2016-01-01

    Longer treatment duration is important for the successful treatment of gambling disorder (GD). This retrospective study investigated the factors and interventions that might enhance treatment duration in GD patients in South Korea. A total of 758 outpatients with a primary diagnosis of GD, who were treated in a clinical practice from 2002 to 2011, were assessed by retrospective chart review. We compared the treatment duration according to pharmacotherapy and group cognitive behavioral therapy (CBT). Pharmacotherapy contributed to a longer duration of treatment maintenance, despite the patients' gambling severity (p gambling severity. The treatment maintenance duration was the longest in those receiving combined antidepressant pharmacotherapy and group CBT (F = 35.79, p prevention and treatment strategies.

  8. Using sorbent waste materials to enhance treatment of micro-point source effluents by constructed wetlands

    Science.gov (United States)

    Green, Verity; Surridge, Ben; Quinton, John; Matthews, Mike

    2014-05-01

    Sorbent materials are widely used in environmental settings as a means of enhancing pollution remediation. A key area of environmental concern is that of water pollution, including the need to treat micro-point sources of wastewater pollution, such as from caravan sites or visitor centres. Constructed wetlands (CWs) represent one means for effective treatment of wastewater from small wastewater producers, in part because they are believed to be economically viable and environmentally sustainable. Constructed wetlands have the potential to remove a range of pollutants found in wastewater, including nitrogen (N), phosphorus (P), biochemical oxygen demand (BOD) and carbon (C), whilst also reducing the total suspended solids (TSS) concentration in effluents. However, there remain particular challenges for P and N removal from wastewater in CWs, as well as the sometimes limited BOD removal within these treatment systems, particularly for micro-point sources of wastewater. It has been hypothesised that the amendment of CWs with sorbent materials can enhance their potential to treat wastewater, particularly through enhancing the removal of N and P. This paper focuses on data from batch and mesocosm studies that were conducted to identify and assess sorbent materials suitable for use within CWs. The aim in using sorbent material was to enhance the combined removal of phosphate (PO4-P) and ammonium (NH4-N). The key selection criteria for the sorbent materials were that they possess effective PO4-P, NH4-N or combined pollutant removal, come from low cost and sustainable sources, have potential for reuse, for example as a fertiliser or soil conditioner, and show limited potential for re-release of adsorbed nutrients. The sorbent materials selected for testing were alum sludge from water treatment works, ochre derived from minewater treatment, biochar derived from various feedstocks, plasterboard and zeolite. The performance of the individual sorbents was assessed through

  9. Enhancement of tumor response by MEK inhibitor in murine HCa-I tumors

    International Nuclear Information System (INIS)

    Kim, Sung Hee; Seong, Jin Sil

    2003-01-01

    Extracellular signal-regulated kinase (ERK), which is part of the mitogen-activated protein kinase cascade, opposes initiation of the apoptotic cell death which is programmed by diverse cytotoxic stimuli. In this regard, the inhibition of ERK may be useful in improving the therapeutic efficacy of established anticancer agents. Murine hepatocarcinoma, HCa-l is known to be highly radioresistant with a TCD50 (radiation dose yield in 50% cure) of more than 80 Gy. Various anticancer drugs have been found to enhance the radioresponse of this particular tumor but none were successful. The objective of this study was to explore whether the selective inhibition of MEK could potentiate the antitumor efficacy of radiation in vivo, particularly in the case of radioresistant tumor. C3H/HeJ mice bearing 7.5-8 mm. HCa-l, were treated with PD98059 (intratumoral injection of 0.16 μg in 50 μl). Downregulation of ERK by PD98059 was most prominent 1h after the treatment. In the tumor growth delay assay, the drug was found to increase the effect of the tumor radioresponse with an enhancement factor (EF) of 1.6 and 1.87. Combined treatment of 25 Gy radiation with PD98059 significantly increased radiation induced apoptosis. The peak apoptotic index (number of apoptotic nuclei in 1000 nuclei X100) was 1.2% in the case of radiation treatment alone, 0.9% in the case of drug treatment alone and 4.9%, 5.3% in the combination treatment group. An analysis of apoptosis regulating molecules with Western blotting showed up regulation of p53, p21 WAF1 / CIP1 and Bcl-X s in the combination treatment group as compared to their levels in either the radiation alone or drug alone treatment groups. The level of other molecules such as Bcl-X L , Bax and BCI-2 were changed to a lesser extent. The selective inhibition of MEK in combination with radiation therapy may have potential benefit in cancer treatment

  10. Enhancement of tumor response by MEK inhibitor in murine HCa-I tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Hee; Seong, Jin Sil [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    2003-09-01

    Extracellular signal-regulated kinase (ERK), which is part of the mitogen-activated protein kinase cascade, opposes initiation of the apoptotic cell death which is programmed by diverse cytotoxic stimuli. In this regard, the inhibition of ERK may be useful in improving the therapeutic efficacy of established anticancer agents. Murine hepatocarcinoma, HCa-l is known to be highly radioresistant with a TCD50 (radiation dose yield in 50% cure) of more than 80 Gy. Various anticancer drugs have been found to enhance the radioresponse of this particular tumor but none were successful. The objective of this study was to explore whether the selective inhibition of MEK could potentiate the antitumor efficacy of radiation in vivo, particularly in the case of radioresistant tumor. C3H/HeJ mice bearing 7.5-8 mm. HCa-l, were treated with PD98059 (intratumoral injection of 0.16 {mu}g in 50 {mu}l). Downregulation of ERK by PD98059 was most prominent 1h after the treatment. In the tumor growth delay assay, the drug was found to increase the effect of the tumor radioresponse with an enhancement factor (EF) of 1.6 and 1.87. Combined treatment of 25 Gy radiation with PD98059 significantly increased radiation induced apoptosis. The peak apoptotic index (number of apoptotic nuclei in 1000 nuclei X100) was 1.2% in the case of radiation treatment alone, 0.9% in the case of drug treatment alone and 4.9%, 5.3% in the combination treatment group. An analysis of apoptosis regulating molecules with Western blotting showed up regulation of p53, p21{sup WAF1}/{sup CIP1} and Bcl-X{sub s} in the combination treatment group as compared to their levels in either the radiation alone or drug alone treatment groups. The level of other molecules such as Bcl-X{sub L}, Bax and BCI-2 were changed to a lesser extent. The selective inhibition of MEK in combination with radiation therapy may have potential benefit in cancer treatment.

  11. Combined polymer-curcumin conjugate and ependymal progenitor/stem cell treatment enhances spinal cord injury functional recovery.

    Science.gov (United States)

    Requejo-Aguilar, Raquel; Alastrue-Agudo, Ana; Cases-Villar, Marta; Lopez-Mocholi, Eric; England, Richard; Vicent, María J; Moreno-Manzano, Victoria

    2017-01-01

    Spinal cord injury (SCI) suffers from a lack of effective therapeutic strategies. Animal models of acute SCI have provided evidence that transplantation of ependymal stem/progenitor cells of the spinal cord (epSPCs) induces functional recovery, while systemic administration of the anti-inflammatory curcumin provides neuroprotection. However, functional recovery from chronic stage SCI requires additional enhancements in available therapeutic strategies. Herein, we report on a combination treatment for SCI using epSPCs and a pH-responsive polymer-curcumin conjugate. The incorporation of curcumin in a pH-responsive polymeric carrier mainchain, a polyacetal (PA), enhances blood bioavailability, stability, and provides a means for highly localized delivery. We find that PA-curcumin enhances neuroprotection, increases axonal growth, and can improve functional recovery in acute SCI. However, when combined with epSPCs, PA-curcumin also enhances functional recovery in a rodent model of chronic SCI. This suggests that combination therapy may be an exciting new therapeutic option for the treatment of chronic SCI in humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. SU-E-T-785: Using Systems Engineering to Design HDR Skin Treatment Operation for Small Lesions to Enhance Patient Safety

    International Nuclear Information System (INIS)

    Saw, C; Baikadi, M; Peters, C; Brereton, H

    2015-01-01

    Purpose: Using systems engineering to design HDR skin treatment operation for small lesions using shielded applicators to enhance patient safety. Methods: Systems engineering is an interdisciplinary field that offers formal methodologies to study, design, implement, and manage complex engineering systems as a whole over their life-cycles. The methodologies deal with human work-processes, coordination of different team, optimization, and risk management. The V-model of systems engineering emphasize two streams, the specification and the testing streams. The specification stream consists of user requirements, functional requirements, and design specifications while the testing on installation, operational, and performance specifications. In implementing system engineering to this project, the user and functional requirements are (a) HDR unit parameters be downloaded from the treatment planning system, (b) dwell times and positions be generated by treatment planning system, (c) source decay be computer calculated, (d) a double-check system of treatment parameters to comply with the NRC regulation. These requirements are intended to reduce human intervention to improve patient safety. Results: A formal investigation indicated that the user requirements can be satisfied. The treatment operation consists of using the treatment planning system to generate a pseudo plan that is adjusted for different shielded applicators to compute the dwell times. The dwell positions, channel numbers, and the dwell times are verified by the medical physicist and downloaded into the HDR unit. The decayed source strength is transferred to a spreadsheet that computes the dwell times based on the type of applicators and prescribed dose used. Prior to treatment, the source strength, dwell times, dwell positions, and channel numbers are double-checked by the radiation oncologist. No dosimetric parameters are manually calculated. Conclusion: Systems engineering provides methodologies to

  13. Pharmacological Inhibition of Protein Kinase G1 Enhances Bone Formation by Human Skeletal Stem Cells Through Activation of RhoA-Akt Signaling

    DEFF Research Database (Denmark)

    Kermani, Abbas Jafari; Siersbaek, Majken S; Chen, Li

    2015-01-01

    for several malignant and nonmalignant conditions. We screened a library of kinase inhibitors to identify small molecules that enhance bone formation by human skeletal (stromal or mesenchymal) stem cells (hMSC). We identified H-8 (known to inhibit protein kinases A, C, and G) as a potent enhancer of ex vivo......Development of novel approaches to enhance bone regeneration is needed for efficient treatment of bone defects. Protein kinases play a key role in regulation of intracellular signal transduction pathways, and pharmacological targeting of protein kinases has led to development of novel treatments...

  14. Dissecting and engineering of the TetR family regulator SACE_7301 for enhanced erythromycin production in Saccharopolyspora erythraea.

    Science.gov (United States)

    Wu, Hang; Chen, Meng; Mao, Yongrong; Li, Weiwei; Liu, Jingtao; Huang, Xunduan; Zhou, Ying; Ye, Bang-Ce; Zhang, Lixin; Weaver, David T; Zhang, Buchang

    2014-11-13

    Saccharopolyspora erythraea was extensively utilized for the industrial-scale production of erythromycin A (Er-A), a macrolide antibiotic commonly used in human medicine. Yet, S. erythraea lacks regulatory genes in the erythromycin biosynthetic gene (ery) cluster, hampering efforts to enhance Er-A production via the engineering of regulatory genes. By the chromosome gene inactivation technique based on homologous recombination with linearized DNA fragments, we have inactivated a number of candidate TetR family transcriptional regulators (TFRs) and identified one TFR (SACE_7301) positively controlling erythromycin biosynthesis in S. erythraea A226. qRT-PCR and EMSA analyses demonstrated that SACE_7301 activated the transcription of erythromycin biosynthetic gene eryAI and the resistance gene ermE by interacting with their promoter regions with low affinities, similar to BldD (SACE_2077) previously identified to regulate erythromycin biosynthesis and morphological differentiation. Therefore, we designed a strategy for overexpressing SACE_7301 with 1 to 3 extra copies under the control of PermE* in A226. Following up-regulated transcriptional expression of SACE_7301, eryAI and ermE, the SACE_7301-overexpressed strains all increased Er-A production over A226 proportional to the number of copies. Likewise, when SACE_7301 was overexpressed in an industrial S. erythraea WB strain, Er-A yields of the mutants WB/7301, WB/2×7301 and WB/3×7301 were respectively increased by 17%, 29% and 42% relative to that of WB. In a 5 L fermentor, Er-A accumulation increased to 4,230 mg/L with the highest-yield strain WB/3×7301, an approximately 27% production improvement over WB (3,322 mg/L). We have identified and characterized a TFR, SACE_7301, in S. erythraea that positively regulated erythromycin biosynthesis, and overexpression of SACE_7301 in wild-type and industrial S. erythraea strains enhanced Er-A yields. This study markedly improves our understanding of the unusual

  15. Enhanced Case Management versus Substance Abuse Treatment Alone among Substance Abusers with Depression

    Science.gov (United States)

    Striley, Catherine W.; Nattala, Prasanthi; Ben Abdallah, Arbi; Dennis, Michael L.; Cottler, Linda B.

    2013-01-01

    This pilot study evaluated the effectiveness of enhanced case management for substance abusers with comorbid major depression, which was an integrated approach to care. One hundred and 20 participants admitted to drug treatment who also met Computerized Diagnostic Interview Schedule criteria for major depression at baseline were randomized to…

  16. Enhancement of discharge performance of Li/CF x cell by thermal treatment of CF x cathode material

    Science.gov (United States)

    Zhang, Sheng S.; Foster, Donald; Read, Jeffrey

    In this work we demonstrate that the thermal treatment of CF x cathode material just below the decomposition temperature can enhance discharge performance of Li/CF x cells. The performance enhancement becomes more effective when heating a mixture of CF x and citric acid (CA) since CA serves as an extra carbon source. Discharge experiments show that the thermal treatment not only reduces initial voltage delay, but also raises discharge voltage. Whereas the measurement of powder impedance indicates the thermal treatment does not increase electronic conductivity of CF x material. Based on these facts, we propose that the thermal treatment results in a limited decomposition of CF x, which yields a subfluorinated carbon (CF x- δ), instead of a highly conductive carbon. In the case of CF x/AC mixture, the AC provides extra carbon that reacts with F 2 and fluorocarbon radicals generated by the thermal decomposition of CF x to form subfluorinated carbon. The process of thermal treatment is studied by thermogravimetric analysis and X-ray diffraction, and the effect of treatment conditions such as heating temperature, heating time and CF x/CA ratio on the discharge performance of CF x cathode is discussed. As an example, a Li/CF x cell using CF x treated with CA at 500 °C under nitrogen for 2 h achieved theretical specific capacity when being discharged at C/5. Impedance analysis indicates that the enhanced performance is attributed to a significant reduction in the cell reaction resistance.

  17. Nurses’ Roles and Experiences with Enhancing Adherence to Tuberculosis Treatment among Patients in Burundi: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Marie Carlsson

    2014-01-01

    Full Text Available Background. In TB control, poor treatment adherence is a major cause of relapse and drug resistance. Nurses have a critical role in supporting patients in TB treatment process. Yet, very little research has been done to inform policymakers and practitioners on nurses’ experiences of treatment adherence among patients with TB. Aim. To describe nurses’ experiences of supporting treatment adherence among patients with tuberculosis in Burundi. Method. The study adopted qualitative approach with a descriptive design. A purposive sampling was performed. Eight nurses were selected from two TB treatment centers in Burundi. Content analysis was used to analyze the data. Result. According to the nurses, most patients complete their treatment. Educating patients, providing the medication, observing and following up treatment, and communicating with the patients were the key tasks by nurses to support adherence. Causes for interruption were medication-related difficulties, poverty, and patients’ indiscipline. Treatment adherence could also be affected by patients’ and nurses’ feelings. Providing transportation and meals could enhance treatment compliance. Conclusion. Nurses are critical resources to TB treatment success. In a poverty stricken setting, nurses’ work could be facilitated and adherence further could be enhanced if socioeconomic problems (transportation and nutritional support were alleviated.

  18. A G-protein β subunit, AGB1, negatively regulates the ABA response and drought tolerance by down-regulating AtMPK6-related pathway in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Dong-bei Xu

    Full Text Available Heterotrimeric G-proteins are versatile regulators involved in diverse cellular processes in eukaryotes. In plants, the function of G-proteins is primarily associated with ABA signaling. However, the downstream effectors and the molecular mechanisms in the ABA pathway remain largely unknown. In this study, an AGB1 mutant (agb1-2 was found to show enhanced drought tolerance, indicating that AGB1 might negatively regulate drought tolerance in Arabidopsis. Data showed that AGB1 interacted with protein kinase AtMPK6 that was previously shown to phosphorylate AtVIP1, a transcription factor responding to ABA signaling. Our study found that transcript levels of three ABA responsive genes, AtMPK6, AtVIP1 and AtMYB44 (downstream gene of AtVIP1, were significantly up-regulated in agb1-2 lines after ABA or drought treatments. Other ABA-responsive and drought-inducible genes, such as RD29A (downstream gene of AtMYB44, were also up-regulated in agb1-2 lines. Furthermore, overexpression of AtVIP1 resulted in hypersensitivity to ABA at seed germination and seedling stages, and significantly enhanced drought tolerance in transgenic plants. These results suggest that AGB1 was involved in the ABA signaling pathway and drought tolerance in Arabidopsis through down-regulating the AtMPK6, AtVIP1 and AtMYB44 cascade.

  19. Brief Emotion Regulation Training Facilitates Arousal Control During Sexual Stimuli.

    Science.gov (United States)

    van Overveld, Mark; Borg, Charmaine

    2015-01-01

    Disgust, a negative emotion which evokes strong behavioral avoidance tendencies, has been associated with sexual dysfunction. Recently, it was postulated that healthy sexual functioning requires a balance between excitatory (increased sexual arousal) and inhibitory processes (lowered disgust levels). This suggests that amplification of excitatory processes (like sexual arousal) could be a valuable addition to treatments for affect-based sexual dysfunctions. The major aim of the present study was to establish whether up-regulation could effectively enhance arousal levels during sexual stimuli, and whether such a training would simultaneously reduce disgust. Students (N = 163, mean age = 20.73 years, SD = 2.35) were trained in up-regulation of affect using either a sexual arousal film (i.e., female-friendly erotic movie) or a threat arousal film clip (i.e., horror movie), while control groups viewed the films without training instructions. Following this, participants viewed and rated state emotions during a series of pictures (sexual, disgusting, or neutral). Up-regulation of mood successfully enhanced general arousal in both groups, yet these arousal levels were not paralleled by reductions in disgust. Overall, the findings indicate that emotion regulation training by maximizing positive affect and general arousal could be an effective instrument to facilitate affect-related disturbances in sexual dysfunctions.

  20. Metformin Causes G1-Phase Arrest via Down-Regulation of MiR-221 and Enhances TRAIL Sensitivity through DR5 Up-Regulation in Pancreatic Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Ryoichi Tanaka

    Full Text Available Although many chemotherapeutic strategies against cancer have been developed, pancreatic cancer is one of the most aggressive and intractable types of malignancies. Therefore, new strategies and anti-cancer agents are necessary to treat this disease. Metformin is a widely used drug for type-2 diabetes, and is also known as a promising candidate anti-cancer agent from recent studies in vitro and in vivo. However, the mechanisms of metformin's anti-cancer effects have not been elucidated. We demonstrated that metformin suppressed the expression of miR-221, one of the most well-known oncogenic microRNAs, in human pancreatic cancer PANC-1 cells. Moreover, we showed that the down-regulation of miR-221 by metformin caused G1-phase arrest via the up-regulation of p27, one of the direct targets of miR-221. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL is also a promising agent for cancer treatment. While recent studies showed that treatment with only TRAIL was not effective against pancreatic cancer cells, the present data showed that metformin sensitized p53-mutated pancreatic cancer cells to TRAIL. Metformin induced the expressions of death receptor 5 (DR5, a receptor for TRAIL, and Bim with a pro-apoptotic function in the downstream of TRAIL-DR5 pathway. We suggest that the up-regulation of these proteins may contribute to sensitization of TRAIL-induced apoptosis. The combination therapy of metformin and TRAIL could therefore be effective in the treatment of pancreatic cancer.

  1. Regulation of GAD65 expression by SMAR1 and p53 upon Streptozotocin treatment

    Directory of Open Access Journals (Sweden)

    Singh Sandeep

    2012-09-01

    Full Text Available Abstract Background GAD65 (Glutamic acid decarboxylase 65 KDa isoform is one of the most important auto-antigens involved in Type 1 diabetes induction. Although it serves as one of the first injury markers of β-islets, the mechanisms governing GAD65 expression remain poorly understood. Since the regulation of GAD65 is crucial for the proper functioning of insulin secreting cells, we investigated the stress induced regulation of GAD65 transcription. Results The present study shows that SMAR1 regulates GAD65 expression at the transcription level. Using a novel protein-DNA pull-down assay, we show that SMAR1 binding is very specific to GAD65 promoter but not to the other isoform, GAD67. We show that Streptozotocin (STZ mediated DNA damage leads to upregulation of SMAR1 and p53 expression, resulting in elevated levels of GAD65, in both cell lines as well as mouse β-islets. SMAR1 and p53 act synergistically to up-regulate GAD65 expression upon STZ treatment. Conclusion We propose a novel mechanism of GAD65 regulation by synergistic activities of SMAR1 and p53.

  2. Long-term melatonin treatment reduces ovarian mass and enhances tissue antioxidant defenses during ovulation in the rat

    Directory of Open Access Journals (Sweden)

    L.G.A. Chuffa

    2011-03-01

    Full Text Available Melatonin regulates the reproductive cycle, energy metabolism and may also act as a potential antioxidant indoleamine. The present study was undertaken to investigate whether long-term melatonin treatment can induce reproductive alterations and if it can protect ovarian tissue against lipid peroxidation during ovulation. Twenty-four adult female Wistar rats, 60 days old (± 250-260 g, were randomly divided into two equal groups. The control group received 0.3 mL 0.9% NaCl + 0.04 mL 95% ethanol as vehicle, and the melatonin-treated group received vehicle + melatonin (100 µg·100 g body weight-1·day-1 both intraperitoneally daily for 60 days. All animals were killed by decapitation during the morning estrus at 4:00 am. Body weight gain and body mass index were reduced by melatonin after 10 days of treatment (P < 0.05. Also, a marked loss of appetite was observed with a fall in food intake, energy intake (melatonin 51.41 ± 1.28 vs control 57.35 ± 1.34 kcal/day and glucose levels (melatonin 80.3 ± 4.49 vs control 103.5 ± 5.47 mg/dL towards the end of treatment. Melatonin itself and changes in energy balance promoted reductions in ovarian mass (20.2% and estrous cycle remained extensive (26.7%, arresting at diestrus. Regarding the oxidative profile, lipid hydroperoxide levels decreased after melatonin treatment (6.9% and total antioxidant substances were enhanced within the ovaries (23.9%. Additionally, melatonin increased superoxide dismutase (21.3%, catalase (23.6% and glutathione-reductase (14.8% activities and the reducing power (10.2% GSH/GSSG ratio. We suggest that melatonin alters ovarian mass and estrous cyclicity and protects the ovaries by increasing superoxide dismutase, catalase and glutathione-reductase activities.

  3. Cellular correlates of enhanced anxiety caused by acute treatment with the selective serotonin reuptake inhibitor fluoxetine in rats

    Directory of Open Access Journals (Sweden)

    Shilpa eRavinder

    2011-12-01

    Full Text Available Selective serotonin reuptake inhibitors (SSRIs are used extensively in the treatment of depression and anxiety disorders. The therapeutic benefits of SSRIs typically require several weeks of continuous treatment. Intriguingly, according to clinical reports, symptoms of anxiety may actually increase during the early stages of treatment although more prolonged treatment alleviates affective symptoms. Consistent with earlier studies that have used animal models to capture this paradoxical effect of SSRIs, we find that rats exhibit enhanced anxiety-like behavior on the elevated plus-maze one hour after a single injection of the SSRI fluoxetine. Next we investigated the potential neural substrates underlying the acute anxiogenic effects by analyzing the morphological and physiological impact of acute fluoxetine treatment on principal neurons of the basolateral amygdala (BLA, a brain area that plays a pivotal role in fear and anxiety. Although earlier studies have shown that behavioral or genetic perturbations that are anxiogenic for rodents also increase dendritic spine-density in the BLA, we find that a single injection of fluoxetine does not cause spinogenesis on proximal apical dendritic segments on BLA principal neurons an hour later. However, at the same time point when a single dose of fluoxetine caused enhanced anxiety, it also enhanced action potential firing in BLA neurons in ex vivo slices. Consistent with this finding, in vitro bath application of fluoxetine caused higher spiking frequency and this increase in excitability was correlated with an increase in the input resistance of these neurons. Our results suggest that enhanced excitability of amygdala neurons may contribute to the increase in anxiety-like behavior observed following acute fluoxetine treatment.

  4. FDG-PET/contrast-enhanced CT as a post-treatment tool in head and neck squamous cell carcinoma: comparison with FDG-PET/non-contrast-enhanced CT and contrast-enhanced CT

    Energy Technology Data Exchange (ETDEWEB)

    Suenaga, Yuko; Kitajima, Kazuhiro; Sugimura, Kazuro [Kobe University Graduate School of Medicine, Department of Radiology, Kobe (Japan); Ishihara, Takeaki; Sasaki, Ryohei [Kobe University Graduate, School of Medicine, Department of Radiology, Division of Radiation Oncology, Kobe (Japan); Otsuki, Naoki; Nibu, Ken-ichi [Kobe University Graduate, School of Medicine, Department of Otolaryngology-Head and Neck Surgery, Kobe (Japan); Minamikawa, Tsutomu [Kobe University Graduate School of Medicine, Department of Oral and Maxillofacial Surgery, Kobe (Japan); Kiyota, Naomi [Kobe University Hospital, Department of Medical Oncology and Hematology, Kobe (Japan)

    2016-04-15

    To evaluate the accuracy of PET/CT using {sup 18}F-fluorodeoxyglucose (FDG) with IV contrast for suspected recurrent head and neck squamous cell carcinoma (HNSCC). One hundred and seventy patients previously treated for HNSCC underwent PET/CT, consisting of non-contrast-enhanced and contrast-enhanced CT, to investigate suspected recurrence. Diagnostic performance of PET/contrast-enhanced CT (PET/ceCT), PET/non-contrast-enhanced CT (PET/ncCT) and contrast-enhanced CT (ceCT) for local or regional recurrence, distant metastasis, overall recurrence and second primary cancer was evaluated. The reference standard included histopathology, treatment change and imaging follow-up. The patient-based areas under the receiver operating characteristic curves (AUC) for ceCT, PET/ncCT and PET/ceCT were 0.82, 0.96 and 0.98 for local recurrence, 0.73, 0.86 and 0.86 for regional recurrence, 0.86, 0.91 and 0.92 for distant metastasis, 0.72, 0.86 and 0.87 for overall recurrence, and 0.86, 0.89 and 0.91 for a second primary cancer. Both PET/ceCT and PET/ncCT statistically showed larger AUC than ceCT for recurrence, and the difference between PET/ceCT and PET/ncCT for local recurrence reached a significant level (p = 0.039). The accuracy of PET/ceCT for diagnosing overall recurrence was high, irrespective of the time interval after the last treatment (83.3-94.1 %). FDG-PET/CT was a more accurate HNSCC restaging tool than ceCT. The added value of ceCT at FDG-PET/CT is minimal. (orig.)

  5. Genome-scale regression analysis reveals a linear relationship for promoters and enhancers after combinatorial drug treatment

    KAUST Repository

    Rapakoulia, Trisevgeni

    2017-08-09

    Motivation: Drug combination therapy for treatment of cancers and other multifactorial diseases has the potential of increasing the therapeutic effect, while reducing the likelihood of drug resistance. In order to reduce time and cost spent in comprehensive screens, methods are needed which can model additive effects of possible drug combinations. Results: We here show that the transcriptional response to combinatorial drug treatment at promoters, as measured by single molecule CAGE technology, is accurately described by a linear combination of the responses of the individual drugs at a genome wide scale. We also find that the same linear relationship holds for transcription at enhancer elements. We conclude that the described approach is promising for eliciting the transcriptional response to multidrug treatment at promoters and enhancers in an unbiased genome wide way, which may minimize the need for exhaustive combinatorial screens.

  6. l-Methionine anti-biofilm activity against Pseudomonas aeruginosa is enhanced by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor.

    Science.gov (United States)

    Cho, Do-Yeon; Lim, Dong-Jin; Mackey, Calvin; Weeks, Christopher G; Peña Garcia, Jaime A; Skinner, Daniel; Grayson, Jessica W; Hill, Harrison S; Alexander, David K; Zhang, Shaoyan; Woodworth, Bradford A

    2018-05-01

    Biofilms may contribute to refractory chronic rhinosinusitis (CRS), as they lead to antibiotic resistance and failure of effective clinical treatment. l-Methionine is an amino acid with reported biofilm-inhibiting properties. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator with mild antimicrobial activity via inhibition of bacterial DNA gyrase and topoisomerase IV. The objective of this study was to evaluate whether co-treatment with ivacaftor and l-methionine can reduce the formation of Pseudomonas aeruginosa biofilms. P aeruginosa (PAO-1 strain) biofilms were studied in the presence of l-methionine and/or ivacaftor. For static biofilm assays, PAO-1 was cultured in a 48-well plate for 72 hours with stepwise combinations of these agents. Relative biofilm inhibitions were measured according to optical density of crystal violet stain at 590 nm. Live/dead assays (BacTiter-Glo™ assay, Promega) were imaged with laser scanning confocal microscopy. An agar diffusion test was used to confirm antibacterial effects of the drugs. l-Methionine (0.5 μM) significantly reduced PAO-1 biofilm mass (32.4 ± 18.0%; n = 4; p l-methionine (two-way analysis of variane, p = 0.0415) compared with corresponding concentrations of l-methionine alone. Ivacaftor enhanced the anti-biofilm activity of l-methionine against the PAO-1 strain of P aeruginosa. Further studies evaluating the efficacy of ivacaftor/l-methionine combinations for P aeruginosa sinusitis are planned. © 2018 ARS-AAOA, LLC.

  7. Enhancement of porous silicon photoluminescence property by lithium chloride treatment

    Science.gov (United States)

    Azaiez, Khawla; Zaghouani, Rabia Benabderrahmane; Khamlich, Saleh; Meddeb, Hosny; Dimassi, Wissem

    2018-05-01

    Porous silicon (PS) decorated by several nanostructured metal elements has still aroused interests as promising composites in many industrial applications. With the focus mainly on the synthesis, the aspect of stability against optical irradiation of such materials has so far not been thoroughly addressed. This work focuses primarily on the influence of lithium chloride solution (LiCl) treatment on the physical properties of PS. Variations in the structural and optoelectronic properties of PS were observed after immersion in (LiCl), as revealed by the obtained analyses. Moreover, enhanced photoluminescence (PL) property of the PS after passivation by lithium particles was clearly shown, and their presence on the surface of the microporous silicon was confirmed by FTIR spectroscopy and atomic force microscopy. An improvement of the minority carrier lifetime was also obtained, which was attributed to the decrease of the surface recombination velocity after LiCl treatment.

  8. How effective is aeration with vortex flow regulators? Pilot scale experiments

    Science.gov (United States)

    Wójtowicz, Patryk; Szlachta, Małgorzata

    2017-11-01

    Vortex flow regulators (VFR) are used in urban drainage systems as a replacement for traditional flow throttling devices. Vortex regulators are not only very efficient energy dissipators but also atomizers which are beneficial for sewer aeration. A deficit of dissolved oxygen can be a problem in both natural waters and sewerage. Hydrodynamic flow regulators can boost oxygen concentration preventing putrefaction and improving treatment of stormwater and wastewater. We were first to investigate the aeration efficiency of semi-commercial scale cylindrical vortex flow regulators to determine the potential of their application in environmental engineering and to propose modification to enhance the aeration capacity of basic designs. Different device geometries and arrangements of active outlets for both single and double discharge vortex regulators were tested in a recirculating system. In this study, we present a concise review of the current state of our extensive research on the aeration efficiency of vortex flow regulators and their application in sewerage systems.

  9. Gold nanoparticles regulate the blimp1/pax5 pathway and enhance antibody secretion in B-cells

    International Nuclear Information System (INIS)

    Lee, Chia-Hui; Syu, Shih-Han; Steven Huang, G; Chen, Yu-Shiun; Chen, Wen Liang; Hussain, Saber M; Aleksandrovich Onischuk, Andrei

    2014-01-01

    Nanoparticles are potential threats to human health and the environment; however, their medical applications as drug carriers targeting cancer cells bring hope to contemporary cancer therapy. As a model drug carrier, gold nanoparticles (GNPs) have been investigated extensively for in vivo toxicity. The effect of GNPs on the immune system, however, has rarely been examined. Antibody-secreting cells were treated with GNPs with diameters ranging from 2 to 50 nm. The GNPs enhanced IgG secretion in a size-dependent manner, with a peak of efficacy at 10 nm. The immune-stimulatory effect reached a maximum at 12 h after treatment but returned to control levels 24 h after treatment. This enhancing effect was validated ex vivo using B-cells isolated from mouse spleen. Evidence from RT-PCR and western blot experiments indicates that GNP-treatment upregulated B-lymphocyte-induced maturation protein 1 (blimp1) and downregulated paired box 5 (pax5). Immunostaining for blimp1 and pax5 in B-cells confirmed that the GNPs stimulated IgG secretion through the blimp1/pax5 pathway. The immunization of mice using peptide-conjugated GNPs indicated that the GNPs were capable of enhancing humoral immunity in a size-dependent manner. This effect was consistent with the bio-distribution of the GNPs in mouse spleen. In conclusion, in vitro, ex vivo, and in vivo evidence supports our hypothesis that GNPs enhance humoral immunity in mouse. The effect on the immune system should be taken into account if nanoparticles are used as carriers for drug delivery. In addition to their toxicity, the immune-stimulatory activity of nanoparticles could play an important role in human health and could have an environmental impact. (paper)

  10. Transcriptome alteration in a rice introgression line with enhanced alkali tolerance.

    Science.gov (United States)

    Zhang, Yunhong; Lin, Xiuyun; Ou, Xiufang; Hu, Lanjuan; Wang, Jinming; Yang, Chunwu; Wang, Shucai; Liu, Bao

    2013-07-01

    Alkali stress inhibits plant growth and development and thus limits crop productivity. To investigate the possible genetic basis of alkali tolerance in rice, we generated an introgressed rice line (K83) with significantly enhanced tolerance to alkali stress compared to its recipient parental cultivar (Jijing88). By using microarray analysis, we examined the global gene expression profiles of K83 and Jijing88, and found that more than 1200 genes were constitutively and differentially expressed in K83 in comparison to Jijing88 with 572 genes up- and 654 down-regulated. Upon alkali treatment, a total of 347 genes were found up- and 156 down-regulated in K83 compared to 591 and 187, respectively, in Jijing88. Among the up-regulated genes in both K83 and Jijing88, only 34 were constitutively up-regulated in K83, suggesting that both the constitutive differentially expressed genes in K83 and those induced by alkali treatment are most likely responsible for enhanced alkali tolerance. A gene ontology analysis based on all annotated, differentially expressed genes revealed that genes with expression alterations were enriched in pathways involved in metabolic processes, catalytic activity, and transport and transcription factor activities, suggesting that these pathways are associated with alkali stress tolerance in rice. Our results illuminated the novel genetic aspects of alkali tolerance in rice and established a repertory of potential target genes for biotechnological manipulations that can be used to generate alkali-tolerant rice cultivars. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  11. Enhancing Electrochemical Performance of Graphene Fiber-Based Supercapacitors by Plasma Treatment.

    Science.gov (United States)

    Meng, Jie; Nie, Wenqi; Zhang, Kun; Xu, Fujun; Ding, Xin; Wang, Shiren; Qiu, Yiping

    2018-04-25

    Graphene fiber-based supercapacitors (GFSCs) hold high power density, fast charge-discharge rate, ultralong cycling life, exceptional mechanical/electrical properties, and safe operation conditions, making them very promising to power small wearable electronics. However, the electrochemical performance is still limited by the severe stacking of graphene sheets, hydrophobicity of graphene fibers, and complex preparation process. In this work, we develop a facile but robust strategy to easily enhance electrochemical properties of all-solid-state GFSCs by simple plasma treatment. We find that 1 min plasma treatment under an ambient condition results in 33.1% enhancement of areal specific capacitance (36.25 mF/cm 2 ) in comparison to the as-prepared GFSC. The energy density reaches 0.80 μW h/cm 2 in polyvinyl alcohol/H 2 SO 4 gel electrolyte and 18.12 μW h/cm 2 in poly(vinylidene difluoride)/ethyl-3-methylimidazolium tetrafluoroborate electrolyte, which are 22 times of that of as-prepared ones. The plasma-treated GFSCs also exhibit ultrahigh rate capability (69.13% for 40 s plasma-treated ones) and superior cycle stability (96.14% capacitance retention after 20 000 cycles for 1 min plasma-treated ones). This plasma strategy can be extended to mass-manufacture high-performance carbonaceous fiber-based supercapacitors, such as graphene and carbon nanotube-based ones.

  12. Metabolic Enhancer Piracetam Attenuates the Translocation of Mitochondrion-Specific Proteins of Caspase-Independent Pathway, Poly [ADP-Ribose] Polymerase 1 Up-regulation and Oxidative DNA Fragmentation.

    Science.gov (United States)

    Verma, Dinesh Kumar; Gupta, Sonam; Biswas, Joyshree; Joshi, Neeraj; Sivarama Raju, K; Wahajuddin, Mu; Singh, Sarika

    2018-03-12

    Piracetam, a nootropic drug, has been clinically used for decades; however, its mechanism of action still remains enigmatic. The present study was undertaken to evaluate the role of mitochondrion-specific factors of caspase-independent pathway like apoptotic-inducing factor (AIF) and endonuclease-G (endo-G) in piracetam-induced neuroprotection. N2A cells treated with lipopolysaccharide (LPS) exhibited significant cytotoxicity, impaired mitochondrial activity, and reactive oxygen species generation which was significantly attenuated with piracetam co-treatment. Cells co-treated with LPS and piracetam exhibited significant uptake of piracetam in comparison to only piracetam-treated cells as estimated by liquid chromatography-mass spectrometry (LC-MSMS). LPS treatment caused significant translocation of AIF and endonuclease-G in neuronal N2A cells which were significantly attenuated with piracetam co-treatment. Significant over-expression of proinflammatory cytokines was also observed after treatment of LPS to cells which was inhibited with piracetam co-treatment demonstrating its anti-inflammatory property. LPS-treated cells exhibited significant oxidative DNA fragmentation and poly [ADP-ribose] polymerase-1 (PARP-1) up-regulation in nucleus, both of which were attenuated with piracetam treatment. Antioxidant melatonin but not z-VAD offered the inhibited LPS-induced DNA fragmentation indicating the involvement of oxidative DNA fragmentation. Further, we did not observe the altered caspase-3 level after LPS treatment initially while at a later time point, significantly augmented level of caspase-3 was observed which was not inhibited with piracetam treatment. In total, our findings indicate the interference of piracetam in mitochondrion-mediated caspase-independent pathway, as well as its anti-inflammatory and antioxidative properties. Graphical Abstract Graphical abstract indicating the novel interference of metabolic enhancer piracetam (P) in neuronal death

  13. Dual-directional regulation of drug permeating amount by combining the technique of ion-pair complexation with chemical enhancers for the synchronous permeation of indapamide and bisoprolol in their compound patch through rabbit skin.

    Science.gov (United States)

    Song, Wenting; Cun, Dongmei; Quan, Peng; Liu, Nannan; Chen, Yang; Cui, Hongxia; Xiang, Rongwu; Fang, Liang

    2015-04-01

    To achieve the synchronous skin permeation of indapamide (IND) and bisoprolol (BSP) in their compound patch, the techniques of ion-pair complexation and chemical enhancers were combined to dual-directionally regulate drug permeating amounts. Ion-pair complexes of BSP and various organic acids were formed by the technique of ion-pair complexation. Among the complexes formed, bisoprolol tartrate (BSP.T) down-regulated the permeating amount of BSP to the same extent as that of IND. Then, to simultaneously up-regulate the amounts of the two drugs, an enhancer combination of 15.8% Span80 (SP), 6.0% Azone (AZ) and 2.2% N-methyl pyrrolidone (NMP) was obtained by central composite design and exhibited an outstanding and simultaneous enhancement on IND and BSP with enhancing ratio (ER) of 4.52 and 3.49, respectively. The effect of the dual-directional regulation was evaluated by in vitro permeation experiments and in vivo pharmacokinetic studies. For IND and BSP, their observed permeation profiles were comparable and their MAT (mean absorption time) showed no significant difference, which both demonstrated these two drugs achieved the synchronous skin permeation in their compound patch by the dual-directional regulation strategy of combining the technique of ion-pair complexation with chemical enhancers. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. CCAAT/Enhancer Binding Protein β Regulates Expression of Indian Hedgehog during Chondrocytes Differentiation

    Science.gov (United States)

    Ushijima, Takahiro; Okazaki, Ken; Tsushima, Hidetoshi; Ishihara, Kohei; Doi, Toshio; Iwamoto, Yukihide

    2014-01-01

    Background CCAAT/enhancer binding protein β (C/EBPβ) is a transcription factor that promotes hypertrophic differentiation of chondrocytes. Indian hedgehog (Ihh) also stimulates the hypertrophic transition of chondrocytes. Furthermore, runt-related transcription factor-2 (RUNX2) was reported to regulate chondrocyte maturation during skeletal development and to directly regulate transcriptional activity of Ihh. In this study, we investigated whether the interaction of C/EBPβ and RUNX2 regulates the expression of Ihh during chondrocyte differentiation. Methodology/Results Immunohistochemistry of embryonic growth plate revealed that both C/EBPβ and Ihh were strongly expressed in pre-hypertrophic and hypertrophic chondrocytes. Overexpression of C/EBPβ by adenovirus vector in ATDC5 cells caused marked stimulation of Ihh and Runx2. Conversely, knockdown of C/EBPβ by lentivirus expressing shRNA significantly repressed Ihh and Runx2 in ATDC5 cells. A reporter assay revealed that C/EBPβ stimulated transcriptional activity of Ihh. Deletion and mutation analysis showed that the C/EBPβ responsive element was located between −214 and −210 bp in the Ihh promoter. An electrophoretic mobility shift assay (EMSA) and a chromatin immunoprecipitation (ChIP) assay also revealed the direct binding of C/EBPβ to this region. Moreover, reporter assays demonstrated that RUNX2 failed to stimulate the transcriptional activity of the Ihh promoter harboring a mutation at the C/EBPβ binding site. EMSA and ChIP assays showed that RUNX2 interacted to this element with C/EBPβ. Immunoprecipitation revealed that RUNX2 and C/EBPβ formed heterodimer complex with each other in the nuclei of chondrocytes. These data suggested that the C/EBPβ binding element is also important for RUNX2 to regulate the expression of Ihh. Ex vivo organ culture of mouse limbs transfected with C/EBPβ showed that the expression of Ihh and RUNX2 was increased upon ectopic C/EBPβ expression. Conclusions C

  15. CCAAT/enhancer binding protein β regulates expression of Indian hedgehog during chondrocytes differentiation.

    Directory of Open Access Journals (Sweden)

    Takahiro Ushijima

    Full Text Available CCAAT/enhancer binding protein β (C/EBPβ is a transcription factor that promotes hypertrophic differentiation of chondrocytes. Indian hedgehog (Ihh also stimulates the hypertrophic transition of chondrocytes. Furthermore, runt-related transcription factor-2 (RUNX2 was reported to regulate chondrocyte maturation during skeletal development and to directly regulate transcriptional activity of Ihh. In this study, we investigated whether the interaction of C/EBPβ and RUNX2 regulates the expression of Ihh during chondrocyte differentiation.Immunohistochemistry of embryonic growth plate revealed that both C/EBPβ and Ihh were strongly expressed in pre-hypertrophic and hypertrophic chondrocytes. Overexpression of C/EBPβ by adenovirus vector in ATDC5 cells caused marked stimulation of Ihh and Runx2. Conversely, knockdown of C/EBPβ by lentivirus expressing shRNA significantly repressed Ihh and Runx2 in ATDC5 cells. A reporter assay revealed that C/EBPβ stimulated transcriptional activity of Ihh. Deletion and mutation analysis showed that the C/EBPβ responsive element was located between -214 and -210 bp in the Ihh promoter. An electrophoretic mobility shift assay (EMSA and a chromatin immunoprecipitation (ChIP assay also revealed the direct binding of C/EBPβ to this region. Moreover, reporter assays demonstrated that RUNX2 failed to stimulate the transcriptional activity of the Ihh promoter harboring a mutation at the C/EBPβ binding site. EMSA and ChIP assays showed that RUNX2 interacted to this element with C/EBPβ. Immunoprecipitation revealed that RUNX2 and C/EBPβ formed heterodimer complex with each other in the nuclei of chondrocytes. These data suggested that the C/EBPβ binding element is also important for RUNX2 to regulate the expression of Ihh. Ex vivo organ culture of mouse limbs transfected with C/EBPβ showed that the expression of Ihh and RUNX2 was increased upon ectopic C/EBPβ expression.C/EBPβ and RUNX2 cooperatively stimulate

  16. Silvicultural treatments enhance growth rates of future crop trees in a tropical dry forest

    NARCIS (Netherlands)

    Villegas, Z.; Peña-Claros, M.; Mostacedo, B.; Alarcón, A.; Licona, J.C.; Leaño, C.; Pariona, W.; Choque, U.

    2009-01-01

    Silvicultural treatments are often needed in selectively logged tropical forest to enhance the growth rates of many commercial tree species and, consequently, for recovering a larger proportion of the initial volume harvested over the next cutting cycle. The available data in the literature suggest,

  17. Differential effect of prior heat treatment on the thermal enhancement of radiation damage in the ear of the mouse

    International Nuclear Information System (INIS)

    Law, M.P.; Ahier, R.G.

    1982-01-01

    The effect of prior heat treatment on thermal enhancement of radiodermatitis was investigated in the ear of the mouse. Ears were heated by immersion in hot water. A priming treatment of 43.5 0 C for 30 min (H) was given at various times before a second combined treatment of hypethermia at 43.5 0 C (h) given immediately before (hX) or after (Xh) a dose of X rays (X). The effect of H was measured in two ways. The heating time h, required to cause a given enhancement of radiodermatitis was estimated by fixing X and varying the duration of h. The thermal enhancement ratio, defined as the dose of X rays alone divided by the dose of X rays with heat required to cause a given reaction, was measured by fixing h and varying X. The priming treatment H reduced the skin response to hX. This effect was such that at 24 to 96 hr after H, the heating time h, had to be increased to about 1.5 times that required without prior hyperthermia. In contrast, the priming treatment had no effect on the response to Xh

  18. Regulation of the glucocorticoid receptor via a BET-dependent enhancer drives antiandrogen resistance in prostate cancer.

    Science.gov (United States)

    Shah, Neel; Wang, Ping; Wongvipat, John; Karthaus, Wouter R; Abida, Wassim; Armenia, Joshua; Rockowitz, Shira; Drier, Yotam; Bernstein, Bradley E; Long, Henry W; Freedman, Matthew L; Arora, Vivek K; Zheng, Deyou; Sawyers, Charles L

    2017-09-11

    In prostate cancer, resistance to the antiandrogen enzalutamide (Enz) can occur through bypass of androgen receptor (AR) blockade by the glucocorticoid receptor (GR). In contrast to fixed genomic alterations, here we show that GR-mediated antiandrogen resistance is adaptive and reversible due to regulation of GR expression by a tissue-specific enhancer. GR expression is silenced in prostate cancer by a combination of AR binding and EZH2-mediated repression at the GR locus, but is restored in advanced prostate cancers upon reversion of both repressive signals. Remarkably, BET bromodomain inhibition resensitizes drug-resistant tumors to Enz by selectively impairing the GR signaling axis via this enhancer. In addition to revealing an underlying molecular mechanism of GR-driven drug resistance, these data suggest that inhibitors of broadly active chromatin-readers could have utility in nuanced clinical contexts of acquired drug resistance with a more favorable therapeutic index.

  19. Analytic treatments of matter-enhanced solar-neutrino oscillations

    International Nuclear Information System (INIS)

    Haxton, W.C.

    1987-01-01

    Mikheyev and Smirnov have pointed out that flavor oscillations of solar neutrinos could be greatly enhanced. The Mikheyev-Smirnov-Wolfenstein mechanism depends on the effective electron neutrino mass that arises from charged-current scattering off solar electrons, a phenomenon first discussed by Wolfenstein. Two analytic treatments, the adiabatic approximation and Landau-Zener (LZ) approximation, have been used in studies of this mechanism. I discuss a simple extension of the LZ approximation that merges naturally with the adiabatic approximation and is free of certain troublesome pathologies that arise in the conventional treatment. In this extension the solar density is approximated as in the conventional treatment, except that the starting and ending densities are the physical ones. Results of this finite LZ approximation are compared to those from the standard LZ approximation, the adiabatic approximation, and ''exact'' numerical integrations. The new approximation is virtually exact regardless of the point of origin of the neutrino in the solar core. This approximation is used to efficiently calculate the solar-neutrino capture rates for /sup 37/Cl, /sup 71/Ga, and /sup 98/Mo. The spatial extent of the solar core, the contributions of minor neutrino species, and the effects of 8 B neutrino capture to excited nuclear states are treated with care. Limits imposed on δm 2 and sin 2 2theta/sub v/ by the nonzero /sup 37/Cl capture rate are derived by considering the expected uncertainties in standard-solar-model flux estimates. Those oscillation parameters are determined that could account for the /sup 37/Cl puzzle and yet lead to a /sup 71/Ga counting rate above the minimum astronomical value

  20. Emotion Regulation as a Transdiagnostic Feature Among Eating Disorders: Cross-sectional and Longitudinal Approach.

    Science.gov (United States)

    Mallorquí-Bagué, Núria; Vintró-Alcaraz, Cristina; Sánchez, Isabel; Riesco, Nadine; Agüera, Zaida; Granero, Roser; Jiménez-Múrcia, Susana; Menchón, José M; Treasure, Janet; Fernández-Aranda, Fernando

    2018-01-01

    Emotion regulation (ER) difficulties are observed in eating disorders (EDs). However, few studies have explored ER before and after treatment. The aims are as follows: to explore ER difficulties across ED types and a healthy control (HC) group (Study 1) and to assess pretreatment and post-treatment changes among ED types (Study 2). In Study 1, adult women with EDs (n = 438) and HC (n = 126) completed an assessment including Eating Disorders Inventory-2, Difficulties in Emotion Regulation Scale and Symptom Checklist-90-Revised. Patients in Study 2 (n = 69) were also reassessed after treatment. All ED types reported worse ER compared with HC (p eating disorder might be enhanced by targeting ER skills. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

  1. Two weeks of metformin treatment induces AMPK dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Treebak, Jonas Thue; Schjerling, Peter

    2014-01-01

    signaling. Methods: Oral doses of metformin or saline treatment were given muscle-specific kinase α2 dead AMPK mice (KD) and wild type (WT) littermates either once or chronically for 2 weeks. Soleus and Extensor Digitorum Longus (EDL) muscles were used for measurements of glucose transport and Western blot......Background: Metformin-induced activation of AMPK has been associated with enhanced glucose uptake in skeletal muscle but so far no direct causality has been examined. We hypothesized that an effect of in vivo metformin treatment on glucose uptake in mouse skeletal muscles is dependent upon AMPK...... analyzes. Results: Chronic treatment with metformin enhanced insulin-stimulated glucose uptake in soleus muscles of WT (45%, P...

  2. Genetic analysis of pathway regulation for enhancing branched-chain amino acid biosynthesis in plants

    KAUST Repository

    Chen, Hao

    2010-08-01

    The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids that play critical roles in animal growth and development. Animals cannot synthesize these amino acids and must obtain them from their diet. Plants are the ultimate source of these essential nutrients, and they synthesize BCAAs through a conserved pathway that is inhibited by its end products. This feedback inhibition has prevented scientists from engineering plants that accumulate high levels of BCAAs by simply over-expressing the respective biosynthetic genes. To identify components critical for this feedback regulation, we performed a genetic screen for Arabidopsis mutants that exhibit enhanced resistance to BCAAs. Multiple dominant allelic mutations in the VALINE-TOLERANT 1 (VAT1) gene were identified that conferred plant resistance to valine inhibition. Map-based cloning revealed that VAT1 encodes a regulatory subunit of acetohydroxy acid synthase (AHAS), the first committed enzyme in the BCAA biosynthesis pathway. The VAT1 gene is highly expressed in young, rapidly growing tissues. When reconstituted with the catalytic subunit in vitro, the vat1 mutant-containing AHAS holoenzyme exhibits increased resistance to valine. Importantly, transgenic plants expressing the mutated vat1 gene exhibit valine tolerance and accumulate higher levels of BCAAs. Our studies not only uncovered regulatory characteristics of plant AHAS, but also identified a method to enhance BCAA accumulation in crop plants that will significantly enhance the nutritional value of food and feed. © 2010 Blackwell Publishing Ltd.

