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Sample records for agonist enhances resistance

  1. Synthetic RORγt Agonists Enhance Protective Immunity.

    Science.gov (United States)

    Chang, Mi Ra; Dharmarajan, Venkatasubramanian; Doebelin, Christelle; Garcia-Ordonez, Ruben D; Novick, Scott J; Kuruvilla, Dana S; Kamenecka, Theodore M; Griffin, Patrick R

    2016-04-15

    The T cell specific RORγ isoform RORγt has been shown to be the key lineage-defining transcription factor to initiate the differentiation program of TH17 and TC17 cells, cells that have demonstrated antitumor efficacy. RORγt controls gene networks that enhance immunity including increased IL17 production and decreased immune suppression. Both synthetic and putative endogenous agonists of RORγt have been shown to increase the basal activity of RORγt enhancing TH17 cell proliferation. Here, we show that activation of RORγt using synthetic agonists drives proliferation of TH17 cells while decreasing levels of the immune checkpoint protein PD-1, a mechanism that should enhance antitumor immunity while blunting tumor associated adaptive immune resistance. Interestingly, putative endogenous agonists drive proliferation of TH17 cells but do not repress PD-1. These findings suggest that synthetic agonists of RORγt should activate TC17/TH17 cells (with concomitant reduction in the Tregs population), repress PD-1, and produce IL17 in situ (a factor associated with good prognosis in cancer). Enhanced immunity and blockage of immune checkpoints has transformed cancer treatment; thus such a molecule would provide a unique approach for the treatment of cancer. PMID:26785144

  2. Tomato PYR/PYL/RCAR abscisic acid receptors show high expression in root, differential sensitivity to the abscisic acid agonist quinabactin, and the capability to enhance plant drought resistance.

    Science.gov (United States)

    González-Guzmán, Miguel; Rodríguez, Lesia; Lorenzo-Orts, Laura; Pons, Clara; Sarrión-Perdigones, Alejandro; Fernández, Maria A; Peirats-Llobet, Marta; Forment, Javier; Moreno-Alvero, Maria; Cutler, Sean R; Albert, Armando; Granell, Antonio; Rodríguez, Pedro L

    2014-08-01

    Abscisic acid (ABA) plays a crucial role in the plant's response to both biotic and abiotic stress. Sustainable production of food faces several key challenges, particularly the generation of new varieties with improved water use efficiency and drought tolerance. Different studies have shown the potential applications of Arabidopsis PYR/PYL/RCAR ABA receptors to enhance plant drought resistance. Consequently the functional characterization of orthologous genes in crops holds promise for agriculture. The full set of tomato (Solanum lycopersicum) PYR/PYL/RCAR ABA receptors have been identified here. From the 15 putative tomato ABA receptors, 14 of them could be grouped in three subfamilies that correlated well with corresponding Arabidopsis subfamilies. High levels of expression of PYR/PYL/RCAR genes was found in tomato root, and some genes showed predominant expression in leaf and fruit tissues. Functional characterization of tomato receptors was performed through interaction assays with Arabidopsis and tomato clade A protein phosphatase type 2Cs (PP2Cs) as well as phosphatase inhibition studies. Tomato receptors were able to inhibit the activity of clade A PP2Cs differentially in an ABA-dependent manner, and at least three receptors were sensitive to the ABA agonist quinabactin, which inhibited tomato seed germination. Indeed, the chemical activation of ABA signalling induced by quinabactin was able to activate stress-responsive genes. Both dimeric and monomeric tomato receptors were functional in Arabidopsis plant cells, but only overexpression of monomeric-type receptors conferred enhanced drought resistance. In summary, gene expression analyses, and chemical and transgenic approaches revealed distinct properties of tomato PYR/PYL/RCAR ABA receptors that might have biotechnological implications. PMID:24863435

  3. beta-Adrenoceptor agonists enhance 5-hydroxytryptamine-mediated behavioural responses.

    OpenAIRE

    Cowen, P. J.; Grahame-Smith, D.G.; Green, A R; Heal, D. J.

    1982-01-01

    The beta-adrenoceptor agonists, salbutamol, terbutaline and clenbuterol, were investigated for their effect on 5-hydroxytryptamine-mediated (5-HT) hyperactivity. 2 The lipophilic beta-adrenoceptor agonist, clenbuterol (5 mg/kg) enhanced the behaviours induced by quipazine (25 mg/kg), including headweaving, forepaw treading and hind-limb abduction and thus increased automated activity recording. Clenbuterol (5 mg/kg) also enhanced the hyperactivity syndrome produced by the 5-HT agonist, 5-meth...

  4. Effects of inspiratory resistance, inhaled beta-agonists and histamine on canine tracheal blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, W.T.; Baile, E.M.; Brancatisano, A.; Pare, P.D.; Engel, L.A. (Dept. of Respiratory Medicine, Westmead Hospital, Westmead, NSW (Australia))

    1992-01-01

    Tracheobronchial blood flow is potentially important in asthma as it could either influence the clearance of mediators form the airways, thus affecting the duration and severity of bronchoispasm, or enhance oedema formation with a resultant increase in airflow obstruction. In anaesthetized dogs, spontaneously breathing via a tracheostomy, we investigated the effects of three interventions which are relevant to acute asthma attacks and could potentially influence blood flow and its distribution to the mucosa and remaining tissues of the trachea: (1) increased negative intrathoracic pressure swings (-25[+-]1 cmH[sub 2]O) induced by an inspiratory resistance; (2) variable inhaled doses of a beta-adrenoceptor-agonist (terbutaline); and (3) aerosolized histamine sufficient to produce a threefold increase in pulmonary resistance. Microspheres labelled with different radioisotopes were used to measure blood flow. Resistive breathing did not influence tracheobronchial blood flow. Following a large dose of terbutaline, mucosal blood flow (Qmb) increased by 50%. After inhaled histamine, Qmb reached 265% of the baseline value. We conclude that, whereas increased negative pressure swings do not influence tracheobronchial blood flow or its distribution, inhalation of aerosolized terbutaline, corresponding to a conventionally nebulized dose, increases mucosal blood flow. Our results also confirm that inhaled histamine, in a dose sufficient to produce moderate bronchoconstriction, increases tracheal mucosal blood flow in the area of deposition. (au).

  5. TLR9 agonist acts by different mechanisms synergizing with bevacizumab in sensitive and cetuximab-resistant colon cancer xenografts.

    Science.gov (United States)

    Damiano, Vincenzo; Caputo, Rosa; Garofalo, Sonia; Bianco, Roberto; Rosa, Roberta; Merola, Gerardina; Gelardi, Teresa; Racioppi, Luigi; Fontanini, Gabriella; De Placido, Sabino; Kandimalla, Ekambar R; Agrawal, Sudhir; Ciardiello, Fortunato; Tortora, Giampaolo

    2007-07-24

    Synthetic agonists of Toll-like receptor 9 (TLR9), a class of agents that induce specific immune response, exhibit antitumor activity and are currently being investigated in cancer patients. Intriguingly, their mechanisms of action on tumor growth and angiogenesis are still incompletely understood. We recently discovered that a synthetic agonist of TLR9, immune modulatory oligonucleotide (IMO), acts by impairing epidermal growth factor receptor (EGFR) signaling and potently synergizes with anti-EGFR antibody cetuximab in GEO human colon cancer xenografts, whereas it is ineffective in VEGF-overexpressing cetuximab-resistant GEO cetuximab-resistant (GEO-CR) tumors. VEGF is activated by EGFR, and its overexpression causes resistance to EGFR inhibitors. Therefore, we used IMO and the anti-VEGF antibody bevacizumab as tools to study IMO's role on EGFR and angiogenesis and to explore its therapeutic potential in GEO, LS174T, and GEO-CR cancer xenografts. We found that IMO enhances the antibody-dependent cell-mediated cytotoxicity (ADCC) activity of cetuximab, that bevacizumab has no ADCC, and IMO is unable to enhance it. Nevertheless, the IMO-plus-bevacizumab combination synergistically inhibits the growth of GEO and LS174T as well as of GEO-CR tumors, preceded by inhibition of signaling protein expression, microvessel formation, and human, but not murine, VEGF secretion. Moreover, IMO inhibited the growth, adhesion, migration, and capillary formation of VEGF-stimulated endothelial cells. The antitumor activity was irrespective of the TLR9 expression on tumor cells. These studies demonstrate that synthetic agonists of TLR9 interfere with growth and angiogenesis also by EGFR- and ADCC-independent mechanisms affecting endothelial cell functions and provide a strong rationale to combine IMO with bevacizumab and EGFR inhibitory drugs in colon cancer patients.

  6. Targeting the ABCG2-overexpressing multidrug resistant (MDR) cancer cells by PPARγ agonists

    Science.gov (United States)

    To, Kenneth K W; Tomlinson, Brian

    2013-01-01

    Background and Purpose Multidrug resistance (MDR), usually mediated by overexpression of efflux transporters such as P-gp, ABCG2 and/or MRP1, remains a major obstacle hindering successful cancer chemotherapy. There has been great interest in the development of inhibitors towards these transporters to circumvent resistance. However, since the inhibition of transporter is not specific to cancer cells, a decrease in the cytotoxic drug dosing may be needed to prevent excess toxicity, thus undermining the potential benefit brought about by a drug efflux inhibitor. The design of potent MDR modulators specific towards resistant cancer cells and devoid of drug-drug interactions will be needed to effect MDR reversal. Experimental Approach Recent evidence suggests that the PTEN/PI3K/Akt pathway may be exploited to alter ABCG2 subcellular localization, thereby circumventing MDR. Three PPARγ agonists (telmisartan, pioglitazone and rosiglitazone) that have been used in the clinics were tested for their effect on the PTEN/PI3K/Akt pathway and possible reversal of ABCG2-mediated drug resistance. Key Results The PPARγ agonists were found to be weak ABCG2 inhibitors by drug efflux assay. They were also shown to elevate the reduced PTEN expression in a resistant and ABCG2-overexpressing cell model, which inhibit the PI3K-Akt pathway and lead to the relocalization of ABCG2 from the plasma membrane to the cytoplasma, thus apparently circumventing the ABCG2-mediated MDR. Conclusions and Implications Since this PPARγ/PTEN/PI3K/Akt pathway regulating ABCG2 is only functional in drug-resistant cancer cells with PTEN loss, the PPARγ agonists identified may represent promising agents targeting resistant cells for MDR reversal. PMID:24032744

  7. Selective Human Estrogen Receptor Partial Agonists (ShERPAs) for Tamoxifen-Resistant Breast Cancer.

    Science.gov (United States)

    Xiong, Rui; Patel, Hitisha K; Gutgesell, Lauren M; Zhao, Jiong; Delgado-Rivera, Loruhama; Pham, Thao N D; Zhao, Huiping; Carlson, Kathryn; Martin, Teresa; Katzenellenbogen, John A; Moore, Terry W; Tonetti, Debra A; Thatcher, Gregory R J

    2016-01-14

    Almost 70% of breast cancers are estrogen receptor α (ERα) positive. Tamoxifen, a selective estrogen receptor modulator (SERM), represents the standard of care for many patients; however, 30-50% develop resistance, underlining the need for alternative therapeutics. Paradoxically, agonists at ERα such as estradiol (E2) have demonstrated clinical efficacy in patients with heavily treated breast cancer, although side effects in gynecological tissues are unacceptable. A drug that selectively mimics the actions of E2 in breast cancer therapy but minimizes estrogenic effects in other tissues is a novel, therapeutic alternative. We hypothesized that a selective human estrogen receptor partial agonist (ShERPA) at ERα would provide such an agent. Novel benzothiophene derivatives with nanomolar potency in breast cancer cell cultures were designed. Several showed partial agonist activity, with potency of 0.8-76 nM, mimicking E2 in inhibiting growth of tamoxifen-resistant breast cancer cell lines. Three ShERPAs were tested and validated in xenograft models of endocrine-independent and tamoxifen-resistant breast cancer, and in contrast to E2, ShERPAs did not cause significant uterine growth.

  8. Selective Human Estrogen Receptor Partial Agonists (ShERPAs) for Tamoxifen-Resistant Breast Cancer.

    Science.gov (United States)

    Xiong, Rui; Patel, Hitisha K; Gutgesell, Lauren M; Zhao, Jiong; Delgado-Rivera, Loruhama; Pham, Thao N D; Zhao, Huiping; Carlson, Kathryn; Martin, Teresa; Katzenellenbogen, John A; Moore, Terry W; Tonetti, Debra A; Thatcher, Gregory R J

    2016-01-14

    Almost 70% of breast cancers are estrogen receptor α (ERα) positive. Tamoxifen, a selective estrogen receptor modulator (SERM), represents the standard of care for many patients; however, 30-50% develop resistance, underlining the need for alternative therapeutics. Paradoxically, agonists at ERα such as estradiol (E2) have demonstrated clinical efficacy in patients with heavily treated breast cancer, although side effects in gynecological tissues are unacceptable. A drug that selectively mimics the actions of E2 in breast cancer therapy but minimizes estrogenic effects in other tissues is a novel, therapeutic alternative. We hypothesized that a selective human estrogen receptor partial agonist (ShERPA) at ERα would provide such an agent. Novel benzothiophene derivatives with nanomolar potency in breast cancer cell cultures were designed. Several showed partial agonist activity, with potency of 0.8-76 nM, mimicking E2 in inhibiting growth of tamoxifen-resistant breast cancer cell lines. Three ShERPAs were tested and validated in xenograft models of endocrine-independent and tamoxifen-resistant breast cancer, and in contrast to E2, ShERPAs did not cause significant uterine growth. PMID:26681208

  9. Control of Methicillin-Resistant Staphylococcus aureus Pneumonia Utilizing TLR2 Agonist Pam3CSK4.

    Directory of Open Access Journals (Sweden)

    Yi-Guo Chen

    Full Text Available The spread of methicillin-resistant Staphylococcus aureus (MRSA is a critical health issue that has drawn greater attention to the potential use of immunotherapy. Toll-like receptor 2 (TLR2, a pattern recognition receptor, is an essential component in host innate defense system against S. aureus infection. However, little is known about the innate immune response, specifically TLR2 activation, against MRSA infection. Here, we evaluate the protective effect and the mechanism of MRSA murine pneumonia after pretreatment with Pam3CSK4, a TLR2 agonist. We found that the MRSA-pneumonia mouse model, pretreated with Pam3CSK4, had reduced bacteria and mortality in comparison to control mice. As well, lower protein and mRNA levels of TNF-α, IL-1β and IL-6 were observed in lungs and bronchus of the Pam3CSK4 pretreatment group. Conversely, expression of anti-inflammatory cytokine IL-10, but not TGF-β, increased in Pam3CSK4-pretreated mice. Our additional studies showed that CXCL-2 and CXCL1, which are necessary for neutrophil recruitment, were less evident in the Pam3CSK4-pretreated group compared to control group, whereas the expression of Fcγ receptors (FcγⅠ/Ⅲ and complement receptors (CR1/3 increased in murine lungs. Furthermore, we found that increased survival and improved bacterial clearance were not a result of higher levels of neutrophil infiltration, but rather a result of enhanced phagocytosis and bactericidal activity of neutrophils in vitro and in vivo as well as increased robust oxidative activity and release of lactoferrin. Our cumulative findings suggest that Pam3CSK4 could be a novel immunotherapeutic candidate against MRSA pneumonia.

  10. Control of Methicillin-Resistant Staphylococcus aureus Pneumonia Utilizing TLR2 Agonist Pam3CSK4.

    Science.gov (United States)

    Chen, Yi-Guo; Zhang, Yong; Deng, Lin-Qiang; Chen, Hui; Zhang, Yu-Juan; Zhou, Nan-Jin; Yuan, Keng; Yu, Li-Zhi; Xiong, Zhang-Hua; Gui, Xiao-Mei; Yu, Yan-Rong; Wu, Xiao-Mu; Min, Wei-Ping

    2016-01-01

    The spread of methicillin-resistant Staphylococcus aureus (MRSA) is a critical health issue that has drawn greater attention to the potential use of immunotherapy. Toll-like receptor 2 (TLR2), a pattern recognition receptor, is an essential component in host innate defense system against S. aureus infection. However, little is known about the innate immune response, specifically TLR2 activation, against MRSA infection. Here, we evaluate the protective effect and the mechanism of MRSA murine pneumonia after pretreatment with Pam3CSK4, a TLR2 agonist. We found that the MRSA-pneumonia mouse model, pretreated with Pam3CSK4, had reduced bacteria and mortality in comparison to control mice. As well, lower protein and mRNA levels of TNF-α, IL-1β and IL-6 were observed in lungs and bronchus of the Pam3CSK4 pretreatment group. Conversely, expression of anti-inflammatory cytokine IL-10, but not TGF-β, increased in Pam3CSK4-pretreated mice. Our additional studies showed that CXCL-2 and CXCL1, which are necessary for neutrophil recruitment, were less evident in the Pam3CSK4-pretreated group compared to control group, whereas the expression of Fcγ receptors (FcγⅠ/Ⅲ) and complement receptors (CR1/3) increased in murine lungs. Furthermore, we found that increased survival and improved bacterial clearance were not a result of higher levels of neutrophil infiltration, but rather a result of enhanced phagocytosis and bactericidal activity of neutrophils in vitro and in vivo as well as increased robust oxidative activity and release of lactoferrin. Our cumulative findings suggest that Pam3CSK4 could be a novel immunotherapeutic candidate against MRSA pneumonia. PMID:26974438

  11. MUC-1 Tumor Antigen Agonist Epitopes for Enhancing T-cell Responses to Human Tumors | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    Scientists at NIH have identified 7 new agonist epitopes of the MUC-1 tumor associated antigen. Compared to their native epitope counterparts, peptides reflecting these agonist epitopes have been shown to enhance the generation of human tumor cells, which in turn have a greater ability to kill human tumor cells endogenously expressing the native MUC-1 epitope.

  12. nAChR agonist-induced cognition enhancement: integration of cognitive and neuronal mechanisms.

    Science.gov (United States)

    Sarter, Martin; Parikh, Vinay; Howe, William M

    2009-10-01

    The identification and characterization of drugs for the treatment of cognitive disorders has been hampered by the absence of comprehensive hypotheses. Such hypotheses consist of (a) a precisely defined cognitive operation that fundamentally underlies a range of cognitive abilities and capacities and, if impaired, contributes to the manifestation of diverse cognitive symptoms; (b) defined neuronal mechanisms proposed to mediate the cognitive operation of interest; (c) evidence indicating that the putative cognition enhancer facilitates these neuronal mechanisms; (d) and evidence indicating that the cognition enhancer facilitates cognitive performance by modulating these underlying neuronal mechanisms. The evidence on the neuronal and attentional effects of nAChR agonists, specifically agonists selective for alpha4beta2* nAChRs, has begun to support such a hypothesis. nAChR agonists facilitate the detection of signals by augmenting the transient increases in prefrontal cholinergic activity that are necessary for a signal to gain control over behavior in attentional contexts. The prefrontal microcircuitry mediating these effects include alpha4beta2* nAChRs situated on the terminals of thalamic inputs and the glutamatergic stimulation of cholinergic terminals via ionotropic glutamate receptors. Collectively, this evidence forms the basis for hypothesis-guided development and characterization of cognition enhancers.

  13. Differential effects of peroxisome proliferator-activated receptor agonists on doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells.

    Science.gov (United States)

    Yousefi, B; Samadi, N; Baradaran, B; Rameshknia, V; Shafiei-Irannejad, V; Majidinia, M; Targhaze, N; Zarghami, N

    2015-01-01

    P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in tumor cells is still a main obstacle for the chemotherapeutic treatment of cancers. Therefore, identification of safe and effective MDR reversing compounds with minimal adverse side effects is an important approach in the cancer treatment. Studies show that peroxisome proliferator-activated receptor (PPARs) ligands can inhibit cell growth in many cancers. Here, we investigated the effect of different PPAR agonists include fenofibrate, troglitazone and aleglitazar on doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells. The effects of doxorubicin (DOX) following treatment with PPAR agonists on cell viability were evaluated using MTT assay and the reversal fold (RF) values. Rhodamine123 (Rh123) assays were used to determine P-gp functioning. P-gp mRNA/protein expression was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analysis after incubation with troglitazone and aleglitazar. Our results showed that troglitazone and aleglitazar significantly enhanced the cytotoxicity of DOX and decreased the RF values in K562/DOX cells, however, no such results were found for fenofibrate. Troglitazone and aleglitazar significantly down regulated P-gp expression in K562/DOX cells; in addition, the present study revealed that aleglitazar elevated intracellular accumulation of Rh123in K562/DOX cells as short-term effects, which also contribute to the reversal of MDR. These findings show that troglitazone and especially aleglitazar exhibited potent effects in the reversal of P-gp-mediated MDR, suggesting that these compounds may be effective for combination therapy strategies and circumventing MDR in K562/DOX cells to other conventional chemotherapeutic drugs. PMID:26718439

  14. Neuroprotective and memory enhancing properties of a dual agonist of the FGF receptor and NCAM

    DEFF Research Database (Denmark)

    Enevoldsen, Maj N; Kochoyan, Artur; Jurgenson, Monika;

    2012-01-01

    subcutaneous administration, enhances long-term memory in normal mice and ameliorates memory deficit in mice with induced brain inflammation. Moreover, Enreptin reduces cognitive impairment and neuronal death induced by Aß25-35 in a rat model of Alzheimer's disease, and reduces the mortality rate and clinical...... NCAM. We demonstrate that this dual specificity agonist induces phosphorylation of FGFR and differentiation and survival of primary neurons in vitro, and that these effects are inhibited by abrogation of both NCAM and FGFR signaling pathways. Furthermore, Enreptin crosses the blood-brain barrier after...

  15. Dopamine agonist resistance-related endocan promotes angiogenesis and cells viability of prolactinomas.

    Science.gov (United States)

    Cai, Lin; Leng, Zhi Gen; Guo, Yu Hang; Lin, Shao Jian; Wu, Ze Rui; Su, Zhi Peng; Lu, Jiang Long; Wei, Li Fei; Zhuge, Qi Chuan; Jin, Kunlin; Wu, Zhe Bao

    2016-06-01

    Dopamine agonists (DAs) are the first-line treatment of prolactinomas. They function through the dopamine 2 receptor (D2R) in the tumor cells. Endocan, also called endothelial cell-specific molecule-1 (ESM1), has been described as a marker of neoangiogenesis. However, whether ESM1 promotes the resistance of prolactinomas to DA therapy is largely unknown. In our study, 25 patients with prolactinomas were divided into resistant- and sensitive- groups according to the clinical response to bromocriptine. We found that ESM1-microvessel density of resistant prolactinomas was significantly higher than that of sensitive prolactinomas (47.9 ± 11.6, n = 8, vs 13.1 ± 2.8, n = 17, p = 0.0006), indicating that ESM1 was a DA resistance-related gene. Immunostaining showed that ESM1 was expressed in tumor vessels and sporadic tumor cells, and ESM1 was overlapped with the Smooth Muscle Actin (SMA) and von Willebrand Factor (VWF) in the tumor vessels. Silencing of ESM1 markedly suppressed the viability of GH3 and MMQ cells in vitro, and furthermore, significantly increased the sensitivity of GH3 and MMQ cells to DA treatment. Additionally, silencing of ESM1 down-regulated the angiogenesis-associated genes, such as VEGFR2, FGF2, CD34, CD31, VWF, and EGFR. Knockdown of ESM1 decreased endothelial tube formation of HUVECs, and significantly increased the sensitivity of HUVECs to Avastin treatment. Therefore, we first demonstrate that DA resistance-related ESM1 promotes the angiogenesis and tumor cells growth of prolactinomas, suggesting that ESM1 may be a novel therapeutic target for prolactinomas. PMID:26662185

  16. FXR agonist INT-747 upregulates DDAH expression and enhances insulin sensitivity in high-salt fed Dahl rats.

    Directory of Open Access Journals (Sweden)

    Yohannes T Ghebremariam

    Full Text Available AIMS: Genetic and pharmacological studies have shown that impairment of the nitric oxide (NO synthase (NOS pathway is associated with hypertension and insulin-resistance (IR. In addition, inhibition of NOS by the endogenous inhibitor, asymmetric dimethylarginine (ADMA, may also result in hypertension and IR. On the other hand, overexpression of dimethylarginine dimethylaminohydrolase (DDAH, an enzyme that metabolizes ADMA, in mice is associated with lower ADMA, increased NO and enhanced insulin sensitivity. Since DDAH carries a farnesoid X receptor (FXR-responsive element, we aimed to upregulate its expression by an FXR-agonist, INT-747, and evaluate its effect on blood pressure and insulin sensitivity. METHODS AND RESULTS: In this study, we evaluated the in vivo effect of INT-747 on tissue DDAH expression and insulin sensitivity in the Dahl rat model of salt-sensitive hypertension and IR (Dahl-SS. Our data indicates that high salt (HS diet significantly increased systemic blood pressure. In addition, HS diet downregulated tissue DDAH expression while INT-747 protected the loss in DDAH expression and enhanced insulin sensitivity compared to vehicle controls. CONCLUSION: Our study may provide the basis for a new therapeutic approach for IR by modulating DDAH expression and/or activity using small molecules.

  17. PKCa Agonists Enhance the Protective Effect of Hyaluronic Acid on Nitric Oxide-Induced Apoptosis of Articular Chondrocytes in Vitro

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    Jian-lin Zhou

    2013-12-01

    The results may be showed that PKCa regulate the expresion of caspase-3, which contribute to the apoptosis of chondrocytes induced by NO. PKC α agonists enhance the protective effect of hyaluronic acid on nitric oxide-induced articular chondrocytes apoptosis.

  18. Multivalent porous silicon nanoparticles enhance the immune activation potency of agonistic CD40 antibody.

    Science.gov (United States)

    Gu, Luo; Ruff, Laura E; Qin, Zhengtao; Corr, Maripat; Hedrick, Stephen M; Sailor, Michael J

    2012-08-01

    One of the fundamental paradigms in the use of nanoparticles to treat disease is to evade or suppress the immune system in order to minimize systemic side effects and deliver sufficient nanoparticle quantities to the intended tissues. However, the immune system is the body's most important and effective defense against diseases. It protects the host by identifying and eliminating foreign pathogens as well as self-malignancies. Here we report a nanoparticle engineered to work with the immune system, enhancing the intended activation of antigen presenting cells (APCs). We show that luminescent porous silicon nanoparticles (LPSiNPs), each containing multiple copies of an agonistic antibody (FGK45) to the APC receptor CD40, greatly enhance activation of B cells. The cellular response to the nanoparticle-based stimulators is equivalent to a 30-40 fold larger concentration of free FGK45. The intrinsic near-infrared photoluminescence of LPSiNPs is used to monitor degradation and track the nanoparticles inside APCs.