  3. RNA interference for performance enhancement and detection in doping control.

    Science.gov (United States)

    Kohler, Maxie; Schänzer, Wilhelm; Thevis, Mario

    2011-10-01

    RNA interference represents a comparably new route of regulating and manipulating specific gene expression. Promising results were obtained in experimental therapies aim at the treatment of different kinds of diseases including cancer, diabetes mellitus or Dychenne muscular dystrophy. While studies on down-regulation efficiency are often performed by analyzing the regulated protein, the direct detection of small, interfering RNA molecules and antisense oligonucleotides is of great interest for the investigation of the metabolism and degradation and also for the detection of a putative misuse of these molecules in sports. Myostatin down-regulation was shown to result in increased performance and muscle growth and the regulation of several other proteins could be relevant for performance enhancement. This mini-review summarizes current approaches for the mass spectrometric analysis of siRNA and antisense oligonucleotides from biological matrices and the available data on biodistribution, metabolism, and half-life of relevant substances are discussed. Copyright © 2011 John Wiley & Sons, Ltd.

  4. He-Ne laser treatment improves the photosynthetic efficiency of wheat exposed to enhanced UV-B radiation

    International Nuclear Information System (INIS)

    Chen, Huize; Han, Rong

    2014-01-01

    The level of ultraviolet-B (UV-B) radiation on the Earth’s surface has increased due to depletion of the ozone layer. Here, we explored the effects of continuous wave He-Ne laser irradiation (632 nm, 5 mW mm –2 , 2 min d –1 ) on the physiological indexes of wheat seedlings exposed to enhanced UV-B radiation (10 KJ m –2 d –1 ) at the early growth stages. Wheat seedlings were irradiated with enhanced UV-B, He-Ne laser treatment or a combination of the two. Enhanced UV-B radiation had deleterious effects on wheat photosynthesis parameters including photosystem II (chlorophyll content, Hill reaction, chlorophyll fluorescence parameters, electron transport rate (ETR), and yield), the thylakoid (optical absorption ability, cyclic photophosphorylation, Mg 2+ -ATPase, and Ca 2+ -ATPase) and some enzymes in the dark reaction (phosphoenolpyruvate carboxylase (PEPC), carbonic anhydrase (CA), malic dehydrogenase (MDH), and chlorophyllase). These parameters were improved in UV-B-exposed wheat treated with He-Ne laser irradiation; the parameters were near control levels and the enzyme activities increased, suggesting that He-Ne laser treatment partially alleviates the injury caused by enhanced UV-B irradiation. Furthermore, the use of He-Ne laser alone had a favourable effect on seedling photosynthesis compared with the control. Therefore, He-Ne laser irradiation can enhance the adaptation capacity of crops. (paper)

  5. High Performance Enhancement-Mode AlGaN/GaN MIS-HEMT with Selective Fluorine Treatment

    Directory of Open Access Journals (Sweden)

    Chao Yang

    2015-01-01

    Full Text Available A novel enhancement-mode (E-mode Metal-Insulator-Semiconductor- (MIS- HEMT with selective fluorine ion (F− treatment is proposed and its mechanism is investigated. The HEMT features the Selective F− treatment both in the AlGaN channel region and in the thick passivation layer between the gate and drain (SFCP-MIS-HEMT. First, the F− in the passivation layer not only extends the depletion region and thus enhances the average electric field (E-field between the gate and drain by the assisted depletion effect but also reduces the E-field peak at the gate end, leading to a higher breakdown voltage (BV. Second, in the AlGaN channel region, the F− region realizes the E-mode and the region without F− maintains a high drain current (ID. Third, MIS structure suppresses the gate leakage current, increasing the gate swing voltage and the BV. Compared with a MIS-HEMT with F− treatment in whole channel (FC-MIS-HEMT, SFCP-MIS-HEMT increases the BV by 46% and the saturation drain current (ID,sat by 28%.

  6. ENHANCEMENT OF PHENOL REMOVAL EFFICIENCY IN DORA REFINERY WASTEWATER TREATMENT PLANT

    Directory of Open Access Journals (Sweden)

    Salah F. Sharif

    2013-05-01

    Full Text Available Because the sanctions imposed on Iraq by the United Nations, programmed maintenance and wearing parts replacement has not been performed according to schedules in DORA Refinery Wastewater Unit, which resulted in higher phenol content and BOD5 in effluents disposed to river. The investigations showed that two main reasons were behind this problem: Firstly, increased emissions of hydrocarbons in the complexity of refinery equipment and Secondly, the decreased efficiency of the aerators in the biological. During the last few months, phenol average concentration in the effluent, after biological treatment was found to be between 0.06-0.13 mg/L, while COD was exceeding 110 mg/L after treatment in the same period. Considerable enhancement, has been indicated recently, after the following performances: First: Recycling wastewater from some heat exchangers, and the segregation of low and high strength of wastewaters, Second: Minimizing emissions of hydrocarbons from fluid catalytic cracking and steam cracking, Third: Replacement of driving motors of the aerators in the biological treatment unit. After replacement of these units, a significant decrease in phenol concentration was obtained in purified water (0.03-0.05 mg/L and COD of 60 mg/L before the tertiary treatment. It is concluded that a better quality of effluents has been obtained after a series of emissions control and wastewater treatment unit equipment maintenance performances.

  7. Differentially expressed miRNAs after GnRH treatment and their potential roles in FSH regulation in porcine anterior pituitary cell.

    Directory of Open Access Journals (Sweden)

    Rui-Song Ye

    Full Text Available Hypothalamic gonadotropin-releasing hormone (GnRH is a major regulator of follicle-stimulating hormone (FSH secretion in gonadotrope cell in the anterior pituitary gland. microRNAs (miRNAs are small RNA molecules that control gene expression by imperfect binding to the 3'-untranslated region (3'-UTR of mRNA at the post-transcriptional level. It has been proven that miRNAs play an important role in hormone response and/or regulation. However, little is known about miRNAs in the regulation of FSH secretion. In this study, primary anterior pituitary cells were treated with 100 nM GnRH. The supernatant of pituitary cell was collected for FSH determination by enzyme-linked immunosorbent assay (ELISA at 3 hours and 6 hours post GnRH treatment respectively. Results revealed that GnRH significantly promoted FSH secretion at 3 h and 6 h post-treatment by 1.40-fold and 1.80-fold, respectively. FSHβ mRNA at 6 h post GnRH treatment significantly increased by 1.60-fold. At 6 hours, cells were collected for miRNA expression profile analysis using MiRCURY LNA Array and quantitative PCR (qPCR. Consequently, 21 up-regulated and 10 down-regulated miRNAs were identified, and qPCR verification of 10 randomly selected miRNAs showed a strong correlation with microarray results. Chromosome location analysis indicated that 8 miRNAs were mapped to chromosome 12 and 4 miRNAs to chromosome X. Target and pathway analysis showed that some miRNAs may be associated with GnRH regulation pathways. In addition, In-depth analysis indicated that 10 up-regulated and 3 down-regulated miRNAs probably target FSHβ mRNA 3'-UTR directly, including miR-361-3p, a highly conserved X-linked miRNA. Most importantly, functional experimental results showed that miR-361-3p was involved in FSH secretion regulation, and up-regulated miR-361-3p expression inhibited FSH secretion, while down-regulated miR-361-3p expression promoted FSH secretion in pig pituitary cell model. These differentially

  8. Enhancing the mechanical properties of electrospun polyester mats by heat treatment

    Directory of Open Access Journals (Sweden)

    M. Kancheva

    2015-01-01

    Full Text Available Microfibrous materials with a targeted design based on poly(L-lactic acid (PLA and poly(ε-caprolactone (PCL were prepared by electrospinning and by combining electrospinning and electrospraying. Several approaches were used: (i electrospinning of a common solution of the two polymers, (ii simultaneous electrospinning of two separate solutions of PLA and PCL, (iii electrospinning of PLA solution in conjunction with electrospraying of PCL solution, and (iv alternating layer-by-layer deposition by electrospinning of separate PLA and PCL solutions. The mats were heated at the melting temperature of PCL (60°", thus achieving melting of PCL fibers/particles and thermal sealing of the fibers. The mats subjected to thermal treatment were characterized by greater mean fiber diameters and reduced values of the water contact angle compared to the pristine mats. Heat treatment of the mats affected their thermal stability and led to an increase in the crystallinity degree of PLA incorporated in the mats, whereas that of PCL was reduced. All mats were characterized by enhanced mechanical properties after thermal treatment as compared to the non-treated fibrous materials.

  9. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Sandra C. [Translational Sciences - Translational Medicine, Novartis Institutes for Biomedical Research, Inc., 220 Massachusetts Avenue, Cambridge, MA 02139 (United States); Chau, Mary D.L.; Yang, Qing [Cardiovascular and Metabolism Disease Area, Novartis Institutes for Biomedical Research, Inc., 100 Technology Square, Cambridge, MA 02139 (United States); Gauthier, Marie-Soleil [Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02140 (United States); Clairmont, Kevin B.; Wu, Zhidan; Gromada, Jesper [Cardiovascular and Metabolism Disease Area, Novartis Institutes for Biomedical Research, Inc., 100 Technology Square, Cambridge, MA 02139 (United States); Dole, William P., E-mail: bill.dole@novartis.com [Translational Sciences - Translational Medicine, Novartis Institutes for Biomedical Research, Inc., 220 Massachusetts Avenue, Cambridge, MA 02139 (United States)

    2011-07-08

    Highlights: {yields} Treatment of differentiated human adipocytes with atrial natriuretic peptide (ANP) increased lipolysis and oxygen consumption by activating AMP-activated protein kinase (AMPK). {yields} ANP stimulated lipid mobilization by selective activation of the alpha2 subunit of AMPK and increased energy utilization through activation of both the alpha1 and alpha2 subunits of AMPK. {yields} ANP enhanced adipocyte mitochondrial oxidative capacity as evidenced by induction of oxidative mitochondrial genes and increase in oxygen consumption. {yields} Exposure of human adipocytes to fatty acids and (TNF{alpha}) induced insulin resistance and decreased expression of mitochondrial genes which was restored to normal by ANP. -- Abstract: Atrial natriuretic peptide (ANP) has been shown to regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation. ANP exerts a potent lipolytic effect via cGMP-dependent protein kinase (cGK)-I mediated-stimulation of AMP-activated protein kinase (AMPK). Activation of the ANP/cGK signaling cascade also promotes muscle mitochondrial biogenesis and fat oxidation. Here we demonstrate that ANP regulates lipid metabolism and oxygen utilization in differentiated human adipocytes by activating the alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, both of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be mediated by the alpha2 subunit of AMPK as introduction of dominant-negative alpha2 subunit of AMPK attenuated ANP effects on lipolysis. ANP-induced activation of AMPK enhanced mitochondrial oxidative capacity as evidenced by a two fold increase in oxygen consumption and induction of mitochondrial genes, including carnitine palmitoyltransferase 1A (CPT1a) by 1.4-fold, cytochrome C (CytC) by 1.3-fold, and

  10. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK

    International Nuclear Information System (INIS)

    Souza, Sandra C.; Chau, Mary D.L.; Yang, Qing; Gauthier, Marie-Soleil; Clairmont, Kevin B.; Wu, Zhidan; Gromada, Jesper; Dole, William P.

    2011-01-01

    Highlights: → Treatment of differentiated human adipocytes with atrial natriuretic peptide (ANP) increased lipolysis and oxygen consumption by activating AMP-activated protein kinase (AMPK). → ANP stimulated lipid mobilization by selective activation of the alpha2 subunit of AMPK and increased energy utilization through activation of both the alpha1 and alpha2 subunits of AMPK. → ANP enhanced adipocyte mitochondrial oxidative capacity as evidenced by induction of oxidative mitochondrial genes and increase in oxygen consumption. → Exposure of human adipocytes to fatty acids and (TNFα) induced insulin resistance and decreased expression of mitochondrial genes which was restored to normal by ANP. -- Abstract: Atrial natriuretic peptide (ANP) has been shown to regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation. ANP exerts a potent lipolytic effect via cGMP-dependent protein kinase (cGK)-I mediated-stimulation of AMP-activated protein kinase (AMPK). Activation of the ANP/cGK signaling cascade also promotes muscle mitochondrial biogenesis and fat oxidation. Here we demonstrate that ANP regulates lipid metabolism and oxygen utilization in differentiated human adipocytes by activating the alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, both of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be mediated by the alpha2 subunit of AMPK as introduction of dominant-negative alpha2 subunit of AMPK attenuated ANP effects on lipolysis. ANP-induced activation of AMPK enhanced mitochondrial oxidative capacity as evidenced by a two fold increase in oxygen consumption and induction of mitochondrial genes, including carnitine palmitoyltransferase 1A (CPT1a) by 1.4-fold, cytochrome C (CytC) by 1.3-fold, and peroxisome proliferator

  11. Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

    Directory of Open Access Journals (Sweden)

    Sayeda Yasmin-Karim

    2018-04-01

    Full Text Available Over the years, many in vitro and in vivo studies have shown the antineoplastic effects of cannabinoids (CBDs, with reports advocating for investigations of combination therapy approaches that could better leverage these effects in clinical translation. This study explores the potential of combination approaches employing CBDs with radiotherapy (RT or smart biomaterials toward enhancing therapeutic efficacy during treatment of pancreatic and lung cancers. In in vitro studies, clonogenic assay results showed greater effective tumor cell killing, when combining CBDs and RT. Meanwhile, in vivo study results revealed major increase in survival when employing smart biomaterials for sustained delivery of CBDs to tumor cells. The significance of these findings, considerations for further research, and viable roadmap to clinical translation are discussed.

  12. Hypocretin-1 receptors regulate the reinforcing and reward-enhancing effects of cocaine: Pharmacological and behavioral genetics evidence

    Directory of Open Access Journals (Sweden)

    Jonathan eHollander

    2012-07-01

    Full Text Available Considerable evidence suggests that transmission at hypocretin-1 (orexin-1 receptors (Hcrt-R1 plays an important role in the reinstatement of extinguished cocaine-seeking behaviors in rodents. However, far less is known about the role for hypocretin transmission in regulating ongoing cocaine-taking behavior. Here, we investigated the effects of the selective Hcrt-R1 antagonist SB-334867 on cocaine intake, as measured by intravenous (IV cocaine self-administration in rats. The stimulatory effects of cocaine on brain reward systems contribute to the establishment and maintenance of cocaine-taking behaviors. Therefore, we also assessed the effects of SB-334867 on the reward-enhancing properties of cocaine, as measured by cocaine-induced lowering of intracranial self-stimulation (ICSS thresholds. Finally, to definitively establish a role for Hcrt-R1 in regulating cocaine intake, we assessed IV cocaine self-administration in Hcrt-R1 knockout mice. We found that SB-334867 (1-4 mg/kg dose-dependently decreased cocaine (0.5 mg/kg/infusion self-administration in rats but did not alter responding for food rewards under the same schedule of reinforcement. This suggests that SB-334867 decreased cocaine reinforcement without negatively impacting operant performance. SB-334867 (1-4 mg/kg also dose-dependently attenuated the stimulatory effects of cocaine (10 mg/kg on brain reward systems, as measured by reversal of cocaine-induced lowering of ICSS thresholds in rats. Finally, we found that Hcrt-R1 knockout mice self-administered far less cocaine than wildtype mice across the entire dose-response function. These data demonstrate that Hcrt-R1 play an important role in regulating the reinforcing and reward-enhancing properties of cocaine, and suggest that hypocretin transmission is likely essential for establishing and maintaining the cocaine habit in human addicts.

  13. Regulating specific organic substances and heavy metals in industrial wastewater discharged to municipal wastewater treatment plants

    DEFF Research Database (Denmark)

    Grüttner, Henrik; Munk, L.; Pedersen, F.

    1994-01-01

    Due to the extension of wastewater treatment plants to nutrient removal and the development towards reuse of sludge m agriculture, new guidelines for regulating industrial discharges m Denmark were needed. The paper describes how a concept for regulating the discharge of specific organic substances...... substances, present knowledge of fate and effects in biological treatment plants is too scarce to underpin the setting of general standards. Therefore, it has been decided to base the developed priority system on the data used in the EEC-system for classification of hazardous chemicals. This includes ready...... degradability, defined by the OECD-test, bio-sorption and bio-accumulation, defined by the octanol/water distribution coefficient and toxic effects on water organisms. Several potential effects of seven heavy metals have been evaluated, and the most critical effects were found to be the quality criteria...

  14. Hemostatic mechanism underlying microbubble-enhanced non-focused ultrasound in the treatment of a rabbit liver trauma model

    Science.gov (United States)

    Zhao, Da-wei; Tian, Meng; Yang, Jian-zheng; Du, Peng; Bi, Jie; Zhu, Xinjian

    2016-01-01

    The aim of our study was to investigate the hemostatic mechanism underlying microbubble-enhanced non-focused ultrasound treatment of liver trauma. Thirty rabbits with liver trauma were randomly divided into three groups—the microbubble-enhanced ultrasound (MEUS; further subdivided based on exposure intensity into MEUS1 [0.11 W/cm2], MEUS2 [0.55 W/cm2], and MEUS3 [1.1 W/cm2]), ultrasound without microbubbles (US), and microbubbles without ultrasound (MB) groups. The pre- and post-treatment bleeding weight and visual bleeding scores were evaluated. The serum liver enzyme concentrations as well as the blood perfusion level represented by mean peak contrast intensity (PI) ratio in the treatment area were analyzed. The hemostatic mechanism was evaluated by histological and transmission electron microscopic examination of liver tissue samples. The MEUS subgroups 1–3 (grade 0–1, grade 0–2, and grade 1–2, respectively) exhibited significantly lower post-treatment visual bleeding scores than the US and MB groups (both, grade 3–4; all, P hepatic cells became edematous and compressed the hepatic sinus and associated blood vessels. However, the serum liver enzyme levels were not significantly altered. Microbubble-enhanced non-focused ultrasound does not significantly affect blood perfusion and liver function and can be used to induce rapid hemostasis in case of liver trauma. PMID:27633577

  15. MR-guided HIFU treatment of symptomatic uterine fibroids using novel feedback-regulated volumetric ablation: effectiveness and clinical practice.

    Science.gov (United States)

    Ruhnke, H; Eckey, T; Bohlmann, M K; Beldoch, M P; Neumann, A; Agic, A; Hägele, J; Diedrich, K; Barkhausen, J; Hunold, P

    2013-09-01

    To evaluate a novel feedback-regulated volumetric sonication method in MR-guided HIFU treatment of symptomatic uterine fibroids. 27 fibroids with an average volume of 124.9 ± 139.8 cc in 18 women with symptomatic uterine fibroids were ablated using the new HIFU system Sonalleve (1.5 T MR system Achieva, Philips). 21 myomas in 13 women were reevaluated 6 months later. Standard (treatment) cells (TC) and feedback-regulated (feedback) cells (FC) with a diameter of 4, 8, 12, and 16 mm were used and compared concerning sonication success, diameter of induced necrosis, and maximum achieved temperature. The non-perfused volume ratio (NPV related to myoma volume) was quantified. The fibroid volume was measured before, 1 month, and 6 months after therapy. Symptoms were quantified using a specific questionnaire (UFS-QoL). In total, 205 TC and 227 FC were applied. The NPV ratio was 23 ± 15 % (2 - 55). The TC were slightly smaller than intended (-3.9 ± 52 %; range, -100 - 81), while the FC were 20.1 ± 25.3 % bigger (p = 0.02). Feedback mechanism is less diversifying in diameter (p feedback cells leads to more contiguous necrosis in diameter and a less diversifying temperature. ▶ MR-guided HIFU ablation of symptomatic uterine fibroids is a valuable treatment option. ▶ By non-invasive HIFU fibroid volumes can be reduced and symptoms improved. ▶ The novel feedback-regulated treatment cells offer advantages over standard treatment cells. © Georg Thieme Verlag KG Stuttgart · New York.

  16. ZRF1 controls the retinoic acid pathway and regulates leukemogenic potential in acute myeloid leukemia.

    Science.gov (United States)

    Demajo, S; Uribesalgo, I; Gutiérrez, A; Ballaré, C; Capdevila, S; Roth, M; Zuber, J; Martín-Caballero, J; Di Croce, L

    2014-11-27

    Acute myeloid leukemia (AML) is frequently linked to epigenetic abnormalities and deregulation of gene transcription, which lead to aberrant cell proliferation and accumulation of undifferentiated precursors. ZRF1, a recently characterized epigenetic factor involved in transcriptional regulation, is highly overexpressed in human AML, but it is not known whether it plays a role in leukemia progression. Here, we demonstrate that ZRF1 depletion decreases cell proliferation, induces apoptosis and enhances cell differentiation in human AML cells. Treatment with retinoic acid (RA), a differentiating agent currently used to treat certain AMLs, leads to a functional switch of ZRF1 from a negative regulator to an activator of differentiation. At the molecular level, ZRF1 controls the RA-regulated gene network through its interaction with the RA receptor α (RARα) and its binding to RA target genes. Our genome-wide expression study reveals that ZRF1 regulates the transcription of nearly half of RA target genes. Consistent with our in vitro observations that ZRF1 regulates proliferation, apoptosis, and differentiation, ZRF1 depletion strongly inhibits leukemia progression in a xenograft mouse model. Finally, ZRF1 knockdown cooperates with RA treatment in leukemia suppression in vivo. Taken together, our data reveal that ZRF1 is a key transcriptional regulator in leukemia progression and suggest that ZRF1 inhibition could be a novel strategy to be explored for AML treatment.

  17. Affect labeling enhances exposure effectiveness for public speaking anxiety.

    Science.gov (United States)

    Niles, Andrea N; Craske, Michelle G; Lieberman, Matthew D; Hur, Christopher

    2015-05-01

    Exposure is an effective treatment for anxiety but many patients do not respond fully. Affect labeling (labeling emotional experience) attenuates emotional responding. The current project examined whether affect labeling enhances exposure effectiveness in participants with public speaking anxiety. Participants were randomized to exposure with or without affect labeling. Physiological arousal and self-reported fear were assessed before and after exposure and compared between groups. Consistent with hypotheses, participants assigned to Affect Labeling, especially those who used more labels during exposure, showed greater reduction in physiological activation than Control participants. No effect was found for self-report measures. Also, greater emotion regulation deficits at baseline predicted more benefit in physiological arousal from exposure combined with affect labeling than exposure alone. The current research provides evidence that behavioral strategies that target prefrontal-amygdala circuitry can improve treatment effectiveness for anxiety and these effects are particularly pronounced for patients with the greatest deficits in emotion regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. The Legal Regulation of Health-Resort Treatment of Employees Under the Legislation of Subjects of the Russian Federation

    Directory of Open Access Journals (Sweden)

    Anufrieva A. V.

    2015-10-01

    Full Text Available The article analyzes the rules for health-resort treatment of employees established at the level of subjects of the Russian Federation, determines the place of these rules in the system of current legal regulation of health-resort treatment and also it evaluates their significance in the social security of employees

  19. Regulation of Intrinsic and Extrinsic Apoptotic Pathways in Osteosarcoma Cells Following Oleandrin Treatment.

    Science.gov (United States)

    Ma, Yunlong; Zhu, Bin; Yong, Lei; Song, Chunyu; Liu, Xiao; Yu, Huilei; Wang, Peng; Liu, Zhongjun; Liu, Xiaoguang

    2016-11-23

    Our previous study has reported the anti-tumor effect of oleandrin on osteosarcoma (OS) cells. In the current study, we mainly explored its potential regulation on intrinsic and extrinsic apoptotic pathway in OS cells. Cells apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected using fluorescence staining and flow cytometry. Caspase-3 activity was detected using a commercial kit. The levels of cytoplasmic cytochrome c, mitochondrial cytochrome c, bcl-2, bax, caspase-9, Fas, FasL, caspase-8 and caspase-3 were detected by Western blotting. z-VAD-fmk was applied to block both intrinsic and extrinsic apoptosis pathways, and cells apoptosis was also tested. Furthermore, we used z-LEHD-fmk and Fas blocking antibody to inhibit intrinsic and extrinsic pathways, separately, and the selectivity of oleandrin on these pathways was explored. Results showed that oleandrin induced the apoptosis of OS cells, which was accompanied by an increase in ROS and a decrease in MMP. Furthermore, cytochrome c level was reduced in mitochondria but elevated in the cytoplasm. Caspase-3 activity was enhanced by oleandrin in a concentration- and time-dependent manner. Oleandrin also down-regulated the expression of bcl-2, but up-regulated bax, caspase-9, Fas, FasL, caspase-8 and caspase-3. In addition, the suppression of both apoptotic pathways by z-VAD-fmk greatly reverted the oleandrin-induced apoptosis. Moreover, the suppression of one pathway by a corresponding inhibitor did not affect the regulation of oleandrin on another pathway. Taken together, we concluded that oleandrin induced apoptosis of OS cells via activating both intrinsic and extrinsic apoptotic pathways.

  20. The incorporation of emotion-regulation skills into couple- and family-based treatments for post-traumatic stress disorder.

    Science.gov (United States)

    Perlick, Deborah A; Sautter, Frederic J; Becker-Cretu, Julia J; Schultz, Danielle; Grier, Savannah C; Libin, Alexander V; Schladen, Manon Maitland; Glynn, Shirley M

    2017-01-01

    Post-traumatic stress disorder (PTSD) is a disabling, potentially chronic disorder that is characterized by re-experience and hyperarousal symptoms as well as the avoidance of trauma-related stimuli. The distress experienced by many veterans of the Vietnam War and their partners prompted a strong interest in developing conjoint interventions that could both alleviate the core symptoms of PTSD and strengthen family bonds. We review the evolution of and evidence base for conjoint PTSD treatments from the Vietnam era through the post-911 era. Our review is particularly focused on the use of treatment strategies that are designed to address the emotions that are generated by the core symptoms of the disorder to reduce their adverse impact on veterans, their partners and the relationship. We present a rationale and evidence to support the direct incorporation of emotion-regulation skills training into conjoint interventions for PTSD. We begin by reviewing emerging evidence suggesting that high levels of emotion dysregulation are characteristic of and predict the severity of both PTSD symptoms and the level of interpersonal/marital difficulties reported by veterans with PTSD and their family members. In doing so, we present a compelling rationale for the inclusion of formal skills training in emotional regulation in couple-/family-based PTSD treatments. We further argue that increased exposure to trauma-related memories and emotions in treatments based on learning theory requires veterans and their partners to learn to manage the uncomfortable emotions that they previously avoided. Conjoint treatments that were developed in the last 30 years all acknowledge the importance of emotions in PTSD but vary widely in their relative emphasis on helping participants to acquire strategies to modulate them compared to other therapeutic tasks such as learning about the disorder or disclosing the trauma to a loved one. We conclude our review by describing two recent innovative

  1. Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment.

    Science.gov (United States)

    Katsushima, Keisuke; Natsume, Atsushi; Ohka, Fumiharu; Shinjo, Keiko; Hatanaka, Akira; Ichimura, Norihisa; Sato, Shinya; Takahashi, Satoru; Kimura, Hiroshi; Totoki, Yasushi; Shibata, Tatsuhiro; Naito, Mitsuru; Kim, Hyun Jin; Miyata, Kanjiro; Kataoka, Kazunori; Kondo, Yutaka

    2016-12-06

    Targeting self-renewal is an important goal in cancer therapy and recent studies have focused on Notch signalling in the maintenance of stemness of glioma stem cells (GSCs). Understanding cancer-specific Notch regulation would improve specificity of targeting this pathway. In this study, we find that Notch1 activation in GSCs specifically induces expression of the lncRNA, TUG1. TUG1 coordinately promotes self-renewal by sponging miR-145 in the cytoplasm and recruiting polycomb to repress differentiation genes by locus-specific methylation of histone H3K27 via YY1-binding activity in the nucleus. Furthermore, intravenous treatment with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system induces GSC differentiation and efficiently represses GSC growth in vivo. Our results highlight the importance of the Notch-lncRNA axis in regulating self-renewal of glioma cells and provide a strong rationale for targeting TUG1 as a specific and potent therapeutic approach to eliminate the GSC population.

  2. Treatment of Alkaline Stripped Effluent in Aerated Constructed Wetlands: Feasibility Evaluation and Performance Enhancement

    Directory of Open Access Journals (Sweden)

    Keli He

    2016-09-01

    Full Text Available Ammonium stripping has gained increasing interest for nitrogen recovery in anaerobically digested effluents. However, the stripped effluents often still do not meet discharge standards, having high pH and residual pollutants. Constructed wetlands (CWs are an easy to operate ecosystem and have a long history of application in treatment of wastewaters with extreme pH, such as acid mine drainage. However, knowledge of the mechanistic details involved in the use of CWs to treat high alkaline drainage, such as stripped effluent, is insufficient. This study explored the feasibility and effectiveness of using three sub-surface horizontal flow CWs to treat high alkaline stripped effluent (pH > 10. Two intensification strategies—intermittent aeration and effluent recirculation—were evaluated to enhance nitrogen depuration performance. The results show that the treatment of alkaline stripped effluent is feasible due to the high buffering capacity of the wetlands. Effluent recirculation combined with intermittent artificial aeration improves nitrogen removal, with 71% total nitrogen (TN removal. Ammonia volatilization from the surface of the wetlands in high alkaline conditions only contributed to 3% of the total removed ammonium. The microbial abundance and activity had significant diversity for the various enhancement strategies used in the constructed wetland systems. Anammox is an important process for nitrogen removal in CWs treating alkaline stripped effluent, and possible enhancements of this process should be investigated further.

  3. Legal frameworks and key concepts regulating diversion and treatment of mentally disordered offenders in European Union member states.

    Science.gov (United States)

    Dressing, Harald; Salize, Hans Joachim; Gordon, Harvey

    2007-10-01

    There is only limited research on the various legal regulations governing assessment, placement and treatment of mentally ill offenders in European Union member states (EU-member states). To provide a structured description and cross-boundary comparison of legal frameworks regulating diversion and treatment of mentally disordered offenders in EU-member states before the extension in May 2004. A special focus is on the concept of criminal responsibility. Information on legislation and practice concerning the assessment, placement and treatment of mentally ill offenders was gathered by means of a detailed, structured questionnaire which was filled in by national experts. The legal regulations relevant for forensic psychiatry in EU-member states are outlined. Definitions of mental disorders given within these acts are introduced and compared with ICD-10 diagnoses. Finally the application of the concept of criminal responsibility by the law and in routine practice is presented. Legal frameworks for the processing and placement of mentally disordered offenders varied markedly across EU-member states. Since May 2004 the European Union has expanded to 25 member states and in January 2007 it will reach 27. With increasing mobility across Europe, the need for increasing trans-national co-operation is becoming apparent in which great variation in legal tradition pertains.

  4. A Randomized Trial of Comparing the Efficacy of Two Neurofeedback Protocols for Treatment of Clinical and Cognitive Symptoms of ADHD: Theta Suppression/Beta Enhancement and Theta Suppression/Alpha Enhancement

    Directory of Open Access Journals (Sweden)

    Arash Mohagheghi

    2017-01-01

    Full Text Available Introduction. Neurofeedback (NF is an adjuvant or alternative therapy for children with Attention Deficit Hyperactivity Disorder (ADHD. This study intended to compare the efficacy of two different NF protocols on clinical and cognitive symptoms of ADHD. Materials and Methods. In this clinical trial, sixty children with ADHD aged 7 to 10 years old were randomly grouped to receive two different NF treatments (theta suppression/beta enhancement protocol and theta suppression/alpha enhancement protocol. Clinical and cognitive assessments were conducted prior to and following the treatment and also after an eight-week follow-up. Results. Both protocols alleviated the symptoms of ADHD in general (p<0.001, hyperactivity (p<0.001, inattention (p<0.001, and omission errors (p<0.001; however, they did not affect the oppositional and impulsive scales nor commission errors. These effects were maintained after an eight-week intervention-free period. The only significant difference between the two NF protocols was that high-frequency alpha enhancement protocol performed better in suppressing omission errors (p<0.001. Conclusion. The two NF protocols with theta suppression/beta enhancement and theta suppression/alpha enhancement have considerable and comparable effect on clinical symptoms of ADHD. Alpha enhancement protocol was more effective in suppressing omission errors.

  5. Bestatin treatment enhances the recovery of radiation induced impairments of the immunological reactivity of the blood lymphocyte population in bladder cancer patients

    International Nuclear Information System (INIS)

    Blomgren, H.; Edsmyr, F.; Stedingk, L.V. von; Wasserman, J.

    1986-01-01

    Bestatin, an immunostimulating substance of microbial origin, was examined for its capacity to augment immune responses of blood lymphocytes in bladder cancer patients having received a full course of local irradiation (64 Gy). Following irradiation the patients became lymphopenic and the lymphocytes exhibited impaired mitogenic responses to phytohemagglutinin (PHA) and purified protein derivative of tuberculin (PPD) and reduced poke weed mitogen induced secretion of immunoglobulins in vitro. Patients who were randomized to receive daily oral Bestatin treatment exhibited enhanced recoveries of PHA- and PPD- responses and enhanced recovery of the IgM secreting capacity compared to irradiated patients who did not receive Bestatin. Repopulation of the blood lymphocyte population, however, was not enhanced by Bestatin treatment. It is concluded that Bestatin treatment may enhance the recovery of radiation induced functional defects of the immune system in cancer patients

  6. Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment.

    Science.gov (United States)

    Chen, Aiping; Zhang, Yonghui; Meng, Gang; Jiang, Dengxu; Zhang, Hailin; Zheng, Meihong; Xia, Mao; Jiang, Aiqin; Wu, Junhua; Beltinger, Christian; Wei, Jiwu

    2017-07-12

    There is an urgent need for novel effective treatment for hepatocellular carcinoma (HCC). Oncolytic viruses (OVs) not only directly lyse malignant cells, but also induce potent antitumour immune responses. The potency and precise mechanisms of antitumour immune activation by attenuated measles virus remain unclear. In this study, we investigated the potency of the measles virus vaccine strain Edmonston (MV-Edm) in improving adoptive CD8 + NKG2D + cells for HCC treatment. We show that MV-Edm-infected HCC enhanced the antitumour activity of CD8 + NKG2D + cells, mediated by at least three distinct mechanisms. First, MV-Edm infection compelled HCC cells to express the specific NKG2D ligands MICA/B, which may contribute to the activation of CD8 + NKG2D + cells. Second, MV-Edm-infected HCC cells stimulated CD8 + NKG2D + cells to express high level of FasL resulting in enhanced induction of apoptosis. Third, intratumoural administration of MV-Edm enhanced infiltration of intravenously injected CD8 + NKG2D + cells. Moreover, we found that MV-Edm and adoptive CD8 + NKG2D + cells, either administered alone or combined, upregulated the immune suppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) in HCC. Elimination of IDO1 by fludarabine enhanced antitumour responses. Taken together, our data provide a novel and clinically relevant strategy for treatment of HCC.

  7. Enhancing Self-Regulation and Approaches to Learning in First-Year College Students: A Narrative-Based Programme Assessed in the Iberian Peninsula

    Science.gov (United States)

    Rosario, Pedro; Nunez, Jose C.; Gonzalez-Pienda, Julio; Valle, Antonio; Trigo, Luisa; Guimaraes, Carina

    2010-01-01

    A programme to enhance first-year college students' self-regulated learning strategies is proposed and assessed in two samples, one from the University of Oviedo (Spain) and the other from the University of Minho (Portugal). Each sample was divided into two groups (experimental and control). The Spanish sample comprised 44 students in the…

  8. Effects of Pulsed Electric Field (PEF) Treatment on Enhancing Activity and Conformation of α-Amylase.

    Science.gov (United States)

    Tian, Mei-ling; Fang, Ting; Du, Mu-ying; Zhang, Fu-sheng

    2016-04-01

    To explore an efficient, safe, and speedy application of pulsed electric field (PEF) technology for enzymatic modification, effects of PEF treatment on the enzymatic activity, property and kinetic parameters of α-amylase were investigated. Conformational transitions were also studied with the aid of circular dichroism (CD) and fluorescence spectra. The maximum enzymatic activity of α-amylase was obtained under 15 kV/cm electric field intensity and 100 mL/min flow velocity PEF treatment, in which the enzymatic activity increased by 22.13 ± 1.14% compared with control. The activation effect could last for 18 h at 4 °C. PEF treatment could widen the range of optimum temperature for α-amylase, however, it barely exerted any effect on the optimum pH. On the other hand, α-amylase treated by PEF showed an increase of Vmax, t1/2 and ΔG, whereas a decrease of Km and k were observed. Furthermore, it can be observed from fluorescence and CD spectra that PEF treatment had increased the number of amino acid residues, especially that of tryptophan, on α-amylase surface with enhanced α-helices by 34.76% and decreased random coil by 12.04% on α-amylase when compared with that of untreated. These changes in structure had positive effect on enhancing α-amylase activity and property.

  9. Enhanced photocatalytic CO₂-reduction activity of electrospun mesoporous TiO₂ nanofibers by solvothermal treatment.

    Science.gov (United States)

    Fu, Junwei; Cao, Shaowen; Yu, Jiaguo; Low, Jingxiang; Lei, Yongpeng

    2014-06-28

    Photocatalytic reduction of CO2 into renewable hydrocarbon fuels using semiconductor photocatalysts is considered as a potential solution to the energy deficiency and greenhouse effect. In this work, mesoporous TiO2 nanofibers with high specific surface areas and abundant surface hydroxyl groups are prepared using an electrospinning strategy combined with a subsequent calcination process, followed by a solvothermal treatment. The solvothermally treated mesoporous TiO2 nanofibers exhibit excellent photocatalytic performance on CO2 reduction into hydrocarbon fuels. The significantly improved photocatalytic activity can be attributed to the enhanced CO2 adsorption capacity and the improved charge separation after solvothermal treatment. The highest activity is achieved for the sample with a 2-h solvothermal treatment, showing 6- and 25-fold higher CH4 production rate than those of TiO2 nanofibers without solvothermal treatment and P25, respectively. This work may also provide a prototype for studying the effect of solvothermal treatment on the structure and photocatalytic activity of semiconductor photocatalysts.

  10. Enhancing cellulase production by overexpression of xylanase regulator protein gene, xlnR, in Talaromyces cellulolyticus cellulase hyperproducing mutant strain.

    Science.gov (United States)

    Okuda, Naoyuki; Fujii, Tatsuya; Inoue, Hiroyuki; Ishikawa, Kazuhiko; Hoshino, Tamotsu

    2016-10-01

    We obtained strains with the xylanase regulator gene, xlnR, overexpressed (HXlnR) and disrupted (DXlnR) derived from Talaromyces cellulolyticus strain C-1, which is a cellulase hyperproducing mutant. Filter paper degrading enzyme activity and cellobiohydrolase I gene expression was the highest in HXlnR, followed by C-1 and DXlnR. These results indicate that the enhancement of cellulase productivity was succeeded by xlnR overexpression.

  11. Enhancing motivation for change in treatment-resistant eating disorders.

    Science.gov (United States)

    Vitousek, K; Watson, S; Wilson, G T

    1998-06-01

    Denial and resistance to change are prominent features in most patients with anorexia nervosa. The egosyntonic quality of symptoms can contribute to inaccuracy in self-report, avoidance of treatment, difficulties in establishing a therapeutic relationship, and high rates of attrition and relapse. Individuals with bulimia nervosa are typically more motivated to recover, but often ambivalent about forfeiting the ideal of slenderness and the protective functions of binge-purge behavior. Few attempts have been made to assess denial and resistance in the eating disorders, or to examine alternative strategies for enhancing motivation to change. Review of the clinical literature indicates a striking convergence of recommendations across conceptually distinct treatment approaches. Clinicians are encouraged to acquire a frame of reference that can help them understand the private experience of individuals with eating disorders, empathize with their distress at the prospect of weight gain, and acknowledge the difficulty of change. The Socratic method seems particularly well-suited to work with this population because of its emphasis on collaboration, openness, curiosity, patience, focused and systematic inquiry, and individual discovery. Four themes are crucial in engaging reluctant eating-disordered clients in therapy: the provision of psychoeducational material, an examination of the advantages and disadvantages of symptoms, the explicit use of experimental strategies, and an exploration of personal values.

  12. Glucocorticoid Regulation of the Vitamin D Receptor

    Science.gov (United States)

    Hidalgo, Alejandro A.; Trump, Donald L.; Johnson, Candace S.

    2010-01-01

    Many studies indicate calcitriol has potent anti-tumor activity in different types of cancers. However, high levels of vitamin D can produce hypercalcemia in some patients. Glucocorticoids are used to ameliorate hypercalcemia and to enhance calcitriol anti-tumor activity. Calcitriol in combination with the glucocorticoid dexamethasone (Dex) increased vitamin D receptor (VDR) protein levels and ligand binding in squamous cell carcinoma VII (SCC). In this study we found that both calcitriol and Dex induce VDR- and glucocorticoid receptor (GR)-mediated transcription respectively, indicating both hormone receptors are active in SCC. Pre-treatment with Dex increases VDR-mediated transcription at the human CYP24A1 promoter. Whereas, pre-treatment with other steroid hormones, including dihydrotestosterone and R1881, has no effect on VDR-mediated transcription. Real-time PCR indicates treatment with Dex increases Vdr transcripts in a time-dependent manner, suggesting Dex may directly regulate expression of Vdr. Numerous putative glucocorticoid response elements (GREs) were found in the Vdr gene. Chromatin immunoprecipitation (ChIP) assay demonstrated GR binding at several putative GREs located within the mouse Vdr gene. However, none of the putative GREs studied increase GR-mediated transcription in luciferase reporter assays. In an attempt to identify the response element responsible for Vdr transcript regulation, future studies will continue to analyze newly identified GREs more distal from the Vdr gene promoter. PMID:20398752

  13. New treatment strategies for multiple myeloma by targeting Bcl-2 and the mevalonate pathway

    NARCIS (Netherlands)

    Donk, N.W.C.J. van de

    2003-01-01

    Multiple myeloma is a B-lineage neoplasia. Enhanced proliferation and defects in the regulation of programmed cell death account for the expansion of the malignant clone. Emergence of drug resistance is the primary cause of treatment failure in myeloma. Various studies have indicated that inhibition

  14. Microbubble-based enhancement of radiation effect: Role of cell membrane ceramide metabolism.

    Directory of Open Access Journals (Sweden)

    Azza Al-Mahrouki

    Full Text Available Ultrasound (US stimulated microbubbles (MB is a new treatment approach that sensitizes cancer cells to radiation (XRT. The molecular pathways in this response remain unelucidated, however, previous data has supported a role for cell membrane-metabolism related pathways including an up regulation of UDP glycosyltransferase 8 (UGT8, which catalyzes the transfer of galactose to ceramide, a lipid that is associated with the induction of apoptotic signalling. In this study, the role of UGT8 in responses of prostate tumours to ultrasound-stimulated microbubble radiation enhancement therapy is investigated. Experiments were carried out with cells in vitro and tumours in vivo in which UGT8 levels had been up regulated or down regulated. Genetically modified PC3 cells were treated with XRT, US+MB, or a combination of XRT+US+MB. An increase in the immunolabelling of ceramide was observed in cells where UGT8 was down-regulated as opposed to cells where UGT8 was either not regulated or was up-regulated. Clonogenic assays have revealed a decreased level of cellular survival with the down-regulation of UGT8. Xenograft tumours generated from stably transfected PC3 cells were also treated with US+MB, XRT or US+MB+XRT. Histology demonstrated more cellular damage in tumours with down-regulated UGT8 in comparison with control tumours. In contrast, tumours with up-regulated UGT8 had less damage than control tumours. Power Doppler imaging indicated a reduction in the vascular index with UGT8 down-regulation and photoacoustic imaging revealed a reduction in oxygen saturation. This was contrary to when UGT8 was up regulated. The down regulation of UGT8 led to the accumulation of ceramide resulting in more cell death signalling and therefore, a greater enhancement of radiation effect when vascular disruption takes place through the use of ultrasound-stimulated microbubbles.

  15. Enhanced suppression of tumor growth by concomitant treatment of human lung cancer cells with suberoylanilide hydroxamic acid and arsenic trioxide

    International Nuclear Information System (INIS)

    Chien, Chia-Wen; Yao, Ju-Hsien; Chang, Shih-Yu; Lee, Pei-Chih; Lee, Te-Chang

    2011-01-01

    The efficacy of arsenic trioxide (ATO) against acute promyelocytic leukemia (APL) and relapsed APL has been well documented. ATO may cause DNA damage by generating reactive oxygen intermediates. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, modulates gene and protein expression via histone-dependent or -independent pathways that may result in chromatin decondensation, cell cycle arrest, differentiation, and apoptosis. We investigated whether ATO and SAHA act synergistically to enhance the death of cancer cells. Our current findings showed that combined treatment with ATO and SAHA resulted in enhanced suppression of non-small-cell lung carcinoma in vitro in H1299 cells and in vivo in a xenograft mouse model. Flow cytometric analysis of annexin V+ cells showed that apoptotic cell death was significantly enhanced after combined treatment with ATO and SAHA. At the doses used, ATO did not interfere with cell cycle progression, but SAHA induced p21 expression and led to G1 arrest. A Comet assay demonstrated that ATO, but not SAHA, induced DNA strand breaks in H1299 cells; however, co-treatment with SAHA significantly increased ATO-induced DNA damage. Moreover, SAHA enhanced acetylation of histone H3 and sensitized genomic DNA to DNase I digestion. Our results suggest that SAHA may cause chromatin relaxation and increase cellular susceptibility to ATO-induced DNA damage. Combined administration of SAHA and ATO may be an effective approach to the treatment of lung cancer. -- Highlights: ► ATO and SAHA are therapeutic agents with different action modes. ► Combination of ATO and SAHA synergistically inhibits tumor cell growth. ► SAHA loosens chromatin structure resulting in increased sensitivity to DNase I. ► ATO-induced DNA damage and apoptosis are enhanced by co-treatment with SAHA.

  16. Vorinostat enhances the cisplatin-mediated anticancer effects in small cell lung cancer cells.

    Science.gov (United States)

    Pan, Chun-Hao; Chang, Ying-Fang; Lee, Ming-Shuo; Wen, B-Chen; Ko, Jen-Chung; Liang, Sheng-Kai; Liang, Mei-Chih

    2016-11-07

    Vorinostat, a histone deacetylase (HDAC) inhibitor, is a promising agent for cancer therapy. Combining vorinostat with cisplatin may relax the chromatin structure and facilitate the accessibility of cisplatin, thus enhancing its cytotoxicity. Studies have not yet investigated the effects of the combination of vorinostat and cisplatin on small cell lung cancer (SCLC). We first assessed the efficacy of vorinostat with etoposide/cisplatin (EP; triple combination) and then investigated the effects of cotreatment with vorinostat and cisplatin on H209 and H146 SCLC cell lines. The anticancer effects of various combinations were determined in terms of cell viability, apoptosis, cell cycle distribution, and vorinostat-regulated proteins. We also evaluated the efficacy of vorinostat/cisplatin combination in H209 xenograft nude mice. Our data revealed that the triple combination engendered a significant reduction of cell viability and high apoptotic cell death. In addition, vorinostat combined with cisplatin enhanced cell growth inhibition, induced apoptosis, and promoted cell cycle arrest. We observed that the acetylation levels of histone H3 and α-tubulin were higher in combination treatments than in vorinostat treatment alone. Moreover, vorinostat reduced the expression of thymidylate synthase (TS), and TS remained inhibited after cotreament with cisplatin. Furthermore, an in vivo study revealed that the combination of vorinostat and cisplatin significantly inhibited tumor growth in xenograft nude mice (tumor growth inhibition T/C% = 20.5 %). Combined treatments with vorinostat promote the cytotoxicity of cisplatin and induce the expression of vorinostat-regulated acetyl proteins, eventually enhancing antitumor effects in SCLC cell lines. Triple combinations with a low dosage of cisplatin demonstrate similar therapeutic effects. Such triple combinations, if applied clinically, may reduce the undesired adverse effects of cisplatin. The effects of the combination of

  17. Advance directives as autonomy enhancers: reality or myth?

    OpenAIRE

    Navarro Michel, Mónica

    2015-01-01

    In the last few decades there has been a wealth of literature and legislation on advance directives. As you all know, it is an instrument by which a person can express their wishes as regards what treatment they should be given or, more to the point, not to be given, when he is in a situation when he can not do so himself. Regulations in the western world seem to promote advance directives as a way to enhance patient¿s autonomy in the context of human rights, and the media has presen...

  18. Enhanced Anti-Mycobacterium tuberculosis Immunity over Time with Combined Drug and Immunotherapy Treatment

    Directory of Open Access Journals (Sweden)

    Sasha E. Larsen

    2018-05-01

    Full Text Available It is estimated that one third of the world’s population is infected with Mycobacterium tuberculosis (Mtb. This astounding statistic, in combination with costly and lengthy treatment regimens make the development of therapeutic vaccines paramount for controlling the global burden of tuberculosis. Unlike prophylactic vaccination, therapeutic immunization relies on the natural pulmonary infection with Mtb as the mucosal prime that directs boost responses back to the lung. The purpose of this work was to determine the protection and safety profile over time following therapeutic administration of our lead Mtb vaccine candidate, ID93 with a synthetic TLR4 agonist (glucopyranosyl lipid adjuvant in a stable emulsion (GLA-SE, in combination with rifampicin, isoniazid, and pyrazinamide (RHZ drug treatment. We assessed the host inflammatory immune responses and lung pathology 7–22 weeks post infection, and determined the therapeutic efficacy of combined treatment by enumeration of the bacterial load and survival in the SWR/J mouse model. We show that drug treatment alone, or with immunotherapy, tempered the inflammatory responses measured in brochoalveolar lavage fluid and plasma compared to untreated cohorts. RHZ combined with therapeutic immunizations significantly enhanced TH1-type cytokine responses in the lung over time, corresponding to decreased pulmonary pathology evidenced by a significant decrease in the percentage of lung lesions and destructive lung inflammation. These data suggest that bacterial burden assessment alone may miss important correlates of lung architecture that directly contribute to therapeutic vaccine efficacy in the preclinical mouse model. We also confirmed our previous finding that in combination with antibiotics therapeutic immunizations provide an additive survival advantage. Moreover, therapeutic immunizations with ID93/GLA-SE induced differential T cell immune responses over the course of infection that correlated

  19. Helping Others Regulate Emotion Predicts Increased Regulation of One's Own Emotions and Decreased Symptoms of Depression.

    Science.gov (United States)

    Doré, Bruce P; Morris, Robert R; Burr, Daisy A; Picard, Rosalind W; Ochsner, Kevin N

    2017-05-01

    Although much research considers how individuals manage their own emotions, less is known about the emotional benefits of regulating the emotions of others. We examined this topic in a 3-week study of an online platform providing training and practice in the social regulation of emotion. We found that participants who engaged more by helping others (vs. sharing and receiving support for their own problems) showed greater decreases in depression, mediated by increased use of reappraisal in daily life. Moreover, social regulation messages with more other-focused language (i.e., second-person pronouns) were (a) more likely to elicit expressions of gratitude from recipients and (b) predictive of increased use of reappraisal over time for message composers, suggesting perspective-taking enhances the benefits of practicing social regulation. These findings unpack potential mechanisms of socially oriented training in emotion regulation and suggest that by helping others regulate, we may enhance our own regulatory skills and emotional well-being.

  20. Interferon-Lambda: A Potent Regulator of Intestinal Viral Infections.

    Science.gov (United States)

    Lee, Sanghyun; Baldridge, Megan T

    2017-01-01

    Interferon-lambda (IFN-λ) is a recently described cytokine found to be of critical importance in innate immune regulation of intestinal viruses. Endogenous IFN-λ has potent antiviral effects and has been shown to control multiple intestinal viruses and may represent a factor that contributes to human variability in response to infection. Importantly, recombinant IFN-λ has therapeutic potential against enteric viral infections, many of which lack other effective treatments. In this mini-review, we describe recent advances regarding IFN-λ-mediated regulation of enteric viruses with important clinical relevance including rotavirus, reovirus, and norovirus. We also briefly discuss IFN-λ interactions with other cytokines important in the intestine, and how IFN-λ may play a role in regulation of intestinal viruses by the commensal microbiome. Finally, we indicate currently outstanding questions regarding IFN-λ control of enteric infections that remain to be explored to enhance our understanding of this important immune molecule.

  1. Enhanced energy efficiency in waste water treatment plants; Steigerung der Energieeffizienz auf kommunalen Klaeranlagen

    Energy Technology Data Exchange (ETDEWEB)

    Haberkern, Bernd; Maier, Werner; Schneider, Ursula [iat - Ingenieurberatung fuer Abwassertechnik, Darmstadt und Stuttgart, Darmstadt (Germany)

    2008-03-15

    In order to implement the requests of EU-IPCC-directive in a new decree for waste water treatment in Germany, best available techniques have to be defined to optimize energy efficiency in waste water treatment plants (WWTP). Therefore energy efficiency was investigated for common treatment processes and new technologies like membrane filtration, co-digestion or phosphorus recycling. In addition, the occurrence of different technologies for waste water and sludge treatment was evaluated for different size ranges of treatment plants (in population equivalents, PE) nationwide in Germany. The definition of actual and aimed values for specific energy consumption (in kWh/(PE.a)) allowed to calculate the potential energy savings in WWTP and the additional consumption due to new processes on a national level. Under consideration of the reciprocations between optimized energy consumption in WWTP and operation practice, toe-holds to increase energy efficiency according to their relevancy for the national balance could be listed. Case studies prove the feasibility of the investigated techniques and allow proposals for minimum requirements in legal regulation concerning energy efficiency in WWTP. (orig.)

  2. Two weeks of metformin treatment induces AMPK-dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle

    Science.gov (United States)

    Kristensen, Jonas Møller; Treebak, Jonas T.; Schjerling, Peter; Goodyear, Laurie

    2014-01-01

    Metformin-induced activation of the 5′-AMP-activated protein kinase (AMPK) has been associated with enhanced glucose uptake in skeletal muscle, but so far no direct causality has been examined. We hypothesized that an effect of in vivo metformin treatment on glucose uptake in mouse skeletal muscles is dependent on AMPK signaling. Oral doses of metformin or saline treatment were given to muscle-specific kinase dead (KD) AMPKα2 mice and wild-type (WT) littermates either once or chronically for 2 wk. Soleus and extensor digitorum longus muscles were used for measurements of glucose transport and Western blot analyses. Chronic treatment with metformin enhanced insulin-stimulated glucose uptake in soleus muscles of WT (∼45%, P metformin treatment. Insulin signaling at the level of Akt and TBC1D4 protein expression as well as Akt Thr308/Ser473 and TBC1D4 Thr642/Ser711 phosphorylation were not changed by metformin treatment. Also, protein expressions of Rab4, GLUT4, and hexokinase II were unaltered after treatment. The acute metformin treatment did not affect glucose uptake in muscle of either of the genotypes. In conclusion, we provide novel evidence for a role of AMPK in potentiating the effect of insulin on glucose uptake in soleus muscle in response to chronic metformin treatment. PMID:24644243

  3. Enhanced Mucosal Defense and Reduced Tumor Burden in Mice with the Compromised Negative Regulator IRAK-M

    Directory of Open Access Journals (Sweden)

    Daniel E. Rothschild

    2017-02-01

    Full Text Available Aberrant inflammation is a hallmark of inflammatory bowel disease (IBD and colorectal cancer. IRAK-M is a critical negative regulator of TLR signaling and overzealous inflammation. Here we utilize data from human studies and Irak-m−/− mice to elucidate the role of IRAK-M in the modulation of gastrointestinal immune system homeostasis. In human patients, IRAK-M expression is up-regulated during IBD and colorectal cancer. Further functional studies in mice revealed that Irak-m−/− animals are protected against colitis and colitis associated tumorigenesis. Mechanistically, our data revealed that the gastrointestinal immune system of Irak-m−/− mice is highly efficient at eliminating microbial translocation following epithelial barrier damage. This attenuation of pathogenesis is associated with expanded areas of gastrointestinal associated lymphoid tissue (GALT, increased neutrophil migration, and enhanced T-cell recruitment. Further evaluation of Irak-m−/− mice revealed a splice variant that robustly activates NF-κB signaling. Together, these data identify IRAK-M as a potential target for future therapeutic intervention.

  4. Hepatitis B virus enhances cisplatin-induced hepatotoxicity via a mechanism involving suppression of glucose-regulated protein of 78 Kda.

    Science.gov (United States)

    Zhang, Xiaoxue; Zhang, Rui; Yang, HuiOu; Xiang, Qian; Jiang, Qing; He, Qi; Zhang, Ting; Chen, Chen; Zhu, Huifen; Wang, Qiang; Ning, Qin; Li, Yiwu; Lei, Ping; Shen, Guanxin

    2016-07-25

    Cisplatin is a classical platinum-based chemotherapeutic drug used in the treatment of many cancer types, including hepatocellular carcinoma (HCC). The application of cisplatin is significantly limited by its toxicity, which may be affected by various biological factors. Persistence of Hepatitis B virus (HBV) infection leads to HCC development and may be associated with higher incidence of severe hepatitis during chemotherapy. However, whether HBV alters the susceptibility of hepatocytes to cisplatin remains poorly understood. Here, we demonstrate that HBV transfection enhanced cisplatin-induced hepatotoxicity via a mechanism involving suppression of glucose-regulated protein of 78 KDa (Grp78), a major stress-induced chaperone that localizes to the endoplasmic reticulum. Silencing Grp78 gene increased the susceptibility of HepG2 to cisplatin by activating caspase-3. Grp78 expression was down-regulated by HBV infection both in vitro and in liver tissues of patients. We compared the cisplatin sensitivity of hepatoma cells either expressing (HepG2.2.15 cells) or not expressing the entire Hepatitis B Virus genome (HepG2). HepG2.2.15 cells showed increased sensitivity to cisplatin and a higher apoptosis rate. Overexpression of Grp78 counteracted the increase of sensitivity of HepG2.215 cells to cisplatin. Furthermore, we found that HBV disrupted Grp78 synthesis in response to cisplatin stimulation, which may trigger severe and prolonged endoplasmic reticulum (ER) stress that can induce cellular apoptosis. Our findings provide new information into the effect of HBV in the modulation of Grp78 expression, and, consequently on cisplatin-induced hepatotoxicity during viral infection. Copyright © 2016. Published by Elsevier Ireland Ltd.

  5. Enhancing Treatment Outcome of Patients at Risk of Treatment Failure: Meta-Analytic and Mega-Analytic Review of a Psychotherapy Quality Assurance System

    Science.gov (United States)

    Shimokawa, Kenichi; Lambert, Michael J.; Smart, David W.

    2010-01-01

    Objective: Outcome research has documented worsening among a minority of the patient population (5% to 10%). In this study, we conducted a meta-analytic and mega-analytic review of a psychotherapy quality assurance system intended to enhance outcomes in patients at risk of treatment failure. Method: Original data from six major studies conducted…

  6. Cytolethal Distending Toxin Enhances Radiosensitivity in Prostate Cancer Cells by Regulating Autophagy

    Directory of Open Access Journals (Sweden)

    Hwai-Jeng Lin

    2017-06-01

    Full Text Available Cytolethal distending toxin (CDT produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Among these three toxin subunits, CdtB is the toxic moiety of CDT with DNase I activity, resulting in DNA double-strand breaks (DSB and, consequently, cell cycle arrest at the G2/M stage and apoptosis. Radiation therapy is an effective modality for the treatment of localized prostate cancer (PCa. However, patients often develop radioresistance. Owing to its particular biochemical properties, we previously employed CdtB as a therapeutic agent for sensitizing radioresistant PCa cells to ionizing radiation (IR. In this study, we further demonstrated that CDT suppresses the IR-induced autophagy pathway in PCa cells by attenuating c-Myc expression and therefore sensitizes PCa cells to radiation. We further showed that CDT prevents the formation of autophagosomes via decreased high-mobility group box 1 (HMGB1 expression and the inhibition of acidic vesicular organelle (AVO formation, which are associated with enhanced radiosensitivity in PCa cells. The results of this study reveal the detailed mechanism of CDT for the treatment of radioresistant PCa.

  7. Memory enhancement by Tamoxifen on amyloidosis mouse model.

    Science.gov (United States)

    Pandey, Deepika; Banerjee, Sugato; Basu, Mahua; Mishra, Nibha

    2016-03-01

    Tamoxifen (TMX) is a selective estrogen receptor modulator (SERM) used in the treatment of breast cancer. Earlier studies show its neuroprotection via regulating apoptosis, microglial functions, and synaptic plasticity. TMX also showed memory enhancement in ovariectomized mice, and protection from amyloid induced damage in hippocampal cell line. These reports encouraged us to explore the role of TMX in relevance to Alzheimer's disease (AD). We report here, the effect of TMX treatment a) on memory, and b) levels of neurotransmitters (acetylcholine (ACh) and dopamine (DA)) in breeding-retired-female mice injected with beta amyloid1-42 (Aβ1-42). Mice were treated with TMX (10mg/kg, i.p.) for 15 days. In Morris water maze test, the TMX treated mice escape latency decreased during training trials. They also spent longer time in the platform quadrant on probe trial, compared to controls. In Passive avoidance test, TMX treated mice avoided stepping on the shock chamber. This suggests that TMX protects memory from Aβ induced toxicity. In frontal cortex, ACh was moderately increased, with TMX treatment. In striatum, dopamine was significantly increased, 3,4-dihydroxyphenylacetic acid (DOPAC) level and DOPAC/DA ratio was decreased post TMX treatment. Therefore, TMX enhances spatial and contextual memory by reducing dopamine metabolism and increasing ACh level in Aβ1-42 injected-breeding-retired-female mice. Copyright © 2015. Published by Elsevier Inc.

  8. A response regulator from a soil metagenome enhances resistance to the β-lactam antibiotic carbenicillin in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Heather K Allen

    Full Text Available Functional metagenomic analysis of soil metagenomes is a method for uncovering as-yet unidentified mechanisms for antibiotic resistance. Here we report an unconventional mode by which a response regulator derived from a soil metagenome confers resistance to the β-lactam antibiotic carbenicillin in Escherichia coli. A recombinant clone (βlr16 harboring a 5,169 bp DNA insert was selected from a metagenomic library previously constructed from a remote Alaskan soil. The βlr16 clone conferred specific resistance to carbenicillin, with limited increases in resistance to other tested antibiotics, including other β-lactams (penicillins and cephalosporins, rifampin, ciprofloxacin, erythromycin, chloramphenicol, nalidixic acid, fusidic acid, and gentamicin. Resistance was more pronounced at 24°C than at 37°C. Zone-of-inhibition assays suggested that the mechanism of carbenicillin resistance was not due to antibiotic inactivation. The DNA insert did not encode any genes known to confer antibiotic resistance, but did have two putative open reading frames (ORFs that were annotated as a metallopeptidase and a two-component response regulator. Transposon mutagenesis and subcloning of the two ORFs followed by phenotypic assays showed that the response regulator gene was necessary and sufficient to confer the resistance phenotype. Quantitative reverse transcriptase PCR showed that the response regulator suppressed expression of the ompF porin gene, independently of the small RNA regulator micF, and enhanced expression of the acrD, mdtA, and mdtB efflux pump genes. This work demonstrates that antibiotic resistance can be achieved by the modulation of gene regulation by heterologous DNA. Functional analyses such as these can be important for making discoveries in antibiotic resistance gene biology and ecology.

  9. Could Moral Enhancement Interventions be Medically Indicated?

    Science.gov (United States)

    Carter, Sarah

    2017-12-01

    This paper explores the position that moral enhancement interventions could be medically indicated (and so considered therapeutic) in cases where they provide a remedy for a lack of empathy, when such a deficit is considered pathological. In order to argue this claim, the question as to whether a deficit of empathy could be considered to be pathological is examined, taking into account the difficulty of defining illness and disorder generally, and especially in the case of mental health. Following this, Psychopathy and a fictionalised mental disorder (Moral Deficiency Disorder) are explored with a view to consider moral enhancement techniques as possible treatments for both conditions. At this juncture, having asserted and defended the position that moral enhancement interventions could, under certain circumstances, be considered medically indicated, this paper then goes on to briefly explore some of the consequences of this assertion. First, it is acknowledged that this broadening of diagnostic criteria in light of new interventions could fall foul of claims of medicalisation. It is then briefly noted that considering moral enhancement technologies to be akin to therapies in certain circumstances could lead to ethical and legal consequences and questions, such as those regarding regulation, access, and even consent.

  10. Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery

    International Nuclear Information System (INIS)

    Clow, D.W.; Hammer, R.P. Jr.

    1991-01-01

    2-[14C]deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine

  11. Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery

    Energy Technology Data Exchange (ETDEWEB)

    Clow, D.W.; Hammer, R.P. Jr. (Univ. of Hawaii School of Medicine, Honolulu (USA))

    1991-01-01

    2-(14C)deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine.

  12. Pesticide regulations and farm worker safety: the need to improve pesticide regulations in Viet Nam.

    Science.gov (United States)

    Phung, Dung Tri; Connell, Des; Miller, Greg; Rutherford, Shannon; Chu, Cordia

    2012-06-01

    Agricultural pesticide use in Viet Nam has more than tripled since 1990. However, pesticide legislation and regulations have not been developed in response to this large increase in usage, as a result of which pesticides pose a serious threat to human health and the environment. This paper identifies the need to improve pesticide regulations in Viet Nam through a comparative analysis of pesticide regulations in Viet Nam and the United States of America, where the rate of acute poisoning among agricultural workers is much lower than in Viet Nam and where information pertaining to pesticide regulations is made accessible to the public. The analysis identified several measures that would help to improve Viet Nam's pesticide regulations. These include enhancing pesticide legislation, clarifying the specific roles and active involvement of both the environmental and health sectors; performing a comprehensive risk-benefit evaluation of pesticide registration and management practices; improving regulations on pesticide suspension and cancellation, transport, storage and disposal; developing import and export policies and enhancing pesticide-related occupational safety programmes.

  13. Ethylene and 1-MCP regulate major volatile biosynthetic pathways in apple fruit.

    Science.gov (United States)

    Yang, Xiaotang; Song, Jun; Du, Lina; Forney, Charles; Campbell-Palmer, Leslie; Fillmore, Sherry; Wismer, Paul; Zhang, Zhaoqi

    2016-03-01

    The effects of ethylene and 1-methylcyclopropene (1-MCP) on apple fruit volatile biosynthesis and gene expression were investigated. Statistical analysis identified 17 genes that changed significantly in response to ethylene and 1-MCP treatments. Genes encoding branched-chain amino acid aminotransferase (BCAT), aromatic amino acid aminotransferase (ArAT) and amino acid decarboxylases (AADC) were up-regulated during ripening and further enhanced by ethylene treatment. Genes related to fatty acid synthesis and metabolism, including acyl-carrier-proteins (ACPs), malonyl-CoA:ACP transacylase (MCAT), acyl-ACP-desaturase (ACPD), lipoxygenase (LOX), hydroperoxide lyase (HPL), alcohol dehydrogenase (ADH), pyruvate decarboxylase (PDC2), β-oxidation, acyl-CoA synthetase (ACS), enoyl-CoA hydratase (ECHD), acyl-CoA dehydrogenase (ACAD), and alcohol acyltransferases (AATs) also increased during ripening and in response to ethylene treatment. Allene oxide synthase (AOS), alcohol dehydrogenase 1 (ADH1), 3-ketoacyl-CoA thiolase and branched-chain amino acid aminotransferase 2 (BCAT2) decreased in ethylene-treated fruit. Treatment with 1-MCP and ethylene generally produced opposite effects on related genes, which provides evidence that regulation of these genes is ethylene dependent. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  14. Integrated basic treatment of activated carbon for enhanced CO{sub 2} selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Adelodun, Adedeji Adebukola; Jo, Young-Min, E-mail: ymjo@khu.ac.kr

    2013-12-01

    We attempted the use of three chemical agents viz nitric acid (HN), calcium nitrate (CaN) and calcium ethanoate (CaEt) to achieve enhanced CO{sub 2} selective adsorption by activated carbon (AC). In dry phase treatment, microporous coconut shell-based carbon (CS) exhibits higher CO{sub 2} capacity than coal-based. However, upon wet-phase pre-treatment, modified CS samples showed lesser CO{sub 2} adsorption efficiency. Surface characterization with X-ray photoelectron spectroscopy confirms the presence of calcium and amine species on the samples with integrated treatment (A-CaN). These samples recorded the highest low-level CO{sub 2} capture despite calcinated CaEt-doped samples (C-CaEt) showing the highest value for pure and high level CO{sub 2} adsorption capacities. The slope and linearity values of isobaric desorption were used to estimate the proportion of CO{sub 2} chemisorbed and heterogeneity of the adsorbents’ surfaces respectively. Consequently, integrated basic impregnation provides the most efficient adsorbents for selective adsorption of both indoor and outdoor CO{sub 2} levels.

  15. An HPLC tracing of the enhancer regulation in selected discrete brain areas of food-deprived rats.

    Science.gov (United States)

    Miklya, I; Knoll, B; Knoll, J

    2003-05-09

    The recent discovery of the enhancer regulation in the mammalian brain brought a different perspective to the brain-organized realization of goal-oriented behavior, which is the quintessence of plastic behavioral descriptions such as drive or motivation. According to this new approach, 'drive' means that special endogenous enhancer substances enhance the impulse-propagation-mediated release of transmitters in a proper population of enhancer-sensitive neurons, and keep these neurons in the state of enhanced excitability until the goal is reached. However, to reach any goal needs the participation of the catecholaminergic machinery, the engine of the brain. We developed a method to detect the specific enhancer effect of synthetic enhancer substances [(-)-deprenyl, (-)-PPAP, (-)-BPAP] by measuring the release of transmitters from freshly isolated selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus, raphe) by the aid of HPLC with electrochemical detection. To test the validity of the working hypothesis that in any form of goal-seeking behavior the catecholaminergic and serotonergic neurons work on a higher activity level, we compared the amount of norepinephrine, dopamine, and serotonin released from selected discrete brain areas isolated from the brain of sated and food-deprived rats. Rats were deprived of food for 48 and 72 hours, respectively, and the state of excitability of their catecholaminergic and serotonergic neurons in comparison to that of sated rats was measured. We tested the orienting-searching reflex activity of the rats in a special open field, isolated thereafter selected discrete brain areas and measured the release of norepinephrine, dopamine, and serotonin from the proper tissue samples into the organ bath. The orienting-searching reflex activity of the rats increased proportionally to the time elapsed from the last feed and the amount of dopamine released from the striatum, substantia nigra and

  16. SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals.

    Directory of Open Access Journals (Sweden)

    Sayaka Akieda-Asai

    Full Text Available BACKGROUND: SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5Kgamma was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268 in PIP5Kgamma and enhanced PIP5Kgamma enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kgamma knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kgamma, PI(4,5P(2, and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. CONCLUSIONS/SIGNIFICANCE: Our findings indicated that the control of TSH release by the SIRT1-PIP5Kgamma pathway is important for regulating the metabolism of the whole body.

  17. Change in contrast enhancement of HCC on 1-month follow-up CT after local radiotherapy: An early predictor of final treatment response

    International Nuclear Information System (INIS)

    Kim, Eun Young; Choi, Dongil; Lim, Do Hoon; Lee, Won Jae; Yoo, Byung Chul; Paik, Seung Woon

    2009-01-01

    Background: The purpose of this study was to evaluate the change in contrast enhancement of HCC on 1-month follow-up CT after local radiotherapy (RT) as an early predictor of final treatment response. Materials: Fifty patients who underwent local RT for HCCs had both pre-RT and post-RT CT scans including 1-month follow-up CT. We assessed the final treatment response by using the change in maximal tumor size on 6-12-month follow-up CT scan after RT. We also evaluated the change in tumor enhancement between pre-RT and 1-month follow-up CT scans. Results: A final treatment response was achieved in 27 (54%) of 50 patients, who showed either a complete response (n = 11) or a partial response (n = 16). Compared with non-responsive patients (n = 23), responsive patients showed a significant decrease in tumor enhancement on 1-month follow-up CT after RT in both objective and subjective analyses (each P < 0.001). Conclusion: The change in contrast enhancement of HCC seen on the 1-month follow-up CT in patients after local RT may be used as an early predictor of final treatment response.

  18. Thermal treatment to enhance saturation magnetization of superparamagnetic Ni nanoparticles while maintaining low coercive force

    Science.gov (United States)

    Ishizaki, Toshitaka; Yatsugi, Kenichi; Akedo, Kunio

    2018-05-01

    Superparamagnetic nanoparticles capped by insulators have the potential to decrease eddy current and hysteresis losses. However, the saturation magnetization ( M s) decreases significantly with decreasing the particle size. In this study, superparamagnetic Ni nanoparticles having the mean size of 11.6 ± 1.8 nm were synthesized from the reduction of Ni(II) acetylacetonate in oleylamine with the addition of trioctylphosphine, indicating the coercive force ( H c) less than 1 Oe. Thermal treatments of the Ni nanoparticles were investigated as a method to enhance the M s. The results indicated that the M s was enhanced by an increase of the Ni mass ratio with increasing thermal treatment temperature. However, the decomposition behavior of the capping layers indicated that their alkyl chains actively decomposed at temperatures above 523 K to form Ni3P via reaction between Ni and P, resulting in particle growth with a significant increase in the H c. Therefore, the optimal temperature was determined to be 473 K, which increased the Ni ratio without formation of Ni3P while maintaining particle sizes with superparamagnetic properties. Further, the M s could be improved by 22% (relative to the as-synthesized Ni nanoparticles) after thermal treatment at 473 K while maintaining the H c to be less than 1 Oe.

  19. Effects of Self-Regulated Vocabulary Learning Process on Self-Efficacy

    Science.gov (United States)

    Mizumoto, Atsushi

    2013-01-01

    Researchers, especially in the field of educational psychology, have argued that self-efficacy plays an important role in self-regulated learning. As such, teaching of self-regulated learning often focuses on enhancing self-efficacy. However, few studies have examined how the process of self-regulated learning might lead to the enhancement of…

  20. The CYP2E1 inhibitor DDC up-regulates MMP-1 expression in hepatic stellate cells via an ERK1/2- and Akt-dependent mechanism.

    Science.gov (United States)

    Liu, Tianhui; Wang, Ping; Cong, Min; Xu, Youqing; Jia, Jidong; You, Hong

    2013-06-05

    DDC (diethyldithiocarbamate) could block collagen synthesis in HSC (hepatic stellate cells) through the inhibition of ROS (reactive oxygen species) derived from hepatocyte CYP2E1 (cytochrome P450 2E1). However, the effect of DDC on MMP-1 (matrix metalloproteinase-1), which is the main collagen degrading matrix metalloproteinase, has not been reported. In co-culture experiments, we found that DDC significantly enhanced MMP-1 expression in human HSC (LX-2) that were cultured with hepatocyte C3A cells either expressing or not expressing CYP2E1. The levels of both proenzyme and active MMP-1 enzyme were up-regulated in LX-2 cells, accompanied by elevated enzyme activity of MMP-1 and decreased collagen I, in both LX-2 cells and the culture medium. H2O2 treatment abrogated DDC-induced MMP-1 up-regulation and collagen I decrease, while catalase treatment slightly up-regulated MMP-1 expression. These data suggested that the decrease in ROS by DDC was partially responsible for the MMP-1 up-regulation. ERK1/2 (extracellular signal-regulated kinase 1/2), Akt (protein kinase B) and p38 were significantly activated by DDC. The ERK1/2 inhibitor (U0126) and Akt inhibitor (T3830) abrogated the DDC-induced MMP-1 up-regulation. In addition, a p38 inhibitor (SB203580) improved MMP-1 up-regulation through the stimulation of ERK1/2. Our data indicate that DDC significantly up-regulates the expression of MMP-1 in LX-2 cells which results in greater MMP-1 enzyme activity and decreased collagen I. The enhancement of MMP-1 expression by DDC was associated with H2O2 inhibition and coordinated regulation by the ERK1/2 and Akt pathways. These data provide some new insights into treatment strategies for hepatic fibrosis.

  1. HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

    Science.gov (United States)

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

    2010-02-01

    Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy.

  2. Gemcitabine enhances cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling.

    Science.gov (United States)

    Xu, Bao-Qing; Fu, Zhi-Guang; Meng, Yao; Wu, Xiao-Qing; Wu, Bo; Xu, Liang; Jiang, Jian-Li; Li, Ling; Chen, Zhi-Nan

    2016-09-20

    Pancreatic cancer, one of the most lethal cancers, has very poor 5-year survival partly due to gemcitabine resistance. Recently, it was reported that chemotherapeutic agents may act as stressors to induce adaptive responses and to promote chemoresistance in cancer cells. During long-term drug treatment, the minority of cancer cells survive and acquire an epithelial-mesenchymal transition phenotype with increased chemo-resistance and metastasis. However, the short-term response of most cancer cells remains unclear. This study aimed to investigate the short-term response of pancreatic cancer cells to gemcitabine stress and to explore the corresponding mechanism. Our results showed that gemcitabine treatment for 24 hours enhanced pancreatic cancer cell invasion. In gemcitabine-treated cells, HAb18G/CD147 was up-regulated; and HAb18G/CD147 down-regulation or inhibition attenuated gemcitabine-enhanced invasion. Mechanistically, HAb18G/CD147 promoted gemcitabine-enhanced invasion by activating the EGFR (epidermal growth factor receptor)-STAT3 (signal transducer and activator of transcription 3) signaling pathway. Inhibition of EGFR-STAT3 signaling counteracted gemcitabine-enhanced invasion, and which relied on HAb18G/CD147 levels. In pancreatic cancer tissues, EGFR was highly expressed and positively correlated with HAb18G/CD147. These data indicate that pancreatic cancer cells enhance cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling. Our findings suggest that inhibiting HAb18G/CD147 is a potential strategy for overcoming drug stress-associated resistance in pancreatic cancer.

  3. Garlic-Derived S-Allylmercaptocysteine Ameliorates Nonalcoholic Fatty Liver Disease in a Rat Model through Inhibition of Apoptosis and Enhancing Autophagy

    Science.gov (United States)

    Fung, Man-Lung; Liong, Emily C.; Chang, Raymond Chuen Chung; Ching, Yick-Pang; Tipoe, George L.

    2013-01-01

    Our previous study demonstrated that administration of garlic-derived antioxidant S-allylmercaptocysteine (SAMC) ameliorated hepatic injury in a nonalcoholic fatty liver disease (NAFLD) rat model. Our present study aimed to investigate the mechanism of SAMC on NAFLD-induced hepatic apoptosis and autophagy. Adult female rats were fed with a high-fat diet for 8 weeks to develop NAFLD with or without intraperitoneal injection of 200 mg/kg SAMC for three times per week. During NAFLD development, increased apoptotic cells and caspase-3 activation were observed in the liver. Increased apoptosis was modulated through both intrinsic and extrinsic apoptotic pathways. NAFLD treatment also enhanced the expression of key autophagic markers in the liver with reduced activity of LKB1/AMPK and PI3K/Akt pathways. Increased expression of proapoptotic regulator p53 and decreased activity of antiautophagic regulator mTOR were also observed. Administration of SAMC reduced the number of apoptotic cells through downregulation of both intrinsic and extrinsic apoptotic mechanisms. SAMC also counteracted the effects of NAFLD on LKB1/AMPK and PI3K/Akt pathways. Treatment with SAMC further enhanced hepatic autophagy by regulating autophagic markers and mTOR activity. In conclusion, administration of SAMC during NAFLD development in rats protects the liver from chronic injury by reducing apoptosis and enhancing autophagy. PMID:23861709

  4. Do phosphoinositides regulate membrane water permeability of tobacco protoplasts by enhancing the aquaporin pathway?

    Science.gov (United States)

    Ma, Xiaohong; Shatil-Cohen, Arava; Ben-Dor, Shifra; Wigoda, Noa; Perera, Imara Y; Im, Yang Ju; Diminshtein, Sofia; Yu, Ling; Boss, Wendy F; Moshelion, Menachem; Moran, Nava

    2015-03-01

    Enhancing the membrane content of PtdInsP 2 , the already-recognized protein-regulating lipid, increased the osmotic water permeability of tobacco protoplasts, apparently by increasing the abundance of active aquaporins in their membranes. While phosphoinositides are implicated in cell volume changes and are known to regulate some ion channels, their modulation of aquaporins activity has not yet been reported for any organism. To examine this, we compared the osmotic water permeability (P f) of protoplasts isolated from tobacco (Nicotiana tabacum) cultured cells (NT1) with different (genetically lowered or elevated relative to controls) levels of inositol trisphosphate (InsP3) and phosphatidyl inositol [4,5] bisphosphate (PtdInsP2). To achieve this, the cells were transformed with, respectively, the human InsP3 5-phosphatase ('Ptase cells') or human phosphatidylinositol (4) phosphate 5-kinase ('PIPK cells'). The mean P f of the PIPK cells was several-fold higher relative to that of controls and Ptase cells. Three results favor aquaporins over the membrane matrix as underlying this excessive P f: (1) transient expression of the maize aquaporin ZmPIP2;4 in the PIPK cells increased P f by 12-30 μm s(-1), while in the controls only by 3-4 μm s(-1). (2) Cytosol acidification-known to inhibit aquaporins-lowered the P f in the PIPK cells down to control levels. (3) The transcript of at least one aquaporin was elevated in the PIPK cells. Together, the three results demonstrate the differences between the PIPK cells and their controls, and suggest a hitherto unobserved regulation of aquaporins by phosphoinositides, which could occur through direct interaction or indirect phosphoinositides-dependent cellular effects.

  5. 77 FR 12227 - Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public...

    Science.gov (United States)

    2012-02-29

    ... Water Treatment Rule: Uncovered Finished Water Reservoirs; Public Meeting AGENCY: Environmental... review of the uncovered finished water reservoir requirement in the Long Term 2 Enhanced Surface Water... uncovered finished water reservoir requirement and the agency's Six Year Review process. EPA also plans to...

  6. Actin filaments regulate the adhesion between the plasma membrane and the cell wall of tobacco guard cells.

    Science.gov (United States)

    Yu, Qin; Ren, Jing-Jing; Kong, Lan-Jing; Wang, Xiu-Ling

    2018-01-01

    During the opening and closing of stomata, guard cells undergo rapid and reversible changes in their volume and shape, which affects the adhesion of the plasma membrane (PM) to the cell wall (CW). The dynamics of actin filaments in guard cells are involved in stomatal movement by regulating structural changes and intracellular signaling. However, it is unclear whether actin dynamics regulate the adhesion of the PM to the CW. In this study, we investigated the relationship between actin dynamics and PM-CW adhesion by the hyperosmotic-induced plasmolysis of tobacco guard cells. We found that actin filaments in guard cells were depolymerized during mannitol-induced plasmolysis. The inhibition of actin dynamics by treatment with latrunculin B or jasplakinolide and the disruption of the adhesion between the PM and the CW by treatment with RGDS peptide (Arg-Gly-Asp-Ser) enhanced guard cell plasmolysis. However, treatment with latrunculin B alleviated the RGDS peptide-induced plasmolysis and endocytosis. Our results reveal that the actin depolymerization is involved in the regulation of the PW-CW adhesion during hyperosmotic-induced plasmolysis in tobacco guard cells.

  7. Motives for choosing growth-enhancing hormone treatment in adolescents with idiopathic short stature: a questionnaire and structured interview study

    NARCIS (Netherlands)

    Visser-van Balen, J.; Geenen, R.; Kamp, G.A.; Huisman, J.; Wit, J.M.; Sinnema, G.

    2005-01-01

    Background Growth-enhancing hormone treatment is considered a possible intervention in short but otherwise healthy adolescents. Although height gain is an obvious measure for evaluating hormone treatment, this may not be the ultimate goal for the person, but rather a means to reach other goals such

  8. Nutritive values of brassica campestris L. oil as affected by growth regulator treatments

    International Nuclear Information System (INIS)

    Bano, A.; Khan, N.

    2009-01-01

    The effects of plant growth regulators, viz. Indole acetic acid (IAA), Gibberellic acid (GA) and Abscisic acid (ABA) were studied on fatty acid compositions, glucosinolate content and protein content of Brassica campestris L subsp. Oleifera (common name yellow sarson). Growth regulators were applied in seed soaking solution as well as foliar spray during vegetative phase and at flowering stage. There were reductions in the amount of long chain fatty acids viz erucic acid, eicosenoic acid and increase in the amount of unsaturated fatty acid viz. linoleic acid by lAA applications. The stimulating effect of lAA which reduced amount of unsaturated fatty acid was more pronounced when applied as foliar spray at vegetative stage. But, foliar spray of ABA during flowering increased the concentration of linoleic acid and reduced the eicosenoic acid and erucic acid. The glucosinolate content was greater in seeds soaked in 10/sup -5/ M lAA than that of control but less in 10/sup -5/ M GA treated seeds than that of control. The ABA treatment (10/sup -5/M) increased the concentration of glucosinolates in the seeds IAA treatments (10/sup -5/M) increased the protein percentage in the seeds. Foliar application of GA (10/sup -5/M) during vegetative growth and ABA (10/sup -5/M) as seed soaking prior to sowing as well as foliar spry during flowering decreased the protein content of seeds. (author)

  9. High-pass filtering and dynamic gain regulation enhance vertical bursts transmission along the mossy fiber pathway of cerebellum

    Directory of Open Access Journals (Sweden)

    Jonathan Mapelli

    2010-05-01

    Full Text Available Signal elaboration in the cerebellum mossy fiber input pathway presents controversial aspects, especially concerning gain regulation and the spot-like (rather than beam-like appearance of granular-to-molecular layer transmission. By using voltage-sensitive dye (VSD imaging in rat cerebellar slices (Mapelli et al., 2010, we found that mossy fiber bursts optimally excited the granular layer above ~50 Hz and the overlaying molecular layer above ~100 Hz, thus generating a cascade of high-pass filters. NMDA receptors enhanced transmission in the granular, while GABA-A receptors depressed transmission in both the granular and molecular layer. Burst transmission gain was controlled through a dynamic frequency-dependent involvement of these receptors. Moreover, while high-frequency transmission was enhanced along vertical lines connecting the granular to molecular layer, no high-frequency enhancement was observed along the parallel fiber axis in the molecular layer. This was probably due to the stronger effect of Purkinje cell GABA-A receptor-mediated inhibition occurring along the parallel fibers than along the granule cell axon ascending branch. The consequent amplification of burst responses along vertical transmission lines could explain the spot-like activation of Purkinje cells observed following punctuate stimulation in vivo .

  10. The key role of extinction learning in anxiety disorders: behavioral strategies to enhance exposure-based treatments.

    Science.gov (United States)

    Pittig, Andre; van den Berg, Linda; Vervliet, Bram

    2016-01-01

    Extinction learning is a major mechanism for fear reduction by means of exposure. Current research targets innovative strategies to enhance fear extinction and thereby optimize exposure-based treatments for anxiety disorders. This selective review updates novel behavioral strategies that may provide cutting-edge clinical implications. Recent studies provide further support for two types of enhancement strategies. Procedural enhancement strategies implemented during extinction training translate to how exposure exercises may be conducted to optimize fear extinction. These strategies mostly focus on a maximized violation of dysfunctional threat expectancies and on reducing context and stimulus specificity of extinction learning. Flanking enhancement strategies target periods before and after extinction training and inform optimal preparation and post-processing of exposure exercises. These flanking strategies focus on the enhancement of learning in general, memory (re-)consolidation, and memory retrieval. Behavioral strategies to enhance fear extinction may provide powerful clinical applications to further maximize the efficacy of exposure-based interventions. However, future replications, mechanistic examinations, and translational studies are warranted to verify long-term effects and naturalistic utility. Future directions also comprise the interplay of optimized fear extinction with (avoidance) behavior and motivational antecedents of exposure.

  11. Increase in tumour permeability following TGF-? type I receptor-inhibitor treatment observed by dynamic contrast-enhanced MRI

    OpenAIRE

    Minowa, T; Kawano, K; Kuribayashi, H; Shiraishi, K; Sugino, T; Hattori, Y; Yokoyama, M; Maitani, Y

    2009-01-01

    Background: To enhance the success rate of nanocarrier-mediated chemotherapy combined with an anti-angiogenic agent, it is crucial to identify parameters for tumour vasculature that can predict a response to the treatment of the anti-angiogenic agent. Methods: To apply transforming growth factor (TGF)-? type I receptor (T?R-I) inhibitor, A-83-01, to combined therapy, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was carried out in mice bearing colon 26 cells using gadolinium ...

  12. Involvement of the K+-Cl- co-transporter KCC2 in the sensitization to morphine-induced hyperlocomotion under chronic treatment with zolpidem in the mesolimbic system.

    Science.gov (United States)

    Shibasaki, Masahiro; Masukawa, Daiki; Ishii, Kazunori; Yamagishi, Yui; Mori, Tomohisa; Suzuki, Tsutomu

    2013-06-01

    Benzodiazepines are commonly used as sedatives, sleeping aids, and anti-anxiety drugs. However, chronic treatment with benzodiazepines is known to induce dependence, which is considered related to neuroplastic changes in the mesolimbic system. This study investigated the involvement of K(+) -Cl(-) co-transporter 2 (KCC2) in the sensitization to morphine-induced hyperlocomotion after chronic treatment with zolpidem [a selective agonist of γ-aminobutyric acid A-type receptor (GABAA R) α1 subunit]. In this study, chronic treatment with zolpidem enhanced morphine-induced hyperlocomotion, which is accompanied by the up-regulation of KCC2 in the limbic forebrain. We also found that chronic treatment with zolpidem induced the down-regulation of protein phosphatase-1 (PP-1) as well as the up-regulation of phosphorylated protein kinase C γ (pPKCγ). Furthermore, PP-1 directly associated with KCC2 and pPKCγ, whereas pPKCγ did not associate with KCC2. On the other hand, pre-treatment with furosemide (a KCC2 inhibitor) suppressed the enhancing effects of zolpidem on morphine-induced hyperlocomotion. These results suggest that the mesolimbic dopaminergic system could be amenable to neuroplastic change through a pPKCγ-PP-1-KCC2 pathway by chronic treatment with zolpidem. © 2013 International Society for Neurochemistry.

  13. Enhancing protein to extremely high content in photosynthetic bacteria during biogas slurry treatment.

    Science.gov (United States)

    Yang, Anqi; Zhang, Guangming; Meng, Fan; Lu, Pei; Wang, Xintian; Peng, Meng

    2017-12-01

    This work proposed a novel approach to achieve an extremely high protein content in photosynthetic bacteria (PSB) using biogas slurry as a culturing medium. The results showed the protein content of PSB could be enhanced strongly to 90% in the biogas slurry, which was much higher than reported microbial protein contents. The slurry was partially purified at the same time. Dark-aerobic was more beneficial than light-anaerobic condition for protein accumulation. High salinity and high ammonia of the biogas slurry were the main causes for protein enhancement. In addition, the biogas slurry provided a good buffer system for PSB to grow. The biosynthesis mechanism of protein in PSB was explored according to theoretical analysis. During biogas slurry treatment, the activities of glutamate synthase and glutamine synthetase were increased by 26.55%, 46.95% respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response

    KAUST Repository

    Liao, Hsin-Wei; Hsu, Jung-Mao; Xia, Weiya; Wang, Hung-Ling; Wang, Ying-Nai; Chang, Wei-Chao; Arold, Stefan T.; Chou, Chao-Kai; Tsou, Pei-Hsiang; Yamaguchi, Hirohito; Fang, Yueh-Fu; Lee, Hong-Jen; Lee, Heng-Huan; Tai, Shyh-Kuan; Yang, Mhu-Hwa; Morelli, Maria P.; Sen, Malabika; Ladbury, John E.; Chen, Chung-Hsuan; Grandis, Jennifer R.; Kopetz, Scott; Hung, Mien-Chie

    2015-01-01

    Posttranslational modifications to the intracellular domain of the EGFR are known to regulate EGFR functions; however, modifications to the extracellular domain and their effects remain relatively unexplored. Here, we determined that methylation at R198 and R200 of the EGFR extracellular domain by protein arginine methyltransferase 1 (PRMT1) enhances binding to EGF and subsequent receptor dimerization and signaling activation. In a mouse orthotopic colorectal cancer xenograft model, expression of a methylation-defective EGFR reduced tumor growth. Moreover, increased EGFR methylation sustained signaling activation and cell proliferation in the presence of the therapeutic EGFR monoclonal antibody cetuximab. In colorectal cancer patients, EGFR methylation level also correlated with a higher recurrence rate after cetuximab treatment and reduced overall survival. Together, these data indicate that R198/R200 methylation of the EGFR plays an important role in regulating EGFR functionality and resistance to cetuximab treatment.

  15. PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response

    KAUST Repository

    Liao, Hsin-Wei

    2015-11-16

    Posttranslational modifications to the intracellular domain of the EGFR are known to regulate EGFR functions; however, modifications to the extracellular domain and their effects remain relatively unexplored. Here, we determined that methylation at R198 and R200 of the EGFR extracellular domain by protein arginine methyltransferase 1 (PRMT1) enhances binding to EGF and subsequent receptor dimerization and signaling activation. In a mouse orthotopic colorectal cancer xenograft model, expression of a methylation-defective EGFR reduced tumor growth. Moreover, increased EGFR methylation sustained signaling activation and cell proliferation in the presence of the therapeutic EGFR monoclonal antibody cetuximab. In colorectal cancer patients, EGFR methylation level also correlated with a higher recurrence rate after cetuximab treatment and reduced overall survival. Together, these data indicate that R198/R200 methylation of the EGFR plays an important role in regulating EGFR functionality and resistance to cetuximab treatment.

  16. PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response

    Science.gov (United States)

    Liao, Hsin-Wei; Hsu, Jung-Mao; Xia, Weiya; Wang, Hung-Ling; Wang, Ying-Nai; Chang, Wei-Chao; Arold, Stefan T.; Chou, Chao-Kai; Tsou, Pei-Hsiang; Yamaguchi, Hirohito; Fang, Yueh-Fu; Lee, Hong-Jen; Lee, Heng-Huan; Tai, Shyh-Kuan; Yang, Mhu-Hwa; Morelli, Maria P.; Sen, Malabika; Ladbury, John E.; Chen, Chung-Hsuan; Grandis, Jennifer R.; Kopetz, Scott; Hung, Mien-Chie

    2015-01-01

    Posttranslational modifications to the intracellular domain of the EGFR are known to regulate EGFR functions; however, modifications to the extracellular domain and their effects remain relatively unexplored. Here, we determined that methylation at R198 and R200 of the EGFR extracellular domain by protein arginine methyltransferase 1 (PRMT1) enhances binding to EGF and subsequent receptor dimerization and signaling activation. In a mouse orthotopic colorectal cancer xenograft model, expression of a methylation-defective EGFR reduced tumor growth. Moreover, increased EGFR methylation sustained signaling activation and cell proliferation in the presence of the therapeutic EGFR monoclonal antibody cetuximab. In colorectal cancer patients, EGFR methylation level also correlated with a higher recurrence rate after cetuximab treatment and reduced overall survival. Together, these data indicate that R198/R200 methylation of the EGFR plays an important role in regulating EGFR functionality and resistance to cetuximab treatment. PMID:26571401

  17. Regulatory Oversight for New Projects - Challenges and Improvement in Regulation

    International Nuclear Information System (INIS)

    Lall, F.

    2016-01-01

    From inception, there has been rise in number of Nuclear Power Plants (NPP) even though very few accidents / events led to intermittent setbacks. However these accidents / events have posed challenges towards enhancement of safety and scope of regulation in all phases of NPP such as siting, design, construction, commissioning and decommissioning. It is essential to ensure compliance to these enhanced safety requirements during all phases of NPP. New and evolutionary reactors are under threshold for regulatory consideration world over. The variety of technologies and genres by themselves pose challenges to regulatory bodies. These challenges are to be addressed through systematic enhancement of the regulation including updating of regulatory documents. The paper touches upon some key elements to be considered towards such enhancement of regulation during all stages of NPP. These being; ensuring quality assurance, regulatory oversight especially over supply chain and contractors, counterfeit material specifically in case of international dealings, emergency handling in case of multi-unit site, feedback and associated enhancements from international events, construction experience database and feedback for safety enhancement, qualification and acceptance of first of a kind systems, regulatory enforcement specifically in case of imported reactors and maintaining interface between safety and security. Regulation in present context has become dynamic and Regulatory bodies need to continue enhancement of its current regulation taking into account the technological developments, feedback from construction, operation and accidents in the current fleet of plants. The paper touches upon some of these elements and highlights the challenges and improvements in regulation. (author)

  18. Targeting DNA double strand break repair with hyperthermia and DNA-PKcs inhibition to enhance the effect of radiation treatment.

    Science.gov (United States)

    van Oorschot, Bregje; Granata, Giovanna; Di Franco, Simone; Ten Cate, Rosemarie; Rodermond, Hans M; Todaro, Matilde; Medema, Jan Paul; Franken, Nicolaas A P

    2016-10-04

    Radiotherapy is based on the induction of lethal DNA damage, primarily DNA double-strand breaks (DSB). Efficient DSB repair via Non-Homologous End Joining or Homologous Recombination can therefore undermine the efficacy of radiotherapy. By suppressing DNA-DSB repair with hyperthermia (HT) and DNA-PKcs inhibitor NU7441 (DNA-PKcsi), we aim to enhance the effect of radiation.The sensitizing effect of HT for 1 hour at 42°C and DNA-PKcsi [1 μM] to radiation treatment was investigated in cervical and breast cancer cells, primary breast cancer sphere cells (BCSCs) enriched for cancer stem cells, and in an in vivo human tumor model. A significant radio-enhancement effect was observed for all cell types when DNA-PKcsi and HT were applied separately, and when both were combined, HT and DNA-PKcsi enhanced radio-sensitivity to an even greater extent. Strikingly, combined treatment resulted in significantly lower survival rates, 2 to 2.5 fold increase in apoptosis, more residual DNA-DSB 6 h post treatment and a G2-phase arrest. In addition, tumor growth analysis in vivo showed significant reduction in tumor growth and elevated caspase-3 activity when radiation was combined with HT and DNA-PKcsi compared to radiation alone. Importantly, no toxic side effects of HT or DNA-PKcsi were found.In conclusion, inhibiting DNA-DSB repair using HT and DNA-PKcsi before radiotherapy leads to enhanced cytotoxicity in cancer cells. This effect was even noticed in the more radio-resistant BCSCs, which are clearly sensitized by combined treatment. Therefore, the addition of HT and DNA-PKcsi to conventional radiotherapy is promising and might contribute to more efficient tumor control and patient outcome.

  19. The effect of fasting on the important molecular mechanisms related to cancer treatment

    OpenAIRE

    Vahideh Keyvani; Mohammad Amin Kerachian

    2014-01-01

    Fasting does have remarkable benefits in the treatment of cancer and another diseases such as metabolic syndrome, diabetes, and a multitude of other chronic diseases. It has been determined that fasting could play an important role during cancer treatment and progression via the regulation of insulin-like growth factor-1 (IGF-1) as well as other growth factors. Also, it has been shown that fasting would enhance the chemotherapy effect in cancer patients, selectively protects normal cells and ...

  20. Overexpression of NtPR-Q Up-Regulates Multiple Defense-Related Genes in Nicotiana tabacum and Enhances Plant Resistance to Ralstonia solanacearum

    Directory of Open Access Journals (Sweden)

    Yuanman Tang

    2017-11-01

    Full Text Available Various classes of plant pathogenesis-related proteins have been identified in the past several decades. PR-Q, a member of the PR3 family encoding chitinases, has played an important role in regulating plant resistance and preventing pathogen infection. In this paper, we functionally characterized NtPR-Q in tobacco plants and found that the overexpression of NtPR-Q in tobacco Yunyan87 resulted in higher resistance to Ralstonia solanacearum inoculation. Surprisingly, overexpression of NtPR-Q led to the activation of many defense-related genes, such as salicylic acid (SA-responsive genes NtPR1a/c, NtPR2 and NtCHN50, JA-responsive gene NtPR1b and ET production-associated genes NtACC Oxidase and NtEFE26. Consistent with the role of NtPR-Q in multiple stress responses, NtPR-Q transcripts were induced by the exogenous hormones SA, ethylene and methyl jasmonate, which could enhance the resistance of tobacco to R. solanacearum. Collectively, our results suggested that NtPR-Q overexpression led to the up-regulation of defense-related genes and enhanced plant resistance to R. solanacearum infection.

  1. Mindfulness meditation improves emotion regulation and reduces drug abuse.

    Science.gov (United States)

    Tang, Yi-Yuan; Tang, Rongxiang; Posner, Michael I

    2016-06-01

    The core clinical symptoms of addiction include an enhanced incentive for drug taking (craving), impaired self-control (impulsivity and compulsivity), emotional dysregulation (negative mood) and increased stress reactivity. Symptoms related to impaired self-control involve reduced activity in anterior cingulate cortex (ACC), adjacent prefrontal cortex (mPFC) and other brain areas. Behavioral training such as mindfulness meditation can increase the function of control networks including those leading to improved emotion regulation and thus may be a promising approach for the treatment of addiction. In a series of randomized controlled trials (RCTs), we tested whether increased ACC/mPFC activity is related to better self-control abilities in executive functions, emotion regulation and stress response in healthy and addicted populations. After a brief mindfulness training (Integrative Body-Mind Training, IBMT), we used the Positive and Negative Affect Schedule (PANAS) and Profile of Mood States (POMS) to measure emotion regulation, salivary cortisol for the stress response and fMRI for brain functional and DTI structural changes. Relaxation training was used to serve as an active control. In both smokers and nonsmokers, improved self-control abilities in emotion regulation and stress reduction were found after training and these changes were related to increased ACC/mPFC activity following training. Compared with nonsmokers, smokers showed reduced ACC/mPFC activity in the self-control network before training, and these deficits were ameliorated after training. These results indicate that promoting emotion regulation and improving ACC/mPFC brain activity can help for addiction prevention and treatment. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  2. Loss of Kdm5c Causes Spurious Transcription and Prevents the Fine-Tuning of Activity-Regulated Enhancers in Neurons

    Directory of Open Access Journals (Sweden)

    Marilyn Scandaglia

    2017-10-01

    Full Text Available During development, chromatin-modifying enzymes regulate both the timely establishment of cell-type-specific gene programs and the coordinated repression of alternative cell fates. To dissect the role of one such enzyme, the intellectual-disability-linked lysine demethylase 5C (Kdm5c, in the developing and adult brain, we conducted parallel behavioral, transcriptomic, and epigenomic studies in Kdm5c-null and forebrain-restricted inducible knockout mice. Together, genomic analyses and functional assays demonstrate that Kdm5c plays a critical role as a repressor responsible for the developmental silencing of germline genes during cellular differentiation and in fine-tuning activity-regulated enhancers during neuronal maturation. Although the importance of these functions declines after birth, Kdm5c retains an important genome surveillance role preventing the incorrect activation of non-neuronal and cryptic promoters in adult neurons.

  3. The importance of need for cognition and educational experience in enhanced and standard substance abuse treatment.

    Science.gov (United States)

    Czuchry, Michael; Dansereau, Donald F

    2004-06-01

    The current study examined the relationship between need for cognition (i.e., cognitive motivation or "will") and educational experience (i.e., cognitive ability or "skill") to perceived improvements during treatment of probationers receiving residential treatment within the criminal justice system. Probationers were randomly assigned to either receive motivational activities developed by the authors (the "enhanced" condition), or treatment as usual (but with access to general reading materials in lieu of the motivational activities). Need for cognition and educational experience were assessed and used as blocking variables, and ratings of progress were assessed midway and toward the end of treatment. The results indicate that both need for cognition and educational experience are important predictors of improvement during treatment, and that the motivational activities developed by the authors were particularly valuable for clients with lower levels of need for cognition.

  4. TaNAC1 acts as a negative regulator of stripe rust resistance in wheat, enhances susceptibility to Pseudomonas syringae, and promotes lateral root development in transgenic Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Fengtao eWang

    2015-02-01

    Full Text Available Plant-specific NAC transcription factors constitute a large family and play important roles in regulating plant developmental processes and responses to environmental stresses, but only some of them have been investigated for effects on disease reaction in cereal crops. Virus-induced gene silencing (VIGS is an effective strategy for rapid functional analysis of genes in plant tissues. In this study, TaNAC1, encoding a new member of the NAC1 subgroup, was cloned from bread wheat and characterized. It is a transcription factor localized in the cell nucleus, and contains an activation domain in its C-terminal. TaNAC1 was strongly expressed in wheat roots and was involved in responses to infection by the obligate pathogen Puccinia striiformis f. sp. tritici and defense-related hormone treatments such as salicylic acid, methyl jasmonate and ethylene. Knockdown of TaNAC1 with barley stripe mosaic virus-induced gene silencing (BSMV-VIGS enhanced stripe rust resistance. TaNAC1-overexpression in Arabidopsis plants gave enhanced susceptibility, attenuated systemic-acquired resistance to Pseudomonas syringae DC3000, and promoted lateral root development. Jasmonic acid-signaling pathway genes PDF1.2 and ORA59 were constitutively expressed in transgenic plants. TaNAC1 overexpression suppressed the expression levels of resistance-related genes PR1 and PR2 involved in SA signaling and AtWRKY70, which functions as a connection node between the JA- and SA-signaling pathways. Collectively, TaNAC1 is a novel NAC member of the NAC1 subgroup, negatively regulates plant disease resistance, and may modulate plant JA- and SA-signaling defense cascades.

  5. Neuraminidase treatment of respiratory syncytial virus-infected cells or virions, but not target cells, enhances cell-cell fusion and infection

    International Nuclear Information System (INIS)

    Barretto, Naina; Hallak, Louay K.; Peeples, Mark E.