  19. Enhanced radiation resistant fiber optics

    Science.gov (United States)

    Lyons, Peter B.; Looney, Larry D.

    1993-01-01

    A process for producing an optical fiber having enhanced radiation resitance is provided, the process including maintaining an optical fiber within a hydrogen-containing atmosphere for sufficient time to yield a hydrogen-permeated optical fiber having an elevated internal hydrogen concentration, and irradiating the hydrogen-permeated optical fiber at a time while the optical fiber has an elevated internal hydrogen concentration with a source of ionizing radiation. The radiation source is typically a cobalt-60 source and the fiber is pre-irradiated with a dose level up to about 1000 kilorads of radiation.

  20. An agonist of human complement fragment C5a enhances vaccine immunity against Coccidioides infection.

    Science.gov (United States)

    Hung, Chiung-Yu; Hurtgen, Brady J; Bellecourt, Michael; Sanderson, Sam D; Morgan, Edward L; Cole, Garry T

    2012-06-29

    Coccidioides is a fungal pathogen and causative agent of a human respiratory disease against which no clinical vaccine exists. In this study we evaluated a novel vaccine adjuvant referred to as EP67, which is a peptide agonist of the biologically active C-terminal region of human complement component C5a. The EP67 peptide was conjugated to live spores of an attenuated vaccine strain (ΔT) of Coccidioides posadasii. The non-conjugated ΔT vaccine provided partial protection to BALB/c mice against coccidioidomycosis. In this report we compared the protective efficacy of the ΔT-EP67 conjugate to the ΔT vaccine in BALB/c mice. Animals immunized subcutaneously with the ΔT-EP67 vaccine showed significant increase in survival and decrease in fungal burden over 75 days postchallenge. Increased pulmonary infiltration of dendritic cells and macrophages was observed on day 7 postchallenge but marked decrease in neutrophil numbers had occurred by 11 days. The reduced influx of neutrophils may have contributed to the observed reduction of inflammatory pathology. Mice immunized with the ΔT-EP67 vaccine also revealed enhanced expression of MHC II molecules on the surface of antigen presenting cells, and in vitro recall assays of immune splenocytes showed elevated Th1- and Th17-type cytokine production. The latter correlated with a marked increase in lung infiltration of IFN-γ- and IL-17-producing CD4(+) T cells. Elevated expression of T-bet and RORc transcription factors in ΔT-EP67-vaccinated mice indicated the promotion of Th1 and Th17 cell differentiation. Higher titers of Coccidioides antigen-specific IgG1 and IgG2a were detected in mice immunized with the EP67-conjugated versus the non-conjugated vaccine. These combined results suggest that the EP67 adjuvant enhances protective efficacy of the live vaccine by augmentation of T-cell immunity, especially through Th1- and Th17-mediated responses to Coccidioides infection.

  1. C333H, a novel PPARα/γ dual agonist, has beneficial effects on insulin resistance and lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    Cheng XU; Li-li WANG; Hong-ying LIU; Xing-bo ZHOU; Ying-lin CAO; Song LI

    2006-01-01

    Aim: To examine the effects of novel peroxisome proliferator-activated receptor (PPAR) α/γdual agonist C333H on insulin resistance and lipid metabolism.Methods: An established dual-luciferase reporter gene assay system was used in vitro to test the activity of C333H with respect to the transcription of human PPARα and PPARγ. A preadipocyte differentiation assay and reverse transcription-polymerase chain reaction were used to detect the functional activities of C333H. In db/db mice, the effects of C333H were investigated with respect to lowering of blood glucose and lipid levels. Results: C333H was determined to be a novel PPARα/γ dual agonist because it strongly induced luciferase activity on human PPARα and PPARγ, promoting the differentiation of preadipocytes to adipocytes, and functioning in upregulating the expression of some glucose and lipid metabolic target genes of the PPAR. In addition, C333H efficiently reduced blood lipid and glucose concentrations in db/db diabetic mice. Conclusion: C333H has dual action on both PPARα and PPARγ, and might be of interest for the amelioration of lipid metabolic disorders and insulin resistance associated with type 2 diabetes.

  2. A dual TLR agonist adjuvant enhances the immunogenicity and protective efficacy of the tuberculosis vaccine antigen ID93.

    Directory of Open Access Journals (Sweden)

    Mark T Orr

    Full Text Available With over eight million cases of tuberculosis each year there is a pressing need for the development of new vaccines against Mycobacterium tuberculosis. Subunit vaccines consisting of recombinant proteins are an attractive vaccine approach due to their inherent safety compared to attenuated live vaccines and the uniformity of manufacture. Addition of properly formulated TLR agonist-containing adjuvants to recombinant protein vaccines enhances the antigen-specific CD4(+ T cell response characterized by IFN-γ and TNF, both of which are critical for the control of TB. We have developed a clinical stage vaccine candidate consisting of a recombinant fusion protein ID93 adjuvanted with the TLR4 agonist GLA-SE. Here we examine whether ID93+GLA-SE can be improved by the addition of a second TLR agonist. Addition of CpG containing DNA to ID93+GLA-SE enhanced the magnitude of the multi-functional TH1 response against ID93 characterized by co-production of IFN-γ, TNF, and IL-2. Addition of CpG also improved the protective efficacy of ID93+GLA-SE. Finally we demonstrate that this adjuvant synergy between GLA and CpG is independent of TRIF signaling, whereas TRIF is necessary for the adjuvant activity of GLA-SE in the absence of CpG.

  3. Resistance exercise enhances cognitive function in mouse.

    Science.gov (United States)

    Suijo, K; Inoue, S; Ohya, Y; Odagiri, Y; Takamiya, T; Ishibashi, H; Itoh, M; Fujieda, Y; Shimomitsu, T

    2013-04-01

    Physical exercise has been shown to increase adult neurogenesis in the hippocampus and to enhance synaptic plasticity. It has been demonstrated that these neuroprotective effects can be observed following aerobic exercise. However, it remains unknown whether plasticity molecules, such as brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB), are expressed in the hippocampus following resistance exercise. We applied voluntary progressive-resistance wheel exercise (RE) for 14 days, and measured BDNF and CREB in the hippocampus. The Morris water maze was also performed to estimate learning and memory. Furthermore, we measured RE effects on mammalian target of rapamycin (mTOR) and 70-kDa ribosomal protein S6 kinase (p70S6K) mediating muscle protein synthesis in the soleus. As a result, we found that RE enhanced cognition and elevated BDNF and CREB expressions in the hippocampus. Also, RE activated the mTOR-p70S6K signaling pathway in the soleus. We found that phosphorylated mTOR and p70S6K were significantly positively correlated with BDNF expression. Our results indicated that resistance exercise drove the protein synthesis signaling pathway in the soleus and enhanced hippocampal synaptic plasticity-related molecules. These results suggest the beneficial effects of resistance exercise on cognitive function. PMID:23041964

  4. Subtype-selective nicotinic acetylcholine receptor agonists enhance the responsiveness to citalopram and reboxetine in the mouse forced swim test.

    Science.gov (United States)

    Andreasen, Jesper T; Nielsen, Elsebet Ø; Christensen, Jeppe K; Olsen, Gunnar M; Peters, Dan; Mirza, Naheed R; Redrobe, John P

    2011-10-01

    Nicotine increases serotonergic and noradrenergic neuronal activity and facilitates serotonin and noradrenaline release. Accordingly, nicotine enhances antidepressant-like actions of reuptake inhibitors selective for serotonin or noradrenaline in the mouse forced swim test and the mouse tail suspension test. Both high-affinity α4β2 and low-affinity α7 nicotinic acetylcholine receptor subtypes are implicated in nicotine-mediated release of serotonin and noradrenaline. The present study therefore investigated whether selective agonism of α4β2 or α7 nicotinic acetylcholine receptors would affect the mouse forced swim test activity of two antidepressants with distinct mechanisms of action, namely the selective serotonin reuptake inhibitor citalopram and the noradrenaline reuptake inhibitor reboxetine. Subthreshold and threshold doses of citalopram (3 and 10 mg/kg) or reboxetine (10 and 20 mg/kg) were tested alone and in combination with the novel α4β2-selective partial nicotinic acetylcholine receptor agonist, NS3956 (0.3 and 1.0 mg/kg) or the α7-selective nicotinic acetylcholine receptor agonist, PNU-282987 (10 and 30 mg/kg). Alone, NS3956 and PNU-282987 were devoid of activity in the mouse forced swim test, but both 1.0 mg/kg NS3956 and 30 mg/kg PNU-282987 enhanced the effect of citalopram and also reboxetine. The data suggest that the activity of citalopram and reboxetine in the mouse forced swim test can be enhanced by agonists at either α4β2 or α7 nicotinic acetylcholine receptors, suggesting that both nicotinic acetylcholine receptor subtypes may be involved in the nicotine-enhanced action of antidepressants.

  5. Synthetic FXR Agonist GW4064 Prevents Diet-induced Hepatic Steatosis and Insulin Resistance

    OpenAIRE

    MA, YONGJIE; Huang, Yixuan; Yan, Linna; Gao, Mingming; Liu, Dexi

    2013-01-01

    The nuclear receptor farnesoid X receptor (FXR), an endogenous sensor for bile acids, plays an important role in cholesterol, lipid and carbohydrate metabolism. The objective of this study is to examine the effect of FXR activation on diet-induced obesity and hepatic steatosis. Activation of FXR by its synthetic agonist, 3-[2-[2-Chloro-4-[[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]benzoic acid (GW4064), suppressed weight gain in C57BL/6 mice fed with either ...

  6. Strength gradient enhances fatigue resistance of steels

    Science.gov (United States)

    Ma, Zhiwei; Liu, Jiabin; Wang, Gang; Wang, Hongtao; Wei, Yujie; Gao, Huajian

    2016-02-01

    Steels are heavily used in infrastructure and the transportation industry, and enhancing their fatigue resistance is a major challenge in materials engineering. In this study, by introducing a gradient microstructure into 304 austenitic steel, which is one of the most widely used types of stainless steel, we show that a strength gradient substantially enhances the fatigue life of the material. Pre-notched samples with negative strength gradients in front of the notch’s tip endure many more fatigue cycles than do samples with positive strength gradients during the crack initiation stage, and samples with either type of gradient perform better than do gradient-free samples with the same average yield strength. However, as a crack grows, samples with positive strength gradients exhibit better resistance to fatigue crack propagation than do samples with negative gradients or no gradient. This study demonstrates a simple and promising strategy for using gradient structures to enhance the fatigue resistance of materials and complements related studies of strength and ductility.

  7. Treating enhanced GABAergic inhibition in Down syndrome: use of GABA α5-selective inverse agonists.

    Science.gov (United States)

    Martínez-Cué, Carmen; Delatour, Benoît; Potier, Marie-Claude

    2014-10-01

    Excess inhibition in the brain of individuals carrying an extra copy of chromosome 21 could be responsible for cognitive deficits observed throughout their lives. A change in the excitatory/inhibitory balance in adulthood would alter synaptic plasticity, potentially triggering learning and memory deficits. γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mature central nervous system and binds to GABAA receptors, opens a chloride channel, and reduces neuronal excitability. In this review we discuss methods to alleviate neuronal inhibition in a mouse model of Down syndrome, the Ts65Dn mouse, using either an antagonist (pentylenetetrazol) or two different inverse agonists selective for the α5-subunit containing receptor. Both inverse agonists, which reduce inhibitory GABAergic transmission, could rescue learning and memory deficits in Ts65Dn mice. We also discuss safety issues since modulation of the excitatory-inhibitory balance to improve cognition without inducing seizures remains particularly difficult when using GABA antagonists.

  8. Sphingosine-1-Phosphate Receptor-1 Selective Agonist Enhances Collateral Growth and Protects against Subsequent Stroke.

    Directory of Open Access Journals (Sweden)

    Masahiko Ichijo

    Full Text Available Collateral growth after acute occlusion of an intracranial artery is triggered by increasing shear stress in preexisting collateral pathways. Recently, sphingosine-1-phosphate receptor-1 (S1PR1 on endothelial cells was reported to be essential in sensing fluid shear stress. Here, we evaluated the expression of S1PR1 in the hypoperfused mouse brain and investigated the effect of a selective S1PR1 agonist on leptomeningeal collateral growth and subsequent ischemic damage after focal ischemia.In C57Bl/6 mice (n = 133 subjected to unilateral common carotid occlusion (CCAO and sham surgery. The first series examined the time course of collateral growth, cell proliferation, and S1PR1 expression in the leptomeningeal arteries after CCAO. The second series examined the relationship between pharmacological regulation of S1PR1 and collateral growth of leptomeningeal anastomoses. Animals were randomly assigned to one of the following groups: LtCCAO and daily intraperitoneal (i.p. injection for 7 days of an S1PR1 selective agonist (SEW2871, 5 mg/kg/day; sham surgery and daily i.p. injection for 7 days of SEW2871 after surgery; LtCCAO and daily i.p. injection for 7 days of SEW2871 and an S1PR1 inverse agonist (VPC23019, 0.5 mg/kg; LtCCAO and daily i.p. injection of DMSO for 7 days after surgery; and sham surgery and daily i.p. injection of DMSO for 7 days. Leptomeningeal anastomoses were visualized 14 days after LtCCAO by latex perfusion method, and a set of animals underwent subsequent permanent middle cerebral artery occlusion (pMCAO 7 days after the treatment termination. Neurological functions 1 hour, 1, 4, and 7 days and infarction volume 7 days after pMCAO were evaluated.In parallel with the increase in S1PR1 mRNA levels, S1PR1 expression colocalized with endothelial cell markers in the leptomeningeal arteries, increased markedly on the side of the CCAO, and peaked 7 days after CCAO. Mitotic cell numbers in the leptomeningeal arteries increased after

  9. Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes.

    Science.gov (United States)

    Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F; Fuxe, Kjell

    2014-01-01

    Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor-receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists.

  10. Experimental Procedures for Demonstration of MicroRNA Mediated Enhancement of Functional Neuroprotective Effects of Estrogen Receptor Agonists.

    Science.gov (United States)

    Chakrabarti, Mrinmay; Ray, Swapan K

    2016-01-01

    Protection of motoneurons is an important therapeutic goal in the treatment of neurological disorders. Recent reports have suggested that specific microRNAs (miRs) could modulate the expression of particular proteins for significant alterations in the pathogenesis of different neurological disorders. Thus, combination of overexpression of a specific neuroprotective miR and treatment with a neuroprotective agent could be a novel strategy for functional protection of motoneurons. The protocols described herein demonstrate that miR-7-1, a neuroprotective miR, can enhance the functional neuroprotective effects of estrogen receptor agonists such as 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT), Way 200070 (WAY), and estrogen (E2) in preventing apoptosis in A23187 calcium ionophore (CI) exposed VSC4.1 motoneurons. This article describes the protocols for the cell viability assay, transfection of VSC4.1 motoneurons with miRs, Annexin V/propidium iodide staining for apoptosis, Western blotting, patch-clamp recording of whole-cell membrane potential, and JC-1 staining for detection of mitochondrial membrane potential. Taken together, these protocols are used to demonstrate that miR-7-1 caused significant enhancement of the efficacy of estrogen receptor agonists for functional neuroprotection in VSC4.1 motoneurons. PMID:26585150

  11. Glucagon and a glucagon-GLP-1 dual-agonist increases cardiac performance with different metabolic effects in insulin-resistant hearts

    DEFF Research Database (Denmark)

    Axelsen, Lene Nygaard; Keung, Wendy; Pedersen, Henrik D;

    2012-01-01

    BACKGROUND AND PURPOSE The prevalence of heart disease continues to rise, particularly in subjects with insulin resistance (IR), and improved therapies for these patients is an important challenge. In this study we evaluated cardiac function and energy metabolism in IR JCR:LA-cp rat hearts before...... state of IR hearts, glucagon-GLP-1 dual-agonist ZP2495 appeared to preserve it. Therefore, a glucagon-GLP-1 dual-agonist may be beneficial compared with glucagon alone in the treatment of severe heart failure or cardiogenic shock in subjects with IR....

  12. [Dmt(1)]DALDA analogues with enhanced μ opioid agonist potency and with a mixed μ/κ opioid activity profile.

    Science.gov (United States)

    Bai, Longxiang; Li, Ziyuan; Chen, Jiajia; Chung, Nga N; Wilkes, Brian C; Li, Tingyou; Schiller, Peter W

    2014-04-01

    Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity, were prepared by replacing Phe(3) with various 2',6'-dialkylated Phe analogues, including 2',6'-dimethylphenylalanine (Dmp), 2',4',6'-trimethylphenylalanine (Tmp), 2'-isopropyl-6'-methylphenylalanine (Imp) and 2'-ethyl-6'-methylphenylalanine (Emp), or with the bulky amino acids 3'-(1-naphthyl)alanine (1-Nal), 3'-(2-naphthyl)alanine (2-Nal) or Trp. Several compounds showed significantly increased μ agonist potency, retained μ receptor selectivity and are of interest as drug candidates for neuropathic pain treatment. Surprisingly, the Dmp(3)-, Imp(3)-, Emp(3)- and 1-Nal(3)-containing analogues showed much increased κ receptor binding affinity and had mixed μ/κ properties. In these cases, molecular dynamics studies indicated conformational preorganization of the unbound peptide ligands due to rotational restriction around the C(β)C(γ) bond of the Xxx(3) residue, in correlation with the observed κ receptor binding enhancement. Compounds with a mixed μ/κ opioid activity profile are known to have therapeutic potential for treatment of cocaine abuse.

  13. CF101, An Agonist to the A3 Adenosine Receptor, Enhances the Chemotherapeutic Effect of 5-Fluorouracil in a Colon Carcinoma Murine Model

    Directory of Open Access Journals (Sweden)

    Sara Bar-Yehuda

    2005-01-01

    Full Text Available NF-κB and the upstream kinase PKB/Akt are highly expressed in chemoresistance tumor cells and may hamper the apoptotic pathway. CF101, a specific agonist to the A3 adenosine receptor, inhibits the development of colon carcinoma growth in cell cultures and xenograft murine models. Because CF101 has been shown to downregulate PKB/Akt and NF-κB protein expression level, we presumed that its combination with chemotherapy will enhance the antitumor effect of the cytotoxic drug. In this study, we utilized 3-[4,5Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT and colony formation assays and a colon carcinoma xenograft model. It has been shown that a combined treatment of CF101 and 5-fluorouracil (5-FU enhanced the cytotoxic effect of the latter on HCT-116 human colon carcinoma growth. Downregulation of PKB/Akt, NF-κB, and cyclin D1, and upregulation of caspase-3 protein expression level were observed in cells and tumor lesions on treatment with a combination of CF101 and 5-FU. Moreover, in mice treated with the combined therapy, myelotoxicity was prevented as was evidenced by normal white blood cell and neutrophil counts. These results show that CF101 potentiates the cytotoxic effect of 5-FU, thus preventing drug resistance. The myeloprotective effect of CF101 suggests its development as an add-on treatment to 5-FU.

  14. The glucagon-like peptide 1 receptor agonist enhances intrinsic peroxisome proliferator-activated receptor γ activity in endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Onuma, Hirohisa; Inukai, Kouichi, E-mail: kinukai@ks.kyorin-u.ac.jp; Kitahara, Atsuko; Moriya, Rie; Nishida, Susumu; Tanaka, Toshiaki; Katsuta, Hidenori; Takahashi, Kazuto; Sumitani, Yoshikazu; Hosaka, Toshio; Ishida, Hitoshi

    2014-08-22

    Highlights: • PPARγ activation was involved in the GLP-1-mediated anti-inflammatory action. • Exendin-4 enhanced endogenous PPARγ transcriptional activity in HUVECs. • H89, a PKA inhibitor, abolished GLP-1-induced PPARγ enhancement. • The anti-inflammatory effects of GLP-1 may be explained by PPARγ activation. - Abstract: Recent studies have suggested glucagon-like peptide-1 (GLP-1) signaling to exert anti-inflammatory effects on endothelial cells, although the precise underlying mechanism remains to be elucidated. In the present study, we investigated whether PPARγ activation is involved in the GLP-1-mediated anti-inflammatory action on endothelial cells. When we treated HUVEC cells with 0.2 ng/ml exendin-4, a GLP-1 receptor agonist, endogenous PPARγ transcriptional activity was significantly elevated, by approximately 20%, as compared with control cells. The maximum PPARγ activity enhancing effect of exendin-4 was observed 12 h after the initiation of incubation with exendin-4. As H89, a PKA inhibitor, abolished GLP-1-induced PPARγ enhancement, the signaling downstream from GLP-1 cross-talk must have been involved in PPARγ activation. In conclusion, our results suggest that GLP-1 has the potential to induce PPARγ activity, partially explaining the anti-inflammatory effects of GLP-1 on endothelial cells. Cross-talk between GLP-1 signaling and PPARγ activation would have major impacts on treatments for patients at high risk for cardiovascular disease.

  15. Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?

    DEFF Research Database (Denmark)

    Schwartz, Thue W; Holst, Birgitte

    2007-01-01

    Many small-molecule agonists also display allosteric properties. Such ago-allosteric modulators act as co-agonists, providing additive efficacy--instead of partial antagonism--and they can affect--and often improve--the potency of the endogenous agonist. Surprisingly, the apparent binding sites...... different binding modes. In another, dimeric, receptor scenario, the endogenous agonist binds to one protomer while the ago-allosteric modulator binds to the other, 'allosteric' protomer. It is suggested that testing for ago-allosteric properties should be an integral part of the agonist drug discovery...... process because a compound that acts with--rather than against--the endogenous agonist could be an optimal agonist drug....

  16. Resistance to dopamine agonists and somatostatin analogues in pituitary tumors: focus on cytoskeleton involvement

    Directory of Open Access Journals (Sweden)

    Erika ePeverelli

    2015-12-01

    Full Text Available Pituitary tumors, that origin from excessive proliferation of a specific subtype of pituitary cell, are mostly benign tumors, but may cause significant morbidity in affected patients, including visual and neurologic manifestations from mass-effect, or endocrine syndromes caused by hormone hypersecretion. Dopamine (DA receptor DRD2 and somatostatin (SS receptors (SSTRs represent the main targets of pharmacological treatment of pituitary tumors since they mediate inhibitory effects on both hormone secretion and cell proliferation, and their expression is retained by most of these tumors. Although long acting DA and SS analogs are currently used in the treatment of prolactin (PRL- and growth hormone (GH-secreting pituitary tumors, respectively, clinical practice indicates a great variability in the frequency and entity of favourable responses. The molecular basis of the pharmacological resistance are still poorly understood, and several potential molecular mechanisms have been proposed, including defective expression or genetic alterations of DRD2 and SSTRs, or an impaired signal transduction. Recently, a role for cytoskeleton protein filamin A (FLNA in DRD2 and SSTRs receptors expression and signalling in PRL- and GH- secreting tumors, respectively, has been demonstrated, first revealing a link between FLNA expression and responsiveness of pituitary tumors to pharmacological therapy. This review provides an overview of the known molecular events involved in SS and DA resistance, focusing on the role played by FLNA.

  17. Stimulation of a Gs-like G protein in the osteoclast inhibits bone resorption but enhances tartrate-resistant acid phosphatase secretion.

    Science.gov (United States)

    Moonga, B S; Pazianas, M; Alam, A S; Shankar, V S; Huang, C L; Zaidi, M

    1993-01-29

    Previous studies have demonstrated that G-protein agonists induce quiescence (Q effect) or retraction (R effect) in isolated osteoclasts. We now report the functional effects of such agonists on osteoclastic bone resorption and enzyme release. Exposure of osteoclasts to tetrafluoro-aluminate anions (AlF4-), a universal G protein stimulator, resulted in a marked concentration-dependent inhibition of bone resorption. This was associated with a dramatic increase in the secretion of the osteoclast-specific enzyme, tartrate-resistant acid phosphatase (TRAP). Cholera toxin, a Gs stimulator and a selective Q effect agonist, similarly abolished bone resorption and enhanced TRAP secretion. In contrast, pertussis toxin, a Gi inhibitor and a selective R effect agonist, inhibited bone resorption significantly, but slightly reduced enzyme release. The results suggest an involvement of a Gs-like G protein in TRAP secretion from the osteoclast, possibly through a cyclic AMP-dependent mechanism.

  18. Dopamine D3 receptor-preferring agonist enhances the subjective effects of cocaine in humans.

    Science.gov (United States)

    Newton, Thomas F; Haile, Colin N; Mahoney, James J; Shah, Ravi; Verrico, Christopher D; De La Garza, Richard; Kosten, Thomas R

    2015-11-30

    Pramipexole is a D3 dopamine receptor-preferring agonist indicated for the treatment of Parkinson disease. Studies associate pramipexole with pathological gambling and impulse control disorders suggesting a role for D3 receptors in reinforcement processes. Clinical studies showed pramipexole decreased cocaine craving and reversed central deficits in individuals with cocaine use disorder. Preclinical studies have shown acute administration of pramipexole increases cocaine's reinforcing effects whereas other reports suggest chronic pramipexole produces tolerance to cocaine. In a randomized, double-blind, placebo-controlled study we examined the impact of pramipexole treatment on the subjective effects produced by cocaine in volunteers with cocaine use disorder. Volunteers received pramipexole titrated up to 3.0mg/d or placebo over 15 days. Participants then received intravenous cocaine (0, 20 and 40mg) on day 15. Cardiovascular and subjective effects were obtained with visual analog scales at time points across the session. Pramipexole alone increased peak heart rate following saline and diastolic blood pressure following cocaine. Pramipexole produced upwards of two-fold increases in positive subjective effects ratings following cocaine. These results indicate that chronic D3 receptor activation increases the subjective effects of cocaine in humans. Caution should be used when prescribing pramipexole to patients that may also use cocaine. PMID:26239766

  19. The opposite effect of a 5-HT1B receptor agonist on 5-HT synthesis, as well as its resistant counterpart, in an animal model of depression

    OpenAIRE

    Skelin, Ivan; Kovačević, Tomislav; Sato, Hiroki; Diksic, Mirko

    2012-01-01

    Flinders Sensitive Line (FSL) rat is as an animal model of depression with altered parameters of the serotonergic (5-HT) system function (5-HT synthesis rates, tissue concentrations, release, receptor density and affinity), as well as an altered sensitivity of these parameters to different 5-HT based antidepressants. The effects of acute and chronic treatments with the 5-HT1B agonist, CP-94253 on 5-HT synthesis, in the FSL rats and the Flinders Resistant Line (FRL) controls were measured usin...