    2003-01-01

    Respiratory syncytial virus (RSV) infection of HeLa cells induces fusion, but transient expression of the three viral glycoproteins induces fusion poorly, if at all. We found that neuraminidase treatment of RSV-infected cells to remove sialic acid (SA) increases fusion dramatically and that the same treatment of transiently transfected cells expressing the three viral glycoproteins, or even cells expressing the fusion (F) protein alone, results in easily detectable fusion. Neuraminidase treatment of the effector cells, expressing the viral glycoproteins, enhanced fusion while treatment of the target cells did not. Likewise, infectivity was increased by treating virions with neuraminidase, but not by treating target cells. Reduction of charge repulsion by removal of the negatively charged SA is unlikely to explain this effect, since removal of negative charges from either membrane would reduce charge repulsion. Infection with neuraminidase-treated virus remained heparan-sulfate-dependent, indicating that a novel attachment mechanism is not revealed by SA removal. Interestingly, neuraminidase enhancement of RSV infectivity was less pronounced in a virus expressing both the G and the F glycoproteins, compared to virus expressing only the F glycoprotein, possibly suggesting that the G protein sterically hinders access of the neuraminidase to its fusion-enhancing target

  6. Irigenin sensitizes TRAIL-induced apoptosis via enhancing pro-apoptotic molecules in gastric cancer cells.

    Science.gov (United States)

    Xu, Ying; Gao, Cheng-Cheng; Pan, Zhen-Guo; Zhou, Chuan-Wen

    2018-02-12

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promising value for cancer therapy due to its capacity to induce apoptosis in cancer cells. Nevertheless, TRAIL therapy is greatly hampered by its resistance. Irigenin (Iri), isoflavonoids, can be isolated from the rhizome of Belamcanda chinensis, and has been shown anti-cancer properties. In this study, we explored if Iri could enhance TRAIL-regulated apoptosis in TRAIL resistant gastric cancer cells. Iri significantly potentiated TRAIL-triggered cytotoxicity. Iri alone and TRAIL alone showed no effective role in apoptosis induction, whereas combined treatment with Iri and TRAIL markedly induced apoptosis in cancer cells, as evidenced by the up-regulation of cleaved Caspase-8/-9/-3 and PARP. Additionally, the sensitization to TRAIL was along with the enhancement of pro-apoptotic proteins, including FAS-associated protein with death domain (FADD), death receptor 5 (DR5) and Bax. And suppressing FADD, DR5 and Bax by si RNA significantly reduced the apoptosis and enhanced the cell viability induced by the co-application of Iri and TRAIL. Moreover, the sensitization to TRAIL was accompanied by the decrease of Cellular-FLICE inhibitory protein (c-FLIP), Bcl-2 and Survivin. Additionally, Iri could sensitize TRAIL to produce reactive oxygen species (ROS). Pre-treatment of N-acetyl-cysteine (NAC), ROS scavenger, attenuated Iri plus TRAIL-induced apoptosis and improved cell viability. Finally, combination of Iri and TRAIL inhibited tumor growth in the xenograft model. Collectively, our present study gave new insights into the effects of Iri on potentiating TRAIL-sensitivity, and suggested that Iri could be a potential candidate for sensitizer of TRAIL-resistant cancer cell treatment. Copyright © 2018. Published by Elsevier Inc.

  7. Functional FRIGIDA allele enhances drought tolerance by regulating the P5CS1 pathway in Arabidopsis thaliana.

    Science.gov (United States)

    Chen, Qian; Zheng, Yan; Luo, Landi; Yang, Yongping; Hu, Xiangyang; Kong, Xiangxiang

    2018-01-01

    Flowering at the right time is important for the reproductive success of plants and their response to environmental stress. In Arabidopsis, a major determinant of natural variation in flowering time is FRIGIDA (FRI). In the present study, we show that overexpression of the functional FRIGIDA gene in wild-type Col background (ColFRI) positively enhances the drought tolerance by activating P5CS1 expression and promoting proline accumulation during water stress. Furthermore, no significant changes in FRI gene and protein expression levels were observed with drought treatment, whereas P5CS1 protein expression significantly increased. In contrast, vernalization treatment efficiently reduced P5CS1 expression levels and resulted in a decrease in drought tolerance in the ColFRI plants. The flc mutants with a functional FRI background also relieved FRI-mediated activation of P5CS1 during drought tolerance. Taken together, our findings reveal the novel function of FRI in enhancing drought resistance through its downstream P5CS1 pathway during water-deficit stress, which is dependent on its target, the FLC gene. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Permeability enhancers dramatically increase zanamivir absolute bioavailability in rats: implications for an orally bioavailable influenza treatment.

    Directory of Open Access Journals (Sweden)

    Eric H Holmes

    Full Text Available We have demonstrated that simple formulations composed of the parent drug in combination with generally regarded as safe (GRAS permeability enhancers are capable of dramatically increasing the absolute bioavailability of zanamivir. This has the advantage of not requiring modification of the drug structure to promote absorption, thus reducing the regulatory challenges involved in conversion of an inhaled to oral route of administration of an approved drug. Absolute bioavailability increases of up to 24-fold were observed when Capmul MCM L8 (composed of mono- and diglycerides of caprylic/capric acids in glycerol was mixed with 1.5 mg of zanamivir and administered intraduodenally to rats. Rapid uptake (t(max of 5 min and a C(max of over 7200 ng/mL was achieved. Variation of the drug load or amount of enhancer demonstrated a generally linear variation in absorption, indicating an ability to optimize a formulation for a desired outcome such as a targeted C(max for enzyme saturation. No absorption enhancement was observed when the enhancer was given 2 hr prior to drug administration, indicating, in combination with the observed tmax, that absorption enhancement is temporary. This property is significant and aligns well with therapeutic applications to limit undesirable drug-drug interactions, potentially due to the presence of other poorly absorbed polar drugs. These results suggest that optimal human oral dosage forms of zanamivir should be enteric-coated gelcaps or softgels for intraduodenal release. There continues to be a strong need and market for multiple neuraminidase inhibitors for influenza treatment. Creation of orally available formulations of inhibitor drugs that are currently administered intravenously or by inhalation would provide a significant improvement in treatment of influenza. The very simple GRAS formulation components and anticipated dosage forms would require low manufacturing costs and yield enhanced convenience. These results

  9. Enhancement of Cellular Antioxidant-Defence Preserves Diastolic Dysfunction via Regulation of Both Diastolic Zn2+ and Ca2+ and Prevention of RyR2-Leak in Hyperglycemic Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Erkan Tuncay

    2014-01-01

    Full Text Available We examined whether cellular antioxidant-defence enhancement preserves diastolic dysfunction via regulation of both diastolic intracellular free Zn2+ and Ca2+ levels (Zn2+i and Ca2+i levels N-acetyl cysteine (NAC treatment (4 weeks of diabetic rats preserved altered cellular redox state and also prevented diabetes-induced tissue damage and diastolic dysfunction with marked normalizations in the resting Zn2+i and Ca2+i. The kinetic parameters of transient changes in Zn2+ and Ca2+ under electrical stimulation and the spatiotemporal properties of Zn2+ and Ca2+ sparks in resting cells are found to be normal in the treated diabetic group. Biochemical analysis demonstrated that the NAC treatment also antagonized hyperphosphorylation of cardiac ryanodine receptors (RyR2 and significantly restored depleted protein levels of both RyR2 and calstabin2. Incubation of cardiomyocytes with 10 µM ZnCl2 exerted hyperphosphorylation in RyR2 as well as higher phosphorphorylations in both PKA and CaMKII in a concentration-dependent manner, similar to hyperglycemia. Our present data also showed that a subcellular oxidative stress marker, NF-κB, can be activated if the cells are exposed directly to Zn2+. We thus for the first time report that an enhancement of antioxidant defence in diabetics via directly targeting heart seems to prevent diastolic dysfunction due to modulation of RyR2 macromolecular-complex thereby leading to normalized Ca2+i and Zn2+i in cardiomyocytes.

  10. The theory of regulation : a review article

    NARCIS (Netherlands)

    Uche, C.U.

    2001-01-01

    This paper examines the various theoretical issues in regulation with a view to enhancing understanding of the regulation arena. Special emphasis has been placed on the banking industry. The paper shows how regulation serves different purposes for different interest groups on different occasions. It

  11. Biochemically enhanced oil recovery and oil treatment

    Science.gov (United States)

    Premuzic, Eugene T.; Lin, Mow

    1994-01-01

    This invention relates to the preparation of new, modified organisms, through challenge growth processes, that are viable in the extreme temperature, pressure and pH conditions and salt concentrations of an oil reservoir and that are suitable for use in microbial enhanced oil recovery. The modified microorganisms of the present invention are used to enhance oil recovery and remove sulfur compounds and metals from the crude oil.

  12. EGCG Enhances Cisplatin Sensitivity by Regulating Expression of the Copper and Cisplatin Influx Transporter CTR1 in Ovary Cancer.

    Directory of Open Access Journals (Sweden)

    Xuemin Wang

    Full Text Available Cisplatin is one of the first-line platinum-based chemotherapeutic agents for treatment of many types of cancer, including ovary cancer. CTR1 (copper transporter 1, a transmembrane solute carrier transporter, has previously been shown to increase the cellular uptake and sensitivity of cisplatin. It is hypothesized that increased CTR1 expression would enhance the sensitivity of cancer cells to cisplatin (cDDP. The present study demonstrates for the first time that (--epigallocatechin-3-gallate (EGCG, a major polyphenol from green tea, can enhance CTR1 mRNA and protein expression in ovarian cancer cells and xenograft mice. EGCG inhibits the rapid degradation of CTR1 induced by cDDP. The combination of EGCG and cDDP increases the accumulation of cDDP and DNA-Pt adducts, and subsequently enhances the sensitivity of ovarian cancer SKOV3 and OVCAR3 cells to the chemotherapeutic agent. In the OVCAR3 ovarian cancer xenograft nude mice model, the combination of the lower concentration of cDDP and EGCG strongly repressed the tumor growth and exhibited protective effect on the nephrotoxicity induced by cisplatin. Overall, these findings uncover a novel chemotherapy mechanism of EGCG as an adjuvant for the treatment of ovarian cancer.

  13. Field test for treatment verification of an in-situ enhanced bioremediation study

    International Nuclear Information System (INIS)

    Taur, C.K.; Chang, S.C.

    1995-01-01

    Due to a leakage from a 12-inch pressurized diesel steel pipe four years ago, an area of approximately 30,000 square meters was contaminated. A pilot study applying the technology of in-situ enhanced bioremediation was conducted. In the study, a field test kit and on-site monitoring equipment were applied for site characterization and treatment verification. Physically, the enhanced bioremediation study consisted of an air extraction and air supply system, and a nutrition supply network. Certain consistent sampling methodology was employed. Progress was verified by daily monitoring and monthly verification. The objective of this study was to evaluate the capabilities of indigenous microorganisms to biodegrade the petroleum hydrocarbons with provision of oxygen and nutrients. Nine extraction wells and eight air sparging wells were installed. The air sparging wells injected the air into geoformation and the extraction wells provided the underground air circulation. The soil samples were obtained monthly for treatment verification by a Minuteman drilling machine with 2.5-foot-long hollow-stem augers. The samples were analyzed on site for TPH-diesel concentration by a field test kit manufactured by HNU-Hanby, Houston, Texas. The analytical results from the field test kit were compared with the results from an environmental laboratory. The TVPH concentrations of the air extracted from the vadose zone by a vacuum blower and the extraction wells were routinely monitored by a Foxboro FID and Cosmos XP-311A combustible air detector. The daily monitoring of TVPH concentrations provided the reliable data for assessing the remedial progress

  14. Enhanced Transmission of Drug-Resistant Parasites to Mosquitoes following Drug Treatment in Rodent Malaria

    OpenAIRE

    Bell, Andrew S.; Huijben, Silvie; Paaijmans, Krijn P.; Sim, Derek G.; Chan, Brian H. K.; Nelson, William A.; Read, Andrew F.

    2012-01-01

    The evolution of drug resistant Plasmodium parasites is a major challenge to effective malaria control. In theory, competitive interactions between sensitive parasites and resistant parasites within infections are a major determinant of the rate at which parasite evolution undermines drug efficacy. Competitive suppression of resistant parasites in untreated hosts slows the spread of resistance; competitive release following treatment enhances it. Here we report that for the murine model Plasm...

  15. Dioxinodehydroeckol Enhances the Differentiation of Osteoblasts by Regulating the Expression of Phospho-Smad1/5/8

    Directory of Open Access Journals (Sweden)

    Byul-Nim Ahn

    2016-09-01

    Full Text Available Lack of bone formation-related health problems are a major problem for the aging population in the modern world. As a part of the ongoing trend of developing natural substances that attenuate osteoporotic bone loss conditions, dioxinodehydroeckol (DHE from edible brown alga Ecklonia cava was tested for its effects on osteoblastogenic differentiation in MC3T3-E1 pre-osteoblasts. DHE was observed to successfully enhance osteoblast differentiation, as indicated by elevated cell proliferation, alkaline phosphatase activity, intracellular cell mineralization, along with raised levels of osteoblastogenesis indicators at the concentration of 20 μM. Results suggested a possible intervening of DHE on the bone morphogenetic protein (BMP signaling pathway, according to elevated protein levels of BMP-2, collagen-I, and Smads. In addition, the presence of DHE was also able to raise the phosphorylated extracellular signal–regulated kinase (ERK and c-Jun N-terminal kinase (JNK levels which are also activated by the BMP signaling pathway. In conclusion, DHE is suggested to be a potential bioactive compound against bone loss that could enhance osteoblastogenesis with a suggested BMP pathway interaction.

  16. Moving from self-regulation to external regulation of Department of Energy facilities

    International Nuclear Information System (INIS)

    Wishau, R.J.; Dawson, J.; Lee, D.W.

    1999-01-01

    This paper discusses the initiative to transfer the regulation of Department of Energy (DOE) nuclear facilities to the US Nuclear Regulatory Commission (NRC). The paper gives an overview of some of the major technical, policy and legal issues that accompany this initiative. The paper focuses on specific issues and how they may be affected by external regulation of occupational radiation protection at DOE facilities. Differences between the NRC and the DOE approach to regulating nuclear safety are compared and contrasted. Some projected impacts from this transition are examined. Finally, recommendations are provided that may enhance the transition, increasing the likelihood of successful external NRC regulation

  17. A high-throughput fluorescence-based assay system for appetite-regulating gene and drug screening.

    Directory of Open Access Journals (Sweden)

    Yasuhito Shimada

    Full Text Available The increasing number of people suffering from metabolic syndrome and obesity is becoming a serious problem not only in developed countries, but also in developing countries. However, there are few agents currently approved for the treatment of obesity. Those that are available are mainly appetite suppressants and gastrointestinal fat blockers. We have developed a simple and rapid method for the measurement of the feeding volume of Danio rerio (zebrafish. This assay can be used to screen appetite suppressants and enhancers. In this study, zebrafish were fed viable paramecia that were fluorescently-labeled, and feeding volume was measured using a 96-well microplate reader. Gene expression analysis of brain-derived neurotrophic factor (bdnf, knockdown of appetite-regulating genes (neuropeptide Y, preproinsulin, melanocortin 4 receptor, agouti related protein, and cannabinoid receptor 1, and the administration of clinical appetite suppressants (fluoxetine, sibutramine, mazindol, phentermine, and rimonabant revealed the similarity among mechanisms regulating appetite in zebrafish and mammals. In combination with behavioral analysis, we were able to evaluate adverse effects on locomotor activities from gene knockdown and chemical treatments. In conclusion, we have developed an assay that uses zebrafish, which can be applied to high-throughput screening and target gene discovery for appetite suppressants and enhancers.

  18. The Commission’s internal conditions for social re-regulation: Market efficiency and wider social goals in setting the rules for financial services in Europe

    Directory of Open Access Journals (Sweden)

    Miriam Hartlapp

    2013-06-01

    Full Text Available The European Union is often considered as a prime example of a liberal regulatory state. We argue, however, that being limited to the regulatory policy does not prevent the European Commission from pursuing political aims going beyond market efficiency. We draw up two ideal-type perspectives of market regulation – being either efficiency or equality enhancing – that differ systematically in terms of rationale, degree of intervention, patterns of stakeholder access and conflict within the regulator. We trace these aspects in three financial services initiatives on the registration and supervision of reinsurers, equal treatment in financial services and the regulation of consumer credit. Our analyses suggest that there is scope for equality-enhancing re-regulation when proactive agents proceed decidedly on the basis of social-treaty concerns and frame regulatory beneficiaries as market participants as well as when they seek the redistribution of rights instead of resources.

  19. Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells

    International Nuclear Information System (INIS)

    Park, Jae Hyeon; Lee, Jeong Eun; Shin, In Chul; Koh, Hyun Chul

    2013-01-01

    Recent studies have shown that up-regulation of autophagy may be a tractable therapeutic intervention for clearing disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in pesticide-induced neurodegeneration. In a previous study, we reported that chlorpyrifos (CPF)-induced mitochondria-dependent apoptosis is mediated through reactive oxygen species in SH-SY5Y cells. In this study, we explored a novel pharmacotherapeutic approach to prevent CPF neurotoxicity involving the regulation of autophagy. We investigated the modulation of CPF-induced apoptosis according to autophagy regulation. We found that CPF induced apoptosis in SH-SY5Y cells, as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, we observed that cells treated with CPF underwent autophagic cell death by monitoring the expression of LC3-II and p62. Pretreatment with the autophagy inducer rapamycin significantly enhanced the cell viability of CPF-exposed cells, and the enhancement of cell viability was partially due to alleviation of CPF-induced apoptosis via a decrease in levels of cleaved caspase-3. Specifically, rapamycin pretreatment decreased Bax and increased Bcl-2 expression in mitochondria. In addition, rapamycin significantly decreased cytochrome c release in from mitochondria into the cytosol. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), remarkably increased CPF toxicity in these cells; this with correlated with increased expression of Bax and decreased expression of Bcl-2 in mitochondria. Our results suggest that CPF-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against CPF-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. - Highlights: ► Chlorpyrifos (CPF) is cytotoxic to SH-SY5Y cells ► CPF-induced cytotoxicity is mediated by

  20. Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jae Hyeon [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Lee, Jeong Eun [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Shin, In Chul [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Koh, Hyun Chul, E-mail: hckoh@hanyang.ac.kr [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of)

    2013-04-01

    Recent studies have shown that up-regulation of autophagy may be a tractable therapeutic intervention for clearing disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in pesticide-induced neurodegeneration. In a previous study, we reported that chlorpyrifos (CPF)-induced mitochondria-dependent apoptosis is mediated through reactive oxygen species in SH-SY5Y cells. In this study, we explored a novel pharmacotherapeutic approach to prevent CPF neurotoxicity involving the regulation of autophagy. We investigated the modulation of CPF-induced apoptosis according to autophagy regulation. We found that CPF induced apoptosis in SH-SY5Y cells, as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, we observed that cells treated with CPF underwent autophagic cell death by monitoring the expression of LC3-II and p62. Pretreatment with the autophagy inducer rapamycin significantly enhanced the cell viability of CPF-exposed cells, and the enhancement of cell viability was partially due to alleviation of CPF-induced apoptosis via a decrease in levels of cleaved caspase-3. Specifically, rapamycin pretreatment decreased Bax and increased Bcl-2 expression in mitochondria. In addition, rapamycin significantly decreased cytochrome c release in from mitochondria into the cytosol. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), remarkably increased CPF toxicity in these cells; this with correlated with increased expression of Bax and decreased expression of Bcl-2 in mitochondria. Our results suggest that CPF-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against CPF-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. - Highlights: ► Chlorpyrifos (CPF) is cytotoxic to SH-SY5Y cells ► CPF-induced cytotoxicity is mediated by

  1. Enhancement drugs: are there limits to what we should enhance and why?

    Directory of Open Access Journals (Sweden)

    Hesse Morten

    2010-08-01

    Full Text Available Abstract Substances, such as alcohol, opiates and cannabis, have been used by humans for millennia. Today, a much wider range of substances are used for a range of purposes, including the enhancement of performance during university studies, sexual experiences, sports, exercise, at celebrations, socializing and the experience of art and music. Substance use is also associated with a range of harmful effects to the individual and society as a whole. Prohibitions, regulation, prevention and treatment have all been used to protect against this harm. In this commentary, it is argued that public health interventions should target relevant harms and not to evaluate which aspects of human endeavors and experiences should be enhanced and which should not. It is argued that interventions should directly target the harmful effects, using the best available evidence. Two examples are given of substances that may be altered to prevent serious harm - one for alcohol and one for cannabis. In the case of alcohol, the addition of dissolved oxygen could reduce both the risk of accidents and the risk of liver damage associated with alcohol consumption. In the case of cannabis, there is strong indication that the reduction of content Δ-tetrahydrocannabinol and the increase of cannabidiol could reduce the risk of psychoses and the addiction associated with its use. The aim of this article is to show that responsible regulation should not necessarily be restricted to preventing the use and/or (in the case of alcohol a reduction in the amounts and frequency of its use, but should also aim to include a range of other strategies that could reduce the burden of illness associated with illicit substance use.

  2. Enhanced current and voltage regulators for stand-alone applications

    DEFF Research Database (Denmark)

    Federico, de Bosio; Pastorelli, Michele; Antonio DeSouza Ribeiro, Luiz

    2016-01-01

    State feedback decoupling permits to achieve a better dynamic response for Voltage Source in stand-alone applications. The design of current and voltage regulators is performed in the discrete-time domain since it provides better accuracy and allows direct pole placement. As the attainable...... bandwidth of the current loop is mainly limited by computational and PWM delays, a lead compensator structure is proposed to overcome this limitation. The design of the voltage regulator is based on the Nyquist criterion, verifying to guarantee a high sensitivity peak. Discrete-time domain implementation...

  3. Contrast enhanced ultrasound in the evaluation and percutaneous treatment of hepatic and renal tumors

    International Nuclear Information System (INIS)

    Meloni, Maria Franca; Smolock, Amanda; Cantisani, Vito; Bezzi, Mario; D'Ambrosio, Ferdinando; Proiti, Maria; Lee, Fred; Aiani, Luca; Calliada, Fabrizio; Ferraioli, Giovanna

    2015-01-01

    Highlights: • Image-guided percutaneous ablation techniques are increasingly being used for the treatment of malignant tumors of the liver and kidney when surgery is not indicated. • Percutaneous ablation relies on imaging at every step of the process in order to detect, guide, and confirm complete tumor coagulation. • CEUS is a real-time dynamic imaging technique that plays an important role in the management of patients treated with ablation for malignant tumors. • This review focuses on the role of CEUS in the evaluation of patients undergoing percutaneous treatments for hepatic and renal tumors. - Abstract: Image-guided percutaneous ablation techniques are increasingly being used for the treatment of malignant tumors of the liver and kidney. Contrast enhanced ultrasound (CEUS) is a real-time dynamic imaging technique that plays an important role in the pre-, intra-, and post-procedural management of these patients. This review will focus on the role of CEUS in the evaluation of patients undergoing treatment with percutaneous ablation for hepatic or renal tumors

  4. Abbreviated Resonant Frequency Training to Augment Heart Rate Variability and Enhance On-Demand Emotional Regulation in Elite Sport Support Staff.

    Science.gov (United States)

    Gross, Mike J; Shearer, David A; Bringer, Joy D; Hall, Ross; Cook, Christian J; Kilduff, Liam P

    2016-09-01

    Support and management staff in elite sport experience work-related stress and emotional disturbance to a similar extent as athletes (Fletcher and Wagstaff 2009). The resonant frequency breathing technique (Lehrer et al. 2000) can inhibit autonomic changes associated with stressful situations or events and as such provides a potential emotional regulation tool. The present study utilised five practitioner-led heart rate variability (HRV) biofeedback sessions and home practice via mobile applications to train support and management staff (n = 9) in resonant frequency breathing techniques. Although baseline HRV did not change from pre to post training, participants increased total HRV (i.e., SDNN; p = .006), parasympathetic HRV (i.e., RMSSD; p = .028) and HRV reflective of baroreflex function (i.e., low frequency power; p = .018) while accurately performing resonant frequency breathing without a breath pacer. Post-intervention questionnaire data revealed an increase (p = .032) in habitual use of somatic strategies for emotional regulation, and social validation data suggested that the technique enhanced emotional regulation at home, work and during international competition. HRV biofeedback and the resonant frequency technique provided an on-demand emotional regulation technique for elite sport support and management staff.

  5. Comparative proteomic and metabolomic profiling of citrus fruit with enhancement of disease resistance by postharvest heat treatment.

    Science.gov (United States)

    Yun, Ze; Gao, Huijun; Liu, Ping; Liu, Shuzhen; Luo, Tao; Jin, Shuai; Xu, Qiang; Xu, Juan; Cheng, Yunjiang; Deng, Xiuxin

    2013-03-16

    From field harvest to the consumer's table, fresh citrus fruit spends a considerable amount of time in shipment and storage. During these processes, physiological disorders and pathological diseases are the main causes of fruit loss. Heat treatment (HT) has been widely used to maintain fruit quality during postharvest storage; however, limited molecular information related to this treatment is currently available at a systemic biological level. Mature 'Kamei' Satsuma mandarin (Citrus unshiu Marc.) fruits were selected for exploring the disease resistance mechanisms induced by HT during postharvest storage. Proteomic analyses based on two-dimensional gel electrophoresis (2-DE), and metabolomic research based on gas chromatography coupled to mass spectrometry (GC-MS), and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF-MS) were conducted. The results show resistance associated proteins were up-regulated in heat treated pericarp, such as beta-1, 3-glucanase, Class III chitinase, 17.7 kDa heat shock protein and low molecular weight heat-shock protein. Also, redox metabolism enzymes were down-regulated in heat treated pericarp, including isoflavone reductase, oxidoreductase and superoxide dismutase. Primary metabolic profiling revealed organic acids and amino acids were down-regulated in heat treated pericarp; but significant accumulation of metabolites, including tetradecanoic acid, oleic acid, ornithine, 2-keto-d-gluconic acid, succinic acid, turanose, sucrose, galactose, myo-inositol, glucose and fructose were detected. Noticeably, H2O2 content decreased, while, lignin content increased in heat treated pericarp compared to the control, which might increase fruit resistibility in response to external stress. Also, flavonoids, substances which are well-known to be effective in reducing external stress, were up-regulated in heat treated pericarp. This study provides a broad picture of differential accumulation of proteins and metabolites in

  6. The Effectiveness of Life Skills Training on Enhancement of Self-Esteem and Marital Satisfaction among Addicts in Treatment Period

    Directory of Open Access Journals (Sweden)

    R Nooripour

    2014-11-01

    Full Text Available Objective: This study has been done to determine the impact of life skills training on enhancement of self-esteem and marital satisfaction among addicts in treatment period. Method: The research design was semi experimental pretest-posttest with witness group. For each group 12men addicts in treatment period in Qazvin city were selected by available sampling. Rosenberg self-esteem and Enrich marital satisfaction questionnaires were administered among selected samples. Training workshop was conducted on role playing, questioning and answering which was taught by psychology professors in experimental group. Results: Results showed life skills training improved self-esteem and marital satisfaction of addicts in treatment period. Conclusion: Life skills training have a positive impact on self-esteem and marital satisfaction of individuals especially on addicts in treatment period, also life skills training in the field of smoking prevention enhances individuals’ skills (such as self-esteem, marital satisfaction, etc…. Life skills training empower person to actualize his knowledge, attitudes and values, and enable him to have motivation for healthy behavior which this will have significant impact on his relationship with his wife.

  7. Light-dependant intraretinal ion regulation by melanopsin in young awake and free moving mice evaluated with manganese-enhanced MRI

    OpenAIRE

    Berkowitz, Bruce A.; Roberts, Robin; Bissig, David

    2010-01-01

    Purpose To test the hypothesis that in young, functionally blind mice, light-dependent intraretinal ion regulation occurs via melanopsin. Methods Postnatal day (P) 7 wild type (WT, C57Bl/6) and melanopsin knockout (KO, opn4−/−, B6129) mice were light or dark adapted. Awake and freely moving animals were injected intraperitoneally (ip) with MnCl2. Four hours later, the mice in both groups were anesthetized and studied with manganese-enhanced MRI (MEMRI) to measure the extent of intraretinal up...

  8. New intelligent multifunctional SiO2/VO2 composite films with enhanced infrared light regulation performance, solar modulation capability, and superhydrophobicity.

    Science.gov (United States)

    Wang, Chao; Zhao, Li; Liang, Zihui; Dong, Binghai; Wan, Li; Wang, Shimin

    2017-01-01

    Highly transparent, energy-saving, and superhydrophobic nanostructured SiO 2 /VO 2 composite films have been fabricated using a sol-gel method. These composite films are composed of an underlying infrared (IR)-regulating VO 2 layer and a top protective layer that consists of SiO 2 nanoparticles. Experimental results showed that the composite structure could enhance the IR light regulation performance, solar modulation capability, and hydrophobicity of the pristine VO 2 layer. The transmittance of the composite films in visible region ( T lum ) was higher than 60%, which was sufficient to meet the requirements of glass lighting. Compared with pristine VO 2 films and tungsten-doped VO 2 film, the near IR control capability of the composite films was enhanced by 13.9% and 22.1%, respectively, whereas their solar modulation capability was enhanced by 10.9% and 22.9%, respectively. The water contact angles of the SiO 2 /VO 2 composite films were over 150°, indicating superhydrophobicity. The transparent superhydrophobic surface exhibited a high stability toward illumination as all the films retained their initial superhydrophobicity even after exposure to 365 nm light with an intensity of 160 mW . cm -2 for 10 h. In addition, the films possessed anti-oxidation and anti-acid properties. These characteristics are highly advantageous for intelligent windows or solar cell applications, given that they can provide surfaces with anti-fogging, rainproofing, and self-cleaning effects. Our technique offers a simple and low-cost solution to the development of stable and visible light transparent superhydrophobic surfaces for industrial applications.

  9. Enhancement of internal ribosome entry site-mediated translation and replication of hepatitis C virus by PD98059

    International Nuclear Information System (INIS)

    Murata, Takayuki; Hijikata, Makoto; Shimotohno, Kunitada

    2005-01-01

    Translation initiation of hepatitis C virus (HCV) occurs in an internal ribosome entry site (IRES)-dependent manner. We found that HCV IRES-dependent protein synthesis is enhanced by PD98059, an inhibitor of the extracellular signal-regulated kinase (ERK) signaling pathway, while cellular cap-dependent translation was relatively unaffected by the compound. Treatment of cells with PD98059 allowed for robust HCV replication following cellular incubation with HCV-positive serum. Though the molecular mechanism underlying IRES enhancement remains elusive, PD98059 is a potent accelerator of HCV RNA replication

  10. Highly stable and degradable multifunctional microgel for self-regulated insulin delivery under physiological conditions

    Science.gov (United States)

    Zhang, Xinjie; Lü, Shaoyu; Gao, Chunmei; Chen, Chen; Zhang, Xuan; Liu, Mingzhu

    2013-06-01

    The response to glucose, pH and temperature, high drug loading capacity, self-regulated drug delivery and degradation in vivo are simultaneously probable by applying a multifunctional microgel under a rational design in a colloid chemistry method. Such multifunctional microgels are fabricated with N-isopropylacrylamide (NIPAAm), (2-dimethylamino)ethyl methacrylate (DMAEMA) and 3-acrylamidephenylboronic acid (AAPBA) through a precipitation emulsion method and cross-linked by reductive degradable N,N'-bis(arcyloyl)cystamine (BAC). This novel kind of microgel with a narrow size distribution (~250 nm) is suitable for diabetes because it can adapt to the surrounding medium of different glucose concentrations over a clinically relevant range (0-20 mM), control the release of preloaded insulin and is highly stable under physiological conditions (pH 7.4, 0.15 M NaCl, 37 °C). When synthesized multifunctional microgels regulate drug delivery, they gradually degrade as time passes and, as a result, show enhanced biocompatibility. This exhibits a new proof-of-concept for diabetes treatment that takes advantage of the properties of each building block from a multifunctional micro-object. These highly stable and versatile multifunctional microgels have the potential to be used for self-regulated therapy and monitoring of the response to treatment, or even simultaneous diagnosis as nanobiosensors.The response to glucose, pH and temperature, high drug loading capacity, self-regulated drug delivery and degradation in vivo are simultaneously probable by applying a multifunctional microgel under a rational design in a colloid chemistry method. Such multifunctional microgels are fabricated with N-isopropylacrylamide (NIPAAm), (2-dimethylamino)ethyl methacrylate (DMAEMA) and 3-acrylamidephenylboronic acid (AAPBA) through a precipitation emulsion method and cross-linked by reductive degradable N,N'-bis(arcyloyl)cystamine (BAC). This novel kind of microgel with a narrow size

  11. Caffeine Induces the Stress Response and Up-Regulates Heat Shock Proteins in Caenorhabditis elegans.

    Science.gov (United States)

    Al-Amin, Mohammad; Kawasaki, Ichiro; Gong, Joomi; Shim, Yhong-Hee

    2016-02-01

    Caffeine has both positive and negative effects on physiological functions in a dose-dependent manner. C. elegans has been used as an animal model to investigate the effects of caffeine on development. Caffeine treatment at a high dose (30 mM) showed detrimental effects and caused early larval arrest. We performed a comparative proteomic analysis to investigate the mode of action of high-dose caffeine treatment in C. elegans and found that the stress response proteins, heat shock protein (HSP)-4 (endoplasmic reticulum [ER] chaperone), HSP-6 (mitochondrial chaperone), and HSP-16 (cytosolic chaperone), were induced and their expression was regulated at the transcriptional level. These findings suggest that high-dose caffeine intake causes a strong stress response and activates all three stress-response pathways in the worms, including the ER-, mitochondrial-, and cytosolic pathways. RNA interference of each hsp gene or in triple combination retarded growth. In addition, caffeine treatment stimulated a food-avoidance behavior (aversion phenotype), which was enhanced by RNAi depletion of the hsp-4 gene. Therefore, up-regulation of hsp genes after caffeine treatment appeared to be the major responses to alleviate stress and protect against developmental arrest.

  12. Cauliflower mosaic virus protein P6 inhibits signaling responses to salicylic acid and regulates innate immunity.

    Directory of Open Access Journals (Sweden)

    Andrew J Love

    Full Text Available Cauliflower mosaic virus (CaMV encodes a multifunctional protein P6 that is required for translation of the 35S RNA and also acts as a suppressor of RNA silencing. Here we demonstrate that P6 additionally acts as a pathogenicity effector of an unique and novel type, modifying NPR1 (a key regulator of salicylic acid (SA- and jasmonic acid (JA-dependent signaling and inhibiting SA-dependent defence responses We find that that transgene-mediated expression of P6 in Arabidopsis and transient expression in Nicotiana benthamiana has profound effects on defence signaling, suppressing expression of representative SA-responsive genes and increasing expression of representative JA-responsive genes. Relative to wild-type Arabidopsis P6-expressing transgenics had greatly reduced expression of PR-1 following SA-treatment, infection by CaMV or inoculation with an avirulent bacterial pathogen Pseudomonas syringae pv tomato (Pst. Similarly transient expression in Nicotiana benthamiana of P6 (including a mutant form defective in translational transactivation activity suppressed PR-1a transcript accumulation in response to Agrobacterium infiltration and following SA-treatment. As well as suppressing the expression of representative SA-regulated genes, P6-transgenic Arabidopsis showed greatly enhanced susceptibility to both virulent and avirulent Pst (titres elevated 10 to 30-fold compared to non-transgenic controls but reduced susceptibility to the necrotrophic fungus Botrytis cinerea. Necrosis following SA-treatment or inoculation with avirulent Pst was reduced and delayed in P6-transgenics. NPR1 an important regulator of SA/JA crosstalk, was more highly expressed in the presence of P6 and introduction of the P6 transgene into a transgenic line expressing an NPR1:GFP fusion resulted in greatly increased fluorescence in nuclei even in the absence of SA. Thus in the presence of P6 an inactive form of NPR1 is mislocalized in the nucleus even in uninduced plants

  13. Superior Long-Term Synaptic Memory Induced by Combining Dual Pharmacological Activation of PKA and ERK with an Enhanced Training Protocol

    Science.gov (United States)

    Liu, Rong-Yu; Neveu, Curtis; Smolen, Paul; Cleary, Leonard J.; Byrne, John H.

    2017-01-01

    Developing treatment strategies to enhance memory is an important goal of neuroscience research. Activation of multiple biochemical signaling cascades, such as the protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) pathways, is necessary to induce long-term synaptic facilitation (LTF), a correlate of long-term memory (LTM).…

  14. Chondroitin sulfate addition to CD44H negatively regulates hyaluronan binding

    International Nuclear Information System (INIS)

    Ruffell, Brian; Johnson, Pauline

    2005-01-01

    CD44 is a widely expressed cell adhesion molecule that binds hyaluronan, an extracellular matrix glycosaminoglycan, in a tightly regulated manner. This regulated interaction has been implicated in inflammation and tumor metastasis. CD44 exists in the standard form, CD44H, or as higher molecular mass isoforms due to alternative splicing. Here, we identify serine 180 in human CD44H as the site of chondroitin sulfate addition and show that lack of chondroitin sulfate addition at this site enhances hyaluronan binding by CD44. A CD44H-immunoglobulin fusion protein expressed in HEK293 cells, and CD44H expressed in murine L fibroblast cells were modified by chondroitin sulfate, as determined by reduced sulfate incorporation after chondroitinase ABC treatment. Mutation of serine 180 or glycine 181 in CD44H reduced chondroitin sulfate addition and increased hyaluronan binding, indicating that serine 180 is the site for chondroitin sulfate addition in CD44H and that this negatively regulates hyaluronan binding

  15. Glucose enhancement of event-related potentials associated with episodic memory and attention.

    Science.gov (United States)

    Brown, Louise A; Riby, Leigh M

    2013-04-30

    Previous studies have reported that increasing glycaemia by a glucose-containing drink enhances memory functioning. The aim of the present study was to extend this literature by examining the effects of glucose on episodic memory as well as attention processes, and to investigate associated event-related potential (ERP) markers. Fifteen minutes after treatment (25 g glucose or placebo drink), 35 participants performed an old/new recognition memory task and a Stroop colour naming task. Consistent with previous research, when controlling for glucose regulation, cognitive facilitation was observed behaviourally for verbal memory, but there was also a trend towards attentional facilitation. Furthermore, across both domains, it was the most demanding task conditions that exhibited glucose sensitivity. In support of the behavioural results, the analysis of ERPs across treatment groups revealed an enhanced left-parietal old/new effect related to recollection, and also suggested modulation of attentional processes. The results suggest that glucose may facilitate attention as well as memory.

  16. Enhancing socially shared regulation in collaborative learning groups: designing for CSCL regulation tools

    NARCIS (Netherlands)

    Järvelä, Sanna; Kirschner, Paul A.; Panadero, Ernesto; Malmberg, Jonna; Phielix, Chris; Jaspers, Jos; Koivuniemi, Marieke; Järvenoja, Hanna

    2016-01-01

    For effective computer supported collaborative learning (CSCL), socially shared regulation of learning (SSRL) is necessary. To this end, this article extends the idea first posited by Ja¨rvela¨ and Hadwin (Educ Psychol 48(1):25–39, 2013) that successful collaboration in CSCL contexts requires

  17. Up-Regulation of P21 Inhibits TRAIL-Mediated Extrinsic Apoptosis, Contributing Resistance to SAHA in Acute Myeloid Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Xing Wu

    2014-08-01

    Full Text Available Background/Aim: P21, a multifunctional cell cycle-regulatory molecule, regulates apoptotic cell death. In this study we examined the effect of altered p21 expression on the sensitivity of acute myeloid leukemia cells in response to HDAC inhibitor SAHA treatment and investigated the underlying mechanism. Methods: Stably transfected HL60 cell lines were established in RPMI-1640 with supplementation of G-418. Cell viability was measured by MTT assay. Western blot was applied to assess the protein expression levels of target genes. Cell apoptosis was monitored by AnnexinV-PE/7AAD assay. Results: We showed HL60 cells that that didn't up-regulate p21 expression were more sensitive to SAHA-mediated apoptosis than NB4 and U937 cells that had increased p21 level. Enforced expression of p21 in HL60 cells reduced sensitivity to SAHA and blocked TRAIL-mediated apoptosis. Conversely, p21 silencing in NB4 cells enhanced SAHA-mediated apoptosis and lethality. Finally, we found that combined treatment with SAHA and rapamycin down-regulated p21 and enhanced apoptosis in AML cells. Conclusion: We conclude that up-regulated p21 expression mediates resistance to SAHA via inhibition of TRAIL apoptotic pathway. P21 may serve as a candidate biomarker to predict responsiveness or resistance to SAHA-based therapy in AML patients. In addition, rapamycin may be an effective agent to override p21-mediated resistance to SAHA in AML patients.

  18. Enhancement of Apoptosis by Titanium Alloy Internal Fixations during Microwave Treatments for Fractures: An Animal Study.

    Directory of Open Access Journals (Sweden)

    Gang Wang

    Full Text Available Microwaves are used in one method of physical therapy and can increase muscle tissue temperature which is useful for improving muscle, tendon and bone injuries. In the study, we sought to determine whether titanium alloy internal fixations influence apoptosis in tissues subjected to microwave treatments at 2,450 MHz and 40 W during the healing of fractures because this issue is not yet fully understood.In this study, titanium alloy internal fixations were used to treat 3.0-mm transverse osteotomies in the middle of New Zealand rabbits' femurs. After the operation, 30-day microwave treatments were applied to the 3.0 mm transverse osteotomies 3 days after the operation. The changes in the temperatures of the muscle tissues in front of the implants or the 3.0 mm transverse osteotomies were measured during the microwave treatments. To characterize the effects of titanium alloy internal fixations on apoptosis in the muscles after microwave treatment, we performed TUNEL assays, fluorescent real-time (quantitative PCR, western blotting analyses, reactive oxygen species (ROS detection and transmission electron microscopy examinations.The temperatures were markedly increased in the animals with the titanium alloy implants. Apoptosis in the muscle cells of the implanted group was significantly more extensive than that in the non-implanted control group at different time points. Transmission electron microscopy examinations of the skeletal muscles of the implanted groups revealed muscular mitochondrial swelling, vacuolization. ROS, Bax and Hsp70 were up-regulated, and Bcl-2 was down-regulated in the implanted group.Our results suggest that titanium alloy internal fixations caused greater muscular tissue cell apoptosis following 2,450 MHz, 40 W microwave treatments in this rabbit femur fracture models.

  19. Enhancement of Thermoelectric Properties of PEDOT:PSS and Tellurium-PEDOT:PSS Hybrid Composites by Simple Chemical Treatment

    Science.gov (United States)

    Jin Bae, Eun; Hun Kang, Young; Jang, Kwang-Suk; Yun Cho, Song

    2016-01-01

    The thermoelectric properties of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and tellurium-PEDOT:PSS (Te-PEDOT:PSS) hybrid composites were enhanced via simple chemical treatment. The performance of thermoelectric materials is determined by their electrical conductivity, thermal conductivity, and Seebeck coefficient. Significant enhancement of the electrical conductivity of PEDOT:PSS and Te-PEDOT:PSS hybrid composites from 787.99 and 11.01 to 4839.92 and 334.68 S cm-1, respectively was achieved by simple chemical treatment with H2SO4. The power factor of the developed materials could be effectively tuned over a very wide range depending on the concentration of the H2SO4 solution used in the chemical treatment. The power factors of the developed thermoelectric materials were optimized to 51.85 and 284 μW m-1 K-2, respectively, which represent an increase of four orders of magnitude relative to the corresponding parameters of the untreated thermoelectric materials. Using the Te-PEDOT:PSS hybrid composites, a flexible thermoelectric generator that could be embedded in textiles was fabricated by a printing process. This thermoelectric array generates a thermoelectric voltage of 2 mV using human body heat.

  20. International cooperation for the development of consistent and stable transportation regulations to promote and enhance safety and security

    International Nuclear Information System (INIS)

    Strosnider, J.

    2004-01-01

    International commerce of radioactive materials crosses national boundaries, linking separate regulatory institutions with a common purpose and making it necessary for these institutions to work together in order to achieve common safety goals in a manner that does not place an undue burden on industry and commerce. Widespread and increasing use of radioactive materials across the world has led to increases in the transport of radioactive materials. The demand for consistency in the oversight of international transport has also increased to prevent unnecessary delays and costs associated with incongruent or redundant regulatory requirements by the various countries through which radioactive material is transported. The International Atomic Energy Agency (IAEA) is the authority for international regulation of transportation of radioactive materials responsible for promulgation of regulations and guidance for the establishment of acceptable methods of transportation for the international community. As such, the IAEA is seen as the focal point for consensus building between its Member States to develop consistency in transportation regulations and reviews and to ensure the safe and secure transport of radioactive material. International cooperation is also needed to ensure stability in our regulatory processes. Changes to transportation regulations should be based on an anticipated safety benefit supported by risk information and insights gained from continuing experience, evaluation, and research studies. If we keep safety as the principle basis for regulatory changes, regulatory stability will be enhanced. Finally, as we endeavour to maintain consistency and stability in our international regulations, we must be mindful of the new security challenges that lay before the international community as a result of a changing terrorist environment. Terrorism is a problem of global concern that also requires international cooperation and support, as we look for ways to

  1. A novel mammal-specific three partite enhancer element regulates node and notochord-specific Noto expression.

    Directory of Open Access Journals (Sweden)

    Leonie Alten

    Full Text Available The vertebrate organizer and notochord have conserved, essential functions for embryonic development and patterning. The restricted expression of developmental regulators in these tissues is directed by specific cis-regulatory modules (CRMs whose sequence conservation varies considerably. Some CRMs have been conserved throughout vertebrates and likely represent ancestral regulatory networks, while others have diverged beyond recognition but still function over a wide evolutionary range. Here we identify and characterize a mammalian-specific CRM required for node and notochord specific (NNC expression of NOTO, a transcription factor essential for node morphogenesis, nodal cilia movement and establishment of laterality in mouse. A 523 bp enhancer region (NOCE upstream the Noto promoter was necessary and sufficient for NNC expression from the endogenous Noto locus. Three subregions in NOCE together mediated full activity in vivo. Binding sites for known transcription factors in NOCE were functional in vitro but dispensable for NOCE activity in vivo. A FOXA2 site in combination with a novel motif was necessary for NOCE activity in vivo. Strikingly, syntenic regions in non-mammalian vertebrates showed no recognizable sequence similarities. In contrast to its activity in mouse NOCE did not drive NNC expression in transgenic fish. NOCE represents a novel, mammal-specific CRM required for the highly restricted Noto expression in the node and nascent notochord and thus regulates normal node development and function.

  2. A novel mammal-specific three partite enhancer element regulates node and notochord-specific Noto expression.

    Science.gov (United States)

    Alten, Leonie; Schuster-Gossler, Karin; Eichenlaub, Michael P; Wittbrodt, Beate; Wittbrodt, Joachim; Gossler, Achim

    2012-01-01

    The vertebrate organizer and notochord have conserved, essential functions for embryonic development and patterning. The restricted expression of developmental regulators in these tissues is directed by specific cis-regulatory modules (CRMs) whose sequence conservation varies considerably. Some CRMs have been conserved throughout vertebrates and likely represent ancestral regulatory networks, while others have diverged beyond recognition but still function over a wide evolutionary range. Here we identify and characterize a mammalian-specific CRM required for node and notochord specific (NNC) expression of NOTO, a transcription factor essential for node morphogenesis, nodal cilia movement and establishment of laterality in mouse. A 523 bp enhancer region (NOCE) upstream the Noto promoter was necessary and sufficient for NNC expression from the endogenous Noto locus. Three subregions in NOCE together mediated full activity in vivo. Binding sites for known transcription factors in NOCE were functional in vitro but dispensable for NOCE activity in vivo. A FOXA2 site in combination with a novel motif was necessary for NOCE activity in vivo. Strikingly, syntenic regions in non-mammalian vertebrates showed no recognizable sequence similarities. In contrast to its activity in mouse NOCE did not drive NNC expression in transgenic fish. NOCE represents a novel, mammal-specific CRM required for the highly restricted Noto expression in the node and nascent notochord and thus regulates normal node development and function.

  3. Improved wound management by regulated negative pressure-assisted wound therapy and regulated, oxygen- enriched negative pressure-assisted wound therapy through basic science research and clinical assessment

    Directory of Open Access Journals (Sweden)

    Moris Topaz

    2012-01-01

    Full Text Available Regulated negative pressure-assisted wound therapy (RNPT should be regarded as a state-of-the-art technology in wound treatment and the most important physical, nonpharmaceutical, platform technology developed and applied for wound healing in the last two decades. RNPT systems maintain the treated wound′s environment as a semi-closed, semi-isolated system applying external physical stimulations to the wound, leading to biological and biochemical effects, with the potential to substantially influence wound-host interactions, and when properly applied may enhance wound healing. RNPT is a simple, safe, and affordable tool that can be utilized in a wide range of acute and chronic conditions, with reduced need for complicated surgical procedures, and antibiotic treatment. This technology has been shown to be effective and safe, saving limbs and lives on a global scale. Regulated, oxygen-enriched negative pressure-assisted wound therapy (RO-NPT is an innovative technology, whereby supplemental oxygen is concurrently administered with RNPT for their synergistic effect on treatment and prophylaxis of anaerobic wound infection and promotion of wound healing. Understanding the basic science, modes of operation and the associated risks of these technologies through their fundamental clinical mechanisms is the main objective of this review.

  4. Challenges for tree officers to enhance the provision of regulating ecosystem services from urban forests.

    Science.gov (United States)

    Davies, Helen J; Doick, Kieron J; Hudson, Malcolm D; Schreckenberg, Kate

    2017-07-01

    Urbanisation and a changing climate are leading to more frequent and severe flood, heat and air pollution episodes in Britain's cities. Interest in nature-based solutions to these urban problems is growing, with urban forests potentially able to provide a range of regulating ecosystem services such as stormwater attenuation, heat amelioration and air purification. The extent to which these benefits are realized is largely dependent on urban forest management objectives, the availability of funding, and the understanding of ecosystem service concepts within local governments, the primary delivery agents of urban forests. This study aims to establish the extent to which British local authorities actively manage their urban forests for regulating ecosystem services, and identify which resources local authorities most need in order to enhance provision of ecosystem services by Britain's urban forests. Interviews were carried out with staff responsible for tree management decisions in fifteen major local authorities from across Britain, selected on the basis of their urban nature and high population density. Local authorities have a reactive approach to urban forest management, driven by human health and safety concerns and complaints about tree disservices. There is relatively little focus on ensuring provision of regulating ecosystem services, despite awareness by tree officers of the key role that urban forests can play in alleviating chronic air pollution, flood risk and urban heat anomalies. However, this is expected to become a greater focus in future provided that existing constraints - lack of understanding of ecosystem services amongst key stakeholders, limited political support, funding constraints - can be overcome. Our findings suggest that the adoption of a proactive urban forest strategy, underpinned by quantified and valued urban forest-based ecosystem services provision data, and innovative private sector funding mechanisms, can facilitate a change to a

  5. Photocurrent Enhancement by a Rapid Thermal Treatment of Nanodisk-Shaped SnS Photocathodes.

    Science.gov (United States)

    Patel, Malkeshkumar; Kumar, Mohit; Kim, Joondong; Kim, Yu Kwon

    2017-12-21

    Photocathodes made from the earth-abundant, ecofriendly mineral tin monosulfide (SnS) can be promising candidates for p/n-type photoelectrochemical cells because they meet the strict requirements of energy band edges for each individual photoelectrode. Herein we fabricated SnS-based cell that exhibited a prolonged photocurrent for 3 h at -0.3 V vs the reversible hydrogen electrode (RHE) in a 0.1 M HCl electrolyte. An enhancement of the cathodic photocurrent from 2 to 6 mA cm -2 is observed through a rapid thermal treatment. Mott-Schottky analysis of SnS samples revealed an anodic shift of 0.7 V in the flat band potential under light illumination. Incident photon-to-current conversion efficiency (IPCE) analysis indicates that an efficient charge transfer appropriate for solar hydrogen generation occurs at the -0.3 V vs RHE potential. This work shows that SnS is a promising material for photocathode in PEC cells and its performance can be enhanced via simple postannealing.

  6. Effectiveness and student perceptions of an active learning activity using a headline news story to enhance in-class learning of cell cycle regulation.

    Science.gov (United States)

    Dirks-Naylor, Amie J

    2016-06-01

    An active learning activity was used to engage students and enhance in-class learning of cell cycle regulation in a PharmD level integrated biological sciences course. The aim of the present study was to determine the effectiveness and perception of the in-class activity. After completion of a lecture on the topic of cell cycle regulation, students completed a 10-question multiple-choice quiz before and after engaging in the activity. The activity involved reading of a headline news article published by ScienceDaily.com entitled "One Gene Lost Equals One limb Regained." The name of the gene was deleted from the article and, thus, the end goal of the activity was to determine the gene of interest by the description in the story. The activity included compiling a list of all potential gene candidates before sufficient information was given to identify the gene of interest (p21). A survey was completed to determine student perceptions of the activity. Quiz scores improved by an average of 20% after the activity (40.1 ± 1.95 vs. 59.9 ± 2.14,Pactivity, found the news article interesting, and believed that the activity improved their understanding of cell cycle regulation. The majority of students agreed that the in-class activity piqued their interest for learning the subject matter and also agreed that if they understand a concept during class, they are more likely to want to study that concept outside of class. In conclusion, the activity improved in-class understanding and enhanced interest in cell cycle regulation. Copyright © 2016 The American Physiological Society.