  20. PPAR agonist-induced reduction of Mcp1 in atherosclerotic plaques of obese, insulin-resistant mice depends on adiponectin-induced Irak3 expression.

    Directory of Open Access Journals (Sweden)

    Maarten Hulsmans

    Full Text Available Synthetic peroxisome proliferator-activated receptor (PPAR agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate and a PPARγ agonist (rosiglitazone on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO were treated with fenofibrate, rosiglitazone or placebo for 12 weeks. Only rosiglitazone improved adipocyte function, restored insulin sensitivity, and inhibited atherosclerosis by decreasing lipid-loaded macrophages. In addition, it increased interleukin-1 receptor-associated kinase-3 (Irak3 and decreased monocyte chemoattractant protein-1 (Mcp1 expressions, indicative of a switch from M1 to M2 macrophages. The differences between fenofibrate and rosiglitazone were independent of Pparγ expression. In bone marrow-derived macrophages (BMDM, we identified the rosiglitazone-associated increase in adiponectin as cause of the increase in Irak3. Interestingly, the deletion of Irak3 in BMDM (IRAK3(-/- BMDM resulted in activation of the canonical NFκB signaling pathway and increased Mcp1 protein secretion. Rosiglitazone could not decrease the elevated Mcp1 secretion in IRAK3(-/- BMDM directly and fenofibrate even increased the secretion, possibly due to increased mitochondrial reactive oxygen species production. Furthermore, aortic extracts of high-fat insulin-resistant LDL-receptor deficient mice, with lower adiponectin and Irak3 and higher Mcp1, showed accelerated atherosclerosis. In aggregate, our results emphasize an interaction between PPAR agonist-mediated increase in adiponectin and macrophage-associated Irak3 in the protection against atherosclerosis by PPAR agonists.

  1. PPAR Agonist-Induced Reduction of Mcp1 in Atherosclerotic Plaques of Obese, Insulin-Resistant Mice Depends on Adiponectin-Induced Irak3 Expression

    Science.gov (United States)

    Arnould, Thierry; Tsatsanis, Christos; Holvoet, Paul

    2013-01-01

    Synthetic peroxisome proliferator-activated receptor (PPAR) agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate) and a PPARγ agonist (rosiglitazone) on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO) were treated with fenofibrate, rosiglitazone or placebo for 12 weeks. Only rosiglitazone improved adipocyte function, restored insulin sensitivity, and inhibited atherosclerosis by decreasing lipid-loaded macrophages. In addition, it increased interleukin-1 receptor-associated kinase-3 (Irak3) and decreased monocyte chemoattractant protein-1 (Mcp1) expressions, indicative of a switch from M1 to M2 macrophages. The differences between fenofibrate and rosiglitazone were independent of Pparγ expression. In bone marrow-derived macrophages (BMDM), we identified the rosiglitazone-associated increase in adiponectin as cause of the increase in Irak3. Interestingly, the deletion of Irak3 in BMDM (IRAK3−/− BMDM) resulted in activation of the canonical NFκB signaling pathway and increased Mcp1 protein secretion. Rosiglitazone could not decrease the elevated Mcp1 secretion in IRAK3−/− BMDM directly and fenofibrate even increased the secretion, possibly due to increased mitochondrial reactive oxygen species production. Furthermore, aortic extracts of high-fat insulin-resistant LDL-receptor deficient mice, with lower adiponectin and Irak3 and higher Mcp1, showed accelerated atherosclerosis. In aggregate, our results emphasize an interaction between PPAR agonist-mediated increase in adiponectin and macrophage-associated Irak3 in the protection against atherosclerosis by PPAR agonists. PMID:23620818

  2. Autoantibodies enhance agonist action and binding to cardiac muscarinic receptors in chronic Chagas' disease.

    Science.gov (United States)

    Hernandez, Ciria C; Nascimento, Jose H; Chaves, Elen A; Costa, Patricia C; Masuda, Masako O; Kurtenbach, Eleonora; Campos DE Carvalho, Antonio C; Gimenez, Luis E

    2008-01-01

    Chronic Chagasic patient immunoglobulins (CChP-IgGs) recognize an acidic amino acid cluster at the second extracellular loop (el2) of cardiac M(2)-muscarinic acetylcholine receptors (M(2)AChRs). These residues correspond to a common binding site for various allosteric agents. We characterized the nature of the M(2)AChR/CChP-IgG interaction in functional and radioligand binding experiments applying the same mainstream strategies previously used for the characterization of other allosteric agents. Dose-response curves of acetylcholine effect on heart rate were constructed with data from isolated heart experiments in the presence of CChP or normal blood donor (NBD) sera. In these experiments, CChP sera but not NBD sera increased the efficacy of agonist action by augmenting the onset of bradyarrhythmias and inducing a Hill slope of 2.5. This effect was blocked by gallamine, an M(2)AChR allosteric antagonist. Correspondingly, CChP-IgGs increased acetylcholine affinity twofold and showed negative cooperativity for [(3)H]-N-methyl scopolamine ([(3)H]-NMS) in allosterism binding assays. A peptide corresponding to the M(2)AChR-el2 blocked this effect. Furthermore, dissociation assays showed that the effect of gallamine on the [(3)H]-NMS off-rate was reverted by CChP-IgGs. Finally, concentration-effect curves for the allosteric delay of W84 on [(3)H]-NMS dissociation right shifted from an IC(50) of 33 nmol/L to 78 nmol/L, 992 nmol/L, and 1670 nmol/L in the presence of 6.7 x 10(- 8), 1.33 x 10(- 7), and 2.0 x 10(- 7) mol/L of anti-el2 affinity-purified CChP-IgGs. Taken together, these findings confirmed a competitive interplay of these ligands at the common allosteric site and revealed the novel allosteric nature of the interaction of CChP-IgGs at the M(2)AChRs as a positive cooperativity effect on acetylcholine action. PMID:18702010

  3. Autoantibodies Enhance Agonist Action and Binding to Cardiac Muscarinic Receptors in Chronic Chagas’ Disease

    Science.gov (United States)

    Hernández, Ciria C.; Nascimento, José H.; Chaves, Elen A.; Costa, Patrícia C.; Masuda, Masako O.; Kurtenbach, Eleonora; Campos de Carvalho, Antônio C.; Giménez, Luis E.

    2009-01-01

    Chronic Chagasic patient immunoglobulins (CChP-IgGs) recognize an acidic amino acid cluster at the second extracellular loop (el2) of cardiac M2-muscarinic acetylcholine receptors (M2AChRs). These residues correspond to a common binding site for various allosteric agents. We characterized the nature of the M2AChR/CChP-IgG interaction in functional and radioligand binding experiments applying the same mainstream strategies previously used for the characterization of other allosteric agents. Dose-response curves of acetylcholine effect on heart rate were constructed with data from isolated heart experiments in the presence of CChP or normal blood donor (NBD) sera. In these experiments, CChP sera but not NBD sera increased the efficacy of agonist action by augmenting the onset of bradyarrhythmias and inducing a Hill slope of 2.5. This effect was blocked by gallamine, an M2AChR allosteric antagonist. Correspondingly, CChP-IgGs increased acetylcholine affinity twofold and showed negative cooperativity for [3H]-N-methyl scopolamine ([3H]-NMS) in allosterism binding assays. A peptide corresponding to the M2AChR-el2 blocked this effect. Furthermore, dissociation assays showed that the effect of gallamine on the [3H]-NMS off-rate was reverted by CChP-IgGs. Finally, concentration-effect curves for the allosteric delay of W84 on [3H]-NMS dissociation right shifted from an IC50 of 33 nmol/L to 78 nmol/L, 992 nmol/L, and 1670 nmol/L in the presence of 6.7 × 10−8, 1.33 × 10−7, and 2.0 × 10−7 mol/L of anti-el2 affinity-purified CChP-IgGs. Taken together, these findings confirmed a competitive interplay of these ligands at the common allosteric site and revealed the novel allosteric nature of the interaction of CChP-IgGs at the M2AChRs as a positive cooperativity effect on acetylcholine action. PMID:18702010

  4. Enhancement of Mucosal Immunogenicity of Viral Vectored Vaccines by the NKT Cell Agonist Alpha-Galactosylceramide as Adjuvant

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    2014-10-01

    Full Text Available Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of alpha-galactosylceramide (α-GalCer, a synthetic glycolipid agonist of natural killer T (NKT cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors.

  5. X-ray Crystal Structure of the Novel Enhanced-Affinity Glucocorticoid Agonist Fluticasone Furoate in the Glucocorticoid Receptor−Ligand Binding Domain

    Energy Technology Data Exchange (ETDEWEB)

    Biggadike, Keith; Bledsoe, Randy K.; Hassell, Anne M.; Kirk, Barrie E.; McLay, Iain M.; Shewchuk, Lisa M.; Stewart, Eugene L. (GSKNC); (GSK)

    2008-07-08

    An X-ray crystal structure is reported for the novel enhanced-affinity glucocorticoid agonist fluticasone furoate (FF) in the ligand binding domain of the glucocorticoid receptor. Comparison of this structure with those of dexamethasone and fluticasone propionate shows the 17{alpha} furoate ester to occupy more fully the lipophilic 17{alpha} pocket on the receptor, which may account for the enhanced glucocorticoid receptor binding of FF.

  6. Novel PPAR pan agonist, ZBH ameliorates hyperlipidemia and insulin resistance in high fat diet induced hyperlipidemic hamster.

    Directory of Open Access Journals (Sweden)

    Wei Chen

    Full Text Available Effective and safe pharmacological interventions for hyperlipidemia remains badly needed. By incorporating the key pharmacophore of fibrates into the natural scaffold of resveratrol, a novel structural compound ZBH was constructed. In present study, we found ZBH reserved approximately one third of the sirtuin 1 (SIRT1 activation produced by resveratrol at in-vitro enzyme activity assay, directly bound to and activated all three peroxisome proliferator-activated receptor (PPAR subtypes respectively in PPAR binding and transactivation assays. Moreover, ZBH (EC₅₀, 1.75 µM activate PPARα 21 fold more efficiently than the well-known PPAR pan agonist bezafibrate (EC₅₀ 37.37 µM in the cellular transactivation assays. In the high fat diet induced hyperlipidemic hamsters, 5-week treatment with ZBH significantly lowered serum triglyceride, total cholesterol, LDL-C, FFA, hyperinsulinemia, and improved insulin sensitivity more potently than bezafibrate. Meanwhile, serum transaminases, creatine phosphokinase and CREA levels were found not altered by ZBH intervention. Mechanism study indicated ZBH promoted the expression of PPARα target genes and SIRT1 mRNA. Hepatic lipogenesis was markedly decreased via down-regulation of lipogenic genes, and fatty acid uptake and oxidation was simultaneously increased in the liver and skeletal muscle via up-regulation of lipolysis genes. Glucose uptake and utilization was also significantly promoted in skeletal muscle. These results suggested that ZBH significantly lowered hyperlipidemia and ameliorated insulin resistance more efficiently than bezafibrate in the hyperlipidemic hamsters primarily by activating of PPARα, and SIRT1 promotion and activation. ZBH thus presents a potential new agent to combat hyperlipidemia.

  7. FXR Agonist INT-747 Upregulates DDAH Expression and Enhances Insulin Sensitivity in High-Salt Fed Dahl Rats

    OpenAIRE

    Ghebremariam, Yohannes T; Keisuke Yamada; Lee, Jerry C.; Christine L C Johnson; Dorothee Atzler; Maike Anderssohn; Rani Agrawal; John P. Higgins; Patterson, Andrew J.; Böger, Rainer H.; Cooke, John P.

    2013-01-01

    AIMS: Genetic and pharmacological studies have shown that impairment of the nitric oxide (NO) synthase (NOS) pathway is associated with hypertension and insulin-resistance (IR). In addition, inhibition of NOS by the endogenous inhibitor, asymmetric dimethylarginine (ADMA), may also result in hypertension and IR. On the other hand, overexpression of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that metabolizes ADMA, in mice is associated with lower ADMA, increased NO and enhanced ...

  8. β2-Adrenoceptor agonist-induced RGS2 expression is a genomic mechanism of bronchoprotection that is enhanced by glucocorticoids.

    Science.gov (United States)

    Holden, Neil S; Bell, Matthew J; Rider, Christopher F; King, Elizabeth M; Gaunt, David D; Leigh, Richard; Johnson, Malcolm; Siderovski, David P; Heximer, Scott P; Giembycz, Mark A; Newton, Robert

    2011-12-01

    In asthma and chronic obstructive pulmonary disease, activation of G(q)-protein-coupled receptors causes bronchoconstriction. In each case, the management of moderate-to-severe disease uses inhaled corticosteroid (glucocorticoid)/long-acting β(2)-adrenoceptor agonist (LABA) combination therapies, which are more efficacious than either monotherapy alone. In primary human airway smooth muscle cells, glucocorticoid/LABA combinations synergistically induce the expression of regulator of G-protein signaling 2 (RGS2), a GTPase-activating protein that attenuates G(q) signaling. Functionally, RGS2 reduced intracellular free calcium flux elicited by histamine, methacholine, leukotrienes, and other spasmogens. Furthermore, protection against spasmogen-increased intracellular free calcium, following treatment for 6 h with LABA plus corticosteroid, was dependent on RGS2. Finally, Rgs2-deficient mice revealed enhanced bronchoconstriction to spasmogens and an absence of LABA-induced bronchoprotection. These data identify RGS2 gene expression as a genomic mechanism of bronchoprotection that is induced by glucocorticoids plus LABAs in human airway smooth muscle and provide a rational explanation for the clinical efficacy of inhaled corticosteroid (glucocorticoid)/LABA combinations in obstructive airways diseases. PMID:22080612

  9. Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life

    Directory of Open Access Journals (Sweden)

    Glen Daniel

    2009-05-01

    Full Text Available Abstract Background The intravenous co-infusion of labradimil, a metabolically stable bradykinin B2 receptor agonist, has been shown to temporarily enhance the transvascular delivery of small chemotherapy drugs, such as carboplatin, across the blood-brain tumor barrier. It has been thought that the primary mechanism by which labradimil does so is by acting selectively on tumor microvasculature to increase the local transvascular flow rate across the blood-brain tumor barrier. This mechanism of action does not explain why, in the clinical setting, carboplatin dosing based on patient renal function over-estimates the carboplatin dose required for target carboplatin exposure. In this study we investigated the systemic actions of labradimil, as well as other bradykinin B2 receptor agonists with a range of metabolic stabilities, in context of the local actions of the respective B2 receptor agonists on the blood-brain tumor barrier of rodent malignant gliomas. Methods Using dynamic contrast-enhanced MRI, the pharmacokinetics of gadolinium-diethyltriaminepentaacetic acid (Gd-DTPA, a small MRI contrast agent, were imaged in rodents bearing orthotopic RG-2 malignant gliomas. Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1st bolus of Gd-DTPA over the first hour, and then re-imaged with a 2nd bolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. Changes in mean arterial blood pressure were recorded. Imaging data was analyzed using both qualitative and quantitative methods. Results The decrease in systemic blood pressure correlated with the known metabolic stability of the bradykinin B2 receptor agonist infused. Metabolically stable bradykinin B2 agonists, methionine-lysine-bradykinin and labradimil, had differential effects on the transvascular flow rate of Gd-DTPA across the blood-brain tumor barrier. Both methionine

  10. Chiglitazar, a novel PPARalpha/gamma dual agonists with beneficial effects on insulin resistance and lipid metabolism in MSG rats

    Institute of Scientific and Technical Information of China (English)

    Ping-pingLI; Yue-tengCHEN; QuanLIU; Su-juanSUN; Zhu-fangSHEN

    2004-01-01

    AIM: Peroxisome proliferator-activated receptor (PPAR) alpha and PPAR gamma agonists lower lipid accumulation by different mechanisms. We investigated whether benefits could be achieved on insulin sensitivity and lipid metabolism by the dual PPARalpha/gamma agonist chiglitazar in MSG rats. METHODS: Chiglitazar was orally administered in 5, 10, 20 mg-kg-~.d~ dosages in MSG rats for 40 d. The drug therapeutic effect was evaluated by glucose tolerance tests, insulin tolerance tests, and hyperinsulinemic-euglycemic clamps technique. The level of

  11. Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: Potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders.

    Science.gov (United States)

    McLean, Samantha L; Grayson, Ben; Marsh, Samuel; Zarroug, Samah H O; Harte, Michael K; Neill, Jo C

    2016-04-01

    Cholinergic dysfunction has been shown to be central to the pathophysiology of Alzheimer's disease and has also been postulated to contribute to cognitive dysfunction observed in various psychiatric disorders, including schizophrenia. Deficits are found across a number of cognitive domains and in spite of several attempts to develop new therapies, these remain an unmet clinical need. In the current study we investigated the efficacy of donepezil, risperidone and selective nicotinic α7 and α4β2 receptor agonists to reverse a delay-induced deficit in recognition memory. Adult female Hooded Lister rats received drug treatments and were tested in the novel object recognition (NOR) task following a 6h inter-trial interval (ITI). In all treatment groups, there was no preference for the left or right identical objects in the acquisition trial. Risperidone failed to enhance recognition memory in this paradigm whereas donepezil was effective such that rats discriminated between the novel and familiar object in the retention trial following a 6h ITI. Although a narrow dose range of PNU-282987 and RJR-2403 was tested, only one dose of each increased recognition memory, the highest dose of PNU-282987 (10mg/kg) and the lowest dose of RJR-2403 (0.1mg/kg), indicative of enhanced cognitive performance. Interestingly, these compounds were also efficacious when administered either before the acquisition or the retention trial of the task, suggesting an important role for nicotinic receptor subtypes in the formation and retrieval of recognition memory. PMID:26327238

  12. Preferred recycling pathway by internalized PGE2 EP4 receptor following agonist stimulation in cultured dorsal root ganglion neurons contributes to enhanced EP4 receptor sensitivity.

    Science.gov (United States)

    St-Jacques, Bruno; Ma, Weiya

    2016-06-21

    Prostaglandin E2 (PGE2), a well-known pain mediator abundantly produced in injured tissues, sensitizes nociceptive dorsal root ganglion (DRG) neurons (nociceptors) through its four EP receptors (EP1-4). Our prior study showed that PGE2 or EP4 agonist stimulates EP4 externalization and this event was not only suppressed by the inhibitor of anterograde export, but also by the recycling inhibitor (St-Jacques and Ma, 2013). These data suggest that EP4 recycling also contributes to agonist-enhanced EP4 surface abundance. In the current study, we tested this hypothesis using antibody-feeding-based internalization assay, recycling assay and FITC-PGE2 binding assay. We observed that selective EP4 agonist 1-hydroxy-PGE1 (1-OH-PGE1) or CAY10850 time- and concentration-dependently increased EP4 internalization in cultured DRG neuron. Internalized EP4 was predominantly localized in the early endosomes and recycling endosomes, but rarely in the late endosomes and lysosomes. These observations were confirmed by FITC-PGE2 binding assay. We further revealed that 1-OH-PGE1 or CAY10850 time- and concentration-dependently increased EP4 recycling. Double exposures to 1-OH-PGE1 induced a greater increase in calcitonin gene-related peptide (CGRP) release than a single exposure or vehicle exposure, an event blocked by pre-treatment with the recycling inhibitor monensin. Our data suggest that EP4 recycling contributes to agonist-induced cell surface abundance and consequently enhanced receptor sensitivity. Facilitating EP4 externalization and recycling is a novel mechanism underlying PGE2-induced nociceptor sensitization.

  13. Reversal of obesity and insulin resistance by a non-peptidic glucagon-like peptide-1 receptor agonist in diet-induced obese mice.

    Directory of Open Access Journals (Sweden)

    Min He

    Full Text Available BACKGROUND: Glucagon-like peptide-1 (GLP-1 is recognized as an important regulator of glucose homeostasis. Efforts to utilize GLP-1 mimetics in the treatment of diabetes have yielded clinical benefits. A major hurdle for an effective oral therapy has been the difficulty of finding a non-peptidic GLP-1 receptor (GLP-1R agonist. While its oral bioavailability still poses significant challenges, Boc5, one of the first such compounds, has demonstrated the attainment of GLP-1R agonism in diabetic mice. The present work was to investigate whether subchronic Boc5 treatment can restore glycemic control and induce sustainable weight loss in diet-induced obese (DIO mice, an animal model of human obesity and insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: DIO mice were treated three times a week with Boc5 (0.3, 1 and 3 mg for 12 weeks. Body weight, body mass index (BMI, food intake, fasting glucose, intraperitoneal glucose tolerance and insulin induced glucose clearance were monitored regularly throughout the treatment. Glucose-stimulated insulin secretion, β-cell mass, islet size, body composition, serum metabolic profiles, lipogenesis, lipolysis, adipose hypertrophy and lipid deposition in the liver and muscle were also measured after 12 weeks of dosing. Boc5 dose-dependently reduced body weight, BMI and food intake in DIO mice. These changes were associated with significant decreases in fat mass, adipocyte hypertrophy and peripheral tissue lipid accumulation. Boc5 treatment also restored glycemic control through marked improvement of insulin sensitivity and normalization of β-cell mass. Administration of Boc5 (3 mg reduced basal but enhanced insulin-mediated glucose incorporation and noradrenaline-stimulated lipolysis in isolated adipocytes from obese mice. Furthermore, circulating leptin, adiponectin, triglyceride, total cholesterol, nonesterified fatty acid and high-density lipoprotein/low-density lipoprotein ratio were normalized to various

  14. Ca2(+)-channel agonist BAY K8644 mimics 1,25(OH)2-vitamin D3 rapid enhancement of Ca2+ transport in chick perfused duodenum

    International Nuclear Information System (INIS)

    To further understand the molecular mechanism by which 1,25(OH)2-vitamin D3 [1,25(OH)2D3] rapidly stimulates intestinal calcium transport (termed transcaltachia), the effect of the calcium channel agonist BAY K8644 was studied in vascularly perfused duodenal loops from normal, vitamin D-replete chicks. BAY K8644, 2 mu M, was found to stimulate 45Ca2+ transport from the lumen to the vascular effluent to the same extent as physiological levels of 1,25(OH)2D3. The sterol and the Ca2+ channel agonist both increased 45Ca2+ transport 70% above control values within 2 min and 200% after 30 min of vascular perfusion. The effect of the Ca2+ channel agonist was dose dependent. Also, 1,25(OH)2D3-enhanced transcaltachia was abolished by the calcium channel blocker nifedipine. Collectively, these results suggest the involvement of 1,25(OH)2D3 in the activation of basal lateral membrane Ca2+ channels as an early effect in the transcaltachic response

  15. FXR agonists enhance the sensitivity of biliary tract cancer cells to cisplatin via SHP dependent inhibition of Bcl-xL expression

    Science.gov (United States)

    Wang, Wei; Zhan, Ming; Li, Qi; Chen, Wei; Chu, Huiling; Huang, Qihong; Hou, Zhaoyuan; Man, Mohan; Wang, Jian

    2016-01-01

    Chemoresistance is common in patients with biliary tract cancer (BTC) including gallbladder cancer (GBC) and cholangiocarcinoma (CC). Therefore, it is necessary to identify effective chemotherapeutic agents for BTC. In the present study, we for the first time tested the effect of farnesoid X receptor (FXR) agonists GW4064 and CDCA (chenodeoxycholic acid) in combination with cisplatin (CDDP) on increasing the chemosensitivity in BTC. Our results show that co-treatment of CDDP with FXR agonists remarkably enhance chemosensitivity of BTC cells. Mechanistically, we found that activation of FXR induced expression of small heterodimer partner (SHP), which in turn inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation and resulted in down-regulation of Bcl-xL expression in BTC cells, leading to increased susceptibility to CDDP. Moreover, the experiments on tumor-bearing mice showed that GW4064/CDDP co-treatment inhibited the tumor growth in vivo by up-regulating SHP expression and down-regulating STAT3 phosphorylation. These results suggest CDDP in combination with FXR agonists could be a potential new therapeutic strategy for BTC. PMID:27127878

  16. Enhancement of apparent resistance to ethanol in Lactobacillus hilgardii

    OpenAIRE

    Couto, José António; Pina, Cristina; Hogg, Tim

    1997-01-01

    The survival of Lactobacillus hilgardii, a highly ethanol-tolerant organism, after an ethanol challenge at 25% (v/v) for 10 min, increased by several log cycles when cells, grown in the absence of ethanol, were pre-treated with 10% (v/v) ethanol, 15% (v/v) methanol or 2% (v/v) butanol for 4 h. A temperature upshift (25 to 40°C) before ethanol challenge demonstrated a similar enhancement of apparent resistance to ethanol. Ethanol shock enhanced apparent resistance to methanol, butanol and heat...

  17. Adjuvant for vaccine immunotherapy of cancer--focusing on Toll-like receptor 2 and 3 agonists for safely enhancing antitumor immunity.

    Science.gov (United States)

    Seya, Tsukasa; Shime, Hiroaki; Takeda, Yohei; Tatematsu, Megumi; Takashima, Ken; Matsumoto, Misako

    2015-12-01

    Immune-enhancing adjuvants usually targets antigen (Ag)-presenting cells to tune up cellular and humoral immunity. CD141(+) dendritic cells (DC) represent the professional Ag-presenting cells in humans. In response to microbial pattern molecules, these DCs upgrade the maturation stage sufficient to improve cross-presentation of exogenous Ag, and upregulation of MHC and costimulators, allowing CD4/CD8 T cells to proliferate and liberating cytokines/chemokines that support lymphocyte attraction and survival. These DCs also facilitate natural killer-mediated cell damage. Toll-like receptors (TLRs) and their signaling pathways in DCs play a pivotal role in DC maturation. Therefore, providing adjuvants in addition to Ag is indispensable for successful vaccine immunotherapy for cancer, which has been approved in comparison with antimicrobial vaccines. Mouse CD8α(+) DCs express TLR7 and TLR9 in addition to the TLR2 family (TLR1, 2, and 6) and TLR3, whereas human CD141(+) DCs exclusively express the TLR2 family and TLR3. Although human and mouse plasmacytoid DCs commonly express TLR7/9 to respond to their agonists, the results on mouse adjuvant studies using TLR7/9 agonists cannot be simply extrapolated to human adjuvant immunotherapy. In contrast, TLR2 and TLR3 are similarly expressed in both human and mouse Ag-presenting DCs. Bacillus Calmette-Guerin peptidoglycan and polyinosinic-polycytidylic acid are representative agonists for TLR2 and TLR3, respectively, although they additionally stimulate cytoplasmic sensors: their functional specificities may not be limited to the relevant TLRs. These adjuvants have been posted up to a certain achievement in immunotherapy in some cancers. We herein summarize the history and perspectives of TLR2 and TLR3 agonists in vaccine-adjuvant immunotherapy for cancer.