  7. Enhancement of micropollutant degradation at the outlet of small wastewater treatment plants.

    Directory of Open Access Journals (Sweden)

    Luca Rossi

    Full Text Available The aim of this work was to evaluate low-cost and easy-to-operate engineering solutions that can be added as a polishing step to small wastewater treatment plants to reduce the micropollutant load to water bodies. The proposed design combines a sand filter/constructed wetland with additional and more advanced treatment technologies (UV degradation, enhanced adsorption to the solid phase, e.g., an engineered substrate to increase the elimination of recalcitrant compounds. The removal of five micropollutants with different physico-chemical characteristics (three pharmaceuticals: diclofenac, carbamazepine, sulfamethoxazole, one pesticide: mecoprop, and one corrosion inhibitor: benzotriazole was studied to evaluate the feasibility of the proposed system. Separate batch experiments were conducted to assess the removal efficiency of UV degradation and adsorption. The efficiency of each individual process was substance-specific. No process was effective on all the compounds tested, although elimination rates over 80% using light expanded clay aggregate (an engineered material were observed. A laboratory-scale flow-through setup was used to evaluate interactions when removal processes were combined. Four of the studied compounds were partially eliminated, with poor removal of the fifth (benzotriazole. The energy requirements for a field-scale installation were estimated to be the same order of magnitude as those of ozonation and powdered activated carbon treatments.

  8. Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Larsen, Steen; Helge, Jørn Wulff

    2013-01-01

    signaling. We investigated this by two weeks of oral metformin treatment of muscle specific kinase dead a(2) (KD) AMPK mice and wild type (WT) littermates. We measured mitochondrial respiration and protein activity and expressions of key enzymes involved in mitochondrial carbohydrate and fat metabolism...... and oxidative phosphorylation. Mitochondrial respiration, HAD and CS activity, PDH and complex I-V and cytochrome c protein expression were all reduced in AMPK KD compared to WT tibialis anterior muscles. Surprisingly, metformin treatment only enhanced respiration in AMPK KD mice and thereby rescued...... the respiration defect compared to the WT mice. Metformin did not influence protein activities or expressions in either WT or AMPK KD mice.We conclude that two weeks of in vivo metformin treatment enhances mitochondrial respiration in the mitochondrial deficient AMPK KD but not WT mice. The improvement seems...

  9. Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL

    International Nuclear Information System (INIS)

    Yu, Cheng-Chia; Chang, Yu-Chao

    2013-01-01

    Cigarette smoking is one of the major risk factors in the development and further progression of tumorigenesis, including oral squamous cell carcinoma (OSCC). Recent studies suggest that interplay cancer stem-like cells (CSCs) and epithelial−mesenchymal transdifferentiation (EMT) properties are responsible for the tumor maintenance and metastasis in OSCC. The aim of the present study was to investigate the effects of long-term exposure with nicotine, a major component in cigarette, on CSCs and EMT characteristics. The possible reversal regulators were further explored in nicotine-induced CSCs and EMT properties in human oral epithelial (OE) cells. Long-term exposure with nicotine was demonstrated to up-regulate ALDH1 population in normal gingival and primary OSCC OE cells dose-dependently. Moreover, long-term nicotine treatment was found to enhance the self-renewal sphere-forming ability and stemness gene signatures expression and EMT regulators in OE cells. The migration/cell invasiveness/anchorage independent growth and in vivo tumor growth by nude mice xenotransplantation assay was enhanced in long-term nicotine-stimulated OE cells. Knockdown of Snail in long-term nicotine-treated OE cells was found to reduce their CSCs properties. Therapeutic delivery of Si-Snail significantly blocked the xenograft tumorigenesis of long-term nicotine-treated OSCC cells and largely significantly improved the recipient survival. The present study demonstrated that the enrichment of CSCs coupled EMT property in oral epithelial cells induced by nicotine is critical for the development of OSCC tumorigenesis. Targeting Snail might offer a new strategy for the treatment of OSCC patients with smoking habit. -- Highlights: ► Sustained nicotine treatment induced CSCs properties of oral epithelial cells. ► Long-term nicotine treatment enhance EMT properties of oral epithelial cells. ► Long-term nicotine exposure increased tumorigenicity of oral epithelial cells. ► Si

  10. Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Cheng-Chia [Institute of Oral Science, Chung Shan Medical University, Taichung, Taiwan (China); School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Chang, Yu-Chao, E-mail: cyc@csmu.edu.tw [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China)

    2013-02-01

    Cigarette smoking is one of the major risk factors in the development and further progression of tumorigenesis, including oral squamous cell carcinoma (OSCC). Recent studies suggest that interplay cancer stem-like cells (CSCs) and epithelial−mesenchymal transdifferentiation (EMT) properties are responsible for the tumor maintenance and metastasis in OSCC. The aim of the present study was to investigate the effects of long-term exposure with nicotine, a major component in cigarette, on CSCs and EMT characteristics. The possible reversal regulators were further explored in nicotine-induced CSCs and EMT properties in human oral epithelial (OE) cells. Long-term exposure with nicotine was demonstrated to up-regulate ALDH1 population in normal gingival and primary OSCC OE cells dose-dependently. Moreover, long-term nicotine treatment was found to enhance the self-renewal sphere-forming ability and stemness gene signatures expression and EMT regulators in OE cells. The migration/cell invasiveness/anchorage independent growth and in vivo tumor growth by nude mice xenotransplantation assay was enhanced in long-term nicotine-stimulated OE cells. Knockdown of Snail in long-term nicotine-treated OE cells was found to reduce their CSCs properties. Therapeutic delivery of Si-Snail significantly blocked the xenograft tumorigenesis of long-term nicotine-treated OSCC cells and largely significantly improved the recipient survival. The present study demonstrated that the enrichment of CSCs coupled EMT property in oral epithelial cells induced by nicotine is critical for the development of OSCC tumorigenesis. Targeting Snail might offer a new strategy for the treatment of OSCC patients with smoking habit. -- Highlights: ► Sustained nicotine treatment induced CSCs properties of oral epithelial cells. ► Long-term nicotine treatment enhance EMT properties of oral epithelial cells. ► Long-term nicotine exposure increased tumorigenicity of oral epithelial cells. ► Si

  11. Enhancement of electron field emission of vertically aligned carbon nanotubes by nitrogen plasma treatment

    Energy Technology Data Exchange (ETDEWEB)

    Wang, B.B. [College of Chemistry and Chemical Engineering, Chongqing University of Technology, 69 Hongguang Rd, Lijiatuo, Banan District, Chongqing 400054 (China); Plasma Nanoscience Centre Australia (PNCA), CSIRO Materials Science and Engineering, P.O. Box 218, Lindfield, NSW 2070 (Australia); Cheng, Q.J. [Plasma Nanoscience Centre Australia (PNCA), CSIRO Materials Science and Engineering, P.O. Box 218, Lindfield, NSW 2070 (Australia); Plasma Nanoscience, School of Physics, University of Sydney, Sydney, NSW 2006 (Australia); Chen, X. [College of Materials Science and Engineering, Chongqing University, Chongqing 400044 (China); Ostrikov, K., E-mail: kostya.ostrikov@csiro.au [Plasma Nanoscience Centre Australia (PNCA), CSIRO Materials Science and Engineering, P.O. Box 218, Lindfield, NSW 2070 (Australia); Plasma Nanoscience, School of Physics, University of Sydney, Sydney, NSW 2006 (Australia)

    2011-09-22

    Highlights: > A new and custom-designed bias-enhanced hot-filament chemical vapor deposition system is developed to synthesize vertically aligned carbon nanotubes. > The carbon nanotubes are later treated with nitrogen plasmas. > The electron field emission characteristics of the carbon nanotubes are significantly improved after the nitrogen plasma treatment. > A new physical mechanism is proposed to interpret the improvement of the field emission characteristics. - Abstract: The electron field emission (EFE) characteristics from vertically aligned carbon nanotubes (VACNTs) without and with treatment by the nitrogen plasma are investigated. The VACNTs with the plasma treatment showed a significant improvement in the EFE property compared to the untreated VACNTs. The morphological, structural, and compositional properties of the VACNTs are extensively examined by scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, and energy dispersive X-ray spectroscopy. It is shown that the significant EFE improvement of the VACNTs after the nitrogen plasma treatment is closely related to the variation of the morphological and structural properties of the VACNTs. The high current density (299.6 {mu}A/cm{sup 2}) achieved at a low applied field (3.50 V/{mu}m) suggests that the VACNTs after nitrogen plasma treatment can serve as effective electron field emission sources for numerous applications.

  12. Enhancement of electron field emission of vertically aligned carbon nanotubes by nitrogen plasma treatment

    International Nuclear Information System (INIS)

    Wang, B.B.; Cheng, Q.J.; Chen, X.; Ostrikov, K.

    2011-01-01

    Highlights: → A new and custom-designed bias-enhanced hot-filament chemical vapor deposition system is developed to synthesize vertically aligned carbon nanotubes. → The carbon nanotubes are later treated with nitrogen plasmas. → The electron field emission characteristics of the carbon nanotubes are significantly improved after the nitrogen plasma treatment. → A new physical mechanism is proposed to interpret the improvement of the field emission characteristics. - Abstract: The electron field emission (EFE) characteristics from vertically aligned carbon nanotubes (VACNTs) without and with treatment by the nitrogen plasma are investigated. The VACNTs with the plasma treatment showed a significant improvement in the EFE property compared to the untreated VACNTs. The morphological, structural, and compositional properties of the VACNTs are extensively examined by scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, and energy dispersive X-ray spectroscopy. It is shown that the significant EFE improvement of the VACNTs after the nitrogen plasma treatment is closely related to the variation of the morphological and structural properties of the VACNTs. The high current density (299.6 μA/cm 2 ) achieved at a low applied field (3.50 V/μm) suggests that the VACNTs after nitrogen plasma treatment can serve as effective electron field emission sources for numerous applications.

  13. Enhancing Growth and Yield of Grey Oyster Mushroom (Plearotussajorcaju Using Different Acoustic Sound Treatments

    Directory of Open Access Journals (Sweden)

    Ibrahim Roshita

    2017-01-01

    Full Text Available Mushroom, as believed by many people, grows on specific time and condition as in the wild it grows after a heavy rain falls. The effects of lightning and thunderstorm may suppress the mychorrizal structure to grow and eventually forming fruiting body. This study was conducted to determine the effect of different acoustic sound treatments on the growth and yield of grey oyster mushroom (Pleurotussajor-caju. Five different acoustic sound treatments had been applied during spawning period which were thunder storm, hardcore music, soothing instrumental, Quranic recital and without any sound treatment applied which served as control. The parameters studied were mycelium growth rate, days of mycelium filled up the bags, days of pinhead emergence, days of fruiting body formation, total weight, percentage biological efficiency, pileus color and texture. There were significant differences (P0.05 observed in other parameters, such as pinhead emergence, fruiting bodies formation, pileus color and texture. In summary, treatments using different acoustic sound at 75 dB could be considered as better treatment to enhance the mycelium growth thus accelerate the mushroom cultivation process as well as increasing the mushroom productivity. This research could help farmers to grow and harvest their mushroom at specific time frame and fulfill customer’s demand.

  14. Enhancement of gas sensor response of nanocrystalline zinc oxide for ammonia by plasma treatment

    International Nuclear Information System (INIS)

    Hou, Yue; Jayatissa, Ahalapitiya H.

    2014-01-01

    The effect of oxygen plasma treatment on nanocrystalline ZnO thin film based gas sensor was investigated. ZnO thin films were synthesized on alkali-free glass substrates by a sol–gel process. ZnO thin films were treated with oxygen plasma to change the number of vacancies/defects in ZnO. The effect of oxygen plasma on the structural, electrical, optical and gas sensing properties was investigated as a function of plasma treatment time. The results suggest that the microstructure and the surface morphology can be tuned by oxygen plasma treatment. The optical transmission in the visible range varies after the oxygen plasma treatment. Moreover, it is found that the oxygen plasma has significant impact on the electrical properties of ZnO thin films indicating a variation of resistivity. The oxygen plasma treated ZnO thin film exhibits an enhanced sensing response towards NH 3 in comparison with that of the as-deposited ZnO sensor. When compared with the as-deposited ZnO film, the sensing response was improved by 50% for the optimum oxygen plasma treatment time of 8 min. The selectivity of 8 min plasma treated ZnO sensor was also examined for an important industrial gas mixture of H 2 , CH 4 and NH 3 .

  15. Assessing Tumor Response to Treatment in Patients with Lung Cancer Using Dynamic Contrast-Enhanced CT

    DEFF Research Database (Denmark)

    Strauch, Louise S; Eriksen, Rie Ø; Sandgaard, Michael

    2016-01-01

    Reviews and Meta-Analyses (PRISMA) guidelines. Only original research articles concerning treatment response in patients with lung cancer assessed with DCE-CT were included. To assess the validity of each study we implemented Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The initial search......The aim of this study was to provide an overview of the literature available on dynamic contrast-enhanced computed tomography (DCE-CT) as a tool to evaluate treatment response in patients with lung cancer. This systematic review was compiled according to Preferred Reporting Items for Systematic...... yielded 651 publications, and 16 articles were included in this study. The articles were divided into groups of treatment. In studies where patients were treated with systemic chemotherapy with or without anti-angiogenic drugs, four out of the seven studies found a significant decrease in permeability...

  16. Resveratrol enhances airway surface liquid depth in sinonasal epithelium by increasing cystic fibrosis transmembrane conductance regulator open probability.

    Directory of Open Access Journals (Sweden)

    Shaoyan Zhang

    Full Text Available Chronic rhinosinusitis engenders enormous morbidity in the general population, and is often refractory to medical intervention. Compounds that augment mucociliary clearance in airway epithelia represent a novel treatment strategy for diseases of mucus stasis. A dominant fluid and electrolyte secretory pathway in the nasal airways is governed by the cystic fibrosis transmembrane conductance regulator (CFTR. The objectives of the present study were to test resveratrol, a strong potentiator of CFTR channel open probability, in preparation for a clinical trial of mucociliary activators in human sinus disease.Primary sinonasal epithelial cells, immortalized bronchoepithelial cells (wild type and F508del CFTR, and HEK293 cells expressing exogenous human CFTR were investigated by Ussing chamber as well as patch clamp technique under non-phosphorylating conditions. Effects on airway surface liquid depth were measured using confocal laser scanning microscopy. Impact on CFTR gene expression was measured by quantitative reverse transcriptase polymerase chain reaction.Resveratrol is a robust CFTR channel potentiator in numerous mammalian species. The compound also activated temperature corrected F508del CFTR and enhanced CFTR-dependent chloride secretion in human sinus epithelium ex vivo to an extent comparable to the recently approved CFTR potentiator, ivacaftor. Using inside out patches from apical membranes of murine cells, resveratrol stimulated an ~8 picosiemens chloride channel consistent with CFTR. This observation was confirmed in HEK293 cells expressing exogenous CFTR. Treatment of sinonasal epithelium resulted in a significant increase in airway surface liquid depth (in µm: 8.08+/-1.68 vs. 6.11+/-0.47,control,p<0.05. There was no increase CFTR mRNA.Resveratrol is a potent chloride secretagogue from the mucosal surface of sinonasal epithelium, and hydrates airway surface liquid by increasing CFTR channel open probability. The foundation for a

  17. Efficiency enhancement of silicon nanowire solar cells by using UV/Ozone treatments and micro-grid electrodes

    Science.gov (United States)

    Chen, Junyi; Subramani, Thiyagu; Sun, Yonglie; Jevasuwan, Wipakorn; Fukata, Naoki

    2018-05-01

    Silicon nanowire solar cells were fabricated by metal catalyzed electroless etching (MCEE) followed by thermal chemical vapor deposition (CVD). In this study, we investigated two effects, a UV/ozone treatment and the use of a micro-grid electrodes, to enhance light absorption and reduce the optic losses in the solar cell device. The UV/ozone treatment successfully improved the conversion efficiency. The micro-grid electrodes were then applied in solar cell devices subjected to a back surface field (BSF) treatment and rapid thermal annealing (RTA). These effects improved the conversion efficiency from 9.4% to 10.9%. Moreover, to reduce surface recombination and improve the continuity of front electrodes, we optimized the etching time of the MCEE process, giving a high efficiency of 12.3%.

  18. [The implementation of the method of enhanced external counter pulsation for the treatment of cardiovascular diseases].

    Science.gov (United States)

    Badtieva, V A; Voroshilova, D N

    2018-05-21

    The cardiovascular diseases occupy a leading place in the structure of overall morbidity affecting the population not only of Russia but also of the majority of the developed countries throughout the world; they thus impose the heavy social and economic burden on both the public healthcare services and the modern society in general. At the same time, systemic atherosclerosis is considered to be one of the most common, severe, and life-threatening condition. Despite the presence of a large number of pharmaceutical and surgical methods for the treatment of this pathology, they are not infrequently lacking the desired effectiveness. The use of the shunting operations and endovascular methods failed to radically resolve the problem of managing systemic atherosclerosis and atherosclerosis of the lower limbs. A relatively novel approach which currently begins to find the ever increasing application for the treatment of patients presenting with cardiovascular pathology is based on the enhanced external counter-pulsation method although both the clinical and theoretical prerequisites of its application were developed rather long ago. This non-invasive therapeutic method allows to increase the perfusion pressure in the coronary arteries in diastole and to reduce the resistance to the cardiac ejection in the systole. The objective of this review article was to perform the analysis of the available literature publications on the use of the enhanced external counter-pulsation technique for the treatment of the patients presenting with the diseases of the cardiovascular system and to evaluate the clinical effectiveness of this approach as well as the availability of the treatment for the patients.

  19. Dual-energy computed tomography for the assessment of early treatment effects of regorafenib in a preclinical tumor model: comparison with dynamic contrast-enhanced CT and conventional contrast-enhanced single-energy CT

    International Nuclear Information System (INIS)

    Knobloch, Gesine; Hamm, Bernd; Jost, Gregor; Pietsch, Hubertus; Huppertz, Alexander

    2014-01-01

    The potential diagnostic value of dual-energy computed tomography (DE-CT) compared to dynamic contrast-enhanced CT (DCE-CT) and conventional contrast-enhanced CT (CE-CT) in the assessment of early regorafenib treatment effects was evaluated in a preclinical setting. A rat GS9L glioma model was examined with contrast-enhanced dynamic DE-CT measurements (80 kV/140 kV) for 4 min before and on days 1 and 4 after the start of daily regorafenib or placebo treatment. Tumour time-density curves (0-240 s, 80 kV), DE-CT (60 s) derived iodine maps and the DCE-CT (0-30 s, 80 kV) based parameters blood flow (BF), blood volume (BV) and permeability (PMB) were calculated and compared to conventional CE-CT (60 s, 80 kV). The regorafenib group showed a marked decrease in the tumour time-density curve, a significantly lower iodine concentration and a significantly lower PMB on day 1 and 4 compared to baseline, which was not observed for the placebo group. CE-CT showed a significant decrease in tumour density on day 4 but not on day 1. The DE-CT-derived iodine concentrations correlated with PMB and BV but not with BF. DE-CT allows early treatment monitoring, which correlates with DCE-CT. Superior performance was observed compared to single-energy CE-CT. circle Regorafenib treatment response was evaluated by CT in a rat tumour model. (orig.)

  20. Dual-energy computed tomography for the assessment of early treatment effects of regorafenib in a preclinical tumor model: comparison with dynamic contrast-enhanced CT and conventional contrast-enhanced single-energy CT

    Energy Technology Data Exchange (ETDEWEB)

    Knobloch, Gesine; Hamm, Bernd [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Jost, Gregor; Pietsch, Hubertus [Bayer Healthcare, MR and CT Contrast Media Research, Berlin (Germany); Huppertz, Alexander [Imaging Science Institute Charite - Siemens, Berlin (Germany)

    2014-08-15

    The potential diagnostic value of dual-energy computed tomography (DE-CT) compared to dynamic contrast-enhanced CT (DCE-CT) and conventional contrast-enhanced CT (CE-CT) in the assessment of early regorafenib treatment effects was evaluated in a preclinical setting. A rat GS9L glioma model was examined with contrast-enhanced dynamic DE-CT measurements (80 kV/140 kV) for 4 min before and on days 1 and 4 after the start of daily regorafenib or placebo treatment. Tumour time-density curves (0-240 s, 80 kV), DE-CT (60 s) derived iodine maps and the DCE-CT (0-30 s, 80 kV) based parameters blood flow (BF), blood volume (BV) and permeability (PMB) were calculated and compared to conventional CE-CT (60 s, 80 kV). The regorafenib group showed a marked decrease in the tumour time-density curve, a significantly lower iodine concentration and a significantly lower PMB on day 1 and 4 compared to baseline, which was not observed for the placebo group. CE-CT showed a significant decrease in tumour density on day 4 but not on day 1. The DE-CT-derived iodine concentrations correlated with PMB and BV but not with BF. DE-CT allows early treatment monitoring, which correlates with DCE-CT. Superior performance was observed compared to single-energy CE-CT. circle Regorafenib treatment response was evaluated by CT in a rat tumour model. (orig.)

  1. Social capital strategies to enhance hepatitis C treatment awareness and uptake among men in prison.

    Science.gov (United States)

    Lafferty, L; Treloar, C; Guthrie, J; Chambers, G M; Butler, T

    2017-02-01

    Prisoner populations are characterized by high rates of hepatitis C (HCV), up to thirty times that of the general population in Australia. Within Australian prisons, less than 1% of eligible inmates access treatment. Public health strategies informed by social capital could be important in addressing this inequality in access to HCV treatment. Twenty-eight male inmates participated in qualitative interviews across three correctional centres in New South Wales, Australia. All participants had recently tested as HCV RNA positive or were receiving HCV treatment. Analysis was conducted with participants including men with experiences of HCV treatment (n=10) (including those currently accessing treatment and those with a history of treatment) and those who were treatment naïve (n=18). Social capital was a resourceful commodity for inmates considering and undergoing treatment while in custody. Inmates were a valuable resource for information regarding HCV treatment, including personal accounts and reassurance (bonding social capital), while nurses a resource for the provision of information and care (linking social capital). Although linking social capital between inmates and nurses appeared influential in HCV treatment access, there remained opportunities for increasing linking social capital within the prison setting (such as nurse-led engagement within the prisons). Bonding and linking social capital can be valuable resources in promoting HCV treatment awareness, uptake and adherence. Peer-based programmes are likely to be influential in promoting HCV outcomes in the prison setting. Engagement in prisons, outside of the clinics, would enhance opportunities for linking social capital to influence HCV treatment outcomes. © 2016 John Wiley & Sons Ltd.

  2. Active Learning and Self-Regulation Enhance Student Teachers’ Professional Competences

    OpenAIRE

    Virtanen, Päivi; Niemi, Hannele M.; Nevgi, Anne

    2017-01-01

    The study identifies the relationships between active learning, student teachers’ self-regulated learning and professional competences. Further, the aim is to investigate how active learning promotes professional competences of student teachers with different self-regulation profiles. Responses from 422 student teachers to an electronic survey were analysed using statistical methods. It was found that the use of active learning methods, such as goal-oriented and intentional learning as well a...

  3. Erythema-directed digital photography for the enhanced evaluation of topical treatments for acne vulgaris.

    Science.gov (United States)

    Micali, G; Dall'Oglio, F; Tedeschi, A; Lacarrubba, F

    2018-01-31

    Erythema-directed digital photography is a novel method for evaluating the efficacy and tolerability of topical acne treatments. Here, we describe three case reports in which erythema-directed digital photography was used to evaluate acne before and after up to 12 weeks of treatment with clindamycin 1%/tretinoin 0.025% (Clin-RA). Erythema-directed digital photography was used to evaluate acne in three patients with mild-to-moderate facial acne, two of whom had refused to continue previous topical acne treatment (benzoyl peroxide 5% and clindamycin 1%/benzoyl peroxide 5%) due to persistent irritation. Acne lesions and erythema were evaluated using standard clinical photography and erythema-directed digital photography (VISIA-CR ™ system) before and after 8-12 weeks of treatment with Clin-RA. Erythema-directed digital photography revealed background erythema from previous topical acne treatments that was not evident from standard clinical photographs and allowed a better visualization of both inflammatory and non-inflammatory lesions. In all patients, there was a clear improvement in background erythema and a reduction in acne lesions following treatment with Clin-RA. This study has demonstrated for the first time that erythema-directed digital photography can enhance the evaluation of the efficacy and tolerability of topical acne treatments. These cases show that Clin-RA was associated with improved efficacy and tolerability vs previous treatments with topical monotherapy (benzoyl peroxide 5%) or a topical fixed-dose combination (clindamycin 1%/benzoyl peroxide 5%). © 2018 The Authors. Skin Research and Technology Published by John Wiley & Sons Ltd.

  4. Thiourea, a ROS scavenger, regulates source-to-sink relationship to enhance crop yield and oil content in Brassica juncea (L..

    Directory of Open Access Journals (Sweden)

    Manish Pandey

    Full Text Available In the present agricultural scenario, the major thrust is to increase crop productivity so as to ensure sustainability. In an earlier study, foliar application of thiourea (TU; a non physiological thiol based ROS scavenger has been demonstrated to enhance the stress tolerance and yield of different crops under field condition. Towards this endeavor, present work deals with the effect of TU on photosynthetic efficiency and source-to-sink relationship of Indian mustard (Brassica juncea for understanding its mode of action. The application of TU increased the efficiency of both PSI and PSII photosystems and vegetative growth of plant. The comparative analysis of sucrose to starch ratio and expression level of sugar transporters confirmed the higher source and sink strength in response to TU treatment. The biochemical evidence in support of this was derived from higher activities of sucrose phosphate synthase and fructose-1,6-bis-phosphatase at source; and sucrose synthase and different classes of invertases at both source and sink. This indicated an overall increase in photoassimilate level at sink. An additional contribution through pod photosynthesis was confirmed through the analysis of phosphoenol pyruvate carboxylase enzyme activity and level of organic acids. The increased photoassimilate level was also co-ordinated with acetyl coA carboxylase mediated oil biosynthesis. All these changes were ultimately reflected in the form of 10 and 20% increase in total yield and oil content, respectively under TU treatment as compared to control. Additionally, no change was observed in oil composition of seeds derived from TU treated plants. The study thus signifies the co-ordinated regulation of key steps of photosynthesis and source-to-sink relationship through the external application of TU resulting in increased crop yield and oil content.

  5. Drinking motives mediate emotion regulation difficulties and problem drinking in college students.

    Science.gov (United States)

    Aurora, Pallavi; Klanecky, Alicia K

    2016-05-01

    Problem drinking in college places students at an increased risk for a wealth of negative consequences including alcohol use disorders. Most research has shown that greater emotion regulation difficulties are related to increased problem drinking, and studies generally assume that drinking is motivated by efforts to cope with or enhance affective experiences. However, there is a lack of research specifically testing this assumption. The current study sought to examine the mediating potential of drinking motives, specifically coping and enhancement, on the relationship between emotion regulation and problem drinking. College participants (N = 200) completed an online survey, consisting of a battery of measures assessing alcohol use behaviors and related variables. Coping drinking motives fully mediated the emotion regulation/problem drinking relationship, and enhancement motives partially mediated this relationship. Exploratory analyses indicated that all four drinking motives (i.e. coping, enhancement, social, and conformity) simultaneously mediated the relationship between emotion regulation and quantity/frequency of alcohol use. However, only coping and enhancement significantly mediated the relationship between emotion regulation and alcohol-related consequences (e.g. alcohol dependence symptoms, alcohol-related injuries). The current results offer direction for potentially modifying brief alcohol interventions in efforts to reduce students' engagement in problem drinking behaviors. For example, interventions might incorporate information on the risks of using alcohol as a means of emotion regulation and offer alternative emotion regulation strategies.

  6. Phosphoproteomic Analysis Reveals a Novel Mechanism of CaMKIIα Regulation Inversely Induced by Cocaine Memory Extinction versus Reconsolidation

    Science.gov (United States)

    Rich, Matthew T.; Abbott, Thomas B.; Chung, Lisa; Gulcicek, Erol E.; Stone, Kathryn L.; Colangelo, Christopher M.; Lam, TuKiet T.; Nairn, Angus C.; Taylor, Jane R.

    2016-01-01

    Successful addiction treatment depends on maintaining long-term abstinence, making relapse prevention an essential therapeutic goal. However, exposure to environmental cues associated with drug use often thwarts abstinence efforts by triggering drug using memories that drive craving and relapse. We sought to develop a dual approach for weakening cocaine memories through phosphoproteomic identification of targets regulated in opposite directions by memory extinction compared with reconsolidation in male Sprague-Dawley rats that had been trained to self-administer cocaine paired with an audiovisual cue. We discovered a novel, inversely regulated, memory-dependent phosphorylation event on calcium-calmodulin-dependent kinase II α (CaMKIIα) at serine (S)331. Correspondingly, extinction-associated S331 phosphorylation inhibited CaMKIIα activity. Intra-basolateral amygdala inhibition of CaMKII promoted memory extinction and disrupted reconsolidation, leading to a reduction in subsequent cue-induced reinstatement. CaMKII inhibition had no effect if the memory was neither retrieved nor extinguished. Therefore, inhibition of CaMKII represents a novel mechanism for memory-based addiction treatment that leverages both extinction enhancement and reconsolidation disruption to reduce relapse-like behavior. SIGNIFICANCE STATEMENT Preventing relapse to drug use is an important goal for the successful treatment of addictive disorders. Relapse-prevention therapies attempt to interfere with drug-associated memories, but are often hindered by unintentional memory strengthening. In this study, we identify phosphorylation events that are bidirectionally regulated by the reconsolidation versus extinction of a cocaine-associated memory, including a novel site on CaMKIIα. Additionally, using a rodent model of addiction, we show that CaMKII inhibition in the amygdala can reduce relapse-like behavior. Together, our data supports the existence of mechanisms that can be used to enhance

  7. MADD knock-down enhances doxorubicin and TRAIL induced apoptosis in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Andrea Turner

    Full Text Available The Map kinase Activating Death Domain containing protein (MADD isoform of the IG20 gene is over-expressed in different types of cancer tissues and cell lines and it functions as a negative regulator of apoptosis. Therefore, we speculated that MADD might be over-expressed in human breast cancer tissues and that MADD knock-down might synergize with chemotherapeutic or TRAIL-induced apoptosis of breast cancer cells. Analyses of breast tissue microarrays revealed over-expression of MADD in ductal and invasive carcinomas relative to benign tissues. MADD knockdown resulted in enhanced spontaneous apoptosis in human breast cancer cell lines. Moreover, MADD knockdown followed by treatment with TRAIL or doxorubicin resulted in increased cell death compared to either treatment alone. Enhanced cell death was found to be secondary to increased caspase-8 activation. These data indicate that strategies to decrease MADD expression or function in breast cancer may be utilized to increase tumor cell sensitivity to TRAIL and doxorubicin induced apoptosis.

  8. Leadership and Licensure for Drug Treatment and the Implementation of Co-Occurring Disorder Treatment in Community Mental Health Centers.

    Science.gov (United States)

    Guerrero, Erick G; Padwa, Howard; Lengnick-Hall, Rebecca; Kong, Yinfei; Perrigo, Judith L

    2015-07-01

    Using a random sample of 48 outpatient mental health programs in low-income and racial and ethnic minority communities, this study examined directorial leadership, drug treatment licensure, and implementation of evidence-based protocols and practices to address co-occurring mental health and substance abuse disorders (COD). Understanding of findings was enhanced with focus groups at six clinics. Most programs (81 %) offered COD treatment. Directorial leadership was positively associated with COD treatment (β = 0.253, p = 0.047, 95 % CI 0.003, 0.502) and COD supervision and training (β = 0.358, p = 0.002, 95 % CI 0.142, 0.575). Licensure was negatively associated with COD treatment (β = -0.235, p = 0.041, 95 % CI -0.460, -0.010) and COD supervision and training (β = -0.195, p = 0.049, 95 % CI -0.389, -0.001). Although lack of financial integration may limit the effect of licensing on COD treatment implementation, the response of leaders to regulation, funding, and human resources issues may encourage COD treatment practices. Implications for leadership interventions and policy are discussed in the context of health care reform.

  9. Von Willebrand factor regulation of blood vessel formation.

    Science.gov (United States)

    Randi, Anna M; Smith, Koval E; Castaman, Giancarlo

    2018-06-04

    Several important physiological processes, from permeability to inflammation to haemostasis, take place at the vessel wall and are regulated by endothelial cells (EC). Thus, proteins that have been identified as regulators of one process are increasingly found to be involved in other vascular functions. Such is the case for Von Willebrand Factor (VWF), a large glycoprotein best known for its critical role in haemostasis. In vitro and in vivo studies have shown that lack of VWF causes enhanced vascularisation, both constitutively and following ischemia. This evidence is supported by studies on blood outgrowth endothelial cells (BOEC) from patients with lack of VWF synthesis (type 3 von Willebrand disease [VWD]). The molecular pathways are likely to involve VWF binding partners, such as integrin αvβ3, and components of Weibel Palade bodies (WPB), such as Angiopoietin-2 and Galectin-3, whose storage is regulated by VWF; these converge on the master regulator of angiogenesis and endothelial homeostasis, vascular endothelial growth factor (VEGF) signalling. Recent studies suggest that the roles of VWF may be tissue-specific. The ability of VWF to regulate angiogenesis has clinical implications for a subset of VWD patients with severe, intractable gastrointestinal bleeding due to vascular malformations. In this article, we review the evidence showing that VWF is involved in blood vessel formation, discuss the role of VWF high molecular weight multimers in regulating angiogenesis, and the value of studies on BOEC in developing a precision medicine approach to validate novel treatments for angiodysplasia in congenital VWD and acquired von Willebrand syndrome. Copyright © 2018 American Society of Hematology.

  10. Ectomycorrhizal fungi enhance nitrogen and phosphorus nutrition of Nothofagus dombeyi under drought conditions by regulating assimilative enzyme activities.

    Science.gov (United States)

    Alvarez, Maricel; Huygens, Dries; Olivares, Erick; Saavedra, Isabel; Alberdi, Miren; Valenzuela, Eduardo

    2009-08-01

    Drought stress conditions (DC) reduce plant growth and nutrition, restraining the sustainable reestablishment of Nothofagus dombeyi in temperate south Chilean forest ecosystems. Ectomycorrhizal symbioses have been documented to enhance plant nitrogen (N) and phosphorus (P) uptake under drought, but the regulation of involved assimilative enzymes remains unclear. We studied 1-year-old N. dombeyi (Mirb.) Oerst. plants in association with the ectomycorrhizal fungi Pisolithus tinctorius (Pers.) Coker & Couch. and Descolea antartica Sing. In greenhouse experiments, shoot and root dry weights, mycorrhizal colonization, foliar N and P concentrations, and root enzyme activities [glutamate synthase (glutamine oxoglutarate aminotransferase (GOGAT), EC 1.4.1.13-14), glutamine synthetase (GS, EC 6.3.1.2), glutamate dehydrogenase (GDH, EC 1.4.1.2-4), nitrate reductase (NR, EC 1.6.6.1), and acid phosphomonoesterase (PME, EC 3.1.3.1-2)] were determined as a function of soil-water content. Inoculation of N. dombeyi with P. tinctorius and D. antartica significantly stimulated plant growth and increased plant foliar N and P concentrations, especially under DC. Ectomycorrhizal inoculation increased the activity of all studied enzymes relative to non-mycorrhizal plants under drought. We speculate that GDH is a key enzyme involved in the enhancement of ectomycorrhizal carbon (C) availability by fuelling the tricarboxylic acid (TCA) cycle under conditions of drought-induced carbon deficit. All studied assimilative enzymes of the ectomycorrhizal associations, involved in C, N, and P transfers, are closely interlinked and interdependent. The up-regulation of assimilative enzyme activities by ectomycorrhizal fungal root colonizers acts as a functional mechanism to increase seedling endurance to drought. We insist upon incorporating ectomycorrhizal inoculation in existing Chilean afforestation programs.

  11. Cooperative Enhancement of Radiosensitivity After Combined Treatment of 17-(Allylamino)-17-Demethoxygeldanamycin and Celecoxib in Human Lung and Colon Cancer Cell Lines

    Science.gov (United States)

    Kim, Young-Mee

    2012-01-01

    We investigated whether the combined treatment of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), an inhibitor of heat-shock protein 90 (hsp90), and celecoxib, an inhibitor of cyclooxygenase-2, can cooperatively enhance the radiosensitivity of various human cancer cells. Combined treatment with 17-AAG and celecoxib, at clinically relevant concentrations, cooperatively induced radiosensitization in all tested cancer cells, but not in normal cells. Cooperative radiosensitization by the drug combination was also shown in a human tumor xenograft system. We found that ataxia-telangiectasia and rad3-related (ATR) and ataxia-telangiectasia mutated (ATM) are novel client proteins of hsp90. Combined treatment with 17-AAG and celecoxib cooperatively induced downregulation of ATR and ATM. In conclusion, combined treatment with 17-AAG and celecoxib at clinically relevant concentrations may significantly enhance the therapeutic efficacy of ionizing radiation. PMID:21830942

  12. Emotion regulation in mothers and young children faced with trauma.

    Science.gov (United States)

    Pat-Horenczyk, Ruth; Cohen, S; Ziv, Y; Achituv, M; Asulin-Peretz, L; Blanchard, T R; Schiff, M; Brom, D

    2015-01-01

    The present study investigated maternal emotion regulation as mediating the association between maternal posttraumatic stress symptoms and children's emotional dysregulation in a community sample of 431 Israeli mothers and children exposed to trauma. Little is known about the specific pathways through which maternal posttraumatic symptoms and deficits in emotion regulation contribute to emotional dysregulation. Inspired by the intergenerational process of relational posttraumatic stress disorder (PTSD), in which posttraumatic distress is transmitted from mothers to children, we suggest an analogous concept of relational emotion regulation, by which maternal emotion regulation problems may contribute to child emotion regulation deficits. Child emotion regulation problems were measured using the Child Behavior Checklist-Dysregulation Profile (CBCL-DP; T.M. Achenbach & I. Rescorla, 2000), which is comprised of three subscales of the CBCL: Attention, Aggression, and Anxiety/Depression. Maternal PTSD symptoms were assessed by the Posttraumatic Diagnostic Scale (E.B. Foa, L. Cashman, L. Jaycox, & K. Perry, 1997) and maternal emotion regulation by the Difficulties in Emotion Regulation Scale (K.L. Gratz & L. Roemer, 2004). Results showed that the child's emotion regulation problems were associated with both maternal posttraumatic symptoms and maternal emotion dysregulation. Further, maternal emotion regulation mediated the association between maternal posttraumatic symptoms and the child's regulation deficits. These findings highlight the central role of mothers' emotion regulation skills in the aftermath of trauma as it relates to children's emotion regulation skills. The degree of mothers' regulatory skills in the context of posttraumatic stress symptoms reflects a key process through which the intergenerational transmission of trauma may occur. Study results have critical implications for planning and developing clinical interventions geared toward the treatment of

  13. Estimation of tumour dose enhancement due to gold nanoparticles during typical radiation treatments: a preliminary Monte Carlo study

    International Nuclear Information System (INIS)

    Cho, S H

    2005-01-01

    A recent mice study demonstrated that gold nanoparticles could be safely administered and used to enhance the tumour dose during radiation therapy. The use of gold nanoparticles seems more promising than earlier methods because of the high atomic number of gold and because nanoparticles can more easily penetrate the tumour vasculature. However, to date, possible dose enhancement due to the use of gold nanoparticles has not been well quantified, especially for common radiation treatment situations. Therefore, the current preliminary study estimated this dose enhancement by Monte Carlo calculations for several phantom test cases representing radiation treatments with the following modalities: 140 kVp x-rays, 4 and 6 MV photon beams, and 192 Ir gamma rays. The current study considered three levels of gold concentration within the tumour, two of which are based on the aforementioned mice study, and assumed either no gold or a single gold concentration level outside the tumour. The dose enhancement over the tumour volume considered for the 140 kVp x-ray case can be at least a factor of 2 at an achievable gold concentration of 7 mg Au/g tumour assuming no gold outside the tumour. The tumour dose enhancement for the cases involving the 4 and 6 MV photon beams based on the same assumption ranged from about 1% to 7%, depending on the amount of gold within the tumour and photon beam qualities. For the 192 Ir cases, the dose enhancement within the tumour region ranged from 5% to 31%, depending on radial distance and gold concentration level within the tumour. For the 7 mg Au/g tumour cases, the loading of gold into surrounding normal tissue at 2 mg Au/g resulted in an increase in the normal tissue dose, up to 30%, negligible, and about 2% for the 140 kVp x-rays, 6 MV photon beam, and 192 Ir gamma rays, respectively, while the magnitude of dose enhancement within the tumour was essentially unchanged. (note)

  14. Characterization and regulation of the bovine stearoyl-CoA desaturase gene promoter

    International Nuclear Information System (INIS)

    Keating, Aileen F.; Kennelly, John J.; Zhao Fengqi

    2006-01-01

    The bovine stearoyl-CoA desaturase (Scd) gene plays an important role in the bovine mammary gland where substrates such as stearic and vaccenic acids are converted to oleic acid and conjugated linoleic acid (CLA), respectively. Up to 90% of the CLA in bovine milk is formed due to the action of this enzyme in the mammary gland. The areas of the bovine promoter of importance in regulating this key enzyme were examined and an area of 36 bp in length was identified as having a critical role in transcriptional activation and is designated the Scd transcriptional enhancer element (STE). Electrophoretic mobility shift assay detected three binding complexes on this area in Mac-T cell nuclear extracts. Treatment of cells with CLA caused a significant reduction in transcriptional activity, with this effect being mediated through the STE region. The bovine Scd gene promoter was up-regulated by insulin and down-regulated by oleic acid

  15. Enhancement of photocurrents due to the oxidation of water and organic compounds at BiZn2VO6 particulate thin film electrodes by treatment with a TiCl4 solution

    International Nuclear Information System (INIS)

    Liu Haimei; Imanishi, Akihito; Yang Wensheng; Nakato, Yoshihiro

    2010-01-01

    Photocurrents due to water oxidation at BiZn 2 VO 6 (E g 2.4 eV) particulate thin film electrodes were largely enhanced by pre-treatment with an aqueous TiCl 4 solution. Photocurrents for BiZn 2 VO 6 electrodes with no TiCl 4 treatment were also enhanced by the addition of organic compounds such as methanol and trimethyl amine to the aqueous electrolyte. Interestingly, such enhanced photocurrents by organic compounds were further enhanced by the TiCl 4 pre-treatment. EDAX and SEM investigations showed the formation of a flock-like TiO 2 overlayer on BiZn 2 VO 6 particles after the TiCl 4 treatment. The photocurrent enhancement by the TiCl 4 pre-treatment is thus mainly attributed to the necking effect of the flock-like TiO 2 overlayer, which facilitates the transport of photogenerated electrons within the BiZn 2 VO 6 particulate thin film electrode.

  16. Dose enhancement by synchrotron radiation and heavy atoms for the treatment of gliomas

    International Nuclear Information System (INIS)

    Bobyk, L.

    2010-11-01

    High grade gliomas are brain tumors of bad prognosis. The standard therapeutic treatment combines surgery, radiotherapy and sometimes use of temozolomide (chemotherapy agent). Healthy tissues radio-sensitivity is a major limitation for radiotherapy treatment. The stereotactic radiotherapy by synchrotron radiation is an innovative technique which combines a low energy radiation (lower 100 keV) with the presence of heavy atoms in the tumoral zone. Such an approach is used to increase the differential of dose deposited in the tumor compared to surrounding healthy tissues. In this study, several compounds containing heavy atoms such as chemotherapy agents: cisplatin/carbo-platin, a DNA base analog: 5-iodo-2'-deoxyuridine (IUdR) and gold nano-particles were considered. The dose enhancement factor induced by the presence of these compounds located for some of them in the extracellular medium or inside the cells for others, was determined using in vitro studies. Thereafter, in vivo studies on rats bearing gliomas, were performed to study the toxicity, the kinetic of distribution and the localization of these compounds together with their potential efficacy of treatment combining intracerebral injection with low energy radiation. (author)

  17. 7 CFR 457.172 - Coverage Enhancement Option.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Coverage Enhancement Option. 457.172 Section 457.172..., DEPARTMENT OF AGRICULTURE COMMON CROP INSURANCE REGULATIONS § 457.172 Coverage Enhancement Option. The Coverage Enhancement Option for the 2009 and succeeding crop years are as follows: FCIC policies: United...

  18. USE OF NEUROFEEDBACK AND MINDFULNESS TO ENHANCE RESPONSE TO HYPNOSIS TREATMENT IN INDIVIDUALS WITH MULTIPLE SCLEROSIS: Results From a Pilot Randomized Clinical Trial.

    Science.gov (United States)

    Jensen, Mark P; Battalio, Samuel L; Chan, Joy F; Edwards, Karlyn A; Day, Melissa A; Sherlin, Leslie H; Ehde, Dawn M

    2018-01-01

    This pilot study evaluated the possibility that 2 interventions hypothesized to increase slower brain oscillations (e.g., theta) may enhance the efficacy of hypnosis treatment, given evidence that hypnotic responding is associated with slower brain oscillations. Thirty-two individuals with multiple sclerosis and chronic pain, fatigue, or both, were randomly assigned to 1 of 2 interventions thought to increase slow wave activity (mindfulness meditation or neurofeedback training) or no enhancing intervention, and then given 5 sessions of self-hypnosis training targeting their presenting symptoms. The findings supported the potential for both neurofeedback and mindfulness to enhance response to hypnosis treatment. Research using larger sample sizes to determine the generalizability of these findings is warranted.

  19. Valproate induced hepatic steatosis by enhanced fatty acid uptake and triglyceride synthesis

    International Nuclear Information System (INIS)

    Bai, Xupeng; Hong, Weipeng; Cai, Peiheng; Chen, Yibei; Xu, Chuncao; Cao, Di; Yu, Weibang; Zhao, Zhongxiang; Huang, Min; Jin, Jing

    2017-01-01

    Steatosis is the characteristic type of VPA-induced hepatotoxicity and may result in life-threatening hepatic lesion. Approximately 61% of patients treated with VPA have been diagnosed with hepatic steatosis through ultrasound examination. However, the mechanisms underlying VPA-induced intracellular fat accumulation are not yet fully understood. Here we demonstrated the involvement of fatty acid uptake and lipogenesis in VPA-induced hepatic steatosis in vitro and in vivo by using quantitative real-time PCR (qRT-PCR) analysis, western blotting analysis, fatty acid uptake assays, Nile Red staining assays, and Oil Red O staining assays. Specifically, we found that the expression of cluster of differentiation 36 (CD36), an important fatty acid transport, and diacylglycerol acyltransferase 2 (DGAT2) were significantly up-regulated in HepG2 cells and livers of C57B/6J mice after treatment with VPA. Furthermore, VPA treatment remarkably enhanced the efficiency of fatty acid uptake mediated by CD36, while this effect was abolished by the interference with CD36-specific siRNA. Also, VPA treatment significantly increased DGAT2 expression as a result of the inhibition of mitogen-activated protein kinase kinase (MEK) – extracellular regulated kinase (ERK) pathway; however, DGAT2 knockdown significantly alleviated VPA-induced intracellular lipid accumulation. Additionally, we also found that sterol regulatory element binding protein-1c (SREBP-1c)-mediated fatty acid synthesis may be not involved in VPA-induced hepatic steatosis. Overall, VPA-triggered over-regulation of CD36 and DGAT2 could be helpful for a better understanding of the mechanisms underlying VPA-induced hepatic steatosis and may offer novel therapeutic strategies to combat VPA-induced hepatotoxicity. - Highlights: • VPA induced hepatic steatosis and modulated genes associated with lipid metabolism. • CD36-mediated fatty acid uptake contributed to VPA-induced lipid accumulation. • PA increased the hepatic

  20. Valproate induced hepatic steatosis by enhanced fatty acid uptake and triglyceride synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Xupeng; Hong, Weipeng; Cai, Peiheng; Chen, Yibei; Xu, Chuncao [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou (China); Cao, Di [School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou (China); Yu, Weibang [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou (China); Zhao, Zhongxiang [School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou (China); Huang, Min [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou (China); Jin, Jing, E-mail: jinjing@mail.sysu.edu.cn [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou (China)

    2017-06-01

    Steatosis is the characteristic type of VPA-induced hepatotoxicity and may result in life-threatening hepatic lesion. Approximately 61% of patients treated with VPA have been diagnosed with hepatic steatosis through ultrasound examination. However, the mechanisms underlying VPA-induced intracellular fat accumulation are not yet fully understood. Here we demonstrated the involvement of fatty acid uptake and lipogenesis in VPA-induced hepatic steatosis in vitro and in vivo by using quantitative real-time PCR (qRT-PCR) analysis, western blotting analysis, fatty acid uptake assays, Nile Red staining assays, and Oil Red O staining assays. Specifically, we found that the expression of cluster of differentiation 36 (CD36), an important fatty acid transport, and diacylglycerol acyltransferase 2 (DGAT2) were significantly up-regulated in HepG2 cells and livers of C57B/6J mice after treatment with VPA. Furthermore, VPA treatment remarkably enhanced the efficiency of fatty acid uptake mediated by CD36, while this effect was abolished by the interference with CD36-specific siRNA. Also, VPA treatment significantly increased DGAT2 expression as a result of the inhibition of mitogen-activated protein kinase kinase (MEK) – extracellular regulated kinase (ERK) pathway; however, DGAT2 knockdown significantly alleviated VPA-induced intracellular lipid accumulation. Additionally, we also found that sterol regulatory element binding protein-1c (SREBP-1c)-mediated fatty acid synthesis may be not involved in VPA-induced hepatic steatosis. Overall, VPA-triggered over-regulation of CD36 and DGAT2 could be helpful for a better understanding of the mechanisms underlying VPA-induced hepatic steatosis and may offer novel therapeutic strategies to combat VPA-induced hepatotoxicity. - Highlights: • VPA induced hepatic steatosis and modulated genes associated with lipid metabolism. • CD36-mediated fatty acid uptake contributed to VPA-induced lipid accumulation. • PA increased the hepatic

  1. Vorinostat approved in Japan for treatment of cutaneous T-cell lymphomas: status and prospects

    Directory of Open Access Journals (Sweden)

    Sato A

    2012-04-01

    Full Text Available Akinori SatoDepartment of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, JapanAbstract: Histone acetylation and deacetylation play important roles in the regulation of gene transcription and in the modulation of chromatin structure. The levels of histone acetylation are determined by the activities of histone acetyltransferases and histone deacetylases (HDACs. HDACs are associated with a number of oncogenes and tumor suppressor genes and can be aberrantly expressed and/or inappropriately activated in cancer cells. HDAC inhibitors have therefore recently emerged as a novel treatment modality against malignancies. They regulate gene expression by enhancing the acetylation of not only histones but also nonhistone proteins, including transcription factors, transcription regulators, signal transduction mediators, and DNA repair enzymes, and they inhibit cancer growth. Vorinostat (suberoylanilide hydroxamic acid is one of the most potent HDAC inhibitors, and was approved in Japan in 2011 for the treatment of cutaneous T-cell lymphoma. Numerous clinical trials have shown it to be effective against cutaneous T-cell lymphoma but less so against other types of cancer. Because vorinostat can overcome resistance to or enhance the efficacy of other anticancer agents, such as 5-fluorouracil, carboplatin, paclitaxel, bortezomib, and tamoxifen, combination therapies using vorinostat and these agents have been investigated. This review introduces the background and mechanism of action of vorinostat and describes the results of clinical trials using vorinostat, both as a single agent and in combination with other anticancer agents, against cutaneous T-cell lymphoma and other malignancies.Keywords: vorinostat, T-cell lymphoma, cancer, novel treatment

  2. Physiological and behavioral response of stonefly nymphs to enhanced limestone treatment of acid mine drainage

    Energy Technology Data Exchange (ETDEWEB)

    Cole, M.B.; Arnold, D.E.; Watten, B.J. [ABR Inc., PO Box 249, OR (USA). Environmental Research and Services

    2001-07-01

    A new acid mine drainage (AMD) treatment system uses pulsed, fluidized beds of limestone, and carbon dioxide pretreatment of influent AMD to enhance limestone neutralization of AMD. Laboratory studies were carried out to evaluate the behavior and physiology of larval stoneflies (Pteronarcys proteus, Plecoptera) exposed to effluents produced by the treatment system. Survival, sodium balance, drift, and feeding responses by P. proteus to treated and untreated AMD were examined. P. proteus nymphs exhibited significant losses of whole body sodium in exposures to untreated AMD. Nymphs exposed to treated effluents experienced no loss of whole-body sodium. No significant differences in feeding or drift behavior occurred between nymphs exposed to treated effluents and those exposed to AMD-free controls. The treatment system, with and without CO{sub 2} pretreatment, provided water that was not toxic to the test animals, and that allowed normal behavioral and physiological function.

  3. β-adrenergic receptor-dependent alterations in murine cardiac transcript expression are differentially regulated by gefitinib in vivo.

    Directory of Open Access Journals (Sweden)

    Jennifer A Talarico

    Full Text Available β-adrenergic receptor (βAR-mediated transactivation of epidermal growth factor receptor (EGFR has been shown to promote cardioprotection in a mouse model of heart failure and we recently showed that this mechanism leads to enhanced cell survival in part via regulation of apoptotic transcript expression in isolated primary rat neonatal cardiomyocytes. Thus, we hypothesized that this process could regulate cardiac transcript expression in vivo. To comprehensively assess cardiac transcript alterations in response to acute βAR-dependent EGFR transactivation, we performed whole transcriptome analysis of hearts from C57BL/6 mice given i.p. injections of the βAR agonist isoproterenol in the presence or absence of the EGFR antagonist gefitinib for 1 hour. Total cardiac RNA from each treatment group underwent transcriptome analysis, revealing a substantial number of transcripts regulated by each treatment. Gefitinib alone significantly altered the expression of 405 transcripts, while isoproterenol either alone or in conjunction with gefitinib significantly altered 493 and 698 distinct transcripts, respectively. Further statistical analysis was performed, confirming 473 transcripts whose regulation by isoproterenol were significantly altered by gefitinib (isoproterenol-induced up/downregulation antagonized/promoted by gefinitib, including several known to be involved in the regulation of numerous processes including cell death and survival. Thus, βAR-dependent regulation of cardiac transcript expression in vivo can be modulated by the EGFR antagonist gefitinib.

  4. Enhanced biodegradation of petrochemical wastewater using ozonation and BAC advanced treatment system

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chi-Kang; Tsai, Tsung-Yueh; Liu, Jiunn-Ching; Chen, Mei-Chen [Energy and Resources Labs., ITRI, Hsinchu (Taiwan)

    2001-07-01

    The characteristics of degradation/conversion of bio-refractory and the growth of a biofilm are investigated in laboratory-scale pre-ozonation and lifted moving-bed biological activated carbon (BAC) advanced treatment processes treating phenol, benzoic acid, aminobenzoic acid and petrochemical industry wastewater which contains acrylonitrile butadiene styrene (ABS). The optimal reaction time and ozone dosage of pre-ozonation for bio-refractory conversion were determined to be 30 min and 100-200mg O{sub 3}/hr, respectively. After pre-ozonation of 30 min treatment, BOD{sub 5}/COD ratio of influent and effluent increased apparently from 20 to 35%, approximately. However, the change of pH in pre-ozonation was inconspicuous. The optimal flow rate of influent and air were controlled at 1.6 1/h and 120-l50nl/min in lifted moving-bed BAC advanced treatment reactor. A COD removal efficiency of 85-95% and 70-90% may be maintained by using an organic loading of 3.2-6.3kg COD/m{sup 3} day and 0.6-1.6 kg-COD/m{sup 3} day with an HRT of 6.0 h as secondary and advanced treatment system, respectively. The time required for the BAC bed to be regenerated by a thermal regeneration is prolonged 4-5 times more than that of GAC system. It can be estimated that the enhanced COD removal capability of the biofilm was not only due to the increase in the COD removal capability of acclimated bacteria, but also due to species succession of bacteria in bio-film ecosystem. (Author)

  5. Enhanced resolution of eosinophilic liver abscess associated with toxocariasis by albendazole treatment.

    Science.gov (United States)

    Jang, Eun Young; Choi, Moon Seok; Gwak, Geum Youn; Koh, Kwang Cheol; Paik, Seung Woon; Lee, Joon Hyeok; Paik, Yong Han; Yoo, Byung Chul

    2015-04-01

    Visceral larva migrans, caused by Toxocara canis and Toxocara cati, has emerged as a significant cause of eosinophilic liver abscess (ELA). Differentiation of ELA associated with toxocariasis (ELA-T) from metastasis or primary liver malignancy is sometimes difficult. However, the role of albendazole treatment remains uncertain in this condition. The aim of this study was to evaluate whether albendazole can enhance the radiologic resolution of ELA-T. We retrospectively reviewed the medical records of the patients diagnosed with ELA-T at our institution between January 2008 and December 2011. ELA-T was diagnosed based on the imaging findings on computed tomography or magnetic resonance imaging and the presence of positive serum IgG antibody for Toxocara canis. Among a total of 163 patients, 32 patients received albendazole (albendazole group) and 131 did not (control group). Baseline characteristics and fate of liver nodules were compared between the two groups. Baseline characteristics (age, sex, number and maximal size of lesions, eosinophil count) were similar between the two groups. Median duration for achieving radiologic resolution in the albendazole group was significantly shorter than in the control group (207 days [range 186-228] vs. 302 days [range 224-380], p=0.023). In Cox regression analysis of the cumulative rates of radiologic resolution, the hazard ratio for albendazole treatment was 1.99 (95% confidence interval, 1.22-3.23). Radiologic resolution of ELA-T can be accelerated with albendazole treatment. Hence, inconvenience associated with long-term follow-up and unnecessary worries among patients can be eliminated with albendazole treatment.

  6. Formula to estimate the thermal enhancement ratio of a single simultaneous hyperthermia and radiation treatment

    International Nuclear Information System (INIS)

    Overgaard, J.

    1984-01-01

    An experimental model composed of a C 3 H mammary carcinoma and its surrounding skin has been exposed to simultaneous radiation and hyperthermia given with different combinations of the heating time and temperature. Based on the thermal enhancement ratio (TER) values obtained in the temperature range 41.5 to 43.5 0 C, a linear relationship between TER and the heating time was achieved at each temperature. The slopes of the curves drawn at each temperature were found to have a log-linear relationship with the treatment temperature. With these relationships it was possible to make a formula expressing the TER as a function of treatment temperature and time. This formula gives a crude but probably acceptable estimate of the TER following a single simultaneous radiation and heat treatment. Although subject to several limitations, the formula represents an attempt to describe a heat dose concept for the radiosensitizing effect of hyperthermia. This may be useful to establish the tolerance level of a given radiation treatment when combined with hyperthermia. (Auth.)

  7. Active Learning and Self-Regulation Enhance Student Teachers' Professional Competences

    Science.gov (United States)

    Virtanen, Päivi; Niemi, Hannele M.; Nevgi, Anne

    2017-01-01

    The study identifies the relationships between active learning, student teachers' self-regulated learning and professional competences. Further, the aim is to investigate how active learning promotes professional competences of student teachers with different self-regulation profiles. Responses from 422 student teachers to an electronic survey…

  8. Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats.

    Science.gov (United States)

    Maeng, L Y; Taha, M B; Cover, K K; Glynn, S S; Murillo, M; Lebron-Milad, K; Milad, M R

    2017-08-01

    Leuprolide acetate (LEU), also known as Lupron, is commonly used to treat prostate cancer in men. As a gonadotropin-releasing hormone (GnRH) receptor agonist, it initially stimulates the release of gonadal hormones, testosterone (T) and estradiol. This surge eventually suppresses these hormones, preventing the further growth and spread of cancer cells. Individuals receiving this treatment often report anxiety and cognitive changes, but LEU's effects on the neural mechanisms that are involved in anxiety during the trajectory of treatment are not well known. In this study, we examined the acute effects of LEU on fear extinction, hypothesizing that increased T levels following a single administration of LEU will facilitate extinction recall by altering neuronal activity within the fear extinction circuitry. Two groups of naïve adult male rats underwent a 3-day fear conditioning, extinction, and recall experiment. The delayed group (n=15) received a single injection of vehicle or LEU (1.2mg/kg) 3weeks before behavioral testing. The acute group (n=25) received an injection one day after fear conditioning, 30min prior to extinction training. Following recall, the brains for all animals were collected for c-fos immunohistochemistry. Blood samples were also collected and assayed for T levels. Acute administration of LEU increased serum T levels during extinction training and enhanced extinction recall 24h later. This enhanced extinction memory was correlated with increased c-fos activity within the infralimbic cortex and amygdala, which was not observed in the delayed group. These results suggest that the elevation in T induced by acute administration of LEU can influence extinction memory consolidation, perhaps through modification of neuronal activity within the infralimbic cortex and amygdala. This may be an important consideration in clinical applications of LEU and its effects on anxiety and cognition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Sequence conservation and combinatorial complexity of Drosophila neural precursor cell enhancers

    Directory of Open Access Journals (Sweden)

    Kuzin Alexander

    2008-08-01

    Full Text Available Abstract Background The presence of highly conserved sequences within cis-regulatory regions can serve as a valuable starting point for elucidating the basis of enhancer function. This study focuses on regulation of gene expression during the early events of Drosophila neural development. We describe the use of EvoPrinter and cis-Decoder, a suite of interrelated phylogenetic footprinting and alignment programs, to characterize highly conserved sequences that are shared among co-regulating enhancers. Results Analysis of in vivo characterized enhancers that drive neural precursor gene expression has revealed that they contain clusters of highly conserved sequence blocks (CSBs made up of shorter shared sequence elements which are present in different combinations and orientations within the different co-regulating enhancers; these elements contain either known consensus transcription factor binding sites or consist of novel sequences that have not been functionally characterized. The CSBs of co-regulated enhancers share a large number of sequence elements, suggesting that a diverse repertoire of transcription factors may interact in a highly combinatorial fashion to coordinately regulate gene expression. We have used information gained from our comparative analysis to discover an enhancer that directs expression of the nervy gene in neural precursor cells of the CNS and PNS. Conclusion The combined use EvoPrinter and cis-Decoder has yielded important insights into the combinatorial appearance of fundamental sequence elements required for neural enhancer function. Each of the 30 enhancers examined conformed to a pattern of highly conserved blocks of sequences containing shared constituent elements. These data establish a basis for further analysis and understanding of neural enhancer function.

  10. Does enhanced regulation improve EIA report quality? Lessons from South Africa

    International Nuclear Information System (INIS)

    Sandham, L.A.; Heerden, A.J. van; Jones, C.E.; Retief, F.P.; Morrison-Saunders, A.N.

    2013-01-01

    Recently, various EIA systems have been subjected to system review processes with a view to improve performance. Many of these reviews resulted in some form of legislative reform. The South African Environmental Impact Assessment (EIA) regulations were modified in 2006 with the express intent to improve EIA effectiveness. In order to evaluate to what extent the desired outcome was achieved, the quality of EIA reports produced under the 2006 regulations was investigated for comparative analysis with the preceding regime. A sample of EIA reports from the two legislative regimes was reviewed using an adapted version of a well established method known colloquially as the “Lee and Colley” review package. Despite some improvements in certain aspects, overall report quality has decreased slightly from the 1997 EIA regime. It therefore appears that the modifications to the regulations, often heralded as the solution to improvements in performance have not resulted in improved quality of EIA reports. - Highlights: ► EIA regulations in South Africa were revised and became more comprehensive in 2006. ► The report quality of a sample of EIAs was reviewed using the Lee and Colley review package. ► Report quality showed a slight decline from the previous regulatory regime. ► EIA good practice needs flexibility rather than over-detailed regulation.

  11. Cyproterone acetate enhances TRAIL-induced androgen-independent prostate cancer cell apoptosis via up-regulation of death receptor 5.

    Science.gov (United States)

    Chen, Linjie; Wolff, Dennis W; Xie, Yan; Lin, Ming-Fong; Tu, Yaping

    2017-03-07

    Virtually all prostate cancer deaths occur due to obtaining the castration-resistant phenotype after prostate cancer cells escaped from apoptosis and/or growth suppression initially induced by androgen receptor blockade. TNF-related apoptosis-inducing ligand (TRAIL) was an attractive cancer therapeutic agent due to its minimal toxicity to normal cells and remarkable apoptotic activity in tumor cells. However, most localized cancers including prostate cancer are resistant to TRAIL-induced apoptosis, thereby creating a therapeutic challenge of inducing TRAIL sensitivity in cancer cells. Herein the effects of cyproterone acetate, an antiandrogen steroid, on the TRAIL-induced apoptosis of androgen receptor-negative prostate cancer cells are reported. Cell apoptosis was assessed by both annexin V/propidium iodide labeling and poly (ADP-ribose) polymerase cleavage assays. Gene and protein expression changes were determined by quantitative real-time PCR and western blot assays. The effect of cyproterone acetate on gene promoter activity was determined by luciferase reporter assay. Cyproterone acetate but not AR antagonist bicalutamide dramatically increased the susceptibility of androgen receptor-negative human prostate cancer PC-3 and DU145 cells to TRAIL-induced apoptosis but no effects on immortalized human prostate stromal PS30 cells and human embryonic kidney HEK293 cells. Further investigation of the TRAIL-induced apoptosis pathway revealed that cyproterone acetate exerted its effect by selectively increasing death receptor 5 (DR5) mRNA and protein expression. Cyproterone acetate treatment also increased DR5 gene promoter activity, which could be abolished by mutation of a consensus binding domain of transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP) in the DR5 gene promoter. Cyproterone acetate increases CHOP expression in a concentration and time-dependent manner and endoplasmic reticulum stress reducer 4-phenylbutyrate could block

  12. Family Partner Intervention Influences Self-Care Confidence and Treatment Self-Regulation in Patients with Heart Failure

    Science.gov (United States)

    Stamp, Kelly D.; Dunbar, Sandra B.; Clark, Patricia C.; Reilly, Carolyn M.; Gary, Rebecca A.; Higgins, Melinda; Ryan, Richard M

    2015-01-01

    Background Heart failure self-care requires confidence in one’s ability and motivation to perform a recommended behavior. Most self-care occurs within a family context, yet little is known about the influence of family on heart failure self-care or motivating factors. Aims To examine the association of family functioning and the self-care antecedents of confidence and motivation among heart failure participants and determine if a family partnership intervention would promote higher levels of perceived confidence and treatment self-regulation (motivation) at four and eight months compared to patient-family education or usual care groups. Methods Heart failure patients (N = 117) and a family member were randomized to a family partnership intervention, patient-family education or usual care groups. Measures of patient’s perceived family functioning, confidence, motivation for medications and following a low-sodium diet were analyzed. Data were collected at baseline, four and eight months. Results Family functioning was related to self-care confidence for diet (p=.02) and autonomous motivation for adhering to their medications (p=.05 and diet p=0.2). The family partnership intervention group significantly improved confidence (p=.05) and motivation (medications (p=.004; diet p=.012) at four months whereas patient-family education group and usual care did not change. Conclusion Perceived confidence and motivation for self-care was enhanced by family partnership intervention, regardless of family functioning. Poor family functioning at baseline contributed to lower confidence. Family functioning should be assessed to guide tailored family-patient interventions for better outcomes. PMID:25673525

  13. Virus-induced down-regulation of GmERA1A and GmERA1B genes enhances the stomatal response to abscisic acid and drought resistance in soybean.

    Directory of Open Access Journals (Sweden)

    Takuya Ogata

    Full Text Available Drought is a major threat to global soybean production. The limited transformation potential and polyploid nature of soybean have hindered functional analysis of soybean genes. Previous research has implicated farnesylation in the plant's response to abscisic acid (ABA and drought tolerance. We therefore used virus-induced gene silencing (VIGS to evaluate farnesyltransferase genes, GmERA1A and GmERA1B (Glycine max Enhanced Response to ABA1-A and -B, as potential targets for increasing drought resistance in soybean. Apple latent spherical virus (ALSV-mediated GmERA1-down-regulated soybean leaves displayed an enhanced stomatal response to ABA and reduced water loss and wilting under dehydration conditions, suggesting that GmERA1A and GmERA1B negatively regulate ABA signaling in soybean guard cells. The findings provide evidence that the ALSV-VIGS system, which bypasses the need to generate transgenic plants, is a useful tool for analyzing gene function using only a single down-regulated leaf. Thus, the ALSV-VIGS system could constitute part of a next-generation molecular breeding pipeline to accelerate drought resistance breeding in soybean.

  14. Anorexia nervosa and childhood sexual abuse: Treatment outcomes of intensive enhanced cognitive behavioural therapy.

    Science.gov (United States)

    Calugi, Simona; Franchini, Cecilia; Pivari, Silvia; Conti, Maddalena; El Ghoch, Marwan; Dalle Grave, Riccardo

    2018-04-01

    Sexual abuse has been widely studied as a risk factor in anorexia nervosa, but data on its influence on treatment outcomes are scarce. Hence, we compared short- and long-term outcomes of inpatient enhanced cognitive-behavioural therapy (CBT-E) in patients with anorexia nervosa who had and had not suffered sexual abuse. Eighty-one patients were recruited, and body mass index (BMI), Eating Disorder Examination, Brief Symptom Inventory, and Work and Social Adjustment Scale scores were recorded before and after treatment, and at 6- and 12-month follow-ups. Twenty patients (24.7%) reported experiencing childhood sexual abuse before anorexia nervosa onset, while 61 (75.3%) reported none. Both groups displayed similar characteristics before treatment, and similarly large increases in BMI, eating-disorder, general psychopathology, and work and social functioning from baseline to 12-month follow-up. Based on these findings, childhood sexual abuse does not appear to compromise outcomes in patients with anorexia nervosa treated via intensive CBT-E. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. 78 FR 67847 - Debt Collection (Regulation F)

    Science.gov (United States)

    2013-11-12

    ... ( www.RegulationRoom.org ), that uses web technologies and approaches to enhance public understanding... that RegulationRoom is not an official United States Government Web site. Although comments made on... range of other businesses. Skip-tracing companies, for instance, provide contact information for...

  16. Circulating IGF1 regulates hippocampal IGF1 levels and brain gene expression during adolescence

    OpenAIRE

    Yan, Han; Mitschelen, Matthew; Bixler, Georgina V; Brucklacher, Robert M; Farley, Julie A; Han, Song; Freeman, Willard M; Sonntag, William E

    2011-01-01

    GH and its anabolic mediator, IGF1, are important not only in somatic growth but also in the regulation of brain function. Even though GH treatment has been used clinically to improve body composition and exercise capacity in adults, its influence on central nervous system function has only recently been recognized. This is also the case for children with childhood-onset GH deficiency (GHD) where GH has been used to stimulate bone growth and enhance final adult height. Circulating IGF1 is tra...

  17. The effect of fasting on the important molecular mechanisms related to cancer treatment

    Directory of Open Access Journals (Sweden)

    Vahideh Keyvani

    2014-11-01

    Full Text Available Fasting does have remarkable benefits in the treatment of cancer and another diseases such as metabolic syndrome, diabetes, and a multitude of other chronic diseases. It has been determined that fasting could play an important role during cancer treatment and progression via the regulation of insulin-like growth factor-1 (IGF-1 as well as other growth factors. Also, it has been shown that fasting would enhance the chemotherapy effect in cancer patients, selectively protects normal cells and organisms from chemotherapy toxicity, while simultaneously sensitizing tumors. In this article, we discuss the benefits of fasting in the treatment of cancer through several different molecular pathways.

  18. Fludarabine inhibits STAT1-mediated up-regulation of caspase-3 expression in dexamethasone-induced osteoblasts apoptosis and slows the progression of steroid-induced avascular necrosis of the femoral head in rats.

    Science.gov (United States)

    Feng, Zhenhua; Zheng, Wenhao; Tang, Qian; Cheng, Liang; Li, Hang; Ni, Wenfei; Pan, Xiaoyun

    2017-08-01

    Steroid-induced avascular necrosis of the femoral head (SANFH) is a major limitation of long-term or excessive clinical administration of glucocorticoids. Fludarabine, which is a compound used to treat various hematological malignancies, such as chronic lymphocytic leukemia, acts by down-regulating signal transducer and activator of transcription 1 (STAT1) by inhibiting STAT1 phosphorylation in both normal and cancer cells. This study assessed the effects of fludarabine in vitro (primary murine osteoblasts) and in vivo (rat SANFH model). In vitro, pretreatment with fludarabine significantly inhibited Dexamethasone (Dex)-induced apoptosis in osteoblasts, which was examined by TUNEL staining. Treatment with Dex caused a remarkable decrease in the expression of Bcl-2; an increase in cytochrome c release; activation of BAX, caspase-9, and caspase-3; and an obvious enhancement in STAT1 phosphorylation. However, treatment resulted in the up-regulation of caspase-3 expression. Enhanced P-STAT1 activity and up-regulation of caspase-3 expression were also observed in osteoblasts. In vivo, the subchondral trabeculae in fludarabine-treated rats exhibited less bone loss and a lower ratio of empty lacunae. Taken together, our results suggest that STAT1-mediated up-regulation of caspase-3 is involved in osteoblast apoptosis induced by Dex and indicates that fludarabine may serve as a potential agent for the treatment of SANFH.

  19. Enhancement of the sludge disintegration and nutrients release by a treatment with potassium ferrate combined with an ultrasonic process.

    Science.gov (United States)

    Li, Wei; Yu, Najiaowa; Liu, Qian; Li, Yiran; Ren, Nanqi; Xing, Defeng

    2018-09-01

    Sludge disintegration by ultrasound is a promising sludge treatment method. In order to enhance the efficiency of the sludge reduction and hydrolysis, potassium ferrate (K 2 FeO 4 ) (PF) was used. A novel method was developed to improve the sludge disintegration-sludge pretreatment by using PF in combination with an ultrasonic treatment (PF + ULT). After a short-term PF + ULT treatment, 17.23% of the volatile suspended solids (VSS) were reduced after a 900-min reaction time, which is 61.3% higher than the VSS reduction for the raw sludge. The supernatant soluble chemical oxygen demand (SCOD), total nitrogen (TN), volatile fatty acids (VFAs), soluble protein and polysaccharides increased by 522.5%, 1029.4%, 878.4%, 2996.6% and 801.9%, respectively. The constituent parts of the dissolved organic matter of the sludge products were released efficiently, which demonstrated the positive effect caused by the PF + ULT. The enhanced sludge disintegration process further alleviates environmental risk and offers a more efficient and convenient method for utilizing sludge. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Cognitive deficits in marijuana users: effects on motivational enhancement therapy plus cognitive behavioral therapy treatment outcome

    Science.gov (United States)

    Aharonovich, Efrat; Brooks, Adam C; Nunes, Edward V; Hasin, Deborah S

    2008-01-01

    Clinical variables that affect treatment outcome for marijuana dependent individuals are not yet well understood, including the effects of cognitive functioning. To address this, level of cognitive functioning and treatment outcome were investigated. Twenty marijuana-dependent outpatients were administered a neuropsychological battery at treatment entry. All patients received 12 weekly individual sessions of combined motivational enhancement therapy and cognitive behavioral therapy. The Wilcoxon Exact Test was used to compare cognitive functioning test scores between completers and dropouts, and the Fisher Exact Test was used to compare proportion of negative urines between those with higher and lower scores on the cognitive tests. Marijuana abstinence was unrelated to cognitive functioning. However, dropouts scored significantly lower than completers on measures of abstract reasoning and processing accuracy, providing initial evidence that cognitive functioning plays a role in treatment retention of adult marijuana dependent patients. If supported by further studies, the findings may help inform the development of interventions tailored for cognitively impaired marijuana dependent patients. PMID:18329188

  1. Enhancement of contractile force generation of artificial skeletal muscle tissues by mild and transient heat treatment.

    Science.gov (United States)

    Sato, Masanori; Ikeda, Kazushi; Kanno, Shota; Ito, Akira; Kawabe, Yoshinori; Kamihira, Masamichi

    2014-01-01

    Artificial skeletal muscle tissues composed of cells are expected to be used for applications of regenerative medicine and drug screening. Generally, however, the physical forces generated by tissue-engineered skeletal muscle are lower than those of skeletal muscle tissues found in the body. Local hyperthermia is used for many diseases including muscle injuries. It was recently reported that mild heat treatment improved skeletal muscle functions. In this study, we investigated the effects of mild heat treatment on the tissue-engineered skeletal muscle tissues in vitro. We used magnetite cationic liposomes to label C2C12 myoblast cells magnetically, and constructed densely packed artificial skeletal muscle tissues by using magnetic force. Cell culture at 39°C promoted the differentiation of myoblast cells into myotubes. Moreover, the mild and transient heat treatment improved the contractile properties of artificial skeletal muscle tissue constructs. These findings indicate that the culture method using heat treatment is a useful approach to enhance functions of artificial skeletal muscle tissue.

  2. Enhancement of tumor radioresponse by wortmannin in C3H/HeJ hepatocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Wonwoo; Seong, Jinsil; An, Jung-Hee; Oh, Hae-Jin [Yonsei Univ., Seoul (Korea, Republic of)

    2007-05-15

    The objective of this study was to explore whether a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), wortmannin, could potentiate the antitumor effect of radiation in vivo, particularly on radioresistant murine tumors. C3H/HeJ mice bearing syngeneic hepatocarcinoma (HCa-I) were treated with 25 Gy radiation, wortmannin, or both. Wortmannin was administered intraperitoneally (1 mg/kg) once daily for 14 days. Tumor response to treatment was determined by a tumor growth delay assay. Possible mechanisms of action were explored by examining the level of apoptosis and regulating molecules. The expression of regulating molecules was analyzed by Western blot for p53 and p21{sup WAF1/CIP1}, and immunohistochemical staining for p21{sup WAF1/CIP1}, CD31 and vascular endothelial growth factor (VEGF). In the tumor growth delay assay, wortmannin increased the effect of tumor radioresponse with an enhancement factor (EF) of 2.00. The level of apoptosis achieved by the combined treatments was shown to be no more than an additive effect; peak apoptotic index was 11% in radiation alone, 13% in wortmannin alone, and 19% in the combination group. Markedly increased areas of necrosis at 24 h in the combination group were noted. Western blotting showed upregulation of p21{sup WAF1/CIP1} in the combination treatment group, which correlated with low levels of VEGF. Microvascular density was evidently also reduced, based on low expression of CD31. In murine hepatocarcinoma, the antitumor effect of radiation was potentiated by wortmannin. The mechanism seems to involve not only the increase of induced apoptosis but also enhanced vascular injury. Wortmannin, in combination with radiation therapy, may have potential benefits in cancer treatment. (author)

  3. Enhancement of tumor radioresponse by wortmannin in C3H/HeJ hepatocarcinoma

    International Nuclear Information System (INIS)

    Kim, Wonwoo; Seong, Jinsil; An, Jung-Hee; Oh, Hae-Jin

    2007-01-01

    The objective of this study was to explore whether a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), wortmannin, could potentiate the antitumor effect of radiation in vivo, particularly on radioresistant murine tumors. C3H/HeJ mice bearing syngeneic hepatocarcinoma (HCa-I) were treated with 25 Gy radiation, wortmannin, or both. Wortmannin was administered intraperitoneally (1 mg/kg) once daily for 14 days. Tumor response to treatment was determined by a tumor growth delay assay. Possible mechanisms of action were explored by examining the level of apoptosis and regulating molecules. The expression of regulating molecules was analyzed by Western blot for p53 and p21 WAF1/CIP1 , and immunohistochemical staining for p21 WAF1/CIP1 , CD31 and vascular endothelial growth factor (VEGF). In the tumor growth delay assay, wortmannin increased the effect of tumor radioresponse with an enhancement factor (EF) of 2.00. The level of apoptosis achieved by the combined treatments was shown to be no more than an additive effect; peak apoptotic index was 11% in radiation alone, 13% in wortmannin alone, and 19% in the combination group. Markedly increased areas of necrosis at 24 h in the combination group were noted. Western blotting showed upregulation of p21 WAF1/CIP1 in the combination treatment group, which correlated with low levels of VEGF. Microvascular density was evidently also reduced, based on low expression of CD31. In murine hepatocarcinoma, the antitumor effect of radiation was potentiated by wortmannin. The mechanism seems to involve not only the increase of induced apoptosis but also enhanced vascular injury. Wortmannin, in combination with radiation therapy, may have potential benefits in cancer treatment. (author)

  4. Treatment planning considerations in contrast-enhanced radiotherapy: energy and beam aperture optimization

    Energy Technology Data Exchange (ETDEWEB)

    Garnica-Garza, H M, E-mail: hgarnica@cinvestav.mx [Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional Unidad Monterrey, Via del Conocimiento 201 Parque de Investigacion e Innovacion Tecnologica, Apodaca NL CP 66600 (Mexico)

    2011-01-21

    It has been shown that the use of kilovoltage x-rays in conjunction with a contrast agent incorporated into the tumor can lead to acceptable treatment plans with regard to the absorbed dose distribution produced in the target as well as in the tissue and organs at risk surrounding it. In this work, several key aspects related to the technology and irradiation techniques necessary to clinically implement this treatment modality are addressed by means of Monte Carlo simulation. The Zubal phantom was used to model a prostate radiotherapy treatment, a challenging site due to the depth of the prostate and the presence of bony structures that must be traversed by the x-ray beam on its way to the target. It is assumed that the concentration levels of the enhancing agent present in the tumor are at or below 10 mg per 1 g of tissue. The Monte Carlo code PENELOPE was used to model a commercial x-ray tube having a tungsten target. X-ray energy spectra for several combinations of peak electron energy and added filtration were obtained. For each energy spectrum, a treatment plan was calculated, with the PENELOPE Monte Carlo code, by modeling the irradiation of the patient as 72 independent conformal beams distributed at intervals of 5{sup 0} around the phantom in order to model a full x-ray source rotation. The Cimmino optimization algorithm was then used to find the optimum beam weight and energy for different treatment strategies. It is shown that for a target dose prescription of 72 Gy covering the whole tumor, the maximum rectal wall and bladder doses are kept below 52 Gy for the largest concentration of contrast agent of 10 mg per 1 g of tissue. It is also shown that concentrations of as little as 5 mg per 1 g of tissue also render dose distributions with excellent sparing of the organs at risk. A treatment strategy to address the presence of non-uniform distributions of the contrast agent in the target is also modeled and discussed.

  5. Enhanced FGF23 production in mice expressing PI3K-insensitive GSK3 is normalized by β-blocker treatment.

    Science.gov (United States)

    Fajol, Abul; Chen, Hong; Umbach, Anja T; Quarles, L Darryl; Lang, Florian; Föller, Michael

    2016-02-01

    Glycogen synthase kinase (GSK)-3 is a ubiquitously expressed kinase inhibited by insulin-dependent Akt/PKB/SGK. Mice expressing Akt/PKB/SGK-resistant GSK3α/GSK3β (gsk3(KI)) exhibit enhanced sympathetic nervous activity and phosphaturia with decreased bone density. Hormones participating in phosphate homeostasis include fibroblast growth factor (FGF)-23, a bone-derived hormone that inhibits 1,25-dihydroxyvitamin D3 (1,25(OH)2D3; calcitriol) formation and phosphate reabsorption in the kidney and counteracts vascular calcification and aging. FGF23 secretion is stimulated by the sympathetic nervous system. We studied the role of GSK3-controlled sympathetic activity in FGF23 production and phosphate metabolism. Serum FGF23, 1,25(OH)2D3, and urinary vanillylmandelic acid (VMA) were measured by ELISA, and serum and urinary phosphate and calcium were measured by photometry in gsk3(KI) and gsk3(WT) mice, before and after 1 wk of oral treatment with the β-blocker propranolol. Urinary VMA excretion, serum FGF23, and renal phosphate and calcium excretion were significantly higher, and serum 1,25(OH)2D3 and phosphate concentrations were lower in gsk3(KI) mice than in gsk3(WT) mice. Propranolol treatment decreased serum FGF23 and loss of renal calcium and phosphate and increased serum phosphate concentration in gsk3(KI) mice. We conclude that Akt/PKB/SGK-sensitive GSK3 inhibition participates in the regulation of FGF23 release, 1,25(OH)2D3 formation, and thus mineral metabolism, by controlling the activity of the sympathetic nervous system. © FASEB.

  6. Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

    International Nuclear Information System (INIS)

    Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya; Hirose, Takahisa; Kawamori, Ryuzo; Fujitani, Yoshio; Watada, Hirotaka

    2009-01-01

    Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4 daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.

  7. Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

    Energy Technology Data Exchange (ETDEWEB)

    Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Hirose, Takahisa [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Kawamori, Ryuzo [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Center for Beta Cell Biology and Regeneration, Juntendo University School of Medicine, Tokyo (Japan); Sportology Center, Juntendo University School of Medicine, Tokyo (Japan); Fujitani, Yoshio, E-mail: fujitani@juntendo.ac.jp [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Watada, Hirotaka, E-mail: hwatada@juntendo.ac.jp [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Sportology Center, Juntendo University School of Medicine, Tokyo (Japan)

    2009-12-18

    Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4 daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.

  8. Does enhanced regulation improve EIA report quality? Lessons from South Africa

    Energy Technology Data Exchange (ETDEWEB)

    Sandham, L.A., E-mail: luke.sandham@nwu.ac.za [Environmental Assessment Research Group, School of Geo and Spatial Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520 (South Africa); Heerden, A.J. van [Environmental Assessment Research Group, School of Geo and Spatial Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520 (South Africa); Jones, C.E. [School of Environment and Development, University of Manchester, Oxford Road, Manchester, M13 9PL (United Kingdom); Retief, F.P.; Morrison-Saunders, A.N. [Environmental Assessment Research Group, School of Geo and Spatial Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520 (South Africa)

    2013-01-15

    Recently, various EIA systems have been subjected to system review processes with a view to improve performance. Many of these reviews resulted in some form of legislative reform. The South African Environmental Impact Assessment (EIA) regulations were modified in 2006 with the express intent to improve EIA effectiveness. In order to evaluate to what extent the desired outcome was achieved, the quality of EIA reports produced under the 2006 regulations was investigated for comparative analysis with the preceding regime. A sample of EIA reports from the two legislative regimes was reviewed using an adapted version of a well established method known colloquially as the 'Lee and Colley' review package. Despite some improvements in certain aspects, overall report quality has decreased slightly from the 1997 EIA regime. It therefore appears that the modifications to the regulations, often heralded as the solution to improvements in performance have not resulted in improved quality of EIA reports. - Highlights: Black-Right-Pointing-Pointer EIA regulations in South Africa were revised and became more comprehensive in 2006. Black-Right-Pointing-Pointer The report quality of a sample of EIAs was reviewed using the Lee and Colley review package. Black-Right-Pointing-Pointer Report quality showed a slight decline from the previous regulatory regime. Black-Right-Pointing-Pointer EIA good practice needs flexibility rather than over-detailed regulation.

  9. Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia

    Science.gov (United States)

    Ferreira, R.; Fonseca, M. C.; Santos, T.; Sargento-Freitas, J.; Tjeng, R.; Paiva, F.; Castelo-Branco, M.; Ferreira, L. S.; Bernardino, L.

    2016-04-01

    Stroke is one of the leading causes of death and disability worldwide. However, current therapies only reach a small percentage of patients and may cause serious side effects. We propose the therapeutic use of retinoic acid-loaded nanoparticles (RA-NP) to safely and efficiently repair the ischaemic brain by creating a favourable pro-angiogenic environment that enhances neurogenesis and neuronal restitution. Our data showed that RA-NP enhanced endothelial cell proliferation and tubule network formation and protected against ischaemia-induced death. To evaluate the effect of RA-NP on vascular regulation of neural stem cell (NSC) survival and differentiation, endothelial cell-conditioned media (EC-CM) were collected. EC-CM from healthy RA-NP-treated cells reduced NSC death and promoted proliferation while EC-CM from ischaemic RA-NP-treated cells decreased cell death, increased proliferation and neuronal differentiation. In parallel, human endothelial progenitor cells (hEPC), which are part of the endogenous repair response to vascular injury, were collected from ischaemic stroke patients. hEPC treated with RA-NP had significantly higher proliferation, which further highlights the therapeutic potential of this formulation. To conclude, RA-NP protected endothelial cells from ischaemic death and stimulated the release of pro-survival, proliferation-stimulating factors and differentiation cues for NSC. RA-NP were shown to be up to 83-fold more efficient than free RA and to enhance hEPC proliferation. These data serve as a stepping stone to use RA-NP as vasculotrophic and neurogenic agents for vascular disorders and neurodegenerative diseases with compromised vasculature.

  10. Quantitative tissue-specific dynamics of in vivo GILZ mRNA expression and regulation by endogenous and exogenous glucocorticoids.

    Science.gov (United States)

    Ayyar, Vivaswath S; Almon, Richard R; Jusko, William J; DuBois, Debra C

    2015-06-01

    Glucocorticoids (GC) are steroid hormones, which regulate metabolism and immune function. Synthetic GCs, or corticosteroids (CS), have appreciable clinical utility via their ability to suppress inflammation in immune-mediated diseases like asthma and rheumatoid arthritis. Recent work has provided insight to novel GC-induced genes that mediate their anti-inflammatory effects, including glucocorticoid-induced leucine zipper (GILZ). Since GILZ comprises an important part of GC action, its regulation by both drug and hormone will influence CS therapy. In addition, GILZ expression is often employed as a biomarker of GC action, which requires judicious selection of sampling time. Understanding the in vivo regulation of GILZ mRNA expression over time will provide insight into both the physiological regulation of GILZ by endogenous GC and the dynamics of its enhancement by CS. A highly quantitative qRT-PCR assay was developed for measuring GILZ mRNA expression in tissues obtained from normal and CS-treated rats. This assay was applied to measure GILZ mRNA expression in eight tissues; to determine its endogenous regulation over time; and to characterize its dynamics in adipose tissue, muscle, and liver following treatment with CS. We demonstrate that GILZ mRNA is expressed in several tissues. GILZ mRNA expression in adipose tissue displayed a robust circadian rhythm that was entrained with the circadian oscillation of endogenous corticosterone; and is strongly enhanced by acute and chronic dosing. Single dosing also enhanced GILZ mRNA in muscle and liver, but the dynamics varied. In conclusion, GILZ is widely expressed in the rat and highly regulated by endogenous and exogenous GCs. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  11. Enhancement of in vitro high-density polyethylene (HDPE) degradation by physical, chemical, and biological treatments.

    Science.gov (United States)

    Balasubramanian, V; Natarajan, K; Rajeshkannan, V; Perumal, P

    2014-11-01

    Partially degraded high-density polyethylene (HDPE) was collected from plastic waste dump yard for biodegradation using fungi. Of various fungi screened, strain MF12 was found efficient in degrading HDPE by weight loss and Fourier transform infrared (FT-IR) spectrophotometric analysis. Strain MF12 was selected as efficient HDPE degraders for further studies, and their growth medium composition was optimized. Among those different media used, basal minimal medium (BMM) was suitable for the HDPE degradation by strain MF12. Strain MF12 was subjected to 28S rRNA sequence analysis and identified as Aspergillus terreus MF12. HDPE degradation was carried out using combinatorial physical and chemical treatments in conjunction to biological treatment. The high level of HDPE degradation was observed in ultraviolet (UV) and KMnO4/HCl with A. terreus MF12 treatment, i.e., FT10. The abiotic physical and chemical factors enhance the biodegradation of HDPE using A. terreus MF12.

  12. Pre-harvest methyl jasmonate treatment enhances cauliflower chemoprotective attributes without a loss in postharvest quality.

    Science.gov (United States)

    Ku, Kang Mo; Choi, Jeong-Hee; Kushad, Mosbah M; Jeffery, Elizabeth H; Juvik, John A

    2013-06-01

    Methyl jasmonate (MeJA) treatment can significantly increase glucosinolate (GS) concentrations in Brassica vegetables and potentially enhance anticancer bioactivity. Although MeJA treatment may promote ethylene biosynthesis, which can be detrimental to postharvest quality, there are no previous reports of its effect on cauliflower postharvest quality. To address this, cauliflower curds in field plots were sprayed with either 0.1 % Triton X-100 (control) or 500 μM MeJA solutions four days prior to harvest, then stored at 4 °C. Tissue subsamples were collected after 0, 10, 20, and 30 days of postharvest storage and assayed for visual color change, ethylene production, GS concentrations, and extract quinone reductase inductive activity. MeJA treatment increased curd GS concentrations of glucoraphanin, glucobrassicin, and neoglucobrassicin by 1.5, 2.4, and 4.6-fold over controls, respectively. MeJA treated cauliflower showed significantly higher quinone reductase activity, a biomarker for anticancer bioactivity, without reducing visual color and postharvest quality for 10 days at 4 °C storage.

  13. MiR-143 enhances the antitumor activity of shikonin by targeting BAG3 expression in human glioblastoma stem cells.

    Science.gov (United States)

    Liu, Jing; Qu, Cheng-Bin; Xue, Yi-Xue; Li, Zhen; Wang, Ping; Liu, Yun-hui

    Therapeutic applications of microRNAs (miRNAs) in chemotherapy were confirmed to be valuable, but there is rare to identify their specific roles and functions in shikonin treatment toward tumors. Here, for the first time, we reported that miR-143 played a critical role in the antitumor activity of shikonin in glioblastoma stem cells (GSCs). The results showed that the expression of miR-143 was downregulated in shikonin treated GSCs within 24 h. MiR-143 overexpression significantly enhanced the inhibitory effect of shikonin toward GSCs on cell viability. Besides, miR-143 overexpression caused a significant increase in the apoptotic fraction and made apoptosis occur earlier. Further investigation identified that BAG3, an apoptotic regulator, was a functional target of miR-143 in shikonin treated GSCs. The expression of BAG3 was upregulated in shikonin treated GSCs within 24 h. MiR-143 overexpression significantly reversed the high expression of BAG3 in shikonin treated GSCs. Moreover, it was confirmed that the enhanced cytotoxicity of shikonin by miR-143 overexpression was reversed by BAG3 overexpression both in vitro and in vivo, suggesting that the enhanced tumor suppressive effects by miR-143 overexpression was at least partly through the regulation of BAG3. Taken together, for the first time, our results demonstrate that miR-143 could enhance the antitumor activity of shikonin toward GSCs through reducing BAG3 expression, which may provide a novel therapeutic strategy for enhancing the treatment efficacy of shikonin toward GSCs. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Changes in self-efficacy for exercise and improved nutrition fostered by increased self-regulation among adults with obesity.

    Science.gov (United States)

    Annesi, James J; Johnson, Ping H; McEwen, Kristin L

    2015-10-01

    Behavioral theory suggests that treatments that increase participants' use of self-regulatory skills and/or their feelings of ability (self-efficacy) will improve exercise and nutrition behaviors. In addition, psychosocial factors associated with increased exercise may carry over to improved eating. Self-regulation might enhance self-efficacy through feelings of ability to manage barriers to maintaining weight-loss behaviors. Sedentary adults with severe or morbid obesity (M age = 43 years; M BMI = 40.1 kg/m(2)) participated in a 6-month study within a community-based YMCA center. We randomly assigned participants to one of the two groups that incorporated the same cognitive-behavioral support of exercise paired with methods for controlled, healthy eating emphasizing either (a) self-efficacy (n = 138), or (b) self-regulation (n = 136) methods. Mixed model repeated measures ANOVAs indicated significant improvements in exercise- and eating-related self-regulation over 3 months, and exercise- and eating-related self-efficacy over 6 months. The Self-Regulation Treatment Group demonstrated greater improvements in self-regulation for eating and fruit and vegetable intake than the Self-Efficacy Group. Regression analyses indicated that for both exercise and eating, self-regulation change significantly predicted self-efficacy change. In separate equations, changes in exercise and fruit and vegetable intake mediated those relationships, and change in self-efficacy and the corresponding behavioral changes demonstrated reciprocal, mutually reinforcing, relationships. There was evidence of carry-over, or generalization, of both self-regulation and self-efficacy changes from an exercise context to an eating context. We discussed findings in terms of leveraging self-regulation to improve self-efficacy, and provide a rationale for why exercise is the strongest predictor of success with weight loss. Results may be used to inform future behavioral weight

  15. A novel use of Moringa oleifera seed powder in enhancing the primary treatment of paper mill effluent.

    Science.gov (United States)

    Boulaadjoul, Soumia; Zemmouri, Hassiba; Bendjama, Zoubida; Drouiche, Nadjib

    2018-05-02

    In this study, Moringa oleifera (M. oleifera) performance as an eco-friendly coagulant in the enhanced primary treatment of paper mill effluent was investigated. Its performance in terms of turbidity removal and COD abatement was examined. Local M. oleifera seed powder from ADRAR-city, South of Algeria, was used. Conventional jar tests were conducted for enhancing the primary treatment of paper mill effluent from paper factory. For this reason, comparative coagulation tests were performed using aluminum sulfate (alum). Indeed, in terms of turbidity abatement, 96.02% and 97.1% were obtained for Moringa and alum, respectively. However, in the case of COD abatement, the abatement rate of M. oleifera seeds was slightly higher than that of alum, 97.28% and 92.67%, respectively. Because M. oleifera is a natural resource that is locally available, an eco-friendly coagulant, non-toxic, and biodegradable and does not affect the pH of water; thus, its use allows to avoid numerous disadvantages of conventional coagulants like alum. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. MicroRNA-221 and -222 Regulate Radiation Sensitivity by Targeting the PTEN Pathway

    International Nuclear Information System (INIS)

    Zhang Chunzhi; Kang Chunsheng; Wang Ping; Cao Yongzhen; Lv Zhonghong; Yu Shizhu; Wang Guangxiu; Zhang Anling; Jia Zhifan; Han Lei; Yang Chunying; Ishiyama, Hiromichi; Teh, Bin S.; Xu Bo; Pu Peiyu

    2011-01-01

    Purpose: MicroRNAs (miRNAs) are noncoding RNAs inhibiting expression of numerous target genes by posttranscriptional regulation. miRNA-221 and miRNA-222 (miRNA-221/-222) expression is elevated in radioresistant tumor cell lines; however, it is not known whether and how miRNAs control cellular responses to ionizing irradiation. Methods and Materials: We used bioinformatic analyses, luciferase reporter assay, and genetic knockdown and biochemical assays to characterize the regulation pathways of miRNA-221/-222 in response to radiation treatment. Results: We identified the PTEN gene as a target of miRNA-221/-222. Furthermore, we found that knocking down miRNA-221/-222 by antisense oligonucleotides upregulated PTEN expression. Upregulated PTEN expression suppressed AKT activity and increased radiation-induced apoptosis, resulting in enhancement of radiosensitivity in tumor cells. Conclusions: miRNA-221/-222 control radiation sensitivity by regulating the PTEN/AKT pathway and can be explored as novel targets for radiosensitization.

  17. IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Takahashi, Yutaka, E-mail: takahash@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Cellular senescence plays an important role in tumorigenesis and aging process. Black-Right-Pointing-Pointer We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. Black-Right-Pointing-Pointer IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. Black-Right-Pointing-Pointer These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated {beta}-galactosidase (SA-{beta}-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, {gamma}H2AX, the increased levels of p53 and p21 proteins, and activated SA-{beta}-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-{beta}-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

  18. IGF-I enhances cellular senescence via the reactive oxygen species–p53 pathway

    International Nuclear Information System (INIS)

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro; Takahashi, Yutaka

    2012-01-01

    Highlights: ► Cellular senescence plays an important role in tumorigenesis and aging process. ► We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. ► IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. ► These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated β-galactosidase (SA-β-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, γH2AX, the increased levels of p53 and p21 proteins, and activated SA-β-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-β-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

  19. Physiological and brain activity after a combined cognitive behavioral treatment plus video game therapy for emotional regulation in bulimia nervosa: a case report.

    Science.gov (United States)

    Fagundo, Ana Beatriz; Via, Esther; Sánchez, Isabel; Jiménez-Murcia, Susana; Forcano, Laura; Soriano-Mas, Carles; Giner-Bartolomé, Cristina; Santamaría, Juan J; Ben-Moussa, Maher; Konstantas, Dimitri; Lam, Tony; Lucas, Mikkel; Nielsen, Jeppe; Lems, Peter; Cardoner, Narcís; Menchón, Jose M; de la Torre, Rafael; Fernandez-Aranda, Fernando

    2014-08-12

    PlayMancer is a video game designed to increase emotional regulation and reduce general impulsive behaviors, by training to decrease arousal and improve decision-making and planning. We have previously demonstrated the usefulness of PlayMancer in reducing impulsivity and improving emotional regulation in bulimia nervosa (BN) patients. However, whether these improvements are actually translated into brain changes remains unclear. The aim of this case study was to report on a 28-year-old Spanish woman with BN, and to examine changes in physiological variables and brain activity after a combined treatment of video game therapy (VGT) and cognitive behavioral therapy (CBT). Ten VGT sessions were carried out on a weekly basis. Anxiety, physiological, and impulsivity measurements were recorded. The patient was scanned in a 1.5-T magnetic resonance scanner, prior to and after the 10-week VGT/CBT combined treatment, using two paradigms: (1) an emotional face-matching task, and (2) a multi-source interference task (MSIT). Upon completing the treatment, a decrease in average heart rate was observed. The functional magnetic resonance imaging (fMRI) results indicated a post-treatment reduction in reaction time along with high accuracy. The patient engaged areas typically active in healthy controls, although the cluster extension of the active areas decreased after the combined treatment. These results suggest a global improvement in emotional regulation and impulsivity control after the VGT therapy in BN, demonstrated by both physiological and neural changes. These promising results suggest that a combined treatment of CBT and VGT might lead to functional cerebral changes that ultimately translate into better cognitive and emotional performances.

  20. Physiological and Brain Activity After a Combined Cognitive Behavioral Treatment Plus Video Game Therapy for Emotional Regulation in Bulimia Nervosa: A Case Report

    Science.gov (United States)

    Fagundo, Ana Beatriz; Via, Esther; Sánchez, Isabel; Jiménez-Murcia, Susana; Forcano, Laura; Soriano-Mas, Carles; Giner-Bartolomé, Cristina; Santamaría, Juan J; Ben-Moussa, Maher; Konstantas, Dimitri; Lam, Tony; Lucas, Mikkel; Nielsen, Jeppe; Lems, Peter; Cardoner, Narcís; Menchón, Jose M; de la Torre, Rafael

    2014-01-01

    Background PlayMancer is a video game designed to increase emotional regulation and reduce general impulsive behaviors, by training to decrease arousal and improve decision-making and planning. We have previously demonstrated the usefulness of PlayMancer in reducing impulsivity and improving emotional regulation in bulimia nervosa (BN) patients. However, whether these improvements are actually translated into brain changes remains unclear. Objective The aim of this case study was to report on a 28-year-old Spanish woman with BN, and to examine changes in physiological variables and brain activity after a combined treatment of video game therapy (VGT) and cognitive behavioral therapy (CBT). Methods Ten VGT sessions were carried out on a weekly basis. Anxiety, physiological, and impulsivity measurements were recorded. The patient was scanned in a 1.5-T magnetic resonance scanner, prior to and after the 10-week VGT/CBT combined treatment, using two paradigms: (1) an emotional face-matching task, and (2) a multi-source interference task (MSIT). Results Upon completing the treatment, a decrease in average heart rate was observed. The functional magnetic resonance imaging (fMRI) results indicated a post-treatment reduction in reaction time along with high accuracy. The patient engaged areas typically active in healthy controls, although the cluster extension of the active areas decreased after the combined treatment. Conclusions These results suggest a global improvement in emotional regulation and impulsivity control after the VGT therapy in BN, demonstrated by both physiological and neural changes. These promising results suggest that a combined treatment of CBT and VGT might lead to functional cerebral changes that ultimately translate into better cognitive and emotional performances. PMID:25116416

  1. Prognosis prediction of non-enhancing T2 high signal intensity lesions in glioblastoma patients after standard treatment: application of dynamic contrast-enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Rihyeon; Yun, Tae Jin; Kim, Ji-Hoon; Sohn, Chul-Ho [Seoul National University Hospital, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Choi, Seung Hong [Seoul National University Hospital, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Department of Radiology, Seoul National University College of Medicine, and Institute of Radiation Medicine, 103 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Seoul National University, Center for Nanoparticle Research, Institute for Basic Science (IBS), Daehak-dong, Gwanak-gu, Seoul (Korea, Republic of); Seoul National University, School of Chemical and Biological Engineering, Daehak-dong, Gwanak-gu, Seoul (Korea, Republic of); Lee, Soon-Tae [Seoul National University Hospital, Department of Neurology, Seoul (Korea, Republic of); Park, Chul-Kee [Seoul National University Hospital, Department of Neurosurgery, Seoul (Korea, Republic of); Kim, Tae Min [Seoul National University Hospital, Department of Internal Medicine, Seoul (Korea, Republic of); Park, Sun-Won [Seoul National University College of Medicine, Department of Radiology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Park, Sung-Hye [Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of); Kim, Il Han [Seoul National University Hospital, Department of Radiation Oncology, Seoul (Korea, Republic of)

    2017-03-15

    To identify candidate imaging biomarkers for early disease progression in glioblastoma multiforme (GBM) patients by analysis of dynamic contrast-enhanced (DCE) MR parameters of non-enhancing T2 high signal intensity (SI) lesions. Forty-nine GBM patients who had undergone preoperative DCE MR imaging and received standard treatment were retrospectively included. According to the Response Assessment in Neuro-Oncology criteria, patients were classified into progression (n = 21) or non-progression (n = 28) groups. We analysed the pharmacokinetic parameters of Ktrans, Ve and Vp within non-enhancing T2 high SI lesions of each tumour. The best percentiles of each parameter from cumulative histograms were identified by the area under the receiver operating characteristic curve (AUC) and were compared using multivariate stepwise logistic regression. For the differentiation of early disease progression, the highest AUC values were found in the 99th percentile of Ktrans (AUC 0.954), the 97th percentile of Ve (AUC 0.815) and the 94th percentile of Vp (AUC 0.786) (all p < 0.05). The 99th percentile of Ktrans was the only significant independent variable from the multivariate stepwise logistic regression (p = 0.002). We found that the Ktrans of non-enhancing T2 high SI lesions in GBM patients holds potential as a candidate prognostic marker in future prospective studies. (orig.)