  18. Combined postconditioning with ischemia and α7nAChR agonist produces an enhanced protection against rat myocardial ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    XIONG Jun; YUAN Yu-jing; XUE Fu-shan; WANG Qiang; LI Shan; LIAO Xu; LIU Jian-hua; CHEN Yi; LI Rui-ping

    2012-01-01

    Background Inflammation is one of important mechanisms for myocardial ischemia reperfusion injury (IRI).Ischemia postconditioning (IPOC) can protect the heart against IRI by inhibiting inflammation,but its cardioprotection is weaker than that of ischemia preconditioning.Recently,the α7 subunit-containing nicotinic acetylcholine receptor (α7nAChR) agonist has shown anti-infiammatory effects in many diseases related to inflammation.This randomized controlled experiment was designed to evaluate whether combined postconditioning with IPOC and the α7nAChR agonist could produce an enhanced cardioprotection in a rat in vivo model of acute myocardial IRI.Methods Fifty Sprague-Dawley rats were randomly divided into five equal groups:sham group,control group,IPOC group,α7nAChR agonist postconditioning group (APOC group) and combined postconditioning with IPOC and α7nAChR agonist group (combined group).Hemodynamic parameters were recorded during the periods of ischemia and reperfusion.Serum concentrations of troponin I (Tnl),tumor necrosis factor α (TNF-α) and high-mobility group box 1 (HMGB-1) at 180 minutes after reperfusion were assayed in all groups.At the end of the experiment,the infarct size was assessed from excised hearts by Evans blue and triphenyl tetrazolium chloride staining.Results As compared to the sham group,the infarct size in the other four groups was significantly increased,serum levels of Tnl,TNF-α and HMGB1 in the control group and TNF-α,HMGB1 in the IPOC group were significantly increased.The infarct size and serum concentrations of TNF-α,HMGB1 and Tnl in the IPOC,APOC and combined groups were significantly lower than those in the control group.As compared to the IPOC group,the infarct size in the combined group was significantly decreased,serum concentrations of Tnl,TNF-α and HMGB1 in the APOC and combined groups were significantly reduced.Although the infarct size was significantly smaller in the combined group than in the APOC group

  19. SAR studies of 3-arylpropionic acids as potent and selective agonists of sphingosine-1-phosphate receptor-1 (S1P1) with enhanced pharmacokinetic properties.

    Science.gov (United States)

    Yan, Lin; Huo, Pei; Hale, Jeffrey J; Mills, Sander G; Hajdu, Richard; Keohane, Carol A; Rosenbach, Mark J; Milligan, James A; Shei, Gan-Ju; Chrebet, Gary; Bergstrom, James; Card, Deborah; Mandala, Suzanne M

    2007-02-01

    Structure-activity relationship (SAR) studies of 3-arylpropionic acids-a class of novel S1P(1) selective agonists-by introducing substitution to the propionic acid chain and replacing the adjacent phenyl ring with pyridine led to a series of modified 3-arylpropionic acids with enhanced half-life in rat. These analogs (e.g., cyclopropanecarboxylic acids) exhibited longer half-life in rat than did unmodified 3-arylpropionic acids. This result suggests that metabolic oxidation at the propionic acid chain, particularly at the C3 benzylic position of 3-arylpropionic acids, is probably responsible for their short half-life in rodent.

  20. A beamformer for CDMA with enhanced near-far resistance

    DEFF Research Database (Denmark)

    Hansen, Henrik; Affes, S.; Mermelstein, P.

    1999-01-01

    The spatio-temporal array-receiver (STAR) achieves good performance in CDMA with multiple receiving antennas where the interference can be characterized as AWGN uncorrelated with the signal. To enhance its near-far resistance in correlated noise environments, we introduce optimal combining of the...

  1. Enhanced Resistance to Sclerotium rolfsii in Populations of Alfalfa Selected for Quantitative Resistance to Sclerotinia trifoliorum.

    Science.gov (United States)

    Pratt, R G; Rowe, D E

    2002-02-01

    ABSTRACT Sclerotinia trifoliorum and Sclerotium rolfsii are pathogens for which similar mechanisms of parasitism have been proposed. This suggested that resistance to these pathogens may be related in a common host plant. This study was undertaken to determine whether selection for quantitative resistance to Sclerotinia trifoliorum in alfalfa also increases resistance to Sclerotium rolfsii as expressed in excised leaf tissues and whole plants. Resistance in excised leaf tissues was evaluated according to the rate of necrosis induced by Sclerotium rolfsii following inoculation with mycelium. Resistance to Sclerotium rolfsii in whole plants was evaluated according to their survival following crown inoculations. Three alfalfa populations previously selected from cv. Delta for quantitative resistance to Sclerotinia trifoliorum exhibited enhanced resistance to Sclerotium rolfsii, in comparison with Delta or with susceptible populations, in excised leaf tissues. When whole plants of Delta and two of these populations, Sclerotinia trifoliorum resistant (STR) and Mississippi Sclerotinia resistant (MSR), were inoculated with Sclerotium rolfsii at 3 to 8 weeks of age, significant (P = 0.01) differences in survival were attributed to plant age at inoculation and alfalfa populations. Survival of both MSR and STR was significantly (P = 0.05) greater than for Delta; the best differential results were obtained by inoculating plants 5 to 7 weeks old. To evaluate relationships of resistance to Sclerotinia trifoliorum and Sclerotium rolfsii over a broader genetic background, additional populations were selected for resistance to Sclerotinia trifoliorum from four other alfalfa cultivars by leaf-inoculation techniques, and this resistance was confirmed by whole-plant inoculations. In excised leaf tissues, all four of these populations also expressed enhanced resistance to Sclerotium rolfsii in comparison with either parent cultivars or populations of comparable size selected at random

  2. Enhanced self-administration of the CB1 receptor agonist WIN55,212-2 in olfactory bulbectomized rats: evaluation of possible serotonergic and dopaminergic underlying mechanisms

    Directory of Open Access Journals (Sweden)

    Petra eAmchova

    2014-03-01

    Full Text Available Depression has been associated with drug consumption, including heavy or problematic cannabis use. According to an animal model of depression and substance use disorder comorbidity, we combined the olfactory bulbectomy model of depression with intravenous drug self-administration procedure to verify whether depressive-like rats displayed higher voluntary intake of the CB1 receptor agonist WIN55,212-2 (WIN, 12.5 µg/kg/infusion. To this aim, olfactory-bulbectomized (OBX and sham-operated (SHAM Lister Hooded rats were allowed to self-administer WIN by lever-pressing under a continuous (FR-1 schedule of reinforcement in 2h daily sessions. Data showed that both OBX and SHAM rats developed stable WIN intake; yet, responses in OBX were constantly higher than in SHAM rats soon after the first week of training. In addition, OBX rats took significantly longer to extinguish the drug-seeking behaviour after vehicle substitution. Acute pre-treatment with serotonin 5HT1B receptor agonist, CGS-12066B (2.5-10 mg/kg, did not significantly modify WIN intake in OBX and SHAM Lister Hooded rats. Furthermore, acute pre-treatment with CGS-12066B (10 and 15 mg/kg did not alter responses in parallel groups of OBX and SHAM Sprague Dawley rats self-administering methamphetamine under higher (FR-2 reinforcement schedule with nose-poking as operandum. Finally, dopamine levels in the nucleus accumbens of OBX rats did not increase in response to a WIN challenge, as in SHAM rats, indicating a dopaminergic dysfunction in bulbectomized rats. Altogether, our findings suggest that a depressive state may alter cannabinoid CB1 receptor agonist-induced brain reward function and that a dopaminergic rather than a 5-HT1B mechanism is likely to underlie enhanced WIN self-administration in OBX rats.

  3. A randomized exploratory trial of an α-7 nicotinic receptor agonist (TC-5619) for cognitive enhancement in schizophrenia.

    Science.gov (United States)

    Lieberman, Jeffrey A; Dunbar, Geoffrey; Segreti, Anthony C; Girgis, Ragy R; Seoane, Frances; Beaver, Jessica S; Duan, Naihua; Hosford, David A

    2013-05-01

    This exploratory trial was conducted to test the effects of an alpha7 nicotinic receptor partial agonist, TC-5619, on cognitive dysfunction and negative symptoms in subjects with schizophrenia. In the United States and India, 185 outpatients (18-60 years; male 69%; 46% tobacco users) with schizophrenia treated with quetiapine or risperidone monotherapy were randomized to 12 weeks of placebo (n=91) or TC-5619 (n=94; orally once daily 1 mg day 1 to week 4, 5 mg week 4 to 8, and 25 mg week 8 to 12). The primary efficacy outcome measure was the Groton Maze Learning Task (GMLT; executive function) of the CogState Schizophrenia Battery (CSB). Secondary outcome measures included: CSB composite score; Scale for Assessment of Negative Symptoms (SANS); Clinical Global Impression-Global Improvement (CGI-I); CGI-severity (CGI-S); and Subject Global Impression-Cognition. GMLT statistically favored TC-5619 (P=0.036) in this exploratory trial. SANS also statistically favored TC-5619 (P=0.030). No other secondary outcome measure demonstrated a drug effect in the total population; there was a statistically significant drug effect on working memory in tobacco users. The results were typically stronger in favor of TC-5619 in tobacco users and occasionally better in the United States than in India. TC-5619 was generally well tolerated with no clinically noteworthy safety findings. These results support the potential benefits of TC-5619 and alpha7 nicotinic receptor partial agonists for cognitive dysfunction and negative symptoms in schizophrenia.

  4. Enhanced Tomato Disease Resistance Primed by Arbuscular Mycorrhizal Fungus

    Directory of Open Access Journals (Sweden)

    Yuanyuan eSong

    2015-09-01

    Full Text Available Roots of most terrestrial plants form symbiotic associations (mycorrhiza with soil- borne arbuscular mycorrhizal fungi (AMF. Many studies show that mycorrhizal colonization enhances plant resistance against pathogenic fungi. However, the mechanism of mycorrhiza-induced disease resistance remains equivocal. In this study, we found that mycorrhizal inoculation with AMF Funneliformis mosseae significantly alleviated tomato (Solanum lycopersicum Mill. early blight disease caused by Alternaria solani Sorauer. AMF pre-inoculation led to significant increases in activities of β-1,3-glucanase, chitinase, phenylalanine ammonia-lyase (PAL and lipoxygenase (LOX in tomato leaves upon pathogen inoculation. Mycorrhizal inoculation alone did not influence the transcripts of most genes tested. However, pathogen attack on AMF-inoculated plants provoked strong defense responses of three genes encoding pathogenesis-related (PR proteins, PR1, PR2 and PR3, as well as defense-related genes LOX, AOC and PAL, in tomato leaves. The induction of defense responses in AMF pre-inoculated plants was much higher and more rapid than that in un-inoculated plants in present of pathogen infection. Three tomato genotypes: a Castlemart wild-type (WT plant, a jasmonate (JA biosynthesis mutant (spr2, and a prosystemin-overexpressing 35S::PS plant were used to examine the role of the JA signaling pathway in AMF-primed disease defense. Pathogen infection on mycorrhizal 35S::PS plants led to higher induction of defense-related genes and enzymes relative to WT plants. However, pathogen infection did not induce these genes and enzymes in mycorrhizal spr2 mutant plants. Bioassays showed that 35S::PS plants were more resistant and spr2 plants were more susceptible to early blight compared with WT plants. Our finding indicates that mycorrhizal colonization enhances tomato resistance to early blight by priming systemic defense response, and the JA signaling pathway is essential for

  5. Enhanced tomato disease resistance primed by arbuscular mycorrhizal fungus.

    Science.gov (United States)

    Song, Yuanyuan; Chen, Dongmei; Lu, Kai; Sun, Zhongxiang; Zeng, Rensen

    2015-01-01

    Roots of most terrestrial plants form symbiotic associations (mycorrhiza) with soil- borne arbuscular mycorrhizal fungi (AMF). Many studies show that mycorrhizal colonization enhances plant resistance against pathogenic fungi. However, the mechanism of mycorrhiza-induced disease resistance remains equivocal. In this study, we found that mycorrhizal inoculation with AMF Funneliformis mosseae significantly alleviated tomato (Solanum lycopersicum Mill.) early blight disease caused by Alternaria solani Sorauer. AMF pre-inoculation led to significant increases in activities of β-1,3-glucanase, chitinase, phenylalanine ammonia-lyase (PAL) and lipoxygenase (LOX) in tomato leaves upon pathogen inoculation. Mycorrhizal inoculation alone did not influence the transcripts of most genes tested. However, pathogen attack on AMF-inoculated plants provoked strong defense responses of three genes encoding pathogenesis-related proteins, PR1, PR2, and PR3, as well as defense-related genes LOX, AOC, and PAL, in tomato leaves. The induction of defense responses in AMF pre-inoculated plants was much higher and more rapid than that in un-inoculated plants in present of pathogen infection. Three tomato genotypes: a Castlemart wild-type (WT) plant, a jasmonate (JA) biosynthesis mutant (spr2), and a prosystemin-overexpressing 35S::PS plant were used to examine the role of the JA signaling pathway in AMF-primed disease defense. Pathogen infection on mycorrhizal 35S::PS plants led to higher induction of defense-related genes and enzymes relative to WT plants. However, pathogen infection did not induce these genes and enzymes in mycorrhizal spr2 mutant plants. Bioassays showed that 35S::PS plants were more resistant and spr2 plants were more susceptible to early blight compared with WT plants. Our finding indicates that mycorrhizal colonization enhances tomato resistance to early blight by priming systemic defense response, and the JA signaling pathway is essential for mycorrhiza

  6. Prokaryotic arsenate reductase enhances arsenate resistance in Mammalian cells.

    Science.gov (United States)

    Wu, Dan; Tao, Xuanyu; Wu, Gaofeng; Li, Xiangkai; Liu, Pu

    2014-01-01

    Arsenic is a well-known heavy metal toxicant in the environment. Bioremediation of heavy metals has been proposed as a low-cost and eco-friendly method. This article described some of recent patents on transgenic plants with enhanced heavy metal resistance. Further, to test whether genetic modification of mammalian cells could render higher arsenic resistance, a prokaryotic arsenic reductase gene arsC was transfected into human liver cancer cell HepG2. In the stably transfected cells, the expression level of arsC gene was determined by quantitative real-time PCR. Results showed that arsC was expressed in HepG2 cells and the expression was upregulated by 3 folds upon arsenate induction. To further test whether arsC has function in HepG2 cells, the viability of HepG2-pCI-ArsC cells exposed to arsenite or arsenate was compared to that of HepG2-pCI cells without arsC gene. The results indicated that arsC increased the viability of HepG2 cells by 25% in arsenate, but not in arsenite. And the test of reducing ability of stably transfected cells revealed that the concentration of accumulated trivalent arsenic increased by 25% in HepG2-pCI-ArsC cells. To determine the intracellular localization of ArsC, a fusion vector with fluorescent marker pEGFP-N1-ArsC was constructed and transfected into.HepG2. Laser confocal microscopy showed that EGFP-ArsC fusion protein was distributed throughout the cells. Taken together, these results demonstrated that prokaryotic arsenic resistant gene arsC integrated successfully into HepG2 genome and enhanced arsenate resistance of HepG2, which brought new insights of arsenic detoxification in mammalian cells.

  7. Resistance transition assisted geometry enhanced magnetoresistance in semiconductors

    International Nuclear Information System (INIS)

    Magnetoresistance (MR) reported in some non-magnetic semiconductors (particularly silicon) has triggered considerable interest owing to the large magnitude of the effect. Here, we showed that MR in lightly doped n-Si can be significantly enhanced by introducing two diodes and proper design of the carrier path [Wan, Nature 477, 304 (2011)]. We designed a geometrical enhanced magnetoresistance (GEMR) device whose room-temperature MR ratio reaching 30% at 0.065 T and 20 000% at 1.2 T, respectively, approaching the performance of commercial MR devices. The mechanism of this GEMR is: the diodes help to define a high resistive state (HRS) and a low resistive state (LRS) in device by their openness and closeness, respectively. The ratio of apparent resistance between HRS and LRS is determined by geometry of silicon wafer and electrodes. Magnetic field could induce a transition from LRS to HRS by reshaping potential and current distribution among silicon wafer, resulting in a giant enhancement of intrinsic MR. We expect that this GEMR could be also realized in other semiconductors. The combination of high sensitivity to low magnetic fields and large high-field response should make this device concept attractive to the magnetic field sensing industry. Moreover, because this MR device is based on a conventional silicon/semiconductor platform, it should be possible to integrate this MR device with existing silicon/semiconductor devices and so aid the development of silicon/semiconductor-based magnetoelectronics. Also combining MR devices and semiconducting devices in a single Si/semiconductor chip may lead to some novel devices with hybrid function, such as electric-magnetic-photonic properties. Our work demonstrates that the charge property of semiconductor can be used in the magnetic sensing industry, where the spin properties of magnetic materials play a role traditionally

  8. Does copy-resistance enhance cooperation in spatial prisoner's dilemma?

    Science.gov (United States)

    Shigaki, K.; Kokubo, S.; Tanimoto, J.; Hagishima, A.; Ikegaya, N.

    2012-05-01

    We propose a novel idea for the so-called pairwise-Fermi process by considering copy-resistance when an agent copies a neighbor's strategy, which implies that the focal agent with relatively affluent payoff vis-à-vis social average might be negative to copy her neighbor's strategy even if her payoff is less than the neighbor's payoff. Simulation results reveal that this idea with a revised strategy adaptation process significantly enhances cooperation for prisoner's dilemma games played on time-constant networks.

  9. Memory Enhancement Induced by Post-Training Intrabasolateral Amygdala Infusions of [beta]-Adrenergic or Muscarinic Agonists Requires Activation of Dopamine Receptors: Involvement of Right, but Not Left, Basolateral Amygdala

    Science.gov (United States)

    LaLumiere, Ryan T.; McGaugh, James L.

    2005-01-01

    Previous findings indicate that the noradrenergic, dopaminergic, and cholinergic innervations of the basolateral amygdala (BLA) modulate memory consolidation. The current study investigated whether memory enhancement induced by post-training intra-BLA infusions of a [beta]-adrenergic or muscarinic cholinergic agonist requires concurrent activation…

  10. Antibody-Dependent Cell-Mediated Cytotoxicity Effector-Enhanced EphA2 Agonist Monoclonal Antibody Demonstrates Potent Activity against Human Tumors

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Bruckheimer

    2009-06-01

    Full Text Available EphA2 is a receptor tyrosine kinase that has been shown to be overexpressed in a variety of human tumor types. Previous studies demonstrated that agonist monoclonal antibodies targeting EphA2 induced the internalization and degradation of the receptor, thereby abolishing its oncogenic effects. In this study, the in vitro and in vivo antibody-dependent cell-mediated cytotoxicity (ADCC activity of EphA2 effector-enhanced agonist monoclonal antibodies was evaluated. With tumor cell lines and healthy human peripheral blood monocytes, the EphA2 antibodies demonstrated ∼80% tumor cell killing. In a dose-dependent manner, natural killer (NK cells were required for the in vitro ADCC activity and became activated as demonstrated by the induction of cell surface expression of CD107a. To assess the role of NK cells on antitumor efficacy in vivo, the EphA2 antibodies were evaluated in xenograft models in severe compromised immunodeficient (SCID mice (which have functional NK cells and monocytes and SCID nonobese diabetic (NOD mice (which largely lack functional NK cells and monocytes. Dosing of EphA2 antibody in the SCID murine tumor model resulted in a 6.2-fold reduction in tumor volume, whereas the SCID/nonobese diabetic model showed a 1.6-fold reduction over the isotype controls. Together, these results demonstrate that the anti-EphA2 monoclonal antibodies may function through at least two mechanisms of action: EphA2 receptor activation and ADCC-mediated activity. These novel EphA2 monoclonal antibodies provide additional means by which host effector mechanisms can be activated for selective destruction of EphA2-expressing tumor cells.

  11. The 5-HT1D/1B receptor agonist sumatriptan enhances fear of simulated speaking and reduces plasma levels of prolactin.

    Science.gov (United States)

    de Rezende, Marcos Gonçalves; Garcia-Leal, Cybele; Graeff, Frederico Guilherme; Del-Ben, Cristina Marta

    2013-12-01

    This study measured the effects of the preferential 5-HT1D/1B receptor agonist sumatriptan in healthy volunteers who performed the Simulated Public Speaking Test (SPST), which recruits the neural network involved in panic disorder and social anxiety disorder. In a double-blind, randomised experiment, 36 males received placebo (12), 50 mg (12) or 100 mg (12) of sumatriptan 2 h before the SPST. Subjective, physiological and hormonal measures were taken before, during and after the test. The dose of 100 mg of sumatriptan increased speech-induced fear more than either a 50mg dose of the drug or placebo. The largest dose of sumatriptan also enhanced vigilance more than placebo, without any change in blood pressure, heart rate or electrical skin conductance. Sumatriptan decreased plasma levels of prolactin. A significant but moderate increase in plasma cortisol after SPST occurred, independent of treatment. Because sumatriptan decreases 5-HT release into the extracellular space, the potentiation of SPST-induced fear caused by the drug supports the hypothesis that 5-HT attenuates this emotional state. As acute administration of antidepressants has also been shown to enhance speaking fear and increase plasma prolactin, in contrast to sumatriptan, the 5-HT regulation of stress-hormone release is likely to be different from that of emotion. PMID:23325368

  12. The 5-HT1D/1B receptor agonist sumatriptan enhances fear of simulated speaking and reduces plasma levels of prolactin.

    Science.gov (United States)

    de Rezende, Marcos Gonçalves; Garcia-Leal, Cybele; Graeff, Frederico Guilherme; Del-Ben, Cristina Marta

    2013-12-01

    This study measured the effects of the preferential 5-HT1D/1B receptor agonist sumatriptan in healthy volunteers who performed the Simulated Public Speaking Test (SPST), which recruits the neural network involved in panic disorder and social anxiety disorder. In a double-blind, randomised experiment, 36 males received placebo (12), 50 mg (12) or 100 mg (12) of sumatriptan 2 h before the SPST. Subjective, physiological and hormonal measures were taken before, during and after the test. The dose of 100 mg of sumatriptan increased speech-induced fear more than either a 50mg dose of the drug or placebo. The largest dose of sumatriptan also enhanced vigilance more than placebo, without any change in blood pressure, heart rate or electrical skin conductance. Sumatriptan decreased plasma levels of prolactin. A significant but moderate increase in plasma cortisol after SPST occurred, independent of treatment. Because sumatriptan decreases 5-HT release into the extracellular space, the potentiation of SPST-induced fear caused by the drug supports the hypothesis that 5-HT attenuates this emotional state. As acute administration of antidepressants has also been shown to enhance speaking fear and increase plasma prolactin, in contrast to sumatriptan, the 5-HT regulation of stress-hormone release is likely to be different from that of emotion.

  13. Pyramids of QTLs enhance host–plant resistance and Bt-mediated resistance to leaf-chewing insects in soybean

    OpenAIRE

    Ortega, María A.; All, John N.; Boerma, H. Roger; Parrott, Wayne A.

    2016-01-01

    Key message QTL-M and QTL-E enhance soybean resistance to insects. Pyramiding these QTLs with cry1Ac increases protection against Bt-tolerant pests, presenting an opportunity to effectively deploy Bt with host–plant resistance genes. Abstract Plant resistance to leaf-chewing insects minimizes the need for insecticide applications, reducing crop production costs and pesticide concerns. In soybean [Glycine max (L.) Merr.], resistance to a broad range of leaf-chewing insects is found in PI 22935...

  14. Selecting against S1P3 enhances the acute cardiovascular tolerability of 3-(N-benzyl)aminopropylphosphonic acid S1P receptor agonists.

    Science.gov (United States)

    Hale, Jeffrey J; Doherty, George; Toth, Leslie; Mills, Sander G; Hajdu, Richard; Keohane, Carol Ann; Rosenbach, Mark; Milligan, James; Shei, Gan-Ju; Chrebet, Gary; Bergstrom, James; Card, Deborah; Forrest, Michael; Sun, Shu-Yu; West, Sarah; Xie, Huijuan; Nomura, Naomi; Rosen, Hugh; Mandala, Suzanne

    2004-07-01

    Structurally modified 3-(N-benzylamino)propylphosphonic acid S1P receptor agonists that maintain affinity for S1P1, and have decreased affinity for S1P3 are efficacious, but exhibit decreased acute cardiovascular toxicity in rodents than do nonselective agonists.

  15. Novel diamantane polymer platform for enhanced etch resistance

    Science.gov (United States)

    Padmanaban, Munirathna; Chakrapani, Srinivasan; Lin, Guanyang; Kudo, Takanori; Parthasarathy, Deepa; Rahman, Dalil; Anyadiegwu, Clement; Antonio, Charito; Dammel, Ralph R.; Liu, Shenggao; Lam, Frederick; Waitz, Anthony; Yamagchi, Masao; Maehara, Takayuki

    2007-03-01

    The dominant current 193 nm photoresist platform is based on adamantane derivatives. This paper reports on the use of derivatives of diamantane, the next higher homolog of adamantane, in the diamondoid series, as monomers in photoresists. Due to their low Ohnishi number and incremental structural parameter (ISP), such molecules are expected to enhance dry etch stability when incorporated into polymers for resist applications. Starting from the diamantane parent, cleavable and non-cleavable acrylate/methacrylate derivatives of diamantane were obtained using similar chemical steps as for adamantane derivatization. This paper reports on the lithographic and etch performance obtained with a number of diamantane-containing monomers, such as 9-hydroxy-4-diamantyl methacrylate (HDiMA), 2-ethyl-2- diamantyl methacrylate (EDiMA), and 2-methyl-2-diamantyl methacrylate (MDiMA). The etch advantage, dry and wet lithographic performance of some of the polymers obtained from these diamantane-containing polymers are discussed.

  16. Genetically enhanced cows resist intramammary Staphylococcus aureus infection.

    Science.gov (United States)

    Wall, Robert J; Powell, Anne M; Paape, Max J; Kerr, David E; Bannerman, Douglas D; Pursel, Vernon G; Wells, Kevin D; Talbot, Neil; Hawk, Harold W

    2005-04-01

    Mastitis, the most consequential disease in dairy cattle, costs the US dairy industry billions of dollars annually. To test the feasibility of protecting animals through genetic engineering, transgenic cows secreting lysostaphin at concentrations ranging from 0.9 to 14 micrograms/ml [corrected] in their milk were produced. In vitro assays demonstrated the milk's ability to kill Staphylococcus aureus. Intramammary infusions of S. aureus were administered to three transgenic and ten nontransgenic cows. Increases in milk somatic cells, elevated body temperatures and induced acute phase proteins, each indicative of infection, were observed in all of the nontransgenic cows but in none of the transgenic animals. Protection against S. aureus mastitis appears to be achievable with as little as 3 micrograms/ml [corrected] of lysostaphin in milk. Our results indicate that genetic engineering can provide a viable tool for enhancing resistance to disease and improve the well-being of livestock.

  17. Differential immediate and sustained memory enhancing effects of alpha7 nicotinic receptor agonists and allosteric modulators in rats

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; El-Sayed, Mona; Mikkelsen, Jens D

    2011-01-01

    The α7 nicotinic acetylcholine receptor (nAChR) is a potential target for the treatment of cognitive deficits in patients with schizophrenia, ADHD and Alzheimer's disease. Here we test the hypothesis that upregulation of α7 nAChR levels underlies the enhanced and sustained procognitive effect....... Subsequent [(125)I]-bungarotoxin autoradiography revealed no direct correlation between α7 nAChR levels in frontal cortical or hippocampal brain regions and short-term memory with either compound. Additionally, repeated treatment with A-582941 did not affect mRNA expression of RIC-3 or the lynx-like gene...

  18. Enhanced methanol production in plants provides broad spectrum insect resistance.

    Directory of Open Access Journals (Sweden)

    Sameer Dixit

    Full Text Available Plants naturally emit methanol as volatile organic compound. Methanol is toxic to insect pests; but the quantity produced by most of the plants is not enough to protect them against invading insect pests. In the present study, we demonstrated that the over-expression of pectin methylesterase, derived from Arabidopsis thaliana and Aspergillus niger, in transgenic tobacco plants enhances methanol production and resistance to polyphagous insect pests. Methanol content in the leaves of transgenic plants was measured using proton nuclear spectroscopy (1H NMR and spectra showed up to 16 fold higher methanol as compared to control wild type (WT plants. A maximum of 100 and 85% mortality in chewing insects Helicoverpa armigera and Spodoptera litura larvae was observed, respectively when fed on transgenic plants leaves. The surviving larvae showed less feeding, severe growth retardation and could not develop into pupae. In-planta bioassay on transgenic lines showed up to 99 and 75% reduction in the population multiplication of plant sap sucking pests Myzus persicae (aphid and Bemisia tabaci (whitefly, respectively. Most of the phenotypic characters of transgenic plants were similar to WT plants. Confocal microscopy showed no deformities in cellular integrity, structure and density of stomata and trichomes of transgenic plants compared to WT. Pollen germination and tube formation was also not affected in transgenic plants. Cell wall enzyme transcript levels were comparable with WT. This study demonstrated for the first time that methanol emission can be utilized for imparting broad range insect resistance in plants.

  19. Enhanced resistance to Spodoptera litura in endophyte infected cauliflower plants.

    Science.gov (United States)

    Thakur, Abhinay; Kaur, Sanehdeep; Kaur, Amarjeet; Singh, Varinder

    2013-04-01

    Endophytic fungi, which live within host plant tissues without causing any visible symptom of disease, are important mediators of plant-herbivore interactions. These endophytes enhance resistance of host plant against insect herbivores mainly by productions of various alkaloid based defensive compounds in the plant tissue or through alterations of plant nutritional quality. Two endophytic fungi, i.e., Nigrospora sp. and Cladosporium sp., were isolated from Tinospora cordifolia (Thunb.) Miers, a traditional indian medicinal plant. Cauliflower (Brassica oleracea L.) plants were inoculated with these two endophytic fungi. The effect of endophyte infected and uninfected cauliflower plants were measured on the survival and development of Spodoptera litura (Fab.), a polyphagous pest. Endophyte infected cauliflower plants showed resistance to S. litura in the form of significant increase in larval and pupal mortality in both the fungi. Inhibitory effects of endophytic fungi also were observed on adult emergence, longevity, reproductive potential, as well as hatchability of eggs. Thus, it is concluded that antibiosis to S. litura could be imparted by artificial inoculation of endophytes and this could be used to develop alternative ecologically safe control strategies. PMID:23575013

  20. Incretin-based treatment of type 2 diabetes: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors

    DEFF Research Database (Denmark)

    Deacon, Carolyn F

    2007-01-01

    infusion results in glucose profiles similar to those in non-diabetic subjects. Incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). Thus, strategies to enhance incretin activity have included development of GLP-1 receptor agonists resistant to the action of DPP-4 (e.g. exenatide...

  1. Memory enhancement induced by post-training intrabasolateral amygdala infusions of β-adrenergic or muscarinic agonists requires activation of dopamine receptors: Involvement of right, but not left, basolateral amygdala

    OpenAIRE

    LaLumiere, Ryan T; McGaugh, James L.

    2005-01-01

    Previous findings indicate that the noradrenergic, dopaminergic, and cholinergic innervations of the basolateral amygdala (BLA) modulate memory consolidation. The current study investigated whether memory enhancement induced by post-training intra-BLA infusions of a β-adrenergic or muscarinic cholinergic agonist requires concurrent activation of dopamine (DA) receptors in the BLA. Rats with implanted BLA cannulae were trained on an inhibitory avoidance (IA) task and, 48 h later, tested for re...

  2. CNTO736, a novel glucagon-like peptide-1 receptor agonist, ameliorates insulin resistance and inhibits very low-density lipoprotein production in high-fat-fed mice

    NARCIS (Netherlands)

    Parlevliet, E.T.; Schröder-van der Elst, J.P.; Corssmit, E.P.M.; Picha, K.; O'Neil, K.; Stojanovic-Susulic, V.; Ort, T.; Havekes, L.M.; Romijn, J.A.; Pijl, H.

    2009-01-01

    CNTO736 is a glucagon-like peptide (GLP) 1 receptor agonist that incorporates a GLP-1 peptide analog linked to the Mimeti-body platform. We evaluate the potential of acute and chronic CNTO736 treatment on insulin sensitivity and very low-density lipoprotein (VLDL) metabolism. For acute studies, diet

  3. Enhanced stab resistance of armor composites with functionalized silica nanoparticles

    Science.gov (United States)

    Mahfuz, Hassan; Clements, Floria; Rangari, Vijaya; Dhanak, Vinod; Beamson, Graham

    2009-03-01

    Traditionally shear thickening fluid (STF) reinforced with Kevlar has been used to develop flexible armor. At the core of the STF-Kevlar composites is a mixture of polyethylene glycol (PEG) and silica particles. This mixture is often known as STF and is consisted of approximately 45 wt % PEG and 55 wt % silica. During rheological tests, STF shows instantaneous spike in viscosity above a critical shear rate. Fabrication of STF-Kevlar composites requires preparation of STF, dilution with ethanol, and then impregnation with Kevlar. In the current approach, nanoscale silica particles were dispersed directly into a mixture of PEG and ethanol through a sonic cavitation process. Two types of silica nanoparticles were used in the investigation: 30 nm crystalline silica and 7 nm amorphous silica. The admixture was then reinforced with Kevlar fabric to produce flexible armor composites. In the next step, silica particles are functionalized with a silane coupling agent to enhance bonding between silica and PEG. The performance of the resulting armor composites improved significantly. As evidenced by National Institute of Justice spike tests, the energy required for zero-layer penetration (i.e., no penetration) jumped twofold: from 12 to 25 J cm2/g. The source of this improvement has been traced to the formation of siloxane (Si-O-Si) bonds between silica and PEG and superior coating of Kevlar filaments with particles. Fourier transform infrared, x-ray photoemission spectroscopy, and scanning electron microscopy studies were performed to examine chemical bonds, elemental composition, and particle dispersion responsible for such improvement. In summary, our experiments have demonstrated that functionalization of silica particles followed by direct dispersion into PEG resulted in superior Kevlar composites having much higher spike resistance.

  4. Nutritional regulation of muscle protein synthesis with resistance exercise: strategies to enhance anabolism

    OpenAIRE

    Churchward-Venne Tyler A; Burd Nicholas A; Phillips Stuart M

    2012-01-01

    Abstract Provision of dietary amino acids increases skeletal muscle protein synthesis (MPS), an effect that is enhanced by prior resistance exercise. As a fundamentally necessary process in the enhancement of muscle mass, strategies to enhance rates of MPS would be beneficial in the development of interventions aimed at increasing skeletal muscle mass particularly when combined with chronic resistance exercise. The purpose of this review article is to provide an update on current findings reg...

  5. Capacitively coupled electrical substitution for resistive bolometer enhancement

    OpenAIRE

    Denoual, Matthieu; Delaunay, Sébastien; Allègre, Gilles; Robbes, Didier

    2009-01-01

    A new electrical substitution method for resistive bolometers is proposed to operate them in a closed-loop configuration. This method was implemented and evaluated with a resistive bolometer based on metallic layers over a 120 μm thick glass membrane. Based on an electrical substitution (ES) directly at the place of the resistive sensing element, the new method allows for space savings and a simplification of the technological manufacturing while maintaining the time response improvement link...

  6. Enhancement of Amoxicillin Resistance after Unsuccessful Helicobacter pylori Eradication▿

    OpenAIRE

    Nishizawa, Toshihiro; Suzuki, Hidekazu; Tsugawa, Hitoshi; Muraoka, Hiroe; Matsuzaki, Juntaro; Hirata, Kenro; Ikeda, Fumiaki; Takahashi, Masahiko; Hibi, Toshifumi

    2011-01-01

    A high rate of resistance (49.5 to 72.7%) to amoxicillin (AMX) was observed in Helicobacter pylori after two or three unsuccessful eradication attempts. Unsuccessful eradication regimens significantly increase resistance to not only clarithromycin (CLR) and metronidazole (MNZ) but also AMX.

  7. Capacitively coupled electrical substitution for resistive bolometer enhancement

    International Nuclear Information System (INIS)

    A new electrical substitution method for resistive bolometers is proposed to operate them in a closed-loop configuration. This method was implemented and evaluated with a resistive bolometer based on metallic layers over a 120 µm thick glass membrane. Based on an electrical substitution (ES) directly at the place of the resistive sensing element, the new method allows for space savings and a simplification of the technological manufacturing while maintaining the time response improvement linked to a closed-loop operation. Compared to a previously available ES solution, this new method is applicable to all resistive bolometers. Time response and signal-to-noise ratio (SNR) were evaluated through measurements and compared for three operation configurations of the resistive bolometer: open loop, classical ES closed loop and with the proposed capacitively coupled electrical substitution (CCES) closed loop

  8. Changes of Resistance During Polyelectrolyte-enhanced Stirred Batch Ultrafiltration

    Institute of Scientific and Technical Information of China (English)

    ZHU Xin-Sheng; Kwang-Ho CHOO

    2007-01-01

    The permeation flux or the resistance in the ultrafiltration process is mainly limited by osmotic pressure,and it may originate from various kinds of polymer interactions. However, the real origin of permeation resistance hasn't been clarified yet in the light of polymer solution nature. The removal of nitrate contamination by polyelectrolytes was carried out with stirred batch ultrafiltration. The polyelectrolyte concentrations both in permeate and retentate were analyzed with total organic carbon analyzer and permeate mass was acquired by electronic balance connected with computer. The total resistance was calculated and interpreted based on the osmotic pressures in three concentration regimes. In the dilute region, the resistance was proportional to polymer concentration; in the semidilute region, the resistance depended on polymer concentration in the parabolic relationship; in the highly concentrated solution regime, the osmotic pressure factor (OPF) would dominate the total resistance; and the deviation from OPF control could come from the electrostatic repulsion between the tightly compacted and charged polyelectrolyte particles at extremely concentrated solution regime. It was first found that dilute and semidilute concentration regions can be easily detected by plotting the log-log curves of the polymer concentration versus the ratio of the total resistance to polymer concentration. The new concept OPF was defined and did work well at highly concentrated regime.

  9. Chronic Treatment With a Melanocortin-4 Receptor Agonist Causes Weight Loss, Reduces Insulin Resistance, and Improves Cardiovascular Function in Diet-Induced Obese Rhesus Macaques

    OpenAIRE

    Kievit, Paul; Halem, Heather; Marks, Daniel L.; Dong, Jesse Z.; Glavas, Maria M.; Sinnayah, Puspha; Pranger, Lindsay; Cowley, Michael A.; Kevin L. Grove; Culler, Michael D.

    2013-01-01

    The melanocortin-4 receptor (MC4R) is well recognized as an important mediator of body weight homeostasis. Activation of MC4R causes dramatic weight loss in rodent models, and mutations in human are associated with obesity. This makes MC4R a logical target for pharmacological therapy for the treatment of obesity. However, previous studies in rodents and humans have observed a broad array of side effects caused by acute treatment with MC4R agonists, including increased heart rate and blood pre...

  10. Elicitin recognition confers enhanced resistance to Phytophthora infestans in potato

    NARCIS (Netherlands)

    Du, J.; Verzaux, E.C.; Chaparro-Garcia, A.; Bijsterbosch, G.; Keizer, L.C.P.; Zhou, J.; Liebrand, T.W.H.; Xie, C.; Govers, F.; Robatzek, S.; Vossen, van der E.A.G.; Jacobsen, E.; Visser, R.G.F.; Kamoun, S.; Vleeshouwers, V.G.A.A.

    2015-01-01

    Potato late blight, caused by the destructive Irish famine pathogen Phytophthora infestans, is a major threat to global food security1,2. All late blight resistance genes identified to date belong to the coiled-coil, nucleotide-binding, leucine-rich repeat class of intracellular immune receptors3. H

  11. Fracture resistance enhancement of layered structures by multiple cracks

    DEFF Research Database (Denmark)

    Goutianos, Stergios; Sørensen, Bent F.

    2016-01-01

    A theoretical model is developed to test if the fracture resistance of a layered structure can be increased by introducing weak layers changing the cracking mechanism. An analytical model, based on the J integral, predicts a linear dependency between the number of cracks and the steady state...

  12. PPAR Agonists and Cardiovascular Disease in Diabetes.

    Science.gov (United States)

    Calkin, Anna C; Thomas, Merlin C

    2008-01-01

    Peroxisome proliferators activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk. However, data from murine models suggests that PPAR agonists also have independent anti-atherosclerotic actions, including the suppression of vascular inflammation, oxidative stress, and activation of the renin angiotensin system. Many of these potentially anti-atherosclerotic effects are thought to be mediated by transrepression of nuclear factor-kB, STAT, and activator protein-1 dependent pathways. In recent clinical trials, PPARalpha agonists have been shown to be effective in the primary prevention of cardiovascular events, while their cardiovascular benefit in patients with established cardiovascular disease remains equivocal. However, the use of PPARgamma agonists, and more recently dual PPARalpha/gamma coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPARgamma receptor. Newer pan agonists, which retain their anti-atherosclerotic activity without weight gain, may provide one solution to this problem. However, the complex biologic effects of the PPARs may mean that only vascular targeted agents or pure transrepressors will realise the goal of preventing atherosclerotic vascular disease.

  13. PPAR Agonists and Cardiovascular Disease in Diabetes

    Directory of Open Access Journals (Sweden)

    Anna C. Calkin

    2008-01-01

    Full Text Available Peroxisome proliferators activated receptors (PPARs are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk. However, data from murine models suggests that PPAR agonists also have independent anti-atherosclerotic actions, including the suppression of vascular inflammation, oxidative stress, and activation of the renin angiotensin system. Many of these potentially anti-atherosclerotic effects are thought to be mediated by transrepression of nuclear factor-kB, STAT, and activator protein-1 dependent pathways. In recent clinical trials, PPAR agonists have been shown to be effective in the primary prevention of cardiovascular events, while their cardiovascular benefit in patients with established cardiovascular disease remains equivocal. However, the use of PPAR agonists, and more recently dual PPAR/ coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPAR receptor. Newer pan agonists, which retain their anti-atherosclerotic activity without weight gain, may provide one solution to this problem. However, the complex biologic effects of the PPARs may mean that only vascular targeted agents or pure transrepressors will realise the goal of preventing atherosclerotic vascular disease.

  14. Enhanced performance thermal diode via thermal boundary resistance at nanoscale

    Science.gov (United States)

    Tovar-Padilla, M.; Licea-Jimenez, L.; Pérez-Garcia, S. A.; Alvarez-Quintana, J.

    2015-08-01

    Hypothetically, a thermal rectifier is a device which leads a greater heat flux in one direction than another one, similarly as the electrical diode works for the electrical flux. Here, a drastic increment in the rectification factor has been obtained in nanoscale layered thermal diodes due to the effect of thermal boundary resistance present on an asymmetrical stack of nanofilms. Measurements show a thermal rectification factor as large as 3.3 under a temperature bias well below 1 K, which is the biggest thermal rectification factor reported at room temperature compared to previously reported thermal diodes so far. According to the direction of the applied heat flux, the observed impact of the thermal boundary resistance on the device is manifested through the presence of an asymmetric temperature rise along the heat transfer axis. Such effect provides an alternative route for the development of high performance thermal diodes.

  15. Enhancement of Corrosion Resistance of Zinc Coatings Using Green Additives

    Science.gov (United States)

    Punith Kumar, M. K.; Srivastava, Chandan

    2014-10-01

    In the present work, morphology, microstructure, and electrochemical behavior of Zn coatings containing non-toxic additives have been investigated. Zn coatings were electrodeposited over mild steel substrates using Zn sulphate baths containing four different organic additives: sodium gluconate, dextrose, dextrin, and saccharin. All these additives are "green" and can be derived from food contents. Morphological and structural characterization using electron microscopy, x-ray diffraction, and texture co-efficient analysis revealed an appreciable alteration in the morphology and texture of the deposit depending on the type of additive used in the Zn plating bath. All the Zn coatings, however, were nano-crystalline irrespective of the type of additive used. Polarization and electrochemical impedance spectroscopic analysis, used to investigate the effect of the change in microstructure and morphology on corrosion resistance behavior, illustrated an improved corrosion resistance for Zn deposits obtained from plating bath containing additives as compared to the pure Zn coatings.

  16. Production of homozygous transgenic rainbow trout with enhanced disease resistance.

    Science.gov (United States)

    Chiou, Pinwen Peter; Chen, Maria J; Lin, Chun-Mean; Khoo, Jenny; Larson, Jon; Holt, Rich; Leong, Jo-Ann; Thorgarrd, Gary; Chen, Thomas T

    2014-06-01

    Previous studies conducted in our laboratory showed that transgenic medaka expressing cecropin B transgenes exhibited resistant characteristic to fish bacterial pathogens, Pseudomonas fluorescens and Vibrio anguillarum. To confirm whether antimicrobial peptide gene will also exhibit anti-bacterial and anti-viral characteristics in aquaculture important fish species, we produced transgenic rainbow trout expressing cecropin P1 or a synthetic cecropin B analog, CF-17, transgene by sperm-mediated gene transfer method. About 30 % of fish recovered from electroporation were shown to carry the transgene as determined by polymerase chain reaction (PCR) amplification assay. Positive P₁ transgenic fish were crossed to non-transgenic fish to establish F₁ transgenic founder families, and subsequently generating F₂, and F₃ progeny. Expression of cecropin P1 and CF-17 transgenes was detected in transgenic fish by reverse transcription (RT)-PCR analysis. The distribution of body sizes among F₁ transgenic fish were not significantly different from those of non-transgenic fish. Results of challenge studies revealed that many families of F₂ and F₃ transgenic fish exhibited resistance to infection by Aeromonas salmonicida and infectious hematopoietic necrosis virus (IHNV). All-male homozygous cecropin P1 transgenic families were produced by androgenesis from sperm of F₃ heterozygous transgenic fish in one generation. The resistant characteristic to A. salmonicida was confirmed in progeny derived from the outcross of all-male fish to non-transgenic females. Results of our current studies confirmed the possibility of producing disease-resistant homozygous rainbow trout strains by transgenesis of cecropin P1 or CF-17 gene and followed by androgenesis. PMID:24085608

  17. Hull-form optimization of KSUEZMAX to enhance resistance performance

    Science.gov (United States)

    Park, Jong-Heon; Choi, Jung-Eun; Chun, Ho-Hwan

    2015-01-01

    This paper deploys optimization techniques to obtain the optimum hull form of KSUEZMAX at the conditions of full-load draft and design speed. The processes have been carried out using a RaPID-HOP program. The bow and the stern hull-forms are optimized separately without altering neither, and the resulting versions of the two are then combined. Objective functions are the minimum values of wave-making and viscous pressure resistance coefficients for the bow and stern. Parametric modification functions for the bow hull-form variation are SAC shape, section shape (U-V type, DLWL type), bulb shape (bulb height and size); and those for the stern are SAC and section shape (U-V type, DLWL type). WAVIS version 1.3 code is used for the potential and the viscous-flow solver. Prior to the optimization, a parametric study has been conducted to observe the effects of design parameters on the objective functions. SQP has been applied for the optimization algorithm. The model tests have been conducted at a towing tank to evaluate the resistance performance of the optimized hull-form. It has been noted that the optimized hull-form brings 2.4% and 6.8% reduction in total and residual resistance coefficients compared to those of the original hull-form. The propulsive efficiency increases by 2.0% and the delivered power is reduced 3.7%, whereas the propeller rotating speed increases slightly by 0.41 rpm.

  18. Asynchronous Dual-Rail Transition Logic for Enhanced DPA Resistance

    Directory of Open Access Journals (Sweden)

    Rajath Srivathsav N

    2015-02-01

    Full Text Available An Asynchronous Dual–Rail Transition Logic (ADTL is proposed in this paper. The new logic style can be used in the encryption circuit of cryptography to counter the differential power analysis (DPA attacks. The resistance to the DPA attacks is achieved by randomizing the power dissipated in the circuit through Manchester input signal coding and unpredictable initial state of the toggle flip-flops (TFF. The proposed logic uses two wires to transmit the signal, in the form of a single transition on either one of the two wires to indicate the input logic value. T-FFs are employed to randomize the power dissipated by the circuit. The randomizing is made possible by making the initial states of the flip-flops un-deterministic. Furthermore, the clock is completely eliminated in the conceived design, thus realizing increased power randomization and resistance to the DPA attacks. The design is demonstrated through the systematic simulations on a typical encryption circuit. The validation of the ADTL is made through extensive comparisons with the existing Dual-rail Transition Logic (DTL for power, delay and the DPA resistance. Industry standard EDA tools with 90nm technology libraries provided by the UMC foundry have been employed in the designs.

  19. Hull-form optimization of KSUEZMAX to enhance resistance performance

    Directory of Open Access Journals (Sweden)

    Park Jong-Heon

    2015-01-01

    Full Text Available This paper deploys optimization techniques to obtain the optimum hull form of KSUEZMAX at the conditions of full-load draft and design speed. The processes have been carried out using a RaPID-HOP program. The bow and the stern hull-forms are optimized separately without altering neither, and the resulting versions of the two are then combined. Objective functions are the minimum values of wave-making and viscous pressure resistance coefficients for the bow and stern. Parametric modification functions for the bow hull-form variation are SAC shape, section shape (U-V type, DLWL type, bulb shape (bulb height and size; and those for the stern are SAC and section shape (U-V type, DLWL type. WAVIS version 1.3 code is used for the potential and the viscous-flow solver. Prior to the optimization, a parametric study has been conducted to observe the effects of design parameters on the objective functions. SQP has been applied for the optimization algorithm. The model tests have been conducted at a towing tank to evaluate the resistance performance of the optimized hull-form. It has been noted that the optimized hull-form brings 2.4% and 6.8% reduction in total and residual resistance coefficients compared to those of the original hull-form. The propulsive efficiency increases by 2.0% and the delivered power is reduced 3.7%, whereas the propeller rotating speed increases slightly by 0.41 rpm.

  20. Hull-form optimization of KSUEZMAX to enhance resistance performance

    OpenAIRE

    Park Jong-Heon; Choi Jung-Eun; Chun Ho-Hwan

    2015-01-01

    This paper deploys optimization techniques to obtain the optimum hull form of KSUEZMAX at the conditions of full-load draft and design speed. The processes have been carried out using a RaPID-HOP program. The bow and the stern hull-forms are optimized separately without altering neither, and the resulting versions of the two are then combined. Objective functions are the minimum values of wave-making and viscous pressure resistance coefficients for the bow and stern. Parametric modification f...

  1. Enhancing US-Japan cooperation to combat antimicrobial resistance.

    Science.gov (United States)

    Gerbin, C Sachi

    2014-01-01

    The Global Health Security Agenda (GHSA) is aimed at preventing, detecting, and responding to infectious disease threats. To move toward these goals, the United States has committed to partner with at least 30 countries around the world. One of the objectives of the GHSA includes "[p]reventing the emergence and spread of antimicrobial drug resistant organisms." Antimicrobial resistance (AMR) has become a growing global health security problem, with inappropriate use of antimicrobial medications in humans and animals and a lack of new antimicrobial medications contributing to this problem. While AMR is a growing global concern, working on it regionally can make this multifaceted problem more manageable. The United States and Japan, both world leaders in the life sciences, are close allies that have established cooperative programs in medical research and global health that can be used to work on combating AMR and advance the GHSA. Although the United States and Japan have cooperated on health issues in the past, their cooperation on the growing problem of AMR has been limited. Their existing networks, cooperative programs, and close relationships can and should be used to work on combating this expanding problem.

  2. Inhibition of oxidative stress-elicited AKT activation facilitates PPARγ agonist-mediated inhibition of stem cell character and tumor growth of liver cancer cells.

    Directory of Open Access Journals (Sweden)

    Lanlan Liu

    Full Text Available Emerging evidence suggests that tumor-initiating cells (TICs are the most malignant cell subpopulation in tumors because of their resistance to chemotherapy or radiation treatment. Targeting TICs may be a key innovation for cancer treatment. In this study, we found that PPARγ agonists inhibited the cancer stem cell-like phenotype and attenuated tumor growth of human hepatocellular carcinoma (HCC cells. Reactive oxygen species (ROS initiated by NOX2 upregulation were partially responsible for the inhibitory effects mediated by PPARγ agonists. However, PPARγ agonist-mediated ROS production significantly activated AKT, which in turn promoted TIC survival by limiting ROS generation. Inhibition of AKT, by either pharmacological inhibitors or AKT siRNA, significantly enhanced PPARγ agonist-mediated inhibition of cell proliferation and stem cell-like properties in HCC cells. Importantly, in nude mice inoculated with HCC Huh7 cells, we demonstrated a synergistic inhibitory effect of the PPARγ agonist rosiglitazone and the AKT inhibitor triciribine on tumor growth. In conclusion, we observed a negative feedback loop between oxidative stress and AKT hyperactivation in PPARγ agonist-mediated suppressive effects on HCCs. Combinatory application of an AKT inhibitor and a PPARγ agonist may provide a new strategy for inhibition of stem cell-like properties in HCCs and treatment of liver cancer.

  3. Contamination resistant coatings for enhanced laser damage thresholds

    Science.gov (United States)

    Weiller, Bruce H.; Fowler, Jesse D.; Villahermosa, Randy M.

    2012-11-01

    This paper describes a novel approach for the suppression of contamination enhanced laser damage to optical components by the use of fluorinated coatings that repel organic contaminates. In prior work we studied laser damage thresholds induced by ppm levels of toluene under nanosecond 1.064 μm irradiation of fused silica optics. That work showed that moderate vapor-phase concentrations (alcohols dramatically increased the laser damage threshold. The data are consistent with the hypothesis that water and alcohols interact more favorably with the hydroxylated silica surface thereby displacing toluene from the surface. In this work, preliminary results show that fluorinated self assembled monolayer coatings can be used to accomplish the same effect. Optics coated with fluorinated films have much higher survival rates compared with uncoated optics under the same conditions. In addition to enhancing survival of laser optics, these coatings have implications for protecting spacecraft imaging optics from organic contamination.

  4. Enhancement of POM thermooxidation resistance through POSS nanoparticles

    OpenAIRE

    Vilà Ramirez, N.; Sánchez Soto, Miguel; Illescas Fernandez, Silvia

    2011-01-01

    Thermooxidative degradation at and beyond processing temperatures has been carried out on polyoxymethylene (POM) enhanced with four different types of POSS, being Glycidyl, GlycidylIsobutyl, Aminopropylisobutyl, and Poly(ethylene glycol). The quantification of such degradation was carried out through FTIR spectrography, color spectrophotometry, and thermogravimetric analysis methods. The results showed that the presence of POSS in the blend improves dramatically the thermal stability of the P...

  5. Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen.

    Science.gov (United States)

    Baldwin, Susan L; Roeffen, Will; Singh, Susheel K; Tiendrebeogo, Regis W; Christiansen, Michael; Beebe, Elyse; Carter, Darrick; Fox, Christopher B; Howard, Randall F; Reed, Steven G; Sauerwein, Robert; Theisen, Michael

    2016-04-27

    A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment of the sexual-stage protein Pfs48/45-6C genetically fused to GMZ2, an asexual vaccine antigen in advanced clinical development. To select the most suitable vaccine formulation for downstream clinical studies, GMZ2.6C was tested with various immune modulators in different adjuvant formulations (stable emulsions, liposomes, and alum) in C57BL/6 mice. Some, but not all, formulations containing either the synthetic TLR4 agonist GLA or SLA elicited the highest parasite-specific antibody titers, the greatest IFN-γ responses in CD4+ TH1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN-γ and TNF in response to GMZ2.6C. Both of these agonists have good safety records in humans. PMID:26994314

  6. Enhancing cognitive functioning in the elderly: multicomponent vs resistance training

    Directory of Open Access Journals (Sweden)

    Forte R

    2013-01-01

    Full Text Available Roberta Forte,1,2 Colin AG Boreham,1 Joao Costa Leite,3 Giuseppe De Vito,1 Lorraine Brennan,3 Eileen R Gibney,3 Caterina Pesce21Institute for Sport and Health, University College Dublin, Dublin, Ireland; 2Department of Human Movement and Sport Science, University of Rome "Foro Italico," Rome, Italy; 3Institute of Food and Health, University College Dublin, Dublin, IrelandPurpose: The primary purpose of this study was to compare the effects of two different exercise training programs on executive cognitive functions and functional mobility in older adults. A secondary purpose was to explore the potential mediators of training effects on executive function and functional mobility with particular reference to physical fitness gains.Methods: A sample of 42 healthy community dwelling adults aged 65 to 75 years participated twice weekly for 3 months in either: (1 multicomponent training, prioritizing neuromuscular coordination, balance, agility, and cognitive executive control; or (2 progressive resistance training for strength conditioning. Participants were tested at baseline (T1, following a 4-week control period (T2, and finally at postintervention (T3 for executive function (inhibition and cognitive flexibility and functional mobility (maximal walking speed with and without additional task requirements. Cardiorespiratory and muscular fitness were also assessed as potential mediators.Results: Indices of inhibition, the functions involved in the deliberate withholding of prepotent or automatic responses, and measures of functional mobility improved after the intervention, independent of training type. Mediation analysis suggested that different mechanisms underlie the effects of multicomponent and progressive resistance training. While multicomponent training seemed to directly affect inhibitory capacity, resistance training seemed to affect it indirectly through gains in muscular strength. Physical fitness and executive function variables did not

  7. The Efficacy of Pramipexole, a Dopamine Receptor Agonist, as an Adjunctive Treatment in Treatment-Resistant Depression: An Open-Label Trial

    OpenAIRE

    Hiroaki Hori; Hiroshi Kunugi

    2012-01-01

    Dopaminergic dysfunction is implicated in the pathophysiology of treatment-resistant depression. Although the efficacy of adjunctive pramipexole treatment has been demonstrated in treatment-resistant bipolar depression, such data are scarce for major depressive disorder (MDD). We recruited 17 patients with DSM-IV major depressive episode who have failed to respond to previous treatment with a selective serotonin reuptake inhibitor. Five patients were diagnosed as having bipolar II disorder an...

  8. Materials That Enhance Efficiency and Radiation Resistance of Solar Cells

    Science.gov (United States)

    Sun, Xiadong; Wang, Haorong

    2012-01-01

    A thin layer (approximately 10 microns) of a novel "transparent" fluorescent material is applied to existing solar cells or modules to effectively block and convert UV light, or other lower solar response waveband of solar radiation, to visible or IR light that can be more efficiently used by solar cells for additional photocurrent. Meanwhile, the layer of fluorescent coating material remains fully "transparent" to the visible and IR waveband of solar radiation, resulting in a net gain of solar cell efficiency. This innovation alters the effective solar spectral power distribution to which an existing cell gets exposed, and matches the maximum photovoltaic (PV) response of existing cells. By shifting a low PV response waveband (e.g., UV) of solar radiation to a high PV response waveband (e.g. Vis-Near IR) with novel fluorescent materials that are transparent to other solar-cell sensitive wavebands, electrical output from solar cells will be enhanced. This approach enhances the efficiency of solar cells by converting UV and high-energy particles in space that would otherwise be wasted to visible/IR light. This innovation is a generic technique that can be readily implemented to significantly increase efficiencies of both space and terrestrial solar cells, without incurring much cost, thus bringing a broad base of economical, social, and environmental benefits. The key to this approach is that the "fluorescent" material must be very efficient, and cannot block or attenuate the "desirable" and unconverted" waveband of solar radiation (e.g. Vis-NIR) from reaching the cells. Some nano-phosphors and novel organometallic complex materials have been identified that enhance the energy efficiency on some state-of-the-art commercial silicon and thin-film-based solar cells by over 6%.

  9. Dexamethasone-induced enhancement of resistance to ionizing radiation and chemotherapeutic agents in human tumor cells

    International Nuclear Information System (INIS)

    Background: Dexamethasone-induced changes in radioresistance have previously been observed by several authors. Here, we examined effects of dexamethasone on resistance to ionizing radiation in 10 additional human cell lines and strains, and on resistance to carboplatin and paclitaxel in 13 fresh tumor samples. Material and Methods: Eight human carcinoma cell lines, a glioblastoma cell line and a strain of normal human diploid fibroblasts were arbitrarily chosen for these in-vitro studies. Effects on radiosensitivity were assessed using a conventional colony formation assay. Effects on resistance to the drugs were investigated prospectively (ATP cell viability assay) using 13 fresh tumor samples from consecutive patients operated for ovarian cancer within the context of a Swiss nation-wide randomized prospective clinical trial (SAKK 45/94). Results: Dexamethasone promoted proliferation of 1 of the cell lines without affecting radiosensitivity, while it completely inhibited proliferation of another cell line (effects on radiosensitivity could thus not be examined). Furthermore, dexamethasone induced enhanced radioresistance in 1 of the 8 carcinoma cell lines examined. In the glioblastoma cell line, there was no effect on growth or radioresistance, nor in the fibroblasts. Treatment with dexamethasone enhanced resistance of the malignant cells to carboplatin in 4 of the 13 fresh tumor samples examined, while no enhancement in resistance to paclitaxel was observed. Conclusions: In agreement with previous reports, we found that dexamethasone may induce radioresistance in human carcinoma cells. Including the published data from the literature, dexamethasone induced enhancement in radioresistance in 4 of 12 carcinoma cell lines (33%), but not in 3 glioblastoma cell lines, nor in 3 fibroblast strains. Dexamethasone also induced enhanced resistance to carboplatin with a similar probability in fresh samples of ovarian cancer evaluated prospectively (in 4 of 13 samples; 31

  10. The potyviral suppressor of RNA silencing confers enhanced resistance to multiple pathogens

    International Nuclear Information System (INIS)

    Helper component-protease (HC-Pro) is a plant viral suppressor of RNA silencing, and transgenic tobacco expressing HC-Pro has increased susceptibility to a broad range of viral pathogens. Here we report that these plants also exhibit enhanced resistance to unrelated heterologous pathogens. Tobacco mosaic virus (TMV) infection of HC-Pro-expressing plants carrying the N resistance gene results in fewer and smaller lesions compared to controls without HC-Pro. The resistance to TMV is compromised but not eliminated by expression of nahG, which prevents accumulation of salicylic acid (SA), an important defense signaling molecule. HC-Pro-expressing plants are also more resistant to tomato black ring nepovirus (TBRV) and to the oomycete Peronospora tabacina. Enhanced TBRV resistance is SA-independent, whereas the response to P. tabacina is associated with early induction of markers characteristic of SA-dependent defense. Thus, a plant viral suppressor of RNA silencing enhances resistance to multiple pathogens via both SA-dependent and SA-independent mechanisms

  11. Rapid identification of bacterial resistance to Ciprofloxacin using surface-enhanced Raman spectroscopy

    Science.gov (United States)

    Kastanos, Evdokia; Hadjigeorgiou, Katerina; Pitris, Costas

    2014-02-01

    Due to its effectiveness and broad coverage, Ciprofloxacin is the fifth most prescribed antibiotic in the US. As current methods of infection diagnosis and antibiotic sensitivity testing (i.e. an antibiogram) are very time consuming, physicians prescribe ciprofloxacin before obtaining antibiogram results. In order to avoid increasing resistance to the antibiotic, a method was developed to provide both a rapid diagnosis and the sensitivity to the antibiotic. Using Surface Enhanced Raman Spectroscopy, an antibiogram was obtained after exposing the bacteria to Ciprofloxacin for just two hours. Spectral analysis revealed clear separation between sensitive and resistant bacteria and could also offer some inside into the mechanisms of resistance.

  12. A Holy Grail of asthma management: toward understanding how long-acting β2-adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids

    Science.gov (United States)

    Giembycz, M A; Kaur, M; Leigh, R; Newton, R

    2007-01-01

    There is unequivocal evidence that the combination of an inhaled corticosteroid (ICS)—i.e. glucocorticoid—and an inhaled long-acting β2-adrenoceptor agonist (LABA) is superior to each component administered as a monotherapy alone in the clinical management of asthma. Moreover, Calverley and colleagues (Lancet 2003, 361: 449–456; N Engl J Med 2007, 356: 775–789) reporting for the ‘TRial of Inhaled STeroids ANd long-acting β2-agonists (TRISTAN)' and ‘TOwards a Revolution in COPD Health (TORCH)' international study groups also demonstrated the superior efficacy of LABA/ICS combination therapies over ICS alone in the clinical management of chronic obstructive pulmonary disease. This finding has been independently confirmed indicating that the therapeutic benefit of LABA/ICS combination therapies is not restricted to asthma and may be extended to other chronic inflammatory diseases of the airways. Despite the unquestionable benefit of LABA/ICS combination therapies, there is a vast gap in our understanding of how these two drugs given together deliver superior clinical efficacy. In this article, we review the history of LABA/ICS combination therapies and critically evaluate how these two classes of drugs might interact at the biochemical level to suppress pro-inflammatory responses. Understanding the molecular basis of this fundamental clinical observation is a Holy Grail of current respiratory diseases research as it could permit the rational exploitation of this effect with the development of new ‘optimized' LABA/ICS combination therapies. PMID:18071293

  13. PPARγ1 phosphorylation enhances proliferation and drug resistance in human fibrosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Xiaojuan; Shu, Yuxin; Niu, Zhiyuan; Zheng, Wei; Wu, Haochen [State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Lu, Yan, E-mail: luyan@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Shen, Pingping, E-mail: ppshen@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Model Animal Research Center (MARC), Nanjing University, Nanjing (China)

    2014-03-10

    Post-translational regulation plays a critical role in the control of cell growth and proliferation. The phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ) is the most important post-translational modification. The function of PPARγ phosphorylation has been studied extensively in the past. However, the relationship between phosphorylated PPARγ1 and tumors remains unclear. Here we investigated the role of PPARγ1 phosphorylation in human fibrosarcoma HT1080 cell line. Using the nonphosphorylation (Ser84 to alanine, S84A) and phosphorylation (Ser84 to aspartic acid, S84D) mutant of PPARγ1, the results suggested that phosphorylation attenuated PPARγ1 transcriptional activity. Meanwhile, we demonstrated that phosphorylated PPARγ1 promoted HT1080 cell proliferation and this effect was dependent on the regulation of cell cycle arrest. The mRNA levels of cyclin-dependent kinase inhibitor (CKI) p21{sup Waf1/Cip1} and p27{sup Kip1} descended in PPARγ1{sup S84D} stable HT1080 cell, whereas the expression of p18{sup INK4C} was not changed. Moreover, compared to the PPARγ1{sup S84A}, PPARγ1{sup S84D} up-regulated the expression levels of cyclin D1 and cyclin A. Finally, PPARγ1 phosphorylation reduced sensitivity to agonist rosiglitazone and increased resistance to anticancer drug 5-fluorouracil (5-FU) in HT1080 cell. Our findings establish PPARγ1 phosphorylation as a critical event in human fibrosarcoma growth. These findings raise the possibility that chemical compounds that prevent the phosphorylation of PPARγ1 could act as anticancer drugs. - Highlights: • Phosphorylation attenuates PPARγ1 transcriptional activity. • Phosphorylated PPARγ1 promotes HT1080 cells proliferation. • PPARγ1 phosphorylation regulates cell cycle by mediating expression of cell cycle regulators. • PPARγ1 phosphorylation reduces sensitivity to agonist and anticancer drug. • Our findings establish PPARγ1 phosphorylation as a critical event in HT1080

  14. The Enhanced metastatic potential of hepatocellular carcinoma (HCC cells with sorafenib resistance.

    Directory of Open Access Journals (Sweden)

    Ariel Ka-Man Chow

    Full Text Available Acquired resistance towards sorafenib treatment was found in HCC patients, which results in poor prognosis. To investigate the enhanced metastatic potential of sorafenib resistance cells, sorafenib-resistant (SorR cell lines were established by long-term exposure of the HCC cells to the maximum tolerated dose of sorafenib. Cell proliferation assay and qPCR of ABC transporter genes (ABCC1-3 were first performed to confirm the resistance of cells. Migration and invasion assays, and immunoblotting analysis on the expression of epithelial to mesenchymal transition (EMT regulatory proteins were performed to study the metastatic potential of SorR cells. The expression of CD44 and CD133 were studied by flow cytometry and the gene expressions of pluripotency factors were studied by qPCR to demonstrate the enrichment of cancer stem cells (CSCs in SorR cells. Control (CTL and SorR cells were also injected orthotopically to the livers of NOD-SCID mice to investigate the development of lung metastasis. Increased expressions of ABCC1-3 were found in SorR cells. Enhanced migratory and invasive abilities of SorR cells were observed. The changes in expression of EMT regulatory proteins demonstrated an activation of the EMT process in SorR cells. Enriched proportion of CD44(+ and CD44(+CD133(+ cells were also observed in SorR cells. All (8/8 mice injected with SorR cells demonstrated lung metastasis whereas only 1/8 mouse injected with CTL cells showed lung metastasis. HCC cells with sorafenib resistance demonstrated a higher metastatic potential, which may be due to the activated EMT process. Enriched CSCs were also demonstrated in the sorafenib resistant cells. This study suggests that advanced HCC patients with acquired sorafenib resistance may have enhanced tumor growth or distant metastasis, which raises the concern of long-term sorafenib treatment in advanced HCC patients who have developed resistance of sorafenib.

  15. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart;

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...

  16. Toughing It Out--Disease-Resistant Potato Mutants Have Enhanced Tuber Skin Defenses.

    Science.gov (United States)

    Thangavel, Tamilarasan; Tegg, Robert S; Wilson, Calum R

    2016-05-01

    Common scab, a globally important potato disease, is caused by infection of tubers with pathogenic Streptomyces spp. Previously, disease-resistant potato somaclones were obtained through cell selections against the pathogen's toxin, known to be essential for disease. Further testing revealed that these clones had broad-spectrum resistance to diverse tuber-invading pathogens, and that resistance was restricted to tuber tissues. The mechanism of enhanced disease resistance was not known. Tuber periderm tissues from disease-resistant clones and their susceptible parent were examined histologically following challenge with the pathogen and its purified toxin. Relative expression of genes associated with tuber suberin biosynthesis and innate defense pathways within these tissues were also examined. The disease-resistant somaclones reacted to both pathogen and toxin by producing more phellem cell layers in the tuber periderm, and accumulating greater suberin polyphenols in these tissues. Furthermore, they had greater expression of genes associated with suberin biosynthesis. In contrast, signaling genes associated with innate defense responses were not differentially expressed between resistant and susceptible clones. The resistance phenotype is due to induction of increased periderm cell layers and suberization of the tuber periderm preventing infection. The somaclones provide a valuable resource for further examination of suberization responses and its genetic control.

  17. Nutritional regulation of muscle protein synthesis with resistance exercise: strategies to enhance anabolism

    Directory of Open Access Journals (Sweden)

    Churchward-Venne Tyler A

    2012-05-01

    Full Text Available Abstract Provision of dietary amino acids increases skeletal muscle protein synthesis (MPS, an effect that is enhanced by prior resistance exercise. As a fundamentally necessary process in the enhancement of muscle mass, strategies to enhance rates of MPS would be beneficial in the development of interventions aimed at increasing skeletal muscle mass particularly when combined with chronic resistance exercise. The purpose of this review article is to provide an update on current findings regarding the nutritional regulation of MPS and highlight nutrition based strategies that may serve to maximize skeletal muscle protein anabolism with resistance exercise. Such factors include timing of protein intake, dietary protein type, the role of leucine as a key anabolic amino acid, and the impact of other macronutrients (i.e. carbohydrate on the regulation of MPS after resistance exercise. We contend that nutritional strategies that serve to maximally stimulate MPS may be useful in the development of nutrition and exercise based interventions aimed at enhancing skeletal muscle mass which may be of interest to elderly populations and to athletes.

  18. Transcriptomic assessment of resistance to effects of an aryl hydrocarbon receptor (AHR agonist in embryos of Atlantic killifish (Fundulus heteroclitus from a marine Superfund site

    Directory of Open Access Journals (Sweden)

    Franks Diana G

    2011-05-01

    Full Text Available Abstract Background Populations of Atlantic killifish (Fundulus heteroclitus have evolved resistance to the embryotoxic effects of polychlorinated biphenyls (PCBs and other halogenated and nonhalogenated aromatic hydrocarbons that act through an aryl hydrocarbon receptor (AHR-dependent signaling pathway. The resistance is accompanied by reduced sensitivity to induction of cytochrome P450 1A (CYP1A, a widely used biomarker of aromatic hydrocarbon exposure and effect, but whether the reduced sensitivity is specific to CYP1A or reflects a genome-wide reduction in responsiveness to all AHR-mediated changes in gene expression is unknown. We compared gene expression profiles and the response to 3,3',4,4',5-pentachlorobiphenyl (PCB-126 exposure in embryos (5 and 10 dpf and larvae (15 dpf from F. heteroclitus populations inhabiting the New Bedford Harbor, Massachusetts (NBH Superfund site (PCB-resistant and a reference site, Scorton Creek, Massachusetts (SC; PCB-sensitive. Results Analysis using a 7,000-gene cDNA array revealed striking differences in responsiveness to PCB-126 between the populations; the differences occur at all three stages examined. There was a sizeable set of PCB-responsive genes in the sensitive SC population, a much smaller set of PCB-responsive genes in NBH fish, and few similarities in PCB-responsive genes between the two populations. Most of the array results were confirmed, and additional PCB-regulated genes identified, by RNA-Seq (deep pyrosequencing. Conclusions The results suggest that NBH fish possess a gene regulatory defect that is not specific to one target gene such as CYP1A but rather lies in a regulatory pathway that controls the transcriptional response of multiple genes to PCB exposure. The results are consistent with genome-wide disruption of AHR-dependent signaling in NBH fish.

  19. Wild Help for Enhancing Genetic Resistance in Lentil Against Fungal Diseases.

    Science.gov (United States)

    Bhadauria, Vijai; Wong, Melissa M L; Bett, Kirstin E; Banniza, Sabine

    2016-01-01

    Lentil (Lens culinaris) is one of the cool season grain legume crops and an important source of dietary proteins and fibre. Fungal diseases are main constraints to lentil production and account for significant yield and quality losses. Lentil has a narrow genetic base presumably due to a bottleneck during domestication and as a result, any resistance to fungal diseases in the cultivated genepool is gradually eroded and overcome by pathogens. New sources of resistance have been identified in wild lentil (Lens ervoides). This article provides an overview of harnessing resistance potential of wild germplasm to enhance genetic resistance in lentil cultivars using next-generation sequencing-based genotyping, comparative genomics and marker-assisted selection breeding. PMID:26363611

  20. Enhanced transmission of drug-resistant parasites to mosquitoes following drug treatment in rodent malaria.

    Directory of Open Access Journals (Sweden)

    Andrew S Bell

    Full Text Available 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 Plasmodium chabaudi, co-infection with drug-sensitive parasites can prevent the transmission of initially rare resistant parasites to mosquitoes. Removal of drug-sensitive parasites following chemotherapy enabled resistant parasites to transmit to mosquitoes as successfully as sensitive parasites in the absence of treatment. We also show that the genetic composition of gametocyte populations in host venous blood accurately reflects the genetic composition of gametocytes taken up by mosquitoes. Our data demonstrate that, at least for this mouse model, aggressive chemotherapy leads to very effective transmission of highly resistant parasites that are present in an infection, the very parasites which undermine the long term efficacy of front-line drugs.

  1. Ti addition to enhance corrosion resistance of Sn–Zn solder alloy by tailoring microstructure

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jian-Chun [Department of Mechanical Engineering, Tsinghua University, Beijing 100084 (China); Zhang, Gong, E-mail: zhangg@tsinghua.edu.cn [Department of Mechanical Engineering, Tsinghua University, Beijing 100084 (China); Ma, Ju-Sheng [Department of Mechanical Engineering, Tsinghua University, Beijing 100084 (China); Suganuma, Katsuaki [Institute of Scientific and Industrial Research, Osaka University, Mihogaoka 8-1, Ibaraki, Osaka 567-0047 (Japan)

    2015-09-25

    Highlights: • Trace amount of Ti was added to Sn–9Zn alloy. • Corrosion resistance of the modified alloy was significantly enhanced. • Zn-rich precipitates within the microstructure were effectively refined. • The enhanced corrosion resistance was attributed to the refined Zn-rich precipitates. - Abstract: The effect of trace addition of Ti on the corrosion behavior of Sn–9Zn (wt.%) solder alloy in NaCl solution was investigated using polarization and electrochemical impedance spectroscopy techniques. It is found that the corrosion resistance of Sn–9Zn alloy can be significantly enhanced by adding 0.05 wt.% of Ti, evidenced by much lower corrosion current density, lower passive current density and higher impedance. Such enhancement results from the refinement of Zn-rich precipitates within the microstructure, which is conducive to forming a relatively more protective passive film on the surface of the modified alloy. This would be an important finding in the design of novel Sn–Zn solder alloys in electronic assemblies operating under aggressive conditions.

  2. ENHANCEMENT OF RESISTANCE TO OXIDATIVE DEGRADATION OF NATURAL RUBBER THROUGH LATEX DEGRADATION

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    A fully characterised natural rubber latex was subjected to mechanical degradation by stirring at intervals. The resistance to oxidative degradation of the different samples were studied by measuring the Plasticity retention indices (PRI).The results show that there is an enhancement of the PRI from 57% for the undegraded rubber to 79% for the one-hour degraded sample. Further degradation resulted in decrease of PRI as time of degradation increased. Therefore, the one-hour degraded sample is a special rubber with high oxidation resistance which is of great importance in engineering.

  3. [Effect of immunomodulators on resistance to gas gangrene. The enhanced resistance of white mice to perfringens toxin type A as affected by prodigiozan].

    Science.gov (United States)

    Konikova, R E; Stepanov, A V; Sviridov, L P

    1986-02-01

    Experiments on 575 noninbred white mice have revealed that the nonspecific resistance of the animals to type A C. perfringens toxin can be enhanced by the administration of Prodigiosan, a commercial immunostimulating agent. Prodigiosan, introduced in 3-4 injections (the last one made 24 hours before intoxication) has been found to enhance the resistance of the animals to the subcutaneous injection of type A C. perfringens toxin by 40-60% and to its intraperitoneal injection by 60-97%. PMID:2870596

  4. Pavlovian conditioning enhances resistance to disruption of dogs performing an odor discrimination.

    Science.gov (United States)

    Hall, Nathaniel J; Smith, David W; Wynne, Clive D L

    2015-05-01

    Domestic dogs are used to aid in the detection of a variety of substances such as narcotics and explosives. Under real-world detection situations there are many variables that may disrupt the dog's performance. Prior research on behavioral momentum theory suggests that higher rates of reinforcement produce greater resistance to disruption, and that this is heavily influenced by the stimulus-reinforcer relationship. The present study tests the Pavlovian interpretation of resistance to change using dogs engaged in an odor discrimination task. Dogs were trained on two odor discriminations that alternated every six trials akin to a multiple schedule in which the reinforcement probability for a correct response was always 1. Dogs then received several sessions of either odor Pavlovian conditioning to the S+ of one odor discrimination (Pavlovian group) or explicitly unpaired exposure to the S+ of one odor discrimination (Unpaired group). The remaining odor discrimination pair for each dog always remained an unexposed control. Resistance to disruption was assessed under presession feeding, a food-odor disruptor condition, and extinction, with baseline sessions intervening between disruption conditions. Equivalent baseline detection rates were observed across experimental groups and odorant pairs. Under disruption conditions, Pavlovian conditioning led to enhanced resistance to disruption of detection performance compared to the unexposed control odor discrimination. Unpaired odor conditioning did not influence resistance to disruption. These results suggest that changes in Pavlovian contingencies are sufficient to influence resistance to change.

  5. Pavlovian conditioning enhances resistance to disruption of dogs performing an odor discrimination.

    Science.gov (United States)

    Hall, Nathaniel J; Smith, David W; Wynne, Clive D L

    2015-05-01

    Domestic dogs are used to aid in the detection of a variety of substances such as narcotics and explosives. Under real-world detection situations there are many variables that may disrupt the dog's performance. Prior research on behavioral momentum theory suggests that higher rates of reinforcement produce greater resistance to disruption, and that this is heavily influenced by the stimulus-reinforcer relationship. The present study tests the Pavlovian interpretation of resistance to change using dogs engaged in an odor discrimination task. Dogs were trained on two odor discriminations that alternated every six trials akin to a multiple schedule in which the reinforcement probability for a correct response was always 1. Dogs then received several sessions of either odor Pavlovian conditioning to the S+ of one odor discrimination (Pavlovian group) or explicitly unpaired exposure to the S+ of one odor discrimination (Unpaired group). The remaining odor discrimination pair for each dog always remained an unexposed control. Resistance to disruption was assessed under presession feeding, a food-odor disruptor condition, and extinction, with baseline sessions intervening between disruption conditions. Equivalent baseline detection rates were observed across experimental groups and odorant pairs. Under disruption conditions, Pavlovian conditioning led to enhanced resistance to disruption of detection performance compared to the unexposed control odor discrimination. Unpaired odor conditioning did not influence resistance to disruption. These results suggest that changes in Pavlovian contingencies are sufficient to influence resistance to change. PMID:25912271

  6. Enhanced microwave absorbing properties and heat resistance of carbonyl iron by electroless plating Co

    Science.gov (United States)

    Wang, Hongyu; Zhu, Dongmei; Zhou, Wancheng; Luo, Fa

    2015-11-01

    Co coated carbonyl iron particles (Co (CI)) are fabricated through electroless plating method, and the electromagnetic microwave absorbing properties are investigated in the frequencies during 8.2-12.4 GHz. The complex permittivity of CI particles after electroless plating Co is higher than that of raw CI particles due to improvment of the polarization process. Furthermore, according to the XRD and TG results, the Co layer can enhance the heat resistance of CI particles. The bandwidth below -10 dB can reach 3.9 GHz for the Co(CI) absorbent. The results indicate that the electroless plating Co not only enhances the absorbing properties but also improves the heat resistance of CI.

  7. Enhancement in resistivity resolution based on the data sets amalgamation technique at Bukit Bunuh, Perak, Malaysia

    International Nuclear Information System (INIS)

    In this paper, we have carried out a study with the main objective to enhance the resolution of the electrical resistivity inversion model by introducing the data sets amalgamation technique to be used in the data processing stage. Based on the model resistivity with topography results, the data sets amalgamation technique for pole-dipole and wenner- schlumberger arrays are successful in identifying the boundary or interface of the overburden and weathered granite. Although the electrical resistivity method is well known, the proper selection of an array and appropriate inversion parameters setting such as damping factors are important in order to achieve the study objective and to image the target at the Earth's subsurface characterizations

  8. Adjuvants Based on Hybrid Antibiotics Overcome Resistance in Pseudomonas aeruginosa and Enhance Fluoroquinolone Efficacy.

    Science.gov (United States)

    Gorityala, Bala Kishan; Guchhait, Goutam; Fernando, Dinesh M; Deo, Soumya; McKenna, Sean A; Zhanel, George G; Kumar, Ayush; Schweizer, Frank

    2016-01-11

    The use of adjuvants that rescue antibiotics against multidrug-resistant (MDR) pathogens is a promising combination strategy for overcoming bacterial resistance. While the combination of β-lactam antibiotics and β-lactamase inhibitors has been successful in restoring antibacterial efficacy in MDR bacteria, the use of adjuvants to restore fluoroquinolone efficacy in MDR Gram-negative pathogens has been challenging. We describe tobramycin-ciprofloxacin hybrid adjuvants that rescue the activity of fluoroquinolone antibiotics against MDR and extremely drug-resistant Pseudomonas aeruginosa isolates in vitro and enhance fluoroquinolone efficacy in vivo. Structure-activity studies reveal that the presence of both tobramycin and ciprofloxacin, which are separated by a C12 tether, is critical for the function of the adjuvant. Mechanistic studies indicate that the antibacterial modes of ciprofloxacin are retained while the role of tobramycin is limited to destabilization of the outer membrane in the hybrid.

  9. Companion cropping with potato onion enhances the disease resistance of tomato against Verticillium dahliae

    Directory of Open Access Journals (Sweden)

    Xuepeng eFu

    2015-09-01

    Full Text Available Intercropping could alleviate soil-borne diseases, however, few studies focused on the immunity of the host plant induced by the interspecific interactions. To test whether or not intercropping could enhance the disease resistance of host plant, we investigated the effect of companion cropping with potato onion on tomato Verticillium wilt caused by Verticillium dahliae (V. dahliae. To investigate the mechanisms, the root exudates were collected from tomato and potato onion which were grown together or separately, and were used to examine the antifungal activities against V. dahliae in vitro, respectively. Furthermore, RNA-seq was used to examine the expression pattern of genes related to disease resistance in tomato companied with potato onion compared to that in tomato grown alone, under the condition of infection with V. dahliae. The results showed that companion cropping with potato onion could alleviate the incidence and severity of tomato Verticillium wilt. The further studies revealed that the root exudates from tomato companied with potato onion significantly inhibited the mycelia growth and spore germination of V. dahliae. However, there were no significant effects on these two measurements for the root exudates from potato onion grown alone or from potato onion grown with tomato. RNA-seq data analysis showed the disease defense genes associated with pathogenesis-related proteins, biosynthesis of lignin, hormone metabolism and signal transduction were expressed much higher in the tomato companied with potato onion than those in the tomato grown alone, which indicated that these defense genes play important roles in tomato against V. dahliae infection, and meant that the disease resistance of tomato against V. dahliae was enhanced in the companion copping with potato onion. We proposed that companion cropping with potato onion could enhance the disease resistance of tomato against V. dahliae by regulating the expression of genes related

  10. Enhanced expression of DNA polymerase eta contributes to cisplatin resistance of ovarian cancer stem cells

    OpenAIRE

    Srivastava, Amit Kumar; Han, Chunhua; Zhao, Ran; Cui, Tiantian; Dai, Yuntao; Mao, Charlene; Zhao, Weiqiang; Zhang, Xiaoli; Yu, Jianhua; Wang, Qi-En

    2015-01-01

    Cancer stem cells (CSCs) exhibit enhanced chemo/radiotherapy resistance, and their survival following cancer treatment is believed to be responsible for tumor recurrence and metastasis. Thus, understanding the mechanisms through which CSCs survive conventional chemotherapy is essential for identification of new therapeutic strategies to prevent tumor relapse. Our findings that ovarian CSCs survive cisplatin treatment through elevated expression of polymerase η represent an opportunity to erad...

  11. Overexpression of Soybean Isoflavone Reductase (GmIFR) Enhances Resistance to Phytophthora sojae in Soybean

    OpenAIRE

    Cheng, Qun; Li, Ninghui; Dong, Lidong; Zhang, Dayong; Fan, Sujie; Jiang, Liangyu; Wang, Xin; Xu, Pengfei; Zhang, Shuzhen

    2015-01-01

    Isoflavone reductase (IFR) is an enzyme involved in the biosynthetic pathway of isoflavonoid phytoalexin in plants. IFRs are unique to the plant kingdom and are considered to have crucial roles in plant response to various biotic and abiotic environmental stresses. Here, we report the characterization of a novel member of the soybean isoflavone reductase gene family GmIFR. Overexpression of GmIFR transgenic soybean exhibited enhanced resistance to Phytophthora sojae. Following stress treatmen...

  12. The Enhancement of Mg Corrosion Resistance by Alloying Mn and Laser-Melting

    Directory of Open Access Journals (Sweden)

    Youwen Yang

    2016-03-01

    Full Text Available Mg has been considered a promising biomaterial for bone implants. However, the poor corrosion resistance has become its main undesirable property. In this study, both alloying Mn and laser-melting were applied to enhance the Mg corrosion resistance. The corrosion resistance, mechanical properties, and microstructure of rapid laser-melted Mg-xMn (x = 0–3 wt % alloys were investigated. The alloys were composed of dendrite grains, and the grains size decreased with increasing Mn. Moreover, Mn could dissolve and induce the crystal lattice distortion of the Mg matrix during the solidification process. Mn ranging from 0–2 wt % dissolved completely due to rapid laser solidification. As Mn contents further increased up to 3 wt %, a small amount of Mn was left undissolved. The compressive strength of Mg-Mn alloys increased first (up to 2 wt % and then decreased with increasing Mn, while the hardness increased continuously. The refinement of grains and the increase in corrosion potential both made contributions to the enhancement of Mg corrosion resistance.

  13. Enhancement of resistance to aphids by introducing the snowdrop lectin gene gna into maize plants.

    Science.gov (United States)

    Wang, Zhaoyu; Zhang, Kewei; Sun, Xiaofen; Tang, Kexuan; Zhang, Juren

    2005-12-01

    In order to enhance the resistance to pests, transgenic maize (Zea mays L.) plants from elite inbred lines containing the gene encoding snowdrop lectin (Galanthus nivalis L. agglutinin; GNA) under control of a phloem-specific promoter were generated through the Agrobacterium tumefaciens-mediated method. The toxicity of GNA-expressing plants to aphids has also been studied. The independently derived plants were subjected to molecular analyses. Polymerase chain reaction (PCR) and Southern blot analyses confirmed that the gna gene was integrated into maize genome and inherited to the following generations. The typical Mendelian patterns of inheritance occurred in most cases. The level of GNA expression at 0.13%-0.28% of total soluble protein was observed in different transgenic plants. The progeny of nine GNA-expressing independent transformants that were derived separately from the elite inbred lines DH4866, DH9942, and 8902, were selected for examination of resistance to aphids. These plants synthesized GNA at levels above 0.22% total soluble protein, and enhanced resistance to aphids was demonstrated by exposing the plants to corn leaf aphid (Rhopalosiphum maidis Fitch) under greenhouse conditions. The nymph production was significantly reduced by 46.9% on GNA-expressing plants. Field evaluation of the transgenic plants supported the results from the inoculation trial. After a series of artificial self-crosses, some homozygous transgenic maize lines expressing GNA were obtained. In the present study, we have obtained new insect-resistant maize material for further breeding work.

  14. Nano zinc phosphate coatings for enhanced corrosion resistance of mild steel

    International Nuclear Information System (INIS)

    Highlights: • Nano zinc phosphate coating on mild steel was developed. • Nano zinc phosphate coatings on mild steel showed enhanced corrosion resistance. • The nano ZnO increases the number of nucleating sites for phosphating. • Faster attainment of steady state during nano zinc phosphating. - Abstract: Nano crystalline zinc phosphate coatings were developed on mild steel surface using nano zinc oxide particles. The chemical composition and morphology of the coatings were analyzed by X-ray diffraction analysis (XRD), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The particles size of the nano zinc phosphate coating developed was also characterized by TEM analysis. Potentiodynamic polarization and electrochemical impedance studies were carried out in 3.5% NaCl solution. Significant variations in the coating weight, morphology and corrosion resistance were observed as nano ZnO concentrations were varied from 0.25 to 2 g/L in the phosphating baths. The results showed that nano ZnO particles in the phosphating solution yielded phosphate coatings of higher coating weight, greater surface coverage and enhanced corrosion resistance than the normal zinc phosphate coatings (developed using normal ZnO particles in the phosphating baths). Better corrosion resistance was observed for coatings derived from phosphating bath containing 1.5 g/L nano ZnO. The activation effect brought about by the nano ZnO reduces the amount of accelerator (NaNO2) required for phosphating

  15. Enhancement of resistance to aphids by introducing the snowdrop lectin gene gna into maize plants

    Indian Academy of Sciences (India)

    Zhaoyu Wang; Kewei Zhang; Xiaofen Sun; Kexuan Tang; Juren Zhang

    2005-12-01

    In order to enhance the resistance to pests, transgenic maize (Zea mays L.) plants from elite inbred lines containing the gene encoding snowdrop lectin (Galanthus nivalis L. agglutinin; GNA) under control of a phloemspecific promoter were generated through the Agrobacterium tumefaciens-mediated method. The toxicity of GNA-expressing plants to aphids has also been studied. The independently derived plants were subjected to molecular analyses. Polymerase chain reaction (PCR) and Southern blot analyses confirmed that the gna gene was integrated into maize genome and inherited to the following generations. The typical Mendelian patterns of inheritance occurred in most cases. The level of GNA expression at 0.13%–0.28% of total soluble protein was observed in different transgenic plants. The progeny of nine GNA-expressing independent transformants that were derived separately from the elite inbred lines DH4866, DH9942, and 8902, were selected for examination of resistance to aphids. These plants synthesized GNA at levels above 0.22% total soluble protein, and enhanced resistance to aphids was demonstrated by exposing the plants to corn leaf aphid (Rhopalosiphum maidis Fitch) under greenhouse conditions. The nymph production was significantly reduced by 46.9% on GNA-expressing plants. Field evaluation of the transgenic plants supported the results from the inoculation trial. After a series of artificial self-crosses, some homozygous transgenic maize lines expressing GNA were obtained. In the present study, we have obtained new insect-resistant maize material for further breeding work.

  16. Peculiarities of Enhancing Resistant Starch in Ruminants Using Chemical Methods: Opportunities and Challenges

    Directory of Open Access Journals (Sweden)

    Qendrim Zebeli

    2013-06-01

    Full Text Available High-producing ruminants are fed high amounts of cereal grains, at the expense of dietary fiber, to meet their high energy demands. Grains consist mainly of starch, which is easily degraded in the rumen by microbial glycosidases, providing energy for rapid growth of rumen microbes and short-chain fatty acids (SCFA as the main energy source for the host. Yet, low dietary fiber contents and the rapid accumulation of SCFA lead to rumen disorders in cattle. The chemical processing of grains has become increasingly important to confer their starch resistances against rumen microbial glycosidases, hence generating ruminally resistant starch (RRS. In ruminants, unlike monogastric species, the strategy of enhancing resistant starch is useful, not only in lowering the amount of carbohydrate substrates available for digestion in the upper gut sections, but also in enhancing the net hepatic glucose supply, which can be utilized by the host more efficiently than the hepatic gluconeogenesis of SCFA. The use of chemical methods to enhance the RRS of grains and the feeding of RRS face challenges in the practice; therefore, the present article attempts to summarize the most important achievements in the chemical processing methods used to generate RRS, and review advantages and challenges of feeding RRS to ruminants

  17. A nanometric cushion for enhancing scratch and wear resistance of hard films.

    Science.gov (United States)

    Gotlib-Vainshtein, Katya; Girshevitz, Olga; Sukenik, Chaim N; Barlam, David; Cohen, Sidney R

    2014-01-01

    Scratch resistance and friction are core properties which define the tribological characteristics of materials. Attempts to optimize these quantities at solid surfaces are the subject of intense technological interest. The capability to modulate these surface properties while preserving both the bulk properties of the materials and a well-defined, constant chemical composition of the surface is particularly attractive. We report herein the use of a soft, flexible underlayer to control the scratch resistance of oxide surfaces. Titania films of several nm thickness are coated onto substrates of silicon, kapton, polycarbonate, and polydimethylsiloxane (PDMS). The scratch resistance measured by scanning force microscopy is found to be substrate dependent, diminishing in the order PDMS, kapton/polycarbonate, Si/SiO2. Furthermore, when PDMS is applied as an intermediate layer between a harder substrate and titania, marked improvement in the scratch resistance is achieved. This is shown by quantitative wear tests for silicon or kapton, by coating these substrates with PDMS which is subsequently capped by a titania layer, resulting in enhanced scratch/wear resistance. The physical basis of this effect is explored by means of Finite Element Analysis, and we suggest a model for friction reduction based on the "cushioning effect" of a soft intermediate layer.

  18. Transgenic banana expressing Pflp gene confers enhanced resistance to Xanthomonas wilt disease.

    Science.gov (United States)

    Namukwaya, B; Tripathi, L; Tripathi, J N; Arinaitwe, G; Mukasa, S B; Tushemereirwe, W K

    2012-08-01

    Banana Xanthomonas wilt (BXW), caused by Xanthomonas campestris pv. musacearum, is one of the most important diseases of banana (Musa sp.) and currently considered as the biggest threat to banana production in Great Lakes region of East and Central Africa. The pathogen is highly contagious and its spread has endangered the livelihood of millions of farmers who rely on banana for food and income. The development of disease resistant banana cultivars remains a high priority since farmers are reluctant to employ labor-intensive disease control measures and there is no host plant resistance among banana cultivars. In this study, we demonstrate that BXW can be efficiently controlled using transgenic technology. Transgenic bananas expressing the plant ferredoxin-like protein (Pflp) gene under the regulation of the constitutive CaMV35S promoter were generated using embryogenic cell suspensions of banana. These transgenic lines were characterized by molecular analysis. After challenge with X. campestris pv. musacearum transgenic lines showed high resistance. About 67% of transgenic lines evaluated were completely resistant to BXW. These transgenic lines did not show any disease symptoms after artificial inoculation of in vitro plants under laboratory conditions as well as potted plants in the screen-house, whereas non-transgenic control plants showed severe symptoms resulting in complete wilting. This study confirms that expression of the Pflp gene in banana results in enhanced resistance to BXW. This transgenic technology can provide a timely solution to the BXW pandemic.

  19. A nanometric cushion for enhancing scratch and wear resistance of hard films

    Directory of Open Access Journals (Sweden)

    Katya Gotlib-Vainshtein

    2014-07-01

    Full Text Available Scratch resistance and friction are core properties which define the tribological characteristics of materials. Attempts to optimize these quantities at solid surfaces are the subject of intense technological interest. The capability to modulate these surface properties while preserving both the bulk properties of the materials and a well-defined, constant chemical composition of the surface is particularly attractive. We report herein the use of a soft, flexible underlayer to control the scratch resistance of oxide surfaces. Titania films of several nm thickness are coated onto substrates of silicon, kapton, polycarbonate, and polydimethylsiloxane (PDMS. The scratch resistance measured by scanning force microscopy is found to be substrate dependent, diminishing in the order PDMS, kapton/polycarbonate, Si/SiO2. Furthermore, when PDMS is applied as an intermediate layer between a harder substrate and titania, marked improvement in the scratch resistance is achieved. This is shown by quantitative wear tests for silicon or kapton, by coating these substrates with PDMS which is subsequently capped by a titania layer, resulting in enhanced scratch/wear resistance. The physical basis of this effect is explored by means of Finite Element Analysis, and we suggest a model for friction reduction based on the "cushioning effect” of a soft intermediate layer.

  20. Enhancing disease resistances of Super Hybrid Rice with four antifungal genes

    Institute of Scientific and Technical Information of China (English)

    ZHU HuaChen; XU XinPing; XIAO GuoYing; YUAN LongPing; LI BaoJian

    2007-01-01

    A plant expression vector harboring four antifungal genes was delivered into the embryogenic calli of '9311', an indica restorer line of Super Hybrid Rice, via modified biolistic particle bombardment. Southern blot analysis indicated that in the regenerated hygromycin-resistant plants, all the four antifungal genes, including RCH10, RAC22, β-Glu and B-RIP, were integrated into the genome of '9311', co-transmitted altogether with the marker gene hpt in a Mendelian pattern. Some transgenic R1 and R2 progenies, with all transgenes displaying a normal expression level in the Northern blot analysis, showed high resistance to Magnaporthe grisea when tested in the typical blast nurseries located in Yanxi and Sanya respectively. Furthermore, transgenic F1 plants, resulting from a cross of R2 homozygous lines with high resistance to rice blast with the non-transgenic male sterile line Peiai 64S, showed not only high resistance to M. grisea but also enhanced resistance to rice false smut (a disease caused by Ustilaginoidea virens) and rice kernel smut (another disease caused by Tilletia barclayana).

  1. Enhancing disease resistances of Super Hybrid Rice with four antifungal genes

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A plant expression vector harboring four antifungal genes was delivered into the embryogenic calli of ‘9311’, an indica restorer line of Super Hybrid Rice, via modified biolistic particle bombardment. Southern blot analysis indicated that in the regenerated hygromycin-resistant plants, all the four anti-fungal genes, including RCH10, RAC22, β-Glu and B-RIP, were integrated into the genome of ‘9311’, co-transmitted altogether with the marker gene hpt in a Mendelian pattern. Some transgenic R1 and R2 progenies, with all transgenes displaying a normal expression level in the Northern blot analysis, showed high resistance to Magnaporthe grisea when tested in the typical blast nurseries located in Yanxi and Sanya respectively. Furthermore, transgenic F1 plants, resulting from a cross of R2 homo-zygous lines with high resistance to rice blast with the non-transgenic male sterile line Peiai 64S, showed not only high resistance to M. grisea but also enhanced resistance to rice false smut (a disease caused by Ustilaginoidea virens) and rice kernel smut (another disease caused by Tilletia barclayana).

  2. Increased burst firing in substantia nigra pars reticulata neurons and enhanced response to selective D2 agonist in hemiparkinsonian rats after repeated administration of apomorphine.

    OpenAIRE

    Lee, J. I.; Nam, D H; J.S. Kim; Hong, S.C.; Shin, H. J.; K. Park; Eoh, W.; Kim, J. H.; Lee, W.Y.

    2001-01-01

    Intermittent administrations of dopaminergic agents in hemiparkinsonian rat enhances the behavioral response to subsequent administration of the drugs. This phenomenon is known as "priming" and thought as comparable to drug-induced dyskinesia in patients with Parkinson's disease. We investigated the behavioral and electrophysiological changes in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats after repeated administrations of apomorphine. Administration of apomorphine (0.32 mg/kg, i...

  3. A Lipid Transfer Protein Increases the Glutathione Content and Enhances Arabidopsis Resistance to a Trichothecene Mycotoxin.

    Directory of Open Access Journals (Sweden)

    John E McLaughlin

    Full Text Available Fusarium head blight (FHB or scab is one of the most important plant diseases worldwide, affecting wheat, barley and other small grains. Trichothecene mycotoxins such as deoxynivalenol (DON accumulate in the grain, presenting a food safety risk and health hazard to humans and animals. Despite considerable breeding efforts, highly resistant wheat or barley cultivars are not available. We screened an activation tagged Arabidopsis thaliana population for resistance to trichothecin (Tcin, a type B trichothecene in the same class as DON. Here we show that one of the resistant lines identified, trichothecene resistant 1 (trr1 contains a T-DNA insertion upstream of two nonspecific lipid transfer protein (nsLTP genes, AtLTP4.4 and AtLTP4.5. Expression of both nsLTP genes was induced in trr1 over 10-fold relative to wild type. Overexpression of AtLTP4.4 provided greater resistance to Tcin than AtLTP4.5 in Arabidopsis thaliana and in Saccharomyces cerevisiae relative to wild type or vector transformed lines, suggesting a conserved protection mechanism. Tcin treatment increased reactive oxygen species (ROS production in Arabidopsis and ROS stain was associated with the chloroplast, the cell wall and the apoplast. ROS levels were attenuated in Arabidopsis and in yeast overexpressing AtLTP4.4 relative to the controls. Exogenous addition of glutathione and other antioxidants enhanced resistance of Arabidopsis to Tcin while the addition of buthionine sulfoximine, an inhibitor of glutathione synthesis, increased sensitivity, suggesting that resistance was mediated by glutathione. Total glutathione content was significantly higher in Arabidopsis and in yeast overexpressing AtLTP4.4 relative to the controls, highlighting the importance of AtLTP4.4 in maintaining the redox state. These results demonstrate that trichothecenes cause ROS accumulation and overexpression of AtLTP4.4 protects against trichothecene-induced oxidative stress by increasing the glutathione

  4. Gonadotropin releasing hormone agonists: Expanding vistas

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2011-01-01

    Full Text Available Gonadotropin-releasing hormone (GnRH agonists are derived from native GnRH by amino acid substitution which yields the agonist resistant to degradation and increases its half-life. The hypogonadotropic hypogonadal state produced by GnRH agonists has been often dubbed as "pseudomenopause" or "medical oophorectomy," which are both misnomers. GnRH analogues (GnRH-a work by temporarily "switching off" the ovaries. Ovaries can be "switched off" for the therapy and therapeutic trial of many conditions which include but are not limited to subfertility, endometriosis, adenomyosis, uterine leiomyomas, precocious puberty, premenstrual dysphoric disorder, chronic pelvic pain, or the prevention of menstrual bleeding in special clinical situations. Rapidly expanding vistas of usage of GnRH agonists encompass use in sex reassignment of male to female transsexuals, management of final height in cases of congenital adrenal hyperplasia, and preserving ovarian function in women undergoing cytotoxic chemotherapy. Hypogonadic side effects caused by the use of GnRH agonists can be tackled with use of "add-back" therapy. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice. GnRH-a have provided us a powerful therapeutic approach to the treatment of numerous conditions in reproductive medicine. Recent synthesis of GnRH antagonists with a better tolerability profile may open new avenues for both research and clinical applications. All stakeholders who are partners in women′s healthcare need to join hands to spread awareness so that these drugs can be used to realize their full potential.

  5. 2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice

    Science.gov (United States)

    Miller, E. S.; Bates, R. A.; Koebel, D. A.; Fuchs, B. B.; Sonnenfeld, G.

    1998-01-01

    Exposure to different forms of psychological and physiological stress can elicit a host stress response, which alters normal parameters of neuroendocrine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administered to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial growth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infection demonstrated an enhanced resistance to the listeria challenge. The enhanced bacterial clearance in vivo could not be explained by 2-DG exerting a toxic effect on the listeria, based on the results of two experiments. First, 2-DG did not inhibit listeria replication in trypticase soy broth. Second, replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2-DG, which correlated with the increased resistance to L. monocytogenes. These results support the contention that the host response to 2-DG-induced metabolic stress can influence the capacity of the immune system to resist infection by certain classes of microbial pathogens.

  6. Salicylic acid confers enhanced resistance to Glomerella leaf spot in apple.

    Science.gov (United States)

    Zhang, Ying; Shi, Xiangpeng; Li, Baohua; Zhang, Qingming; Liang, Wenxing; Wang, Caixia

    2016-09-01

    Glomerella leaf spot (GLS) caused by Glomerella cingulata is a newly emergent disease that results in severe defoliation and fruit spots in apple. Currently, there are no effective means to control this disease except for the traditional fungicide sprays. Induced resistance by elicitors against pathogens infection is a widely accepted eco-friendly strategy. In the present study, we investigated whether exogenous application of salicylic acid (SA) could improve resistance to GLS in a highly susceptible apple cultivar (Malus domestica Borkh. cv. 'Gala') and the underlying mechanisms. The results showed that pretreatment with SA, at 0.1-1.0 mM, induced strong resistance against GLS in 'Gala' apple leaves, with SA treated leaves showing significant reduction in lesion numbers and disease index. Concurrent with the enhanced disease resistance, SA treatment markedly increased the total antioxidant capacity (T-AOC) and defence-related enzyme activities, including catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO). As expected, SA treatment also induced the expression levels of five pathogenesis-related (PR) genes including PR1, PR5, PR8, Chitinase and β-1,3-glucanase. Furthermore, the most pronounced and/or rapid increase was observed in leaves treated with SA and subsequently inoculated with G. cingulata compared to the treatment with SA or inoculation with the pathogen. Together, these results suggest that exogenous SA triggered increase in reactive oxygen species levels and the antioxidant system might be responsible for enhanced resistance against G. cingulata in 'Gala' apple leaves. PMID:27139585

  7. Enhanced Disease Susceptibility1 Mediates Pathogen Resistance and Virulence Function of a Bacterial Effector in Soybean.

    Science.gov (United States)

    Wang, Jialin; Shine, M B; Gao, Qing-Ming; Navarre, Duroy; Jiang, Wei; Liu, Chunyan; Chen, Qingshan; Hu, Guohua; Kachroo, Aardra

    2014-05-28

    Enhanced disease susceptibility1 (EDS1) and phytoalexin deficient4 (PAD4) are well-known regulators of both basal and resistance (R) protein-mediated plant defense. We identified two EDS1-like (GmEDS1a/GmEDS1b) proteins and one PAD4-like (GmPAD4) protein that are required for resistance signaling in soybean (Glycine max). Consistent with their significant structural conservation to Arabidopsis (Arabidopsis thaliana) counterparts, constitutive expression of GmEDS1 or GmPAD4 complemented the pathogen resistance defects of Arabidopsis eds1 and pad4 mutants, respectively. Interestingly, however, the GmEDS1 and GmPAD4 did not complement pathogen-inducible salicylic acid accumulation in the eds1/pad4 mutants. Furthermore, the GmEDS1a/GmEDS1b proteins were unable to complement the turnip crinkle virus coat protein-mediated activation of the Arabidopsis R protein Hypersensitive reaction to Turnip crinkle virus (HRT), even though both interacted with HRT. Silencing GmEDS1a/GmEDS1b or GmPAD4 reduced basal and pathogen-inducible salicylic acid accumulation and enhanced soybean susceptibility to virulent pathogens. The GmEDS1a/GmEDS1b and GmPAD4 genes were also required for Resistance to Pseudomonas syringae pv glycinea2 (Rpg2)-mediated resistance to Pseudomonas syringae. Notably, the GmEDS1a/GmEDS1b proteins interacted with the cognate bacterial effector AvrA1 and were required for its virulence function in rpg2 plants. Together, these results show that despite significant structural similarities, conserved defense signaling components from diverse plants can differ in their functionalities. In addition, we demonstrate a role for GmEDS1 in regulating the virulence function of a bacterial effector.

  8. Enhancement of the citrus immune system provides effective resistance against Alternaria brown spot disease.

    Science.gov (United States)

    Llorens, Eugenio; Fernández-Crespo, Emma; Vicedo, Begonya; Lapeña, Leonor; García-Agustín, Pilar

    2013-01-15

    In addition to basal defense mechanisms, plants are able to develop enhanced defense mechanisms such as induced resistance (IR) upon appropriate stimulation. We recently described the means by which several carboxylic acids protect Arabidopsis and tomato plants against fungi. In this work, we demonstrate the effectiveness of hexanoic acid (Hx) in the control of Alternaria brown spot (ABS) disease via enhancement of the immune system of Fortune mandarin. The application of 1mM Hx in irrigation water to 2-year-old Fortune plants clearly reduced the incidence of the disease and led to smaller lesions. We observed that several of the most important mechanisms involved in induced resistance were affected by Hx application. Our results demonstrate enhanced callose deposition in infected plants treated with Hx, which suggests an Hx priming mechanism. Plants treated with the callose inhibitor 2-DDG were more susceptible to the fungus. Moreover, polygalacturonase-inhibiting protein (PGIP) gene expression was rapidly and significantly upregulated in treated plants. However, treatment with Hx decreased the levels of reactive oxygen species (ROS) in infected plants. Hormonal and gene analyses revealed that the jasmonic acid (JA) pathway was activated due to a greater accumulation of 12-oxo-phytodienoic acid (OPDA) and JA along with a rapid accumulation of JA-isoleucine (JA-Ile). Furthermore, we observed a more rapid accumulation of abscisic acid (ABA), which could act as a positive regulator of callose deposition. Thus, our results support the hypothesis that both enhanced physical barriers and the JA signaling pathway are involved in hexanoic acid-induced resistance (Hx-IR) to Alternaria alternata.

  9. Effects of the PPARγ agonist troglitazone on endothelial cells in vivo and in vitro: Differences between human and mouse

    International Nuclear Information System (INIS)

    Peroxisome proliferator-activated receptor gamma (PPARγ) agonists and PPARγ/α dual agonists have been or are being developed for clinical use in the treatment of type 2 diabetes mellitus and hyperlipidemias. A common tumor finding in rodent carcinogenicity studies for these agonists is hemangioma/hemangiosarcoma in mice but not in rats. We hypothesized that increased endothelial cell proliferation may be involved in the mechanism of PPAR agonist-induced vascular tumors in mice, and we investigated the effects on endothelial cells utilizing troglitazone, the first clinically used PPARγ agonist, in vivo and in vitro. Troglitazone (400 and 800 mg/kg/day) induced hemangiosarcomas in mice in a 2-year bioassay. We showed that troglitazone increased endothelial cell proliferation in brown and white adipose tissue and liver in mice at sarcomagenic doses after 4 weeks of treatment. Troglitazone was cytotoxic both to human dermal microvascular endothelial cells (HMEC1) and mouse mammary fat pad microvascular endothelial cells (MFP MVEC) at high concentrations. However, MFP MVEC were more resistant to the cytotoxic effects of troglitazone based on the much lower LC50 in HMEC1 (17.4 μM) compared to MFP MVEC (92.2 μM). Troglitazone increased the proliferation and survival of MFP MVEC but not HMEC1 in growth factor reduced conditions. Our data demonstrate that troglitazone may induce hemangiosarcomas in mice, at least in part, through enhancement of survival and proliferation of microvascular endothelial cells. Such an effect does not occur with human cells, suggesting that human may react differently to exposure to PPAR agonists compared with mice.

  10. A natural history of "agonist".

    Science.gov (United States)

    Russo, Ruth

    2002-01-01

    This paper constructs a brief history of the biochemical term agonist by exploring the multiple meanings of the root agôn in ancient Greek literature and describing how agonist first appeared in the scientific literature of the 20th century in the context of neurophysiologists' debates about the existence and properties of cellular receptors. While the narrow scientific definition of agonist may appear colorless and dead when compared with the web of allusions spun by the ancient Greek agôn, the scientific power and creativity of agonist actually resides precisely in its exact, restricted meaning for biomedical researchers.

  11. Enhanced CO2 Resistance for Robust Oxygen Separation Through Tantalum-doped Perovskite Membranes.

    Science.gov (United States)

    Zhang, Chi; Tian, Hao; Yang, Dong; Sunarso, Jaka; Liu, Jian; Liu, Shaomin

    2016-03-01

    Oxygen selective membranes with enhanced oxygen permeability and CO2 resistance are highly required in sustainable clean energy generation technologies. Here, we present novel, cobalt-free, SrFe1-x Tax O3-δ (x=0, 0.025, 0.05, 0.1, 0.2) perovskite membranes. Ta-doping induced lattice structure progression from orthorhombic (x=0) to cubic (x=0.05). SrFe0.95 Ta0.05 O3-δ (SFT0.05) showed the highest oxygen flux rates reaching 0.85 mL min(-1) cm(-2) at 950 °C on a 1.0 mm-thick membrane. Surface decoration can increase the permeation rate further. Ta inclusion within the perovskite lattice of SrFeO3-δ (SF) enhanced the CO2 resistance of the membranes significantly as evidenced by the absence of the carbonate functional groups on the FTIR spectrum when exposed to CO2 atmosphere at 850 °C. The CO2 resistance of Ta-doped SF compounds correlates with the lower basicity and the higher binding energy for the lattice oxygen. SFT0.05 demonstrated high stability during long-term permeation tests under 10% CO2 atmosphere. PMID:26813048

  12. The Protein Elicitor PevD1 Enhances Resistance to Pathogens and Promotes Growth in Arabidopsis.

    Science.gov (United States)

    Liu, Mengjie; Khan, Najeeb Ullah; Wang, Ningbo; Yang, Xiufen; Qiu, Dewen

    2016-01-01

    The protein elicitor PevD1, isolated from Verticillium dahlia, could enhance resistance to TMV in tobacco and Verticillium wilt in cotton. Here, the pevd1 gene was over-expressed in wild type (WT) Arabidopsis, and its biological functions were investigated. Our results showed that the transgenic lines were more resistant to Botrytis cinerea and Pseudomonas syringae pv. tomato DC3000 than the WT line was. In transgenic plants, both the germination time and bolting time required were significantly shorter and fresh weights and plant heights were significantly higher than those in the WT line. A transcriptomics study using digital gene expression profiling (DGE) was performed in transgenic and WT Arabidopsis. One hundred and thirty-six differentially expressed genes were identified. In transgenic Arabidopsis, three critical regulators of JA biosynthesis were up-regulated and JA levels were slightly increased. Three important repressors of the ABA-responsive pathway were up-regulated, indicating that ABA signal transduction may be suppressed. One CML and two WRKY TFs involved in Ca(2+)-responsive pathways were up-regulated, indicating that this pathway may have been triggered. In conclusion, we show that PevD1 is involved in regulating several plant endogenous signal transduction pathways and regulatory networks to enhance resistance and promote growth and development in Arabidopsis. PMID:27489497

  13. Toll-like receptor (TLR)7 and TLR9 agonists enhance interferon (IFN) beta-1a's immunoregulatory effects on B cells in patients with relapsing-remitting multiple sclerosis (RRMS).

    Science.gov (United States)

    Tao, Yazhong; Zhang, Xin; Markovic-Plese, Silva

    2016-09-15

    We report that B cells from patients with RRMS have decreased endogenous IFN-β secretion and deficient IFN receptor (IFNAR)1/2 and TLR7 gene expression in comparison to healthy controls (HCs), which may contribute to disregulation of cytokine secretion by B cells. We propose that TLR7 and TLR9 stimulation with loxorubin (LOX) and CpG, in combination with exogenous IFN-β may effectively reconstitute endogenous IFN-β production deficit and induce the secretion of immunoregulatory cytokines by B cells. Both LOX/IFN-β and CpG/IFN-β in-vitro treatments of B cells from RRMS patients induced higher endogenous IFN-β gene expression in comparison to the exogenous IFN-β alone. CpG/IFN-β combination induced higher secretion of IL-10, TGF-β, and IL-27 in comparison to stimulation with IFN-β. Our study provides a basis for future clinical studies employing IFN-β and TLR7/9 agonists, which may enhance the resolution of the inflammatory response in RRMS. PMID:27609294

  14. Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil

    Directory of Open Access Journals (Sweden)

    Tatiane eCoelho

    2015-04-01

    Full Text Available Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. In this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA to study single combinations between antituberculosis drugs and efflux inhibitors (EIs against multidrug resistant M. tuberculosis clinical isolates using the fully susceptible strain H37Rv as reference. Efflux activity was studied on a real-time basis by a fluorometric method that uses ethidium bromide as efflux substrate. Quantification of efflux pump genes mRNA transcriptional levels were performed by RT-qPCR. The fractional inhibitory concentrations (FIC indicated synergistic activity for the interactions between isoniazid, rifampicin, amikacin, ofloxacin, and ethidium bromide plus the EIs verapamil, thioridazine and chlorpromazine. The FICs ranged from 0.25, indicating a four-fold reduction on the MICs, to 0.015, 64-fold reduction. The detection of active efflux by real-time fluorometry showed that all strains presented intrinsic efflux activity that contributes to the overall resistance which can be inhibited in the presence of the EIs. The quantification of the mRNA levels of the most important efflux pump genes on these strains shows that they are intrinsically predisposed to expel toxic compounds as the exposure to subinhibitory concentrations of antibiotics were not necessary to increase the pump mRNA levels when compared with the non-exposed counterpart. The results obtained in this study confirm that the intrinsic efflux activity contributes to the overall resistance in multidrug resistant clinical isolates of M. tuberculosis and that the inhibition of efflux pumps by the EIs can enhance the clinical effect of antibiotics that are their substrates.

  15. Sensitivity enhancement of chemically amplified resists and performance study using EUV interference lithography

    Science.gov (United States)

    Buitrago, Elizabeth; Nagahara, Seiji; Yildirim, Oktay; Nakagawa, Hisashi; Tagawa, Seiichi; Meeuwissen, Marieke; Nagai, Tomoki; Naruoka, Takehiko; Verspaget, Coen; Hoefnagels, Rik; Rispens, Gijsbert; Shiraishi, Gosuke; Terashita, Yuichi; Minekawa, Yukie; Yoshihara, Kosuke; Oshima, Akihiro; Vockenhuber, Michaela; Ekinci, Yasin

    2016-03-01

    Extreme ultraviolet lithography (EUVL, λ = 13.5 nm) is the most promising candidate to manufacture electronic devices for future technology nodes in the semiconductor industry. Nonetheless, EUVL still faces many technological challenges as it moves toward high-volume manufacturing (HVM). A key bottleneck from the tool design and performance point of view has been the development of an efficient, high power EUV light source for high throughput production. Consequently, there has been extensive research on different methodologies to enhance EUV resist sensitivity. Resist performance is measured in terms of its ultimate printing resolution, line width roughness (LWR), sensitivity (S or best energy BE) and exposure latitude (EL). However, there are well-known fundamental trade-off relationships (LRS trade-off) among these parameters for chemically amplified resists (CARs). Here we present early proof-of-principle results for a multi-exposure lithography process that has the potential for high sensitivity enhancement without compromising other important performance characteristics by the use of a Photosensitized Chemically Amplified Resist (PSCAR). With this method, we seek to increase the sensitivity by combining a first EUV pattern exposure with a second UV flood exposure (λ = 365 nm) and the use of a PSCAR. In addition, we have evaluated over 50 different state-of-the-art EUV CARs. Among these, we have identified several promising candidates that simultaneously meet sensitivity, LWR and EL high performance requirements with the aim of resolving line space (L/S) features for the 7 and 5 nm logic node (16 nm and 13 nm half-pitch HP, respectively) for HVM. Several CARs were additionally found to be well resolved down to 12 nm and 11 nm HP with minimal pattern collapse and bridging, a remarkable feat for CARs. Finally, the performance of two negative tone state-of-the-art alternative resist platforms previously investigated was compared to the CAR performance at and

  16. Air-Impregnated Nanoporous Anodic Aluminum Oxide Layers for Enhancing the Corrosion Resistance of Aluminum.

    Science.gov (United States)

    Jeong, Chanyoung; Lee, Junghoon; Sheppard, Keith; Choi, Chang-Hwan

    2015-10-13

    Nanoporous anodic aluminum oxide layers were fabricated on aluminum substrates with systematically varied pore diameters (20-80 nm) and oxide thicknesses (150-500 nm) by controlling the anodizing voltage and time and subsequent pore-widening process conditions. The porous nanostructures were then coated with a thin (only a couple of nanometers thick) Teflon film to make the surface hydrophobic and trap air in the pores. The corrosion resistance of the aluminum substrate was evaluated by a potentiodynamic polarization measurement in 3.5 wt % NaCl solution (saltwater). Results showed that the hydrophobic nanoporous anodic aluminum oxide layer significantly enhanced the corrosion resistance of the aluminum substrate compared to a hydrophilic oxide layer of the same nanostructures, to bare (nonanodized) aluminum with only a natural oxide layer on top, and to the latter coated with a thin Teflon film. The hydrophobic nanoporous anodic aluminum oxide layer with the largest pore diameter and the thickest oxide layer (i.e., the maximized air fraction) resulted in the best corrosion resistance with a corrosion inhibition efficiency of up to 99% for up to 7 days. The results demonstrate that the air impregnating the hydrophobic nanopores can effectively inhibit the penetration of corrosive media into the pores, leading to a significant improvement in corrosion resistance. PMID:26393523

  17. Physiological Macro-lesions Enhanced Resistance to Blast (Magnaporthe grisea) in Rice Near-isogenic Lines

    Institute of Scientific and Technical Information of China (English)

    HUANG Shi-wen; LU Ji-ying; LUO Kun; ZHANG Xiu-fu; QIAN Qian

    2005-01-01

    Roll-leaf-1 (rl-1) and spot-leaf-1 (spl-1) were two near-isogenic lines, which were obtained after 3 to 4 backcrosses withearly season indica rice Zhefu 802 as recurrent parent. Henna macro-lesions, referred as physiological or morphological markers,began to appear on leaves at 4.5- to 6.0-leaf stage. The rice seedlings were inoculated at 3.5-, 5.0- and 7.0-leaf stages with highpathogenic races Zhong A1 and Zhong B1 of Magnaporthe grisea, respectively. The resistance of rl-1, spl-1 and Zhefu 802 againstblast was significantly different. The seedlings of Zhefu 802 at 3.5- to 7.0-leaf stage were susceptible to races Zhong A1 and ZhongB1 of M. grisea, whereas those of rl-1 and spl-1 at 3.5-, 5.0- and 7.0-leaf stages were susceptible, moderately resistant andresistant, respectively. These results suggested that the enhanced resistance of ri-1 and spl-1 related to the appearance of theirmorphological marker lesions. The experiment provided a basis for studying lesion mimic and hypersensitive response inassociation with disease resistance.

  18. Air-Impregnated Nanoporous Anodic Aluminum Oxide Layers for Enhancing the Corrosion Resistance of Aluminum.

    Science.gov (United States)

    Jeong, Chanyoung; Lee, Junghoon; Sheppard, Keith; Choi, Chang-Hwan

    2015-10-13

    Nanoporous anodic aluminum oxide layers were fabricated on aluminum substrates with systematically varied pore diameters (20-80 nm) and oxide thicknesses (150-500 nm) by controlling the anodizing voltage and time and subsequent pore-widening process conditions. The porous nanostructures were then coated with a thin (only a couple of nanometers thick) Teflon film to make the surface hydrophobic and trap air in the pores. The corrosion resistance of the aluminum substrate was evaluated by a potentiodynamic polarization measurement in 3.5 wt % NaCl solution (saltwater). Results showed that the hydrophobic nanoporous anodic aluminum oxide layer significantly enhanced the corrosion resistance of the aluminum substrate compared to a hydrophilic oxide layer of the same nanostructures, to bare (nonanodized) aluminum with only a natural oxide layer on top, and to the latter coated with a thin Teflon film. The hydrophobic nanoporous anodic aluminum oxide layer with the largest pore diameter and the thickest oxide layer (i.e., the maximized air fraction) resulted in the best corrosion resistance with a corrosion inhibition efficiency of up to 99% for up to 7 days. The results demonstrate that the air impregnating the hydrophobic nanopores can effectively inhibit the penetration of corrosive media into the pores, leading to a significant improvement in corrosion resistance.

  19. Enhanced disease susceptibility 1 and salicylic acid act redundantly to regulate resistance gene-mediated signaling.

    Directory of Open Access Journals (Sweden)

    Srivathsa C Venugopal

    2009-07-01

    Full Text Available Resistance (R protein-associated pathways are well known to participate in defense against a variety of microbial pathogens. Salicylic acid (SA and its associated proteinaceous signaling components, including enhanced disease susceptibility 1 (EDS1, non-race-specific disease resistance 1 (NDR1, phytoalexin deficient 4 (PAD4, senescence associated gene 101 (SAG101, and EDS5, have been identified as components of resistance derived from many R proteins. Here, we show that EDS1 and SA fulfill redundant functions in defense signaling mediated by R proteins, which were thought to function independent of EDS1 and/or SA. Simultaneous mutations in EDS1 and the SA-synthesizing enzyme SID2 compromised hypersensitive response and/or resistance mediated by R proteins that contain coiled coil domains at their N-terminal ends. Furthermore, the expression of R genes and the associated defense signaling induced in response to a reduction in the level of oleic acid were also suppressed by compromising SA biosynthesis in the eds1 mutant background. The functional redundancy with SA was specific to EDS1. Results presented here redefine our understanding of the roles of EDS1 and SA in plant defense.

  20. Enhanced disease susceptibility 1 and salicylic acid act redundantly to regulate resistance gene-mediated signaling.

    Science.gov (United States)

    Venugopal, Srivathsa C; Jeong, Rae-Dong; Mandal, Mihir K; Zhu, Shifeng; Chandra-Shekara, A C; Xia, Ye; Hersh, Matthew; Stromberg, Arnold J; Navarre, DuRoy; Kachroo, Aardra; Kachroo, Pradeep

    2009-07-01

    Resistance (R) protein-associated pathways are well known to participate in defense against a variety of microbial pathogens. Salicylic acid (SA) and its associated proteinaceous signaling components, including enhanced disease susceptibility 1 (EDS1), non-race-specific disease resistance 1 (NDR1), phytoalexin deficient 4 (PAD4), senescence associated gene 101 (SAG101), and EDS5, have been identified as components of resistance derived from many R proteins. Here, we show that EDS1 and SA fulfill redundant functions in defense signaling mediated by R proteins, which were thought to function independent of EDS1 and/or SA. Simultaneous mutations in EDS1 and the SA-synthesizing enzyme SID2 compromised hypersensitive response and/or resistance mediated by R proteins that contain coiled coil domains at their N-terminal ends. Furthermore, the expression of R genes and the associated defense signaling induced in response to a reduction in the level of oleic acid were also suppressed by compromising SA biosynthesis in the eds1 mutant background. The functional redundancy with SA was specific to EDS1. Results presented here redefine our understanding of the roles of EDS1 and SA in plant defense.

  1. Nighttime warming enhances drought resistance of plant communities in a temperate steppe

    Science.gov (United States)

    Yang, Zhongling; Jiang, Lin; Su, Fanglong; Zhang, Qian; Xia, Jianyang; Wan, Shiqiang

    2016-03-01

    Drought events could have profound influence on plant community structure and ecosystem function, and have subsequent impacts on community stability, but we know little about how different climate warming scenarios affect community resistance and resilience to drought. Combining a daytime and nighttime warming experiment in the temperate steppe of north China with a natural drought event during the study period, we tested how daytime and nighttime warming influences drought resistance and resilience. Our results showed that the semi-arid steppe in north China was resistant to both daytime and nighttime warming, but vulnerable to drought. Nighttime warming, but not daytime warming, enhanced community resistance to drought via stimulating carbon sequestration, whereas neither daytime nor nighttime warming affected community resilience to drought. Large decline in plant community cover, primarily caused by the reduction in the cover of dominant and rare species rather than subordinate species during drought, did not preclude rapid ecosystem recovery. These findings suggest that nighttime warming may facilitate ecosystem sustainability and highlight the need to assess the effects of climate extremes on ecosystem functions at finer temporal resolutions than based on diurnal mean temperature.

  2. Enhanced stress resistance of Deinococcus radiodurans cells in the dried state

    Science.gov (United States)

    Bauermeister, Anja; Moeller, Ralf; Reitz, Guenther; Billi, Daniela; Rettberg, Petra

    Liquid water is often regarded as a pre-requisite for life as we know it. However, some organisms can survive prolonged periods in a desiccated state and seem to resist other environmental stres-sors even better when water is absent. We tested this observation in Deinococcus radiodurans, a non-sporeforming soil bacterium well-known for its outstanding resistance to DNA damaging stressors, including high doses of UV and ionizing radiation, oxidants, and desiccation. Due to its polyextremophilic characteristics it has been regarded as a model organism in astrobiological research. To determine if the cellular changes imposed