  2. Enhancement of the recycling of waste Ni-Cd and Ni-MH batteries by mechanical treatment.

    Science.gov (United States)

    Huang, Kui; Li, Jia; Xu, Zhenming

    2011-06-01

    A serious environmental problem was presented by waste batteries resulting from lack of relevant regulations and effective recycling technologies in China. The present work considered the enhancement of waste Ni-Cd and Ni-MH batteries recycling by mechanical treatment. In the process of characterization, two types of waste batteries (Ni-Cd and Ni-MH batteries) were selected and their components were characterized in relation to their elemental chemical compositions. In the process of mechanical separation and recycling, waste Ni-Cd and Ni-MH batteries were processed by a recycling technology without a negative impact on the environment. The technology contained mechanical crushing, size classification, gravity separation, and magnetic separation. The results obtained demonstrated that: (1) Mechanical crushing was an effective process to strip the metallic parts from separators and pastes. High liberation efficiency of the metallic parts from separators and pastes was attained in the crushing process until the fractions reached particle sizes smaller than 2mm. (2) The classified materials mainly consisted of the fractions with the size of particles between 0.5 and 2mm after size classification. (3) The metallic concentrates of the samples were improved from around 75% to 90% by gravity separation. More than 90% of the metallic materials were separated into heavy fractions when the particle sizes were larger than 0.5mm. (4) The size of particles between 0.5 and 2mm and the rotational speed of the separator between 30 and 60 rpm were suitable for magnetic separation during industrial application, with the recycling efficiency exceeding 95%. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Regulation of dopamine transporter activity by carboxypeptidase E

    Directory of Open Access Journals (Sweden)

    Zhang Heping

    2009-05-01

    Full Text Available Abstract Background The dopamine transporter (DAT plays a critical role in terminating the action of dopamine by rapid reuptake into the presynaptic neuron. Previous studies have revealed that the DAT carboxyl terminus (DAT-CT can directly interact with other cellular proteins and regulate DAT function and trafficking. Results Here, we have identified that carboxypeptidase E (CPE, a prohormone processing exopeptidase and sorting receptor for the regulated secretory pathway, interacts with the DAT-CT and affects DAT function. Mammalian cell lines coexpressing CPE and DAT exhibited increased DAT-mediated dopamine uptake activity compared to cells expressing DAT alone. Moreover, coexpression of an interfering DAT-CT minigene inhibited the effects of CPE on DAT. Functional changes caused by CPE could be attributed to enhanced DAT expression and subsequent increase in DAT cell surface localization, due to decreased DAT degradation. In addition, CPE association could reduce the phosphorylation state of DAT on serine residues, potentially leading to reduced internalization, thus stabilizing plasmalemmal DAT localization. Conclusion Taken together, our results reveal a novel role for CPE in the regulation of DAT trafficking and DAT-mediated DA uptake, which may provide a novel target in the treatment of dopamine-governed diseases such as drug addiction and obesity.

  4. Enhanced bonding of chitosan to implant quality titanium via four treatment combinations

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Holly J. [Dave C. Swalm School of Chemical Engineering, James Worth Bagley College of Engineering, Mississippi State University, Box 9595, Mississippi State, Mississippi 39762 (United States)], E-mail: hjp2@msstate.edu; Schulz, Kirk H. [Dave C. Swalm School of Chemical Engineering, James Worth Bagley College of Engineering, Mississippi State University, Box 9595, Mississippi State, Mississippi 39762 (United States); Bumgardner, Joel D. [Department of Biomedical Engineering, Herff College of Engineering, University of Memphis, 330 Engineering Technology Building, Memphis, Tennessee 38152 (United States); Schneider, Judith A. [Department of Mechanical Engineering, James Worth Bagley College of Engineering, Mississippi State University, Box 9552, Mississippi State, Mississippi 39762 (United States)

    2008-07-31

    Bioactive coatings have been investigated to enhance the integration of orthopaedic and dental-craniofacial implants in the surrounding bone tissue. Chitosan has been shown to possess many properties desirable in implant coatings, such as cell attachment and growth, and encouraging ordered bone tissue formation. Previous studies have produced methods to deposit chitosan onto a titanium surface using both two-step and three-step reaction schemes. In the current study, two different titanium surface treatments were evaluated for determining the strength of chitosan coatings bonded to titanium via two reaction processes. The chitosan coatings produced from the four treatment combinations were examined using X-ray Photoelectron Spectroscopy, which demonstrated that the final coatings were similar in composition to the previously reported coatings. Coatings examined by nano-indentation, exhibited hardness (0.19 {+-} 0.08 GPa) and elastic modulus (4.90 {+-} 1.82 GPa) values similar to the hardness and elastic modulus values previously reported. Scanning Electron Microscopy examination of the nano-indentation marks revealed cracks only at sites of applied stress, demonstrating that the chitosan coatings were able to absorb the applied stress. Bulk adhesion of the chitosan coatings demonstrated significant increases in bond strength (19.50 {+-} 1.63 MPa) over previously reported data (1.5-1.8 MPa), but no significant differences were seen between the four treatment combinations. Contact angle testing demonstrated that the chitosan coatings were more hydrophobic (98.0 {+-} 3.6 deg.) than published values (76.4 {+-} 5.1 deg.). Overall, mechanical testing demonstrated that, while the bulk properties of the chitosan coating were unaffected by the four treatment combinations, the bulk adhesion of the chitosan coating was greatly increased and high quality coatings were produced.

  5. IL-27 regulates the adherence, proliferation, and migration of MSCs and enhances their regulatory effects on Th1 and Th2 subset generations.

    Science.gov (United States)

    Xu, Fenghuang; Yi, Junzhu; Wang, Zhuoya; Hu, Yejia; Han, Chunlei; Xue, Qun; Zhang, Xueguang; Luan, Xiying

    2017-08-01

    Interleukin 27 (IL-27) regulates T cell function and is involved in inflammation. It has been reported that human placenta-derived mesenchymal stromal cells (hPMSCs) can inhibit T cell responses and attenuate inflammation reactions. However, it is unclear whether IL-27 can regulate hPMSC function. Here, we examined the effects of IL-27 upon adherence, migration, and proliferation as well as the immunomodulatory effects of hPMSCs. The results show that IL-27 receptor α chain (IL-27Rα) is expressed in hPMSCs. IL-27 at 30 ng/ml inhibited hPMSC adherence and proliferation, while the migration of hPMSCs was promoted with IL-27 at doses of 20 or 30 ng/ml, as determined with use of real-time cell analysis (RTCA). Moreover, IL-27 promoted regulatory effects of hPMSCs through enhancing Th2 and suppressing Th1 subset generation from activated T cells in human peripheral blood. IL-27 also enhanced the ability of hPMSCs to secrete IL-10 from CD4 + T cells through increased expression levels of the programmed death ligand 1 (PDL1) in hPMSCs via the Janus kinase (JAK)/signal transducer and activator of transcription 1 (STAT1) signaling pathway. In conclusion, IL-27 has significant modulatory effects on adherence, proliferation, and migration of hPMSCs. IL-27 increased PDL1 expression levels in hPMSCs via the JAK/STAT1 pathway, which then enhanced the regulatory effects of hPMSCs upon Th1 and Th2 cell generations and IL-10 secretion from CD4 + T cells.

  6. Motives for choosing growth-enhancing hormone treatment in adolescents with idiopathic short stature: a questionnaire and structured interview study.

    Science.gov (United States)

    Visser-van Balen, Hanneke; Geenen, Rinie; Kamp, Gerdine A; Huisman, Jaap; Wit, Jan M; Sinnema, Gerben

    2005-06-08

    Growth-enhancing hormone treatment is considered a possible intervention in short but otherwise healthy adolescents. Although height gain is an obvious measure for evaluating hormone treatment, this may not be the ultimate goal for the person, but rather a means to reach other goals such as the amelioration of current height-related psychosocial problems or the enhancement of future prospects in life and society. The aim of our study was to clarify the motives of adolescents and their parents when choosing to participate in a growth-enhancing trial combining growth hormone and puberty-delaying hormone treatment. Participants were early pubertal adolescents (25 girls, 13 boys) aged from 11 to 13 years (mean age 11.5 years) with a height standard deviation score (SDS) ranging from -1.03 to -3.43. All had been classified as idiopathic short stature or persistent short stature born small for the gestational age (intrauterine growth retardation) on the basis of a height SDS below -2, or had a height SDS between -1 and -2 and a predicted adult height SDS below -2. The adolescents and their parents completed questionnaires and a structured interview on the presence of height-related stressors, parental worries about their child's behavior and future prospects, problems in psychosocial functioning, and treatment expectations. Questionnaire scores were compared to norms of the general Dutch population. The adolescents reported normal psychosocial functioning and highly positive expectations of the treatment in terms of height gain, whereas the parents reported that their children encountered some behavioral problems (being anxious/depressed, and social and attention problems) and height-related stressors (being teased and juvenilized). About 40% of the parents were worried about their children's future prospects for finding a spouse or job. The motives of the adolescents and their parents exhibited rather different profiles. The most prevalent parental worries related to

  7. Motives for choosing growth-enhancing hormone treatment in adolescents with idiopathic short stature: a questionnaire and structured interview study

    Directory of Open Access Journals (Sweden)

    Huisman Jaap

    2005-06-01

    Full Text Available Abstract Background Growth-enhancing hormone treatment is considered a possible intervention in short but otherwise healthy adolescents. Although height gain is an obvious measure for evaluating hormone treatment, this may not be the ultimate goal for the person, but rather a means to reach other goals such as the amelioration of current height-related psychosocial problems or the enhancement of future prospects in life and society. The aim of our study was to clarify the motives of adolescents and their parents when choosing to participate in a growth-enhancing trial combining growth hormone and puberty-delaying hormone treatment. Methods Participants were early pubertal adolescents (25 girls, 13 boys aged from 11 to 13 years (mean age 11.5 years with a height standard deviation score (SDS ranging from -1.03 to -3.43. All had been classified as idiopathic short stature or persistent short stature born small for the gestational age (intrauterine growth retardation on the basis of a height SDS below -2, or had a height SDS between -1 and -2 and a predicted adult height SDS below -2. The adolescents and their parents completed questionnaires and a structured interview on the presence of height-related stressors, parental worries about their child's behavior and future prospects, problems in psychosocial functioning, and treatment expectations. Questionnaire scores were compared to norms of the general Dutch population. Results The adolescents reported normal psychosocial functioning and highly positive expectations of the treatment in terms of height gain, whereas the parents reported that their children encountered some behavioral problems (being anxious/depressed, and social and attention problems and height-related stressors (being teased and juvenilized. About 40% of the parents were worried about their children's future prospects for finding a spouse or job. The motives of the adolescents and their parents exhibited rather different profiles

  8. NOX4-mediated ROS production induces apoptotic cell death via down-regulation of c-FLIP and Mcl-1 expression in combined treatment with thioridazine and curcumin

    Directory of Open Access Journals (Sweden)

    Seung Un Seo

    2017-10-01

    Full Text Available Thioridazine is known to have anti-tumor effects by inhibiting PI3K/Akt signaling, which is an important signaling pathway in cell survival. However, thioridazine alone does not induce apoptosis in head and neck squamous cell carcinoma (AMC-HN4, human breast carcinoma (MDA-MB231, and human glioma (U87MG cells. Therefore, we investigated whether combined treatment with thioridazine and curcumin induces apoptosis. Combined treatment with thioridazine and curcumin markedly induced apoptosis in cancer cells without inducing apoptosis in human normal mesangial cells and human normal umbilical vein cells (EA.hy926. We found that combined treatment with thioridazine and curcumin had synergistic effects in AMC-HN4 cells. Among apoptosis-related proteins, thioridazine plus curcumin induced down-regulation of c-FLIP and Mcl-1 expression at the post-translational levels in a proteasome-dependent manner. Augmentation of proteasome activity was related to the up-regulation of proteasome subunit alpha 5 (PSMA5 expression in curcumin plus thioridazine-treated cells. Combined treatment with curcumin and thioridazine produced intracellular ROS in a NOX4-dependent manner, and ROS-mediated activation of Nrf2/ARE signaling played a critical role in the up-regulation of PSMA5 expression. Furthermore, ectopic expression of c-FLIP and Mcl-1 inhibited apoptosis in thioridazine and curcumin-treated cells. Therefore, we demonstrated that thioridazine plus curcumin induces proteasome activity by up-regulating PSMA5 expression via NOX4-mediated ROS production and that down-regulation of c-FLIP and Mcl-1 expression post-translationally is involved in apoptosis.

  9. Dimethyloxalylglycine may be enhance the capacity of neural-like cells in treatment of Alzheimer disease.

    Science.gov (United States)

    Ghasemi Moravej, Fahimeh; Vahabian, Mehrangiz; Soleimani Asl, Sara

    2016-06-01

    Although using differentiated stem cells is the best proposed option for the treatment of Alzheimer disease (AD), an efficient differentiation and cell therapy require enhanced cell survival and homing and decreased apoptosis. It seems that hypoxia preconditioning via Dimethyloxalylglycine (DMOG) may increase the capacity of MSC to induce neural like stem cells (NSCs). Furthermore, it can likely improve the viability of NSCs when transplanted into the brain of AD rats. © 2016 International Federation for Cell Biology.

  10. Inter-treatment compensation of treatment setup variation to enhance the radiotherapeutic ratio

    International Nuclear Information System (INIS)

    Di, Yan; John, Wong; Michalski, Jeff; Pan, Cheng; Frazier, Arthur; Bosch, Walter; Martinez, Alvaro

    1995-01-01

    Purpose: In radiotherapy, treatment setup error has been one of the major causes of dose variation in the treated volume. With the data acquired from on-line electronic portal imaging, it is now possible not only to adjust the patient setup, but also to modify the treatment plan during the course of clinical treatment based on the setup error measured for each individual patient. In this work, daily clinical portal images were retrospectively analyzed to study (1) the number of initial daily portal images required to give adequate prediction of the systematic and random deviations of treatment setup, and (2) the potential therapeutic gain when the inter-treatment planning modification was established using the setup error of each individual patient. Methods and Materials: Only those patients whose treatment positions had not been adjusted during the course of treatment were selected for the retrospective study. Daily portal images of 27 lung, 25 pelvis, and 12 head and neck (h and n) cancer patients were obtained from two independent clinics with similar setup procedures. The anterior-to-posterior field was analyzed for the pelvis and lung treatments, and the right lateral field for the h and n treatments. Between 13 to 30 daily portal images were acquired for each patient and were analyzed using a 2D alignment tool. Systematic and random deviations of the treatment setup were calculated for each individual patient. The statistical confidence on the convergence of both systematic and random deviations with time were tested to determine the number of initial daily portal images needed to predict these deviations. In addition, a mean deviation for each site was also calculated using the setup errors from all patients. Two treatment planning schemes were simulated to evaluate margin design and prescription dose adjustment. Therapeutic scores were quantified in terms of tumor control probability (TCP) and normal tissue complication probability (NTCP). In the first

  11. Enhancing Neuroplasticity to Augment Cognitive Remediation in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Carol Jahshan

    2017-09-01

    Full Text Available There is a burgeoning need for innovative treatment strategies to improve the cognitive deficits in schizophrenia. Cognitive remediation (CR is effective at the group level, but the variability in treatment response is large. Given that CR may depend on intact neuroplasticity to produce cognitive gains, it is reasonable to combine it with strategies that harness patients’ neuroplastic potential. In this review, we discuss two non-pharmacological approaches that can enhance neuroplasticity and possibly augment the effects of CR in schizophrenia: physical exercise and transcranial direct current stimulation (tDCS. Substantial body of evidence supports the beneficial effect of physical exercise on cognition, and a handful of studies in schizophrenia have shown that physical exercise in conjunction with CR has a larger impact on cognition than CR alone. Physical exercise is thought to stimulate neuroplasticity through the regulation of central growth factors, and current evidence points to brain-derived neurotrophic factor as the potential underlying mechanism through which physical exercise might enhance the effectiveness of CR. tDCS has emerged as a potential tool for cognitive enhancement and seems to affect the cellular mechanisms involved in long-term potentiation (LTP. A few reports have demonstrated the feasibility of integrating tDCS with CR in schizophrenia, but there are insufficient data to determine if this multimodal approach leads to incremental performance gain in patients. Larger randomized controlled trials are necessary to understand the mechanisms of the combined tDCS–CR intervention. Future research should take advantage of new developments in neuroplasticity paradigms to examine the effects of these interventions on LTP.

  12. 40 CFR 133.105 - Treatment equivalent to secondary treatment.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Treatment equivalent to secondary treatment. 133.105 Section 133.105 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS SECONDARY TREATMENT REGULATION § 133.105 Treatment equivalent to secondary treatment...

  13. Study on effects of environmental regulation on competitiveness

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Man Ok; Lim, Hyun Jeong [Korea Environment Institute, Seoul (Korea)

    1999-12-01

    For Korea, the claim that the enhancement of environmental regulation is worsening the international competitiveness of the business is dominant. However, it is too early to reestablish a relationship between environmental regulation and competitiveness with the above new aspect. In fact, the economic development, which is brought a quantitative growth, and the maintenance of environmental quality, which is brought a qualitative growth, are very important on decision making in economic and social policy. In this study, it represents the results of existing positive studies on the relationship between the enhancement of environmental regulation, trade and productivity. Moreover, the objective of this study is on applying it based on the data of Korea. 86 refs., 13 figs., 35 tabs.

  14. A better state-of-mind: deep breathing reduces state anxiety and enhances test performance through regulating test cognitions in children.

    Science.gov (United States)

    Khng, Kiat Hui

    2017-11-01

    A pre-test/post-test, intervention-versus-control experimental design was used to examine the effects, mechanisms and moderators of deep breathing on state anxiety and test performance in 122 Primary 5 students. Taking deep breaths before a timed math test significantly reduced self-reported feelings of anxiety and improved test performance. There was a statistical trend towards greater effectiveness in reducing state anxiety for boys compared to girls, and in enhancing test performance for students with higher autonomic reactivity in test-like situations. The latter moderation was significant when comparing high-versus-low autonomic reactivity groups. Mediation analyses suggest that deep breathing reduces state anxiety in test-like situations, creating a better state-of-mind by enhancing the regulation of adaptive-maladaptive thoughts during the test, allowing for better performance. The quick and simple technique can be easily learnt and effectively applied by most children to immediately alleviate some of the adverse effects of test anxiety on psychological well-being and academic performance.

  15. Enhancing Brief Cognitive Behavioral Therapy with Motivational Enhancement Techniques in Cocaine Users

    Science.gov (United States)

    McKee, Sherry A.; Carroll, Kathleen M.; Sinha, Rajita; Robinson, Jane E.; Nich, Charla; Cavallo, Dana; O’Malley, Stephanie

    2008-01-01

    Background We investigated the impact of enhancing brief cognitive behavioral therapy with motivational interviewing techniques for cocaine abuse or dependence, using a focused intervention paradigm. Methods Participants (n=74) who met current criteria for cocaine abuse or dependence were randomized to 3-session cognitive behavioral therapy (CBT) or 3-session enhanced CBT (MET + CBT), which included an initial session of motivational enhancement therapy (MET). Outcome measures included treatment retention, process measures (e.g., commitment to abstinence, satisfaction with treatment), and cocaine use. Results Participants who received the MET+CBT intervention attended more drug treatment sessions following the study interventions, reported significantly greater desire for abstinence and expectation of success, and they expected greater difficulty in maintaining abstinence compared to the CBT condition. There were no differences across treatment conditions on cocaine use. Conclusions These findings offer mixed support for the addition of MET as an adjunctive approach to CBT for cocaine users. In addition, the study provides evidence for the feasibility of using short-term studies to test the effects of specific treatment components or refinements on measures of therapy process and outcome. PMID:17573205

  16. Enhancer SINEs Link Pol III to Pol II Transcription in Neurons

    Directory of Open Access Journals (Sweden)

    Cristina Policarpi

    2017-12-01

    Full Text Available Summary: Spatiotemporal regulation of gene expression depends on the cooperation of multiple mechanisms, including the functional interaction of promoters with distally located enhancers. Here, we show that, in cortical neurons, a subset of short interspersed nuclear elements (SINEs located in the proximity of activity-regulated genes bears features of enhancers. Enhancer SINEs (eSINEs recruit the Pol III cofactor complex TFIIIC in a stimulus-dependent manner and are transcribed by Pol III in response to neuronal depolarization. Characterization of an eSINE located in proximity to the Fos gene (FosRSINE1 indicated that the FosRSINE1-encoded transcript interacts with Pol II at the Fos promoter and mediates Fos relocation to Pol II factories, providing an unprecedented molecular link between Pol III and Pol II transcription. Strikingly, knockdown of the FosRSINE1 transcript induces defects of both cortical radial migration in vivo and activity-dependent dendritogenesis in vitro, demonstrating that FosRSINE1 acts as a strong enhancer of Fos expression in diverse physiological contexts. : Spatiotemporal regulation of gene expression requires the interaction between promoters and distally located enhancers. Policarpi et al. identify a subset of SINEs that functions as enhancers for activity-dependent neuronal genes. The enhancer SINE FosRSINE1 regulates Fos transcription and is necessary for both activity-dependent dendritogenesis and proper brain development. Keywords: neuroscience, epigenetics, transcription, enhancers, SINEs, neuronal activity, neuronal development

  17. Hydrogen sulfide potentiates interleukin-1β-induced nitric oxide production via enhancement of extracellular signal-regulated kinase activation in rat vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Jeong, Sun-Oh; Pae, Hyun-Ock; Oh, Gi-Su; Jeong, Gil-Saeng; Lee, Bok-Soo; Lee, Seoul; Kim, Du Yong; Rhew, Hyun Yul; Lee, Kang-Min; Chung, Hun-Taeg

    2006-01-01

    Hydrogen sulfide (H 2 S) and nitric oxide (NO) are endogenously synthesized from L-cysteine and L-arginine, respectively. They might constitute a cooperative network to regulate their effects. In this study, we investigated whether H 2 S could affect NO production in rat vascular smooth muscle cells (VSMCs) stimulated with interleukin-1β (IL-1β). Although H 2 S by itself showed no effect on NO production, it augmented IL-β-induced NO production and this effect was associated with increased expression of inducible NO synthase (iNOS) and activation of nuclear factor (NF)-κB. IL-1β activated the extracellular signal-regulated kinase 1/2 (ERK1/2), and this activation was also enhanced by H 2 S. Inhibition of ERK1/2 activation by the selective inhibitor U0126 inhibited IL-1β-induced NF-κB activation, iNOS expression, and NO production either in the absence or presence of H 2 S. Our findings suggest that H 2 S enhances NO production and iNOS expression by potentiating IL-1β-induced NF-κB activation through a mechanism involving ERK1/2 signaling cascade in rat VSMCs

  18. Overexpression of microRNA-132 enhances the radiosensitivity of cervical cancer cells by down-regulating Bmi-1.

    Science.gov (United States)

    Liu, Gui-Feng; Zhang, Shu-Hua; Li, Xue-Feng; Cao, Li-Yan; Fu, Zhan-Zhao; Yu, Shao-Nan

    2017-10-06

    We examined the effects of microRNA-132 (miR-132) on Bmi-1 expression and radiosensitivity in HeLa, SiHa, and C33A cervical cancer (CC) cells and 104 CC patients. MiR-132 expression was decreased and Bmi-1 expression was increased in tumor tissues compared to adjacent normal tissues and in radiotherapy-resistant patients compared to radiotherapy-sensitive patients. MiR-132 expression and Bmi-1 mRNA expression were also negatively correlated in tumor tissues. HeLa, SiHa, and C33A cells were divided into blank, miR-132 negative control (NC), miR-132 inhibitor, miR-132 mimics, siBmi-1, and miR-132 inhibitor + siBmi-1 groups, after which expression of miR-132 and Bmi-1, and the interaction between them and cell survival, proliferation, and apoptosis were examined. Bmi-1 was confirmed as a target of miRNA-132. Survival was higher and apoptosis lower in the miR-132 inhibitor group than the blank group after various doses of radiation. By contrast, survival was lower and apoptosis higher in the miRNA-132 mimics and siBmi-1 groups than in the blank group. Moreover, miR-132 expression increased and Bmi-1 mRNA expression decreased in each group at radiation doses of 6 and 8 Gy. Finally, co-administration of radiotherapy and exogenous miR-132 inhibited the growth of HeLa cell transplant-induced tumors in nude mice more effectively than radiotherapy alone. These results suggest overexpression of miR-132 enhances the radiosensitivity of CC cells by down-regulating Bmi-1 and that miR-132 may be a useful new target for the treatment of CC.

  19. Neuronal MHC Class I Expression Is Regulated by Activity Driven Calcium Signaling.

    Directory of Open Access Journals (Sweden)

    Dan Lv

    Full Text Available MHC class I (MHC-I molecules are important components of the immune system. Recently MHC-I have been reported to also play important roles in brain development and synaptic plasticity. In this study, we examine the molecular mechanism(s underlying activity-dependent MHC-I expression using hippocampal neurons. Here we report that neuronal expression level of MHC-I is dynamically regulated during hippocampal development after birth in vivo. Kainic acid (KA treatment significantly increases the expression of MHC-I in cultured hippocampal neurons in vitro, suggesting that MHC-I expression is regulated by neuronal activity. In addition, KA stimulation decreased the expression of pre- and post-synaptic proteins. This down-regulation is prevented by addition of an MHC-I antibody to KA treated neurons. Further studies demonstrate that calcium-dependent protein kinase C (PKC is important in relaying KA simulation activation signals to up-regulated MHC-I expression. This signaling cascade relies on activation of the MAPK pathway, which leads to increased phosphorylation of CREB and NF-κB p65 while also enhancing the expression of IRF-1. Together, these results suggest that expression of MHC-I in hippocampal neurons is driven by Ca2+ regulated activation of the MAPK signaling transduction cascade.

  20. Self-regulated and technology-enhanced learning: a European perspective

    NARCIS (Netherlands)

    Mooij, Ton; Steffens, Karl; Andrade, Maureen Snow

    2014-01-01

    Self-regulation of learning, learning to learn, and their potential stimulation by specific Information and Communication Technologies (ICTs), are main topics in European policy. This issue of the ‘European Educational Research Journal’ (EERJ) focuses on research to develop, integrate, and evaluate

  1. Self-regulated and technology-enhanced learning: a European perspective

    NARCIS (Netherlands)

    Mooij, Ton; Steffens, Karl; Andrade, Maureen Snow

    2015-01-01

    Self-regulation of learning, learning to learn, and their potential stimulation by specific Information and Communication Technologies (ICTs), are main topics in European policy. This issue of the ‘European Educational Research Journal’ (EERJ) focuses on research to develop, integrate, and evaluate

  2. Enhancement of in vitro interleukin-2 production in normal subjects following a single spinal manipulative treatment

    Directory of Open Access Journals (Sweden)

    Harris Glen M

    2008-05-01

    significant alterations in serum-associated IL-2 levels were observed in any of the study groups. Conclusion The present study demonstrates that, the in vitro T lymphocyte response to a conventional mitogen (SPA, as measured by IL-2 synthesis, can become enhanced following SMT. Furthermore, within a period of time following the manipulative intervention, this effect may be independent of joint cavitation. Thus the results of this study suggest that, under certain physiological conditions, SMT might influence IL-2-regulated biological responses.

  3. A complex interplay between PGC-1 co-activators and mTORC1 regulates hematopoietic recovery following 5-fluorouracil treatment

    Directory of Open Access Journals (Sweden)

    Sunanda Basu

    2014-01-01

    Full Text Available In vitro stimulation of HSCs with growth factors generally leads to their depletion. Understanding the molecular mechanisms underlying expansion of HSCs in vivo following myeloablation could lead to successful expansion of HSCs ex vivo for therapeutic purposes. Current findings show that mTORC1 is activated in HSPCs following 5-fluorouracil treatment and that mTORC1 activation is dependent on mitochondrial ETC capacity of HSPCs. Moreover, expression of PGC-1 family members, proteins that regulate mitochondrial biogenesis, in HSPCs following 5-fluorouracil treatment changes; also, these proteins play a stage specific role in hematopoietic recovery. While PRC regulates HSCs' expansion during early recovery phase, PGC-1α regulates progenitor cell proliferation and recovery of hematopoiesis during later phase. During early recovery phase, PRC expression, mitochondrial activity and mTORC1 activation are relatively higher in PGC-1α−/− HSCs compared to WT HSCs, and PGC-1α−/− HSCs show greater expansion. Administration of rapamycin, but not NAC, during early recovery phase improves WT HSC numbers but decreases PGC-1α−/− HSC numbers. The current findings demonstrate that mTOR activation can increase HSC numbers provided that the energy demand created by mTOR activation is successfully met. Thus, critical tuning between mTORC1 activation and mitochondrial ETC capacity is crucial for HSC maintenance/expansion in response to mitogenic stimulation.

  4. Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: role of IDO.

    Science.gov (United States)

    Basu, Gargi D; Tinder, Teresa L; Bradley, Judy M; Tu, Tony; Hattrup, Christine L; Pockaj, Barbara A; Mukherjee, Pinku

    2006-08-15

    We report that administration of celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, in combination with a dendritic cell-based cancer vaccine significantly augments vaccine efficacy in reducing primary tumor burden, preventing metastasis, and increasing survival. This combination treatment was tested in MMTV-PyV MT mice that develop spontaneous mammary gland tumors with metastasis to the lungs and bone marrow. Improved vaccine potency was associated with an increase in tumor-specific CTLs. Enhanced CTL activity was attributed to a significant decrease in levels of tumor-associated IDO, a negative regulator of T cell activity. We present data suggesting that inhibiting COX-2 activity in vivo regulates IDO expression within the tumor microenvironment; this is further corroborated in the MDA-MB-231 human breast cancer cell line. Thus, a novel mechanism of COX-2-induced immunosuppression via regulation of IDO has emerged that may have implications in designing future cancer vaccines.

  5. Current lipid extraction methods are significantly enhanced adding a water treatment step in Chlorella protothecoides.

    Science.gov (United States)

    Ren, Xiaojie; Zhao, Xinhe; Turcotte, François; Deschênes, Jean-Sébastien; Tremblay, Réjean; Jolicoeur, Mario

    2017-02-11

    Microalgae have the potential to rapidly accumulate lipids of high interest for the food, cosmetics, pharmaceutical and energy (e.g. biodiesel) industries. However, current lipid extraction methods show efficiency limitation and until now, extraction protocols have not been fully optimized for specific lipid compounds. The present study thus presents a novel lipid extraction method, consisting in the addition of a water treatment of biomass between the two-stage solvent extraction steps of current extraction methods. The resulting modified method not only enhances lipid extraction efficiency, but also yields a higher triacylglycerols (TAG) ratio, which is highly desirable for biodiesel production. Modification of four existing methods using acetone, chloroform/methanol (Chl/Met), chloroform/methanol/H 2 O (Chl/Met/H 2 O) and dichloromethane/methanol (Dic/Met) showed respective lipid extraction yield enhancement of 72.3, 35.8, 60.3 and 60.9%. The modified acetone method resulted in the highest extraction yield, with 68.9 ± 0.2% DW total lipids. Extraction of TAG was particularly improved with the water treatment, especially for the Chl/Met/H 2 O and Dic/Met methods. The acetone method with the water treatment led to the highest extraction level of TAG with 73.7 ± 7.3 µg/mg DW, which is 130.8 ± 10.6% higher than the maximum value obtained for the four classical methods (31.9 ± 4.6 µg/mg DW). Interestingly, the water treatment preferentially improved the extraction of intracellular fractions, i.e. TAG, sterols, and free fatty acids, compared to the lipid fractions of the cell membranes, which are constituted of phospholipids (PL), acetone mobile polar lipids and hydrocarbons. Finally, from the 32 fatty acids analyzed for both neutral lipids (NL) and polar lipids (PL) fractions, it is clear that the water treatment greatly improves NL-to-PL ratio for the four standard methods assessed. Water treatment of biomass after the first solvent extraction step

  6. A study for good regulation of the CANDU's in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Se Ki; Shin, Y. K.; Joe, S. K.; Kim, J. S.; Yu, Y. J.; Lee, Y. J. [Ajou Univ., Suwon (Korea, Republic of)

    2002-03-15

    The objective of project is to derive the policy recommendations to improve the efficiency of CANDU plants regulation. These policy recommendations will eventually contribute to the upgrading of Korean nuclear regulatory system and safety enhancement. During the second phase of this 2 years study, following research activities were done. Review the technical basis and framework of the new Canadian Regulation System and IAEA. Analysis on the interview of Wolsung operation staffs to identify important safety issues and regulation problems experienced at operation. Providing a plan of CANDU regulation system enhancement program.

  7. Cognitive enhancement treatments for bipolar disorder

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla W; Carvalho, André F; Vieta, Eduard

    2016-01-01

    Cognitive dysfunction is an emerging treatment target in bipolar disorder (BD). Several trials have assessed the efficacy of novel pharmacological and psychological treatments on cognition in BD but the findings are contradictory and unclear. A systematic search following the PRISMA guidelines...... was conducted on PubMed and PsychInfo. Eligible articles reported randomized, controlled or open-label trials investigating pharmacological or psychological treatments targeting cognitive dysfunction in BD. The quality of the identified randomized controlled trials (RCTs) was evaluated with the Cochrane...... Collaboration's Risk of Bias tool. We identified 19 eligible studies of which 13 were RCTs and six were open-label or non-randomized studies. The findings regarding efficacy on cognition were overall disappointing or preliminary, possibly due to several methodological challenges. For the RCTs, the risk of bias...

  8. Autoimmune Diabetes and Thyroiditis Complicating Treatment with Nivolumab

    Directory of Open Access Journals (Sweden)

    Li Li

    2017-03-01

    Full Text Available Programmed cell death-1 (PD-1 ligand inhibitors have gained popularity in the treatment of advanced non-small-cell lung cancer. The immune system is regulated by stimulatory and inhibitory signaling and aims to achieve the balance between activation and inhibition. Treatment with immune checkpoint inhibitors enhances immune response, but is also known to diminish immune tolerance and increase autoimmune toxicity. Here we present a case of a patient with advanced squamous cell lung cancer who developed type I diabetes and thyroiditis after treatment with PD-1 checkpoint inhibitor nivolumab. The presence of autoimmune diabetes mellitus and thyroiditis were confirmed by markedly elevated titers of the glutamic acid decarboxylase autoantibody and thyroid peroxidase antibody, respectively. This report serves to heighten awareness of potential autoimmune toxicities related to anti-PD-1 therapy, especially as these toxicities are manageable if identified in a timely manner.

  9. Health regulations about radiation oncology in Spain: The legislative dilemma between radiation protection and treatment of cancer

    International Nuclear Information System (INIS)

    Esco, R.; Biete, A.; Pardo, J.; Carceller, J.A.; Veira, C.; Palacios, A.; Vazquez, M.G.

    2001-01-01

    The Royal Decree 1566/1998 of July 17th establishes the criteria on quality in radiation therapy and is a cornerstone in Spanish regulation of this medical field. The Royal Decree gives some rules that, from a medical point of view, are considered as a good practice. Radiation protection of patients is necessary to achieve a high quality radiation oncology treatments. That is the reason why Royal decree 1566/1998 is titled 'quality criteria in radiation therapy'. A quality control program must be tailored to every single radiation oncology department and, for this reason, its standardization is difficult. Nevertheless, some medical procedures are defined by the royal decree and such procedures are the minimum criteria that all the departments must follow in the development of its own quality control program. The authors make some reflections about health regulations about radiation oncology in Spain, pointing out that a legislative dilemma between radiation protection and treatment of cancer due to application of the legislative rules may occur. The social and medical cost of rigid bureaucratic procedures is pointed out. A large amount of equipment controls and measurements takes time that could be used in treating patients. This is more important in an environment of limited technical and human resources. (author)

  10. Enhancement of sludge granulation in anaerobic treatment of concentrated latex wastewater

    Directory of Open Access Journals (Sweden)

    Nugul Intrasungkha

    2008-04-01

    Full Text Available Recently, the upflow anaerobic sludge blanket (UASB reactor has become attractive for wastewater treatment with low energy requirement and biogas production. However, the start-up of an UASB reactor depends on the formation of granules. Therefore, this research aims to study the effect of AlCl3, CaCl2 and temperature on the granule formation process using real concentrated latex wastewater. The result shows that the optimum chemicals concentration of AlCl3 at 300 mg/l enhanced the biomass accumulation and sludge formation process. Approximately 50% of large granular size (0.5 mm 0.8 mm within 35 days, whereas the large granular sizes in reactorwithout AlCl3 supplement (R2 became visible within 63 days. Moreover, this experiment found that R1, R2 and R3 could reach steady state within 40, 55 and 45 days, respectively.

  11. Targeting self-regulation to promote health behaviors in children.

    Science.gov (United States)

    Miller, Alison L; Gearhardt, Ashley N; Fredericks, Emily M; Katz, Benjamin; Shapiro, Lilly Fink; Holden, Kelsie; Kaciroti, Niko; Gonzalez, Richard; Hunter, Christine; Lumeng, Julie C

    2018-02-01

    Poor self-regulation (i.e., inability to harness cognitive, emotional, motivational resources to achieve goals) is hypothesized to contribute to unhealthy behaviors across the lifespan. Enhancing early self-regulation may increase positive health outcomes. Obesity is a major public health concern with early-emerging precursors related to self-regulation; it is therefore a good model for understanding self-regulation and health behavior. Preadolescence is a transition when children increase autonomy in health behaviors (e.g., eating, exercise habits), many of which involve self-regulation. This paper presents the scientific rationale for examining self-regulation mechanisms that are hypothesized to relate to health behaviors, specifically obesogenic eating, that have not been examined in children. We describe novel intervention protocols designed to enhance self-regulation skills, specifically executive functioning, emotion regulation, future-oriented thinking, and approach bias. Interventions are delivered via home visits. Assays of self-regulation and obesogenic eating behaviors using behavioral tasks and self-reports are implemented and evaluated to determine feasibility and psychometrics and to test intervention effects. Participants are low-income 9-12 year-old children who have been phenotyped for self-regulation, stress, eating behavior and adiposity through early childhood. Study goals are to examine intervention effects on self-regulation and whether change in self-regulation improves obesogenic eating. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. ERK inhibition enhances TSA-induced gastric cancer cell apoptosis via NF-κB-dependent and Notch-independent mechanism.

    Science.gov (United States)

    Yao, Jun; Qian, Cui-Juan; Ye, Bei; Zhang, Xin; Liang, Yong

    2012-09-04

    To analyze the combined impact of the histone deacetylase inhibitor (HDACI) Trichostatin A (TSA) and the extracellular-signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 on gastric cancer (GC) cell line SGC7901 growth. SGC7901 cells were treated with TSA, PD98059 or with a TSA-PD98059 combination. Effects of drug treatment on tumor cell proliferation, apoptosis, cell cycle progression, and cell signaling pathways were investigated by MTS assay, flow cytometry, Western blotting, chromatin immunoprecipitation (ChIP) assay, electrophoretic mobility shift assay (EMSA), and luciferase reporter assay, respectively. PD98059 enhanced TSA-induced cell growth arrest, apoptosis and activation of p21(WAF1/CIP1), but reversed TSA-induced activation of ERK1/2 and nuclear factor-κB (NF-κB). TSA alone up-regulated Notch1 and Hes1, and down-regulated Notch2, but PD98059 did not affect the trends of Notch1 and Notch2 induced by TSA. Particularly, PD98059 did potentiate the ability of TSA to down-regulate phospho-histone H3 protein, but increased levels of the acetylated forms of histone H3 bound to the p21(WAF1/CIP1) promoter, leading to enhanced expression of p21(WAF1/CIP1) in SGC7901 cells. PD98059 synergistically potentiates TSA-induced GC growth arrest and apoptosis by manipulating NF-κB and p21(WAF1/CIP1) independent of Notch. Therefore, concomitant administration of HDACIs and ERK1/2 inhibitors may be a promising treatment strategy for individuals with GC. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Remarkably Enhanced Room-Temperature Hydrogen Sensing of SnO₂ Nanoflowers via Vacuum Annealing Treatment.

    Science.gov (United States)

    Liu, Gao; Wang, Zhao; Chen, Zihui; Yang, Shulin; Fu, Xingxing; Huang, Rui; Li, Xiaokang; Xiong, Juan; Hu, Yongming; Gu, Haoshuang

    2018-03-23

    In this work, SnO₂ nanoflowers synthesized by a hydrothermal method were employed as hydrogen sensing materials. The as-synthesized SnO₂ nanoflowers consisted of cuboid-like SnO₂ nanorods with tetragonal structures. A great increase in the relative content of surface-adsorbed oxygen was observed after the vacuum annealing treatment, and this increase could have been due to the increase in surface oxygen vacancies serving as preferential adsorption sites for oxygen species. Annealing treatment resulted in an 8% increase in the specific surface area of the samples. Moreover, the conductivity of the sensors decreased after the annealing treatment, which should be attributed to the increase in electron scattering around the defects and the compensated donor behavior of the oxygen vacancies due to the surface oxygen adsorption. The hydrogen sensors of the annealed samples, compared to those of the unannealed samples, exhibited a much higher sensitivity and faster response rate. The sensor response factor and response rate increased from 27.1% to 80.2% and 0.34%/s to 1.15%/s, respectively. This remarkable enhancement in sensing performance induced by the annealing treatment could be attributed to the larger specific surface areas and higher amount of surface-adsorbed oxygen, which provides a greater reaction space for hydrogen. Moreover, the sensors with annealed SnO₂ nanoflowers also exhibited high selectivity towards hydrogen against CH₄, CO, and ethanol.

  14. Modification of UASB reactor by using CFD simulations for enhanced treatment of municipal sewage.

    Science.gov (United States)

    Das, Suprotim; Sarkar, Supriya; Chaudhari, Sanjeev

    2018-02-01

    Up-flow anaerobic sludge blanket (UASB) has been in use since last few decades for the treatment of organic wastewaters. However, the performance of UASB reactor is quite low for treatment of low strength wastewaters (LSWs) due to less biogas production leading to poor mixing. In the present research work, a modification was done in the design of UASB to improve mixing of reactor liquid which is important to enhance the reactor performance. The modified UASB (MUASB) reactor was designed by providing a slanted baffle along the height of the reactor having an angle of 5.7° with the vertical wall. A two-dimensional computational fluid dynamics (CFD) simulation of three phase gas-liquid-solid flow in MUASB reactor was performed and compared with conventional UASB reactor. The CFD study indicated better mixing in terms of vorticity magnitude in MUASB reactor as compared to conventional UASB, which was reflected in the reactor performance. The performance of MUASB was compared with conventional UASB reactor for the onsite treatment of domestic sewage as LSW. Around 16% higher total chemical oxygen demand removal efficiency was observed in MUASB reactor as compared to conventional UASB during this study. Therefore, this MUASB model demonstrates a qualitative relationship between mixing and performance during the treatment of LSW. From the study, it seems that MUASB holds promise for field applications.

  15. Surface modification of cellulose acetate membrane using thermal annealing to enhance produced water treatment

    Energy Technology Data Exchange (ETDEWEB)

    Kusworo, T. D., E-mail: tdkusworo@che.undip.ac.id; Aryanti, N., E-mail: nita.aryanti@gmail.com; Firdaus, M. M. H.; Sukmawati, H. [Chemical Engineering, Faculty of Engineering, Diponegoro University Prof. Soedarto Street, Tembalang, Semarang, 50239, Phone/Fax : (024)7460058 (Indonesia)

    2015-12-29

    This study is performed primarily to investigate the effect of surface modification of cellulose acetate using thermal annealing on the enhancement of membrane performance for produced water treatment. In this study, Cellulose Acetate membranes were casted using dry/wet phase inversion technique. The effect of additive and post-treatment using thermal annealing on the membrane surface were examined for produced water treatment. Therma annealing was subjected to membrane surface at 60 and 70 °C for 5, 10 and 15 second, respectively. Membrane characterizations were done using membrane flux and rejection with produced water as a feed, Scanning Electron Microscopy (SEM) and Fourier Transform Infra Red (FTIR) analysis. Experimental results showed that asymmetric cellulose acetate membrane can be made by dry/wet phase inversion technique. The results from the Scanning Electron Microscopy (FESEM) analysis was also confirmed that polyethylene glycol as additivie in dope solution and thermal annealing was affected the morphology and membrane performance for produced water treatment, respectively. Scanning electron microscopy micrographs showed that the selective layer and the substructure of membrane became denser and more compact after the thermal annealing processes. Therefore, membrane rejection was significantly increased while the flux was slighty decreased, respectively. The best membrane performance is obtained on the composition of 18 wt % cellulose acetate, poly ethylene glycol 5 wt% with thermal annealing at 70° C for 15 second.

  16. Surface modification of cellulose acetate membrane using thermal annealing to enhance produced water treatment

    International Nuclear Information System (INIS)

    Kusworo, T. D.; Aryanti, N.; Firdaus, M. M. H.; Sukmawati, H.

    2015-01-01

    This study is performed primarily to investigate the effect of surface modification of cellulose acetate using thermal annealing on the enhancement of membrane performance for produced water treatment. In this study, Cellulose Acetate membranes were casted using dry/wet phase inversion technique. The effect of additive and post-treatment using thermal annealing on the membrane surface were examined for produced water treatment. Therma annealing was subjected to membrane surface at 60 and 70 °C for 5, 10 and 15 second, respectively. Membrane characterizations were done using membrane flux and rejection with produced water as a feed, Scanning Electron Microscopy (SEM) and Fourier Transform Infra Red (FTIR) analysis. Experimental results showed that asymmetric cellulose acetate membrane can be made by dry/wet phase inversion technique. The results from the Scanning Electron Microscopy (FESEM) analysis was also confirmed that polyethylene glycol as additivie in dope solution and thermal annealing was affected the morphology and membrane performance for produced water treatment, respectively. Scanning electron microscopy micrographs showed that the selective layer and the substructure of membrane became denser and more compact after the thermal annealing processes. Therefore, membrane rejection was significantly increased while the flux was slighty decreased, respectively. The best membrane performance is obtained on the composition of 18 wt % cellulose acetate, poly ethylene glycol 5 wt% with thermal annealing at 70° C for 15 second

  17. Histone deacetylase regulates insulin signaling via two pathways in pancreatic β cells.

    Directory of Open Access Journals (Sweden)

    Yukina Kawada

    Full Text Available Recent studies demonstrated that insulin signaling plays important roles in the regulation of pancreatic β cell mass, the reduction of which is known to be involved in the development of diabetes. However, the mechanism underlying the alteration of insulin signaling in pancreatic β cells remains unclear. The involvement of epigenetic control in the onset of diabetes has also been reported. Thus, we analyzed the epigenetic control of insulin receptor substrate 2 (IRS2 expression in the MIN6 mouse insulinoma cell line. We found concomitant IRS2 up-regulation and enhanced insulin signaling in MIN6 cells, which resulted in an increase in cell proliferation. The H3K9 acetylation status of the Irs2 promoter was positively associated with IRS2 expression. Treatment of MIN6 cells with histone deacetylase inhibitors led to increased IRS2 expression, but this occurred in concert with low insulin signaling. We observed increased IRS2 lysine acetylation as a consequence of histone deacetylase inhibition, a modification that was coupled with a decrease in IRS2 tyrosine phosphorylation. These results suggest that insulin signaling in pancreatic β cells is regulated by histone deacetylases through two novel pathways affecting IRS2: the epigenetic control of IRS2 expression by H3K9 promoter acetylation, and the regulation of IRS2 activity through protein modification. The identification of the histone deacetylase isoform(s involved in these mechanisms would be a valuable approach for the treatment of type 2 diabetes.

  18. NOX4-mediated ROS production induces apoptotic cell death via down-regulation of c-FLIP and Mcl-1 expression in combined treatment with thioridazine and curcumin.

    Science.gov (United States)

    Seo, Seung Un; Kim, Tae Hwan; Kim, Dong Eun; Min, Kyoung-Jin; Kwon, Taeg Kyu

    2017-10-01

    Thioridazine is known to have anti-tumor effects by inhibiting PI3K/Akt signaling, which is an important signaling pathway in cell survival. However, thioridazine alone does not induce apoptosis in head and neck squamous cell carcinoma (AMC-HN4), human breast carcinoma (MDA-MB231), and human glioma (U87MG) cells. Therefore, we investigated whether combined treatment with thioridazine and curcumin induces apoptosis. Combined treatment with thioridazine and curcumin markedly induced apoptosis in cancer cells without inducing apoptosis in human normal mesangial cells and human normal umbilical vein cells (EA.hy926). We found that combined treatment with thioridazine and curcumin had synergistic effects in AMC-HN4 cells. Among apoptosis-related proteins, thioridazine plus curcumin induced down-regulation of c-FLIP and Mcl-1 expression at the post-translational levels in a proteasome-dependent manner. Augmentation of proteasome activity was related to the up-regulation of proteasome subunit alpha 5 (PSMA5) expression in curcumin plus thioridazine-treated cells. Combined treatment with curcumin and thioridazine produced intracellular ROS in a NOX4-dependent manner, and ROS-mediated activation of Nrf2/ARE signaling played a critical role in the up-regulation of PSMA5 expression. Furthermore, ectopic expression of c-FLIP and Mcl-1 inhibited apoptosis in thioridazine and curcumin-treated cells. Therefore, we demonstrated that thioridazine plus curcumin induces proteasome activity by up-regulating PSMA5 expression via NOX4-mediated ROS production and that down-regulation of c-FLIP and Mcl-1 expression post-translationally is involved in apoptosis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. A Multiplexed Assay That Monitors Effects of Multiple Compound Treatment Times Reveals Candidate Immune-Enhancing Compounds.

    Science.gov (United States)

    Zhao, Ziyan; Henowitz, Liza; Zweifach, Adam

    2018-05-01

    We previously developed a flow cytometry assay that monitored lytic granule exocytosis in cytotoxic T lymphocytes stimulated by contacting beads coated with activating anti-CD3 antibodies. That assay was multiplexed in that responses of cells that did or did not receive the activating stimulus were distinguished via changes in light scatter accompanying binding of cells to beads, allowing us to discriminate compounds that activate responses on their own from compounds that enhance responses in cells that received the activating stimulus, all within a single sample. Here we add a second dimension of multiplexing by developing means to assess in a single sample the effects of treating cells with test compounds for different times. Bar-coding cells before adding them to test wells lets us determine compound treatment time while also monitoring activation status and response amplitude at the point of interrogation. This multiplexed assay is suitable for screening 96-well plates. We used it to screen compounds from the National Cancer Institute, identifying several compounds that enhance anti-LAMP1 responses. Multiple-treatment-time (MTT) screening enabled by bar-coding and read via high-throughput flow cytometry may be a generally useful method for facilitating the discovery of compounds of interest.

  20. Perfusion of surgical cavity wall enhancement in early post-treatment MR imaging may stratify the time-to-progression in glioblastoma.

    Directory of Open Access Journals (Sweden)

    Ji Eun Park

    Full Text Available To determine if perfusion in surgical cavity wall enhancement (SCWE obtained in early post-treatment MR imaging can stratify time-to-progression (TTP in glioblastoma.This study enrolled 60 glioblastoma patients with more than 5-mm-thick SCWEs as detected on contrast-enhanced MR imaging after concurrent chemoradiation therapy. Two independent readers categorized the shape and perfusion state of SCWEs as nodular or non-nodular and as having positive or negative perfusion compared with the contralateral grey matter on arterial spin labeling (ASL. The perfusion fraction on ASL within the contrast-enhancing lesion was calculated. The independent predictability of TTP was analyzed using the Kaplan-Meier method and Cox proportional hazards modelling.The perfusion fraction was higher in the non-progression group, significantly for reader 2 (P = 0.03 and borderline significantly for reader 1 (P = 0.08. A positive perfusion state and (P = 0.02 a higher perfusion fraction of the SCWE were found to become an independent predictor of longer TTP (P = 0.001 for reader 1 and P < 0.001 for reader 2. The contrast enhancement pattern did not become a TTP predictor.Assessment of perfusion in early post-treatment MR imaging can stratify TTP in patients with glioblastoma for adjuvant temozolomide therapy. Positive perfusion in SCWEs can become a predictor of a longer TTP.

  1. Enhanced bonding of chitosan to implant quality titanium via four treatment combinations

    International Nuclear Information System (INIS)

    Martin, Holly J.; Schulz, Kirk H.; Bumgardner, Joel D.; Schneider, Judith A.

    2008-01-01

    Bioactive coatings have been investigated to enhance the integration of orthopaedic and dental-craniofacial implants in the surrounding bone tissue. Chitosan has been shown to possess many properties desirable in implant coatings, such as cell attachment and growth, and encouraging ordered bone tissue formation. Previous studies have produced methods to deposit chitosan onto a titanium surface using both two-step and three-step reaction schemes. In the current study, two different titanium surface treatments were evaluated for determining the strength of chitosan coatings bonded to titanium via two reaction processes. The chitosan coatings produced from the four treatment combinations were examined using X-ray Photoelectron Spectroscopy, which demonstrated that the final coatings were similar in composition to the previously reported coatings. Coatings examined by nano-indentation, exhibited hardness (0.19 ± 0.08 GPa) and elastic modulus (4.90 ± 1.82 GPa) values similar to the hardness and elastic modulus values previously reported. Scanning Electron Microscopy examination of the nano-indentation marks revealed cracks only at sites of applied stress, demonstrating that the chitosan coatings were able to absorb the applied stress. Bulk adhesion of the chitosan coatings demonstrated significant increases in bond strength (19.50 ± 1.63 MPa) over previously reported data (1.5-1.8 MPa), but no significant differences were seen between the four treatment combinations. Contact angle testing demonstrated that the chitosan coatings were more hydrophobic (98.0 ± 3.6 deg.) than published values (76.4 ± 5.1 deg.). Overall, mechanical testing demonstrated that, while the bulk properties of the chitosan coating were unaffected by the four treatment combinations, the bulk adhesion of the chitosan coating was greatly increased and high quality coatings were produced

  2. Hyaluronic acid enhances proliferation of human amniotic mesenchymal stem cells through activation of Wnt/β-catenin signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ru-Ming; Sun, Ren-Gang; Zhang, Ling-Tao; Zhang, Qing-Fang; Chen, Dai-Xiong [Guizhou Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi 563000 (China); Zhong, Jian-Jiang, E-mail: jjzhong@sjtu.edu.cn [State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240 (China); Xiao, Jian-Hui, E-mail: jhxiao@yahoo.com [Guizhou Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi 563000 (China)

    2016-07-15

    This study investigated the pro-proliferative effect of hyaluronic acid (HA) on human amniotic mesenchymal stem cells (hAMSCs) and the underlying mechanisms. Treatment with HA increased cell population growth in a dose- and time-dependent manner. Analyses by flow cytometry and immunocytochemistry revealed that HA did not change the cytophenotypes of hAMSCs. Additionally, the osteogenic, chondrogenic, and adipogenic differentiation capabilities of these hAMSCs were retained after HA treatment. Moreover, HA increased the mRNA expressions of wnt1, wnt3a, wnt8a, cyclin D1, Ki-67, and β-catenin as well as the protein level of β-catenin and cyclin D1 in hAMSCs; and the nuclear localization of β-catenin was also enhanced. Furthermore, the pro-proliferative effect of HA and up-regulated expression of Wnt/β-catenin pathway-associated proteins - wnt3a, β-catenin and cyclin D1 in hAMSCs were significantly inhibited upon pre-treatment with Wnt-C59, an inhibitor of the Wnt/β-catenin pathway. These results suggest that HA may positively regulate hAMSCs proliferation through regulation of the Wnt/β-catenin signaling pathway. - Highlights: • Hyaluronic acid (HA) could promote the proliferation of hAMSCs. • HA treatment dose not affect the pluripotency of hAMSCs. • HA increases hAMSCs proliferation through activation of Wnt/β-catenin signaling.

  3. Predictors and moderators of response to enhanced cognitive behaviour therapy and interpersonal psychotherapy for the treatment of eating disorders.

    Science.gov (United States)

    Cooper, Zafra; Allen, Elizabeth; Bailey-Straebler, Suzanne; Basden, Shawnee; Murphy, Rebecca; O'Connor, Marianne E; Fairburn, Christopher G

    2016-09-01

    Consistent predictors, and more especially moderators, of response to psychological treatments for eating disorders have not been identified. The present exploratory study examined predictors and moderators of outcome in adult patients who took part in a randomised clinical trial comparing two leading treatments for these disorders, enhanced cognitive behavioural therapy (CBT-E) and interpersonal psychotherapy (IPT). Four potentially important findings emerged. Firstly, patients with a longer duration of disorder were less likely to benefit from either treatment. Second, across the two treatments the presence, at baseline, of higher levels of over-evaluation of the importance of shape predicted a less good treatment outcome. Third DSM-IV diagnosis did not predict treatment outcome. Fourth, with the exception of patients with baseline low self-esteem who achieved a better outcome with CBT-E, it was generally not possible to identify a subgroup of patients who would differentially benefit from one or other treatment. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. A new apatinib microcrystal formulation enhances the effect of radiofrequency ablation treatment on hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Xie H

    2018-05-01

    Full Text Available Hui Xie,1,2 Shengtao Tian,2 Haipeng Yu,1 Xueling Yang,1 Jia Liu,3 Huaming Wang,2 Fan Feng,2 Zhi Guo1 1Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Department of Interventional Therapy, 302nd Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 3Department of Blood Transfusion, 302nd Hospital of People’s Liberation Army, Beijing, People’s Republic of China Introduction: Radiofrequency ablation (RFA is the foremost treatment option for advanced hepatocellular carcinoma (HCC, however, rapid and aggressive recurrence of HCC often occurs after RFA due to epithelial–mesenchymal transition process. Although combination of RFA with sorafenib, a molecular targeted agent, could attenuate the recurrence of HCC, application of this molecular targeted agent poses a heavy medical burden and oral administration of sorafenib also brings severe side effects. Materials and methods: In this study, we prepared an apatinib microcrystal formulation (Apa-MS that sustainably releases apatinib, a novel molecular targeted agent, for advanced HCC treatment. We injected apatinib solution or Apa-MS into subcutaneous HCC tumors. Results: It was found that Apa-MS exhibited slow apatinib release in vivo and in turn inhibited the epithelial–mesenchymal transition of HCC cells for extended time. Moreover, in rodent HCC model, Apa-MS enhanced the antitumor effect of RFA treatment. Conclusion: Based on these results, we conclude that Apa-MS, a slow releasing system of apatinib, allows apatinib to remain effective in tumor tissues for a long time and could enhance the antitumor effect of RFA on HCC. Keywords: apatinib microcrystals, radiofrequency ablation, sustained releasing behavior, long-acting efficiency

  5. Video game therapy for emotional regulation and impulsivity control in a series of treated cases with bulimia nervosa.

    Science.gov (United States)

    Fagundo, Ana B; Santamaría, Juan J; Forcano, Laura; Giner-Bartolomé, Cristina; Jiménez-Murcia, Susana; Sánchez, Isabel; Granero, Roser; Ben-Moussa, Maher; Magnenat-Thalmann, Nadia; Konstantas, Dimitri; Lam, Tony; Lucas, Mikkel; Nielsen, Jeppe; Bults, Richard G A; Tarrega, Salomé; Menchón, José M; de la Torre, Rafael; Cardi, Valentina; Treasure, Janet; Fernández-Aranda, Fernando

    2013-11-01

    Although standard psychological treatments have been successful in treating several core features in eating disorders (ED), other characteristics such as emotional regulation or impulsivity appear to be more resistant to change. There is a growing body of evidence to support the efficacy of cognitive remediation for cognitive and emotional difficulties in ED. Playmancer/ Islands is a video game (VG) designed to specifically treat mental disorders, characterized by problems in impulse control. The objective of the game is to increase self-control over emotions, decision making and behaviours. The aim of this study is to describe the results from a consecutive series of nine bulimia nervosa patients who were treated with the VG in addition to cognitive behaviour therapy (CBT). The outcomes included clinical and psychopathological questionnaires, and physiological measures were obtained during the VG. Emotional regulation improved, heart rate variability increased, and respiratory rate and impulsivity measures reduced after the treatment. These findings suggest that VG training may enhance treatment for ED. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.

  6. The performance enhancements of upflow anaerobic sludge blanket (UASB) reactors for domestic sludge treatment--a state-of-the-art review.

    Science.gov (United States)

    Chong, Siewhui; Sen, Tushar Kanti; Kayaalp, Ahmet; Ang, Ha Ming

    2012-07-01

    Nowadays, carbon emission and therefore carbon footprint of water utilities is an important issue. In this respect, we should consider the opportunities to reduce carbon footprint for small and large wastewater treatment plants. The use of anaerobic rather than aerobic treatment processes would achieve this aim because no aeration is required and the generation of methane can be used within the plant. High-rate anaerobic digesters receive great interests due to their high loading capacity and low sludge production. Among them, the upflow anaerobic sludge blanket (UASB) reactors have been most widely used. However, there are still unresolved issues inhibiting the widespread of this technology in developing countries or countries with climate temperature fluctuations (such as subtropical regions). A large number of studies have been carried out in order to enhance the performance of UASB reactors but there is a lack of updated documentation. In face of the existing limitations and the increasing importance of this technology, the authors present an up-to-date review on the performance enhancements of UASB reactors over the last decade. The important aspects of this article are: (i) enhancing the start-up and granulation in UASB reactors, (ii) coupling with post-treatment unit to overcome the temperature constraint, and (iii) improving the removal efficiencies of the organic matter, nutrients and pathogens in the final effluent. Finally the authors have highlighted future research direction based on their critical analysis. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  7. Economic evaluation of Internet-based problem-solving guided self-help treatment in comparison with enhanced usual care for depressed outpatients waiting for face-to-face treatment

    DEFF Research Database (Denmark)

    Kolovos, Spyros; Kenter, Robin M F; Bosmans, Judith E

    2016-01-01

    at outpatient clinics. METHODS: An economic evaluation was performed alongside a randomized controlled trial with 12 months follow-up. Outcomes were improvement in depressive symptom severity (measured by CES-D), response to treatment and Quality-Adjusted Life-Years (QALYs). Statistical uncertainty around cost......BACKGROUND: Previous studies have demonstrated the effectiveness of Internet-based interventions for depression in comparison with usual care. However, evidence on the cost-effectiveness of these interventions when delivered in outpatient clinics is lacking. The aim of this study was to estimate...... the cost-effectiveness of an Internet-based problem-solving guided self-help intervention in comparison with enhanced usual care for outpatients on a waiting list for face-to-face treatment for major depression. After the waiting list period, participants from both groups received the same treatment...

  8. Physiological and behavioral responses of stonefly nymphs to enhanced limestone treatment of acid mine drainage.

    Science.gov (United States)

    Cole, M B; Arnold, D E; Watten, B J

    2001-03-01

    A new acid mine drainage (AMD) treatment system uses pulsed, fluidized beds of limestone, and carbon dioxide pretreatment of influent AMD, to enhance limestone neutralization of AMD. We conducted laboratory studies to evaluate the behavior and physiology of larval stoneflies (Pteronarcys proteus, Plecoptera) exposed to effluents produced by the treatment system. Survival, sodium balance, drift, and feeding responses by P. proteus to treated and untreated AMD were examined. P. proteus nymphs exhibited significant losses of whole body sodium in exposures to untreated AMD. Nymphs exposed to treated effluents experienced no loss of whole-body sodium. Nymphs exposed to untreated AMD showed elevated drift rates and depressed feeding rates relative to those of nymphs exposed to treated AMD, and to AMD-free controls. No significant differences in feeding or drift behavior occurred between nymphs exposed to treated effluents and those exposed to AMD-free controls. The treatment system, with and without CO2 pretreatment, provided water that was not toxic to the test animals, and that allowed normal behavioral and physiological function.

  9. Arthroscopic treatment of impingement of the ankle reduces pain and enhances function

    DEFF Research Database (Denmark)

    Rasmussen, S; Hjorth Jensen, C

    2002-01-01

    A consecutive series of 105 patients with a median age of 35 (16-62) years who were operated on with arthroscopic resection for impingement of the ankle using standardized technique without distraction is presented. All patients complained of painful dorsiflexion and had failed to respond to cons...... synovectomy and intravenous antibiotics. In one patient persistent symptoms were recorded. Ankle arthroscopy yielded good results in the treatment of anterior impingement of the ankle as it effectively reduced pain and enhanced function....... of pain. Gait was improved in 30/41 patients and 22 resumed sporting activities. The results were graded excellent in 67, good in 25, fair in six and poor in seven patients. There were four deep infections and one synovial fistula in this series. The deep infections all responded well to arthroscopic...

  10. Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration.

    Directory of Open Access Journals (Sweden)

    Qian-Shi Zhang

    Full Text Available Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1, also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5, after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1, the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93, or the downstream target, c-Jun N-terminal kinase (SP600125 also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580 had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration.

  11. Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration

    Science.gov (United States)

    Zhang, Qian-Shi; Kurpad, Deepa S.; Mahoney, My G.; Steinbeck, Marla J.

    2017-01-01

    Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO) or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5), after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1), the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93), or the downstream target, c-Jun N-terminal kinase (SP600125) also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580) had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration. PMID:29045420

  12. Free nitrous acid pre-treatment of waste activated sludge enhances volatile solids destruction and improves sludge dewaterability in continuous anaerobic digestion.

    Science.gov (United States)

    Wei, Wei; Wang, Qilin; Zhang, Liguo; Laloo, Andrew; Duan, Haoran; Batstone, Damien J; Yuan, Zhiguo

    2018-03-01

    Previous work has demonstrated that pre-treatment of waste activated sludge (WAS) with free nitrous acid (FNA i.e. HNO 2 ) enhances the biodegradability of WAS, identified by a 20-50% increase in specific methane production in biochemical methane potential (BMP) tests. This suggests that FNA pre-treatment would enhance the destruction of volatile solids (VS) in an anaerobic sludge digester, and reduce overall sludge disposal costs, provided that the dewaterability of the digested sludge is not negatively affected. This study experimentally evaluates the impact of FNA pre-treatment on the VS destruction in anaerobic sludge digestion and on the dewaterability of digested sludge, using continuously operated bench-scale anaerobic digesters. Pre-treatment of full-scale WAS for 24 h at an FNA concentration of 1.8 mg NN/L enhanced VS destruction by 17 ± 1% (from 29.2 ± 0.9% to 34.2 ± 1.1%) and increased dewaterability (centrifuge test) from 12.4 ± 0.4% to 14.1 ± 0.4%. Supporting the VS destruction data, methane production increased by 16 ± 1%. Biochemical methane potential tests indicated that the final digestate stability was also improved with a lower potential from FNA treated digestate. Further, a 2.1 ± 0.2 log improvement in pathogen reduction was also achieved. With inorganic solids representing 15-22% of the full-scale WAS used, FNA pre-treatment resulted in a 16-17% reduction in the volume of dewatered sludge for final disposal. This results in significantly reduced costs as assessed by economic analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Predicting local recurrence following breast-conserving treatment: parenchymal signal enhancement ratio (SER) around the tumor on preoperative MRI

    International Nuclear Information System (INIS)

    Kim, Mi Young; Cho, Nariya; Koo, Hye Ryoung; Yun, Bo La; Bae, Min Sun; Moon, Woo Kyung; Chie, Eui Kyu

    2013-01-01

    Background: The level of background parenchymal enhancement around tumor is known to be associated with breast cancer risk. However, there is no study investigating predictive power of parenchymal signal enhancement ratio (SER) around tumor for ipsilateral breast tumor recurrence (IBTR). Purpose: To investigate whether the breast parenchymal SER around the tumor on preoperative dynamic contrast-enhanced magnetic resonance imaging (MRI) is associated with subsequent IBTR in breast cancer patients who had undergone breast-conserving treatment. Material and Methods: Nineteen consecutive women (mean age, 44 years; range, 34-63 years) with breast cancer who developed IBTR following breast-conserving treatment and 114 control women matched for age, as well as T and N stages were included. We compared the clinicopathologic features of the two groups including nuclear grade, histologic grade, hormonal receptor status, human epidermal growth factor receptor-2 (HER-2) status, lymphovascular invasion, negative margin width, use of adjuvant therapy, and parenchymal SER around the tumor on preoperative DCE-MRI. The SER was measured on a slice showing the largest dimension of the tumor. Multivariate conditional logistic regression analysis was used to identify independent factors associated with IBTR. Results: In univariate analysis, ER negativity (odds ratio [OR] = 4.7; P = 0.040), PR negativity (OR = 4.0; P = 0.013), HER-2 positivity (OR = 3.6; P = 0.026), and a parenchymal SER greater than 0.53 (OR = 23.3; P = 0.011) were associated with IBTR. In multivariate analysis, ER negativity (OR = 3.8; P = 0.015) and a parenchymal SER greater than 0.53 (OR = 13.2; P = 0.040) on preoperative MRI were independent factors associated with IBTR. Conclusion: In addition to ER negativity, a higher parenchymal SER on preoperative MRI was an independent factor associated with subsequent IBTR in patients with breast cancer who had undergone breast-conserving treatment

  14. Enhancing Charge Carrier Lifetime in Metal Oxide Photoelectrodes through Mild Hydrogen Treatment

    KAUST Repository

    Jang, Ji-Wook

    2017-08-25

    Widespread application of solar water splitting for energy conversion is largely dependent on the progress in developing not only efficient but also cheap and scalable photoelectrodes. Metal oxides, which can be deposited with scalable techniques and are relatively cheap, are particularly interesting, but high efficiency is still hindered by the poor carrier transport properties (i.e., carrier mobility and lifetime). Here, a mild hydrogen treatment is introduced to bismuth vanadate (BiVO4), which is one of the most promising metal oxide photoelectrodes, as a method to overcome the carrier transport limitations. Time-resolved microwave and terahertz conductivity measurements reveal more than twofold enhancement of the carrier lifetime for the hydrogen-treated BiVO4, without significantly affecting the carrier mobility. This is in contrast to the case of tungsten-doped BiVO4, although hydrogen is also a donor type dopant in BiVO4. The enhancement in carrier lifetime is found to be caused by significant reduction of trap-assisted recombination, either via passivation or reduction of deep trap states related to vanadium antisite on bismuth or vanadium interstitials according to density functional theory calculations. Overall, these findings provide further insights on the interplay between defect modulation and carrier transport in metal oxides, which benefit the development of low-cost, highly-efficient solar energy conversion devices.

  15. Strength Enhancement of Car Front Bumper for Slow Speed Impact by FEA Method as per IIHS Regulation

    Science.gov (United States)

    Sonawane, Chandrakant Rameshchandra; Shelar, Ajit Lavaji

    2017-05-01

    Low speed collisions happen significantly due to on road slow moving heavy traffic as well as during parking of vehicles. The bumpers are provided in front and back side of a vehicle has two main purposes: first is to absorb the energy generated during these kinds of slow speed impacts and secondly to protect the expensive parts like main engine parts, radiators and connected engine cooling mechanism, headlights, taillights, etc, by slowing down the vehicles. The problem often in various cars bumper is that they doesn't line-up vertically during low speed impact and leads to damage of various parts which are costly to repair. Many a times bumper design does not have sufficient capacity to absorb the energy generated during these impact. Guideline by International Institute Highway Safety (IIHS) regulation provides useful insight for such low speed impact study. In this paper, slow speed impact test were conducted as per IIHS regulation in three positions namely central impact, left hand corner impact and right hand corner impact. Parameters including bumper material, shape, thickness and impact condition are analyzed using fine element analysis (FEA) to enhance crashworthiness design in low speed impact. Then the vehicle front structure has been modified suitably. It has been observed that lining up the front metal bumper with suitable stiffness provides the best result which ultimately reduces the damage to the vehicle parts.

  16. Improve the material absorption of light and enhance the laser tube bending process utilizing laser softening heat treatment

    Science.gov (United States)

    Imhan, Khalil Ibraheem; Baharudin, B. T. H. T.; Zakaria, Azmi; Ismail, Mohd Idris Shah B.; Alsabti, Naseer Mahdi Hadi; Ahmad, Ahmad Kamal

    2018-02-01

    Laser forming is a flexible control process that has a wide spectrum of applications; particularly, laser tube bending. It offers the perfect solution for many industrial fields, such as aerospace, engines, heat exchangers, and air conditioners. A high power pulsed Nd-YAG laser with a maximum average power of 300 W emitting at 1064 nm and fiber-coupled is used to irradiate stainless steel 304 (SS304) tubes of 12.7 mm diameter, 0.6 mm thickness and 70 mm length. Moreover, a motorized rotation stage with a computer controller is employed to hold and rotate the tube. In this paper, an experimental investigation is carried out to improve the laser tube bending process by enhancing the absorption coefficient of the material and the mechanical formability using laser softening heat treatment. The material surface is coated with an oxidization layer; hence, the material absorption of laser light is increased and the temperature rapidly rises. The processing speed is enhanced and the output bending angle is increased to 1.9° with an increment of 70% after the laser softening heat treatment.

  17. BSA treatment to enhance enzymatic hydrolysis of cellulose in lignin containing substrates.

    Science.gov (United States)

    Yang, Bin; Wyman, Charles E

    2006-07-05

    Cellulase and bovine serum albumin (BSA) were added to Avicel cellulose and solids containing 56% cellulose and 28% lignin from dilute sulfuric acid pretreatment of corn stover. Little BSA was adsorbed on Avicel cellulose, while pretreated corn stover solids adsorbed considerable amounts of this protein. On the other hand, cellulase was highly adsorbed on both substrates. Adding a 1% concentration of BSA to dilute acid pretreated corn stover prior to enzyme addition at 15 FPU/g cellulose enhanced filter paper activity in solution by about a factor of 2 and beta-glucosidase activity in solution by about a factor of 14. Overall, these results suggested that BSA treatment reduced adsorption of cellulase and particularly beta-glucosidase on lignin. Of particular note, BSA treatment of pretreated corn stover solids prior to enzymatic hydrolysis increased 72 h glucose yields from about 82% to about 92% at a cellulase loading of 15 FPU/g cellulose or achieved about the same yield at a loading of 7.5 FPU/g cellulose. Similar improvements were also observed for enzymatic hydrolysis of ammonia fiber explosion (AFEX) pretreated corn stover and Douglas fir treated by SO(2) steam explosion and for simultaneous saccharification and fermentation (SSF) of BSA pretreated corn stover. In addition, BSA treatment prior to hydrolysis reduced the need for beta-glucosidase supplementation of SSF. The results are consistent with non-specific competitive, irreversible adsorption of BSA on lignin and identify promising strategies to reduce enzyme requirements for cellulose hydrolysis. (c) 2006 Wiley Periodicals, Inc.

  18. Enhancement of methane gas sensing characteristics of graphene oxide sensor by heat treatment and laser irradiation.

    Science.gov (United States)

    Assar, Mohammadreza; Karimzadeh, Rouhollah

    2016-12-01

    The present study uses a rapid, easy and practical method for cost-effective fabrication of a methane gas sensor. The sensor was made by drop-casting a graphene oxide suspension onto an interdigital circuit surface. The electrical conductivity and gas-sensing characteristics of the sensor were determined and then heat treatment and in situ laser irradiation were applied to improve the device conductivity and gas sensitivity. Real-time monitoring of the evolution of the device current as a function of heat treatment time revealed significant changes in the conductance of the graphene oxide sensor. The use of low power laser irradiation enhanced both the electrical conductivity and sensing response of the graphene oxide sensor. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Cognitive enhancing effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on learning and memory

    Science.gov (United States)

    Nade, V. S.; Kawale, L. A.; Valte, K. D.; Shendye, N. V.

    2015-01-01

    Objective: The present study was designed to investigate cognitive enhancing property of angiotensin-converting enzymes inhibitors (ACEI) and angiotensin receptor blockers (ARBs) in rats. Materials and Methods: The elevated plus maze (EPM), passive avoidance test (PAT), and water maze test (WMT) were used to assess cognitive enhancing activity in young and aged rats. Ramipril (10 mg/kg, p.o.), perindopril (10 mg/kg, i.p), losartan (20 mg/kg, i.p), and valsartan (20 mg/kg, p.o) were administered to assess their effect on learning and memory. Scopolamine (1 mg/kg, i.p) was used to impair cognitive function. Piracetam (200 mg/kg, i.p) was used as reference drug. Results: All the treatments significantly attenuated amnesia induced by aging and scopolamine. In EPM, aged and scopolamine-treated rats showed an increase in transfer latency (TL) whereas, ACEI and ARBs showed a significant decrease in TL. Treatment with ACEI and ARBs significantly increased step down latencies and decreased latency to reach the platform in target quadrant in young, aged and scopolamine-treated animals in PAT and WMT, respectively. The treatments inhibited acetylcholinesterase (AChE) enzyme in the brain. Similarly, all the treatments attenuated scopolamine-induced lipid peroxidation and normalize antioxidant enzymes. Conclusion: The results suggest that the cognitive enhancing effect of ACEI and ARBs may be due to inhibition of AChE or by regulation of antioxidant system or increase in formation of angiotensin IV. PMID:26069362

  20. Antidiabetic phospholipid-nuclear receptor complex reveals the mechanism for phospholipid-driven gene regulation

    Energy Technology Data Exchange (ETDEWEB)

    Musille, Paul M; Pathak, Manish C; Lauer, Janelle L; Hudson, William H; Griffin, Patrick R; Ortlund, Eric A [Emory-MED; (Scripps)

    2013-01-31

    The human nuclear receptor liver receptor homolog-1 (LRH-1) has an important role in controlling lipid and cholesterol homeostasis and is a potential target for the treatment of diabetes and hepatic diseases. LRH-1 is known to bind phospholipids, but the role of phospholipids in controlling LRH-1 activation remains highly debated. Here we describe the structure of both apo LRH-1 and LRH-1 in complex with the antidiabetic phospholipid dilauroylphosphatidylcholine (DLPC). Together with hydrogen-deuterium exchange MS and functional data, our studies show that DLPC binding is a dynamic process that alters co-regulator selectivity. We show that the lipid-free receptor undergoes previously unrecognized structural fluctuations, allowing it to interact with widely expressed co-repressors. These observations enhance our understanding of LRH-1 regulation and highlight its importance as a new therapeutic target for controlling diabetes.

  1. Nitrogen regulation of transpiration controls mass-flow acquisition of nutrients.

    Science.gov (United States)

    Matimati, Ignatious; Verboom, G Anthony; Cramer, Michael D

    2014-01-01

    Transpiration may enhance mass-flow of nutrients to roots, especially in low-nutrient soils or where the root system is not extensively developed. Previous work suggested that nitrogen (N) may regulate mass-flow of nutrients. Experiments were conducted to determine whether N regulates water fluxes, and whether this regulation has a functional role in controlling the mass-flow of nutrients to roots. Phaseolus vulgaris were grown in troughs designed to create an N availability gradient by restricting roots from intercepting a slow-release N source, which was placed at one of six distances behind a 25 μm mesh from which nutrients could move by diffusion or mass-flow (termed 'mass-flow' treatment). Control plants had the N source supplied directly to their root zone so that N was available through interception, mass-flow, and diffusion (termed 'interception' treatment). 'Mass-flow' plants closest to the N source exhibited 2.9-fold higher transpiration (E), 2.6-fold higher stomatal conductance (gs), 1.2-fold higher intercellular [CO2] (Ci), and 3.4-fold lower water use efficiency than 'interception' plants, despite comparable values of photosynthetic rate (A). E, gs, and Ci first increased and then decreased with increasing distance from the N source to values even lower than those of 'interception' plants. 'Mass-flow' plants accumulated phosphorus and potassium, and had maximum concentrations at 10mm from the N source. Overall, N availability regulated transpiration-driven mass-flow of nutrients from substrate zones that were inaccessible to roots. Thus when water is available, mass-flow may partially substitute for root density in providing access to nutrients without incurring the costs of root extension, although the efficacy of mass-flow also depends on soil nutrient retention and hydraulic properties.

  2. Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans

    DEFF Research Database (Denmark)

    Aslan, Derya; Dahl Andersen, Mille; Gede, Lene Bjerring

    2012-01-01

    . However, development of the biochemical measurement of PTH in the 1980s led us to understand the regulation of PTH secretion and calcium metabolism which subsequently paved the way for the use of PTH as an anabolic treatment of osteoporosis as, when given intermittently, it has strong anabolic effects...... in bone. This could not have taken place without the basic understanding achieved by the biochemical measurements of PTH. The stimulatory effects of PTH on bone formation have been explained by the so-called ‘anabolic window’, which means that during PTH treatment, bone formation is in excess over bone...... resorption during the first 6–18 months. This is due to the following: (1) PTH up-regulates c-fos expression in bone cells, (2) IGF is essential for PTH's anabolic effect, (3) bone lining cells are driven to differentiate into osteoblasts, (4) mesenchymal stem cells adhesion to bone surface is enhanced, (5...

  3. MAP Kinase Cascades Regulate the Cold Response by Modulating ICE1 Protein Stability.

    Science.gov (United States)

    Zhao, Chunzhao; Wang, Pengcheng; Si, Tong; Hsu, Chuan-Chih; Wang, Lu; Zayed, Omar; Yu, Zheping; Zhu, Yingfang; Dong, Juan; Tao, W Andy; Zhu, Jian-Kang

    2017-12-04

    Mitogen-activated protein kinase cascades are important signaling modules that convert environmental stimuli into cellular responses. We show that MPK3, MPK4, and MPK6 are rapidly activated after cold treatment. The mpk3 and mpk6 mutants display increased expression of CBF genes and enhanced freezing tolerance, whereas constitutive activation of the MKK4/5-MPK3/6 cascade in plants causes reduced expression of CBF genes and hypersensitivity to freezing, suggesting that the MKK4/5-MPK3/6 cascade negatively regulates the cold response. MPK3 and MPK6 can phosphorylate ICE1, a basic-helix-loop-helix transcription factor that regulates the expression of CBF genes, and the phosphorylation promotes the degradation of ICE1. Interestingly, the MEKK1-MKK2-MPK4 pathway constitutively suppresses MPK3 and MPK6 activities and has a positive role in the cold response. Furthermore, the MAPKKK YDA and two calcium/calmodulin-regulated receptor-like kinases, CRLK1 and CRLK2, negatively modulate the cold activation of MPK3/6. Our results uncover important roles of MAPK cascades in the regulation of plant cold response. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Effect of desipramine and citalopram treatment on forced swimming test-induced changes in cocaine- and amphetamine-regulated transcript (CART) immunoreactivity in mice.

    Science.gov (United States)

    Chung, Sung; Kim, Hee Jeong; Kim, Hyun Ju; Choi, Sun Hye; Kim, Jin Wook; Kim, Jeong Min; Shin, Kyung Ho

    2014-05-01

    Recent study demonstrates antidepressant-like effect of cocaine- and amphetamine-regulated transcript (CART) in the forced swimming test (FST), but less is known about whether antidepressant treatments alter levels of CART immunoreactivity (CART-IR) in the FST. To explore this possibility, we assessed the treatment effects of desipramine and citalopram, which inhibit the reuptake of norepinephrine and serotonin into the presynaptic terminals, respectively, on changes in levels of CART-IR before and after the test swim in mouse brain. Levels of CART-IR in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), and hypothalamic paraventricular nucleus (PVN) were significantly increased before the test swim by desipramine and citalopram treatments. This increase in CART-IR in the AcbSh, dBNST, and PVN before the test swim remained elevated by desipramine treatment after the test swim, but this increase in these brain areas returned to near control levels after test swim by citalopram treatment. Citalopram, but not desipramine, treatment increased levels of CART-IR in the central nucleus of the amygdala (CeA) and the locus ceruleus (LC) before the test swim, and this increase was returned to control levels after the test swim in the CeA, but not in the LC. These results suggest common and distinct regulation of CART by desipramine and citalopram treatments in the FST and raise the possibility that CART in the AcbSh, dBNST, and CeA may be involved in antidepressant-like effect in the FST.

  5. The Comparison of Effectiveness of Cognitive-Behavioral Group Therapy Based on Coping Skills and Methadone Maintenance Treatment in Improvement of Emotional Regulation Strategies and Relapse Prevention

    Directory of Open Access Journals (Sweden)

    Tahereh Ghorbany

    2011-05-01

    Full Text Available Purpose: This study compared the effectiveness of group cognitive-behavioral therapy based on coping skills (CBT and methadone maintenance therapy (MMT in improvement of emotional regulation strategies and prevention of relapse. Method: The method of the present study was semi-experimental research design (pre-test-post-test with witness group. For sampling 45 substance abuse people who had referred to addiction treatment centers were selected and assigned to three groups of cognitive behavior therapy, methadone maintenance treatment and witness group randomly. The participants in all three groups completed the emotional intelligence questionnaire before and after the intervention. Data were analyzed by covariance method. Results: The results showed that cognitive-behavior therapy in comparison to methadone maintenance therapy and witness group led to significant improvement of emotional regulation in substance abusers, but there was no significant difference between the methadone maintenance treatment group and control group. Also, the rate of relapse in individuals who assigned to cognitive-behavior therapy group in comparison to methadone maintenance therapy and the witness group was significantly lower, but there was no significant difference between methadone therapy and witness. Conclusion: Cognitive-behavior therapy was an effective treatment that can change the cognitive and behavioral variables related to substance abuse, such as emotional regulation strategies. Thus, results suggested that drug abuse treatment programs must target these mediator variables.

  6. Enhancing phosphorus removal in constructed wetlands with ochre from mine drainage treatment.

    Science.gov (United States)

    Heal, K V; Dobbie, K E; Bozika, E; McHaffie, H; Simpson, A E; Smith, K A

    2005-01-01

    No single end-use has yet been identified that is capable of consuming the projected production of ochre (mainly iron (III) oxides) from mine drainage treatment. However, the high sorption capacity of ochre for phosphorus (up to 26 mg kg(-1)) means that it could be used in constructed wetlands to enhance phosphorus removal. Laboratory batch experiments showed that coarse-grained ochre removes 90% of all phosphorus forms from sewage effluent after 15 minutes of shaking. From a larger-scale experiment, it is estimated that constructed wetlands with an ochre substrate should remove phosphorus from sewage effluent for up to 200-300 years. The suitability of ochre for phosphorus removal is being investigated at the field scale in a wastewater constructed wetland (175 m2 area) in Berwickshire, UK. The hydraulic and treatment performance of the wetland were monitored for 15 months prior to installation at the inlet in November 2003 of a tank containing approximately 1200 kg ochre. Results so far show that improved hydraulic design is required for ochre to increase the mean phosphorus removal efficiency of the system (27 +/- 28%), but potentially toxic metals (Al, Cd, Cr, Cu, Fe, Ni, Pb, Zn) have not been released from the ochre into the wetland outflow.

  7. Cognitive and Self-regulatory Mechanisms of Obesity Study (COSMOS): Study protocol for a randomized controlled weight loss trial examining change in biomarkers, cognition, and self-regulation across two behavioral treatments.

    Science.gov (United States)

    Hawkins, M A W; Colaizzi, Janna; Gunstad, John; Hughes, Joel W; Mullins, Larry L; Betts, Nancy; Smith, Caitlin E; Keirns, Natalie G; Vohs, Kathleen D; Moore, Shirley M; Forman, Evan M; Lovallo, William R

    2018-03-01

    Obesity is a global epidemic, yet successful interventions are rare. Up to 60% of people fail to achieve clinically meaningful, short-term weight loss (5-10% of start weight), whereas up to 72% are unsuccessful at achieving long-term weight loss (5-10% loss for ≥5years). Understanding how biological, cognitive, and self-regulatory factors work together to promote or to impede weight loss is clearly needed to optimize obesity treatment. This paper describes the methodology of the Cognitive and Self-regulatory Mechanisms of Obesity Study (the COSMOS trial). COSMOS is the first randomized controlled trial to investigate how changes in multiple biopsychosocial and cognitive factors relate to weight loss and one another across two weight loss treatments. The specific aims are to: 1) Confirm that baseline obesity-related physiological dysregulation is linked to cognitive deficits and poorer self-regulation, 2) Evaluate pre- to post-treatment change across time to assess individual differences in biomarkers, cognition, and self-regulation, and 3) Evaluate whether the acceptance-based treatment (ABT) group has greater improvements in outcomes (e.g., greater weight loss and less weight regain, improvements in biomarkers, cognition, and self-regulation), than the standard behavioral treatment group (SBT) from pre- to post-treatment and 1-year follow-up. The results of COSMOS will provide critical information about how dysregulation in biomarkers, cognition, and/or self-regulation is related to weight loss and whether weight loss treatments are differentially associated with these factors. This information will be used to identify promising treatment targets that are informed by biological, cognitive, and self-regulatory factors in order to advance obesity treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Adsorbability Enhancement of Macroporous Resin by Dielectric Barrier Discharge Plasma Treatment to Phenol in Water

    Directory of Open Access Journals (Sweden)

    Shoufeng Tang

    2016-01-01

    Full Text Available In order to enhance the adsorption efficiency and economize the use of macroporous resin, we have treated it with the dielectric barrier discharge (DBD plasma to improve its adsorbing capacity for phenol. The effects of operation conditions, for instance, applied voltage, treated time, and air flow rate on resin, were investigated by adsorption kinetics and isotherms. Results showed that the adsorption data were in good agreement with the pseudo-second-order and Freundlich equation. Experimental results showed that the modified resin was 156.5 mg/g and 39.2% higher than the untreated sample, when the modified conditions were conducted for discharge voltage 20 kV, treatment time 45 min, and air flow rate 1.2 L/min. The resin was characterized by FTIR and nitrogen adsorption isotherms before and after the DBD processes. It was found that the reason for the enhancement of resin adsorbability was attributed to the DBD plasma changing the surface physical and chemical structure.

  9. Anaerobic treatment of antibiotic production wastewater pretreated with enhanced hydrolysis: Simultaneous reduction of COD and ARGs.

    Science.gov (United States)

    Yi, Qizhen; Zhang, Yu; Gao, Yingxin; Tian, Zhe; Yang, Min

    2017-03-01

    The presence of high concentration antibiotics in wastewater can disturb the stability of biological wastewater treatment systems and promote generation of antibiotic resistance genes (ARGs) during the treatment. To solve this problem, a pilot system consisting of enhanced hydrolysis pretreatment and an up-flow anaerobic sludge bed (UASB) reactor in succession was constructed for treating oxytetracycline production wastewater, and the performance was evaluated in a pharmaceutical factory in comparison with a full-scale anaerobic system operated in parallel. After enhanced hydrolysis under conditions of pH 7 and 85 °C for 6 h, oxytetracycline production wastewater with an influent chemical oxygen demand (COD) of 11,086 ± 602 mg L -1 was directly introduced into the pilot UASB reactor. With the effective removal of oxytetracycline and its antibacterial potency (from 874 mg L -1 to less than 0.61 mg L -1 and from 900 mg L -1 to less than 0.84 mg L -1 , respectively) by the enhanced hydrolysis pretreatment, an average COD removal rate of 83.2%, 78.5% and 68.9% was achieved at an organic loading rate of 3.3, 4.8 and 5.9 kg COD m -3  d -1 , respectively. At the same time, the relative abundances of the total tetracycline (tet) genes and a mobile element (Class 1 integron (intI1)) in anaerobic sludge on day 96 were one order of magnitude lower than those in inoculated sludge on day 0 (P anaerobic system treating oxytetracycline production wastewater with an influent COD of 3720 ± 128 mg L -1 after dilution exhibited a COD removal of 51 ± 4% at an organic loading rate (OLR) 1.2 ± 0.2 kg m -3  d -1 , and a total tet gene abundance in sludge was five times higher than the pilot-scale system (P anaerobic treatment of oxytetracycline production wastewater containing high concentrations of oxytetracycline with significantly lower generation of ARGs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Motivation for Compliance with Environmental Regulation

    DEFF Research Database (Denmark)

    Winter, Søren; May, Peter J.

    2001-01-01

    A combination of calculated, normative, and social motivations as well as awareness of rules and capacity to comply are thought to foster compliance with regulations. Hypotheses about these factors were tested with data concerning Danish farmers’ compliance with agro-environmental regulations....... Three key findings emerge: that farmers’ awareness of rules plays a critical role; that normative and social motivations are as influential as calculated motivations in enhancing compliance; and that inspectors’ enforcement style affects compliance differently from that posited in much of the literature...... compliance with social and environmental regulations....

  11. Estrogen enhances mismatch repair by induction of MLH1 expression via estrogen receptor-β.

    Science.gov (United States)

    Lu, Jun-Yu; Jin, Peng; Gao, Wei; Wang, De-Zhi; Sheng, Jian-Qiu

    2017-06-13

    Epidemiological data demonstrated that hormone replace treatment has protective effect against colorectal cancer (CRC). Our previous studies showed that this effect may be associated with DNA mismatch repair. This study aims to investigate the mechanism of estrogen induction of MLH1, and whether colorectal tumor proliferation can be inhibited through induction of MLH1 by estrogen signal pathway. Human CRC cell lines were used to examine the regulation of MLH1 expression by over-expression and depletion of estrogen receptor-α (ERα) and estrogen receptor-β (ERβ), under the treatment with 17β-estradiol or β-Estradiol 6-(O-carboxy-methyl)oxime:BSA, followed by a real-time Q-PCR and Western blotting analysis. Luciferase reporter and chromatin immunoprecipitation assays were used to identify the estrogen response elements in the proximal promoter of MLH1 gene. Then, the influence of estrogen-induced MLH1 on CRC tumor growth were determined in vitro and in vivo. We found that mismatch repair ability and microsatellite stability of cells were enhanced by estrogen via induction of MLH1 expression, which was mediated by ERβ, through a transcriptional activation process. Furthermore, we identified that ERβ exerted an inhibitory effect on CRC tumor proliferation in vitro and in vivo, combined with 5-FU, through up-regulation of MLH1 expression. Finally, we concluded that estrogen enhances mismatch repair ability and tumor inhibition effect in vitro and in vivo, via induction of MLH1 expression mediated by ERβ.

  12. Circulating Estradiol Regulates Brain-Derived Estradiol via Actions at GnRH Receptors to Impact Memory in Ovariectomized Rats.

    Science.gov (United States)

    Nelson, Britta S; Black, Katelyn L; Daniel, Jill M

    2016-01-01

    Systemic estradiol treatment enhances hippocampus-dependent memory in ovariectomized rats. Although these enhancements are traditionally thought to be due to circulating estradiol, recent data suggest these changes are brought on by hippocampus-derived estradiol, the synthesis of which depends on gonadotropin-releasing hormone (GnRH) activity. The goal of the current work is to test the hypothesis that peripheral estradiol affects hippocampus-dependent memory through brain-derived estradiol regulated via hippocampal GnRH receptor activity. In the first experiment, intracerebroventricular infusion of letrozole, which prevents the synthesis of estradiol, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory in a radial-maze task. In the second experiment, hippocampal infusion of antide, a long-lasting GnRH receptor antagonist, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory. In the third experiment, hippocampal infusion of GnRH enhanced hippocampus-dependent memory, the effects of which were blocked by letrozole infusion. Results indicate that peripheral estradiol-induced enhancement of cognition is mediated by brain-derived estradiol via hippocampal GnRH receptor activity.

  13. Issues and future directions of 'introduction of Risk Informed Regulation'

    International Nuclear Information System (INIS)

    2008-01-01

    In 2004, Nuclear Safety Commission of Japan (NSC) set up a taskforce for developing a scheme of Risk Informed Regulation (RIR) introduction, which had discussed various aspects of utilization of risk information in nuclear regulations. In the final report compiled in 2007, the taskforce identified the significance of RIR introduction from viewpoint of enhancement of rationality, consistency and transparency as well as appropriate allocation of regulatory resources in the nuclear safety regulation and major issues for the further promotion were as follows: NSC is to maintain the comprehensively promoting function of the RIR introduction with reviewing global trends and latest technological knowledge, regulatory bodies are to further enhance the RIR in inspection and operational area, utilities and industries are to utilize further risk information in their self-maintenance activities and to gather trouble information data, academic societies are to establish the standards for risk evaluation technology and RIR, and research institutes are to carry out safety research and risk training for risk-communicators. This article presented summary of the final report aiming at upgrading safety regulation with enhancement of RIR introduction. (T. Tanaka)

  14. Municipalities as facilitators, regulators and energy consumers for enhancing the dissemination of biogas technology in Denmark

    Directory of Open Access Journals (Sweden)

    Rikke Lybæk

    2015-06-01

    Full Text Available Biogas provides many potential benefits as far as renewable energy production, environmental protection and job creation etc. Insufficient initiatives from government/municipalities however hamper more biogas plants to be established, and hence that the large manure potential, and other types of digestible organic waste materials, are being utilized for energy purposes. By looking at municipalities as energy consumer’s, that constitutes a local market for biogas, as regulator’s, enforcing new requirements and regulations on the biogas sector, and finally as facilitator’s, assisting and helping involved stakeholders, the development of the biogas sector could be enhanced. We suggest to: Slim the documentation needed; Require that a part of the municipal heat are provided by biogas; Identify alternative heat markets for sale of non-upgraded biogas; Map new types of gas boosters, etc. We conclude that the role of municipalities as facilitator’s is the most important support that local governments can provide to support biogas.

  15. Interferon alpha treatment stimulates interferon gamma expression in type I NKT cells and enhances their antiviral effect against hepatitis C virus.

    Science.gov (United States)

    Miyaki, Eisuke; Hiraga, Nobuhiko; Imamura, Michio; Uchida, Takuro; Kan, Hiromi; Tsuge, Masataka; Abe-Chayama, Hiromi; Hayes, C Nelson; Makokha, Grace Naswa; Serikawa, Masahiro; Aikata, Hiroshi; Ochi, Hidenori; Ishida, Yuji; Tateno, Chise; Ohdan, Hideki; Chayama, Kazuaki

    2017-01-01

    Interferon (IFN) inhibits hepatitis C virus (HCV) replication through up-regulation of intrahepatic IFN-stimulated gene expression but also through activation of host immune cells. In the present study, we analyzed the immune cell-mediated antiviral effects of IFN-α using HCV-infected mice. Urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice with transplanted human hepatocytes were infected with genotype 1b HCV and injected with human peripheral blood mononuclear cells (PBMCs). IFN-α treatment following human PBMC transplantation resulted in a significant reduction in serum HCV RNA titers and a higher human CD45-positive mononuclear cell chimerism compared to mice without human PBMC transplantation. In mice with human PBMCs treated with IFN-α, serum concentrations of IFN-γ increased, and natural killer T (NKT) cells, especially type I NKT cells, produced IFN-γ. Mice in which IFN-γ signaling was blocked using antibody or in which transplanted PBMCs were depleted for type I NKT cells showed similar levels of anti-HCV effect compared with mice treated only with IFN-α. These results show that IFN-α stimulates IFN-γ expression in type 1 NKT cells and enhances the inhibition of HCV replication. We propose that type 1 NKT cells might represent a new therapeutic target for chronic hepatitis C patients.

  16. Morphine treatment enhances glutamatergic input onto neurons of the nucleus accumbens via both disinhibitory and stimulating effect.

    Science.gov (United States)

    Yuan, Kejing; Sheng, Huan; Song, Jiaojiao; Yang, Li; Cui, Dongyang; Ma, Qianqian; Zhang, Wen; Lai, Bin; Chen, Ming; Zheng, Ping

    2017-11-01

    Drug addiction is a chronic brain disorder characterized by the compulsive repeated use of drugs. The reinforcing effect of repeated use of drugs on reward plays an important role in morphine-induced addictive behaviors. The nucleus accumbens (NAc) is an important site where morphine treatment produces its reinforcing effect on reward. However, how morphine treatment produces its reinforcing effect on reward in the NAc remains to be clarified. In the present study, we studied the influence of morphine treatment on the effects of DA and observed whether morphine treatment could directly change glutamatergic synaptic transmission in the NAc. We also explored the functional significance of morphine-induced potentiation of glutamatergic synaptic transmission in the NAc at behavioral level. Our results show that (1) morphine treatment removes the inhibitory effect of DA on glutamatergic input onto NAc neurons; (2) morphine treatment potentiates glutamatergic input onto NAc neurons, especially the one from the basolateral amygdala (BLA) to the NAc; (3) blockade of glutamatergic synaptic transmission in the NAc or ablation of projection neurons from BLA to NAc significantly decreases morphine treatment-induced increase in locomotor activity. These results suggest that morphine treatment enhances glutamatergic input onto neurons of the NAc via both disinhibitory and stimulating effect and therefore increases locomotor activity. © 2016 Society for the Study of Addiction.

  17. Overexpression of let-7a increases neurotoxicity in a PC12 cell model of Alzheimer's disease via regulating autophagy.

    Science.gov (United States)

    Gu, Huizi; Li, Lan; Cui, Chen; Zhao, Zihui; Song, Guijun

    2017-10-01

    Increased deposition of β-amyloid (Aβ) protein is one of the typical characteristics of Alzheimer's disease (AD). Recent evidence has demonstrated that the microRNA let-7 family, which is highly expressed in the central nervous system, participates in the regulation of pathologic processes of AD. In the present study, the effect of let-7a overexpression on Aβ1-40-induced neurotoxicity was evaluated in PC12 and SK-N-SH cells. The results indicated that overexpression of let-7a enhanced the neurotoxicity induced by Aβ1-40 in PC12 and SK-N-SH cells. In addition, the apoptosis induced by Aβ1-40 in PC12 and SK-N-SH cells was increased by let-7a overexpression. Furthermore, Aβ1-40 treatment increased the protein levels of microtubule-associated protein 1A/1B-light chain 3 (LC3) and beclin-1 and increased the LC3 II/I ratio. The mRNA expression levels of beclin-1, autophagy protein 5 (Atg-5) and Atg-7 were also increased by Aβ1-40 treatment in PC12 cells. Let-7a overexpression further upregulated the above autophagy-related markers. Furthermore, the protein level of p62 was increased by Aβ1-40 treatment, and this was further enhanced by let-7a overexpression. Finally, the present results demonstrated that the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was involved in the autophagy regulation by let-7a. In conclusion, the present study demonstrates that the neurotoxicity induced by Aβ1-40 is augmented by let-7a overexpression via regulation of autophagy, and the PI3K/Akt/mTOR signaling pathway also serves a function in this process.

  18. Application of heat treatment and dispersive strengthening concept in interlayer deposition to enhance diamond film adherence

    Energy Technology Data Exchange (ETDEWEB)

    Lin Chiiruey [Tatung Inst. of Technol., Taipei (Taiwan, Province of China). Dept. of Mech. Eng.; Kuo Chengtzu; Chang Rueyming [Institute of Materials Science and Engineering, National Chiao Tung University, 1001 Ta-Hsueh Road, Hsinchu 30050 (Taiwan, Province of China)

    1997-10-31

    Two different deposition processes were carried out to enhance adherence of diamond films on WC+3-5%Co substrate with Ti-Si as the interlayer. One process can be called two-step diamond deposition process. Another process can be called interlayer heat treatment process. Diamond films were deposited by a microwave plasma chemical vapor deposition system. Ti and Si interlayer are deposited by DC sputter and an E-gun, respectively. Film morphologies, interface structure and film quality were examined by SEM, XRD, Auger electron spectroscopy and Raman spectroscopy. The residual stresses and adhesion strengths of the films were determined by Raman spectroscopy and indentation adhesion testing, respectively. Comparing the regular one-step diamond deposition process with the present two different new processes, the average dP/dX values, which are a measure of the adherence of the film, are 354 kgf/mm, 494 kgf/mm and 787 kgf/mm, respectively. In other words, the interlayer heat treatment process gives the best film adherence on average. For the two-step diamond deposition process, the interlayer thickness and the percent diamond surface coverage of the first diamond deposition step are the main parameters, and there exists an optimum Ti thickness and percent diamond coverage for the best film adherence. The main contribution to better film adherence is not a large difference in residual stress, but is due to the following reasons. The interlayer heat treatment can transform amorphous Si to polycrystalline Si, and may form strong TiC and SiC bonding. The polycrystalline Si and the diamond particles from the first diamond deposition step can be an effective seeds to enhance diamond nucleation. (orig.) 11 refs.

  19. Adaptive responses to cefotaxime treatment in ESBL-producing Escherichia coli and the possible use of significantly regulated pathways as novel secondary targets

    DEFF Research Database (Denmark)

    Møller, Thea S. B.; Rau, Martin Holm; Bonde, Charlotte S

    2016-01-01

    The aim of the study was to determine how ESBL-producing Escherichia coli change the expression of metabolic and biosynthesis genes when adapting to inhibitory concentrations of cefotaxime. Secondly, it was investigated whether significantly regulated pathways constitute putative secondary targets......-fold). Inhibition and/or mutations in other genes that were significantly regulated, belonging to energy synthesis, purine synthesis, proline uptake or potassium uptake, also rendered the resistant bacteria more susceptible to cefotaxime. The results show that ESBL-producing E. coli adapt to treatment...

  20. What Teachers Think about Self-Regulated Learning: Investigating Teacher Beliefs and Teacher Behavior of Enhancing Students’ Self-Regulation

    OpenAIRE

    Dignath-van Ewijk, Charlotte; van der Werf, Greetje

    2012-01-01

    In order to foster self-regulated learning (SRL), teachers should provide students with learning strategies, as well as with constructivist learning environments that allow them to self-regulate their learning. These two components complement each other. When investigating teachers’ promotion of SRL, not only teacher behavior, but also teachers’ beliefs as well as their knowledge about SRL are relevant aspects to consider. Therefore, this study seeks to examine teachers’ knowledge and beliefs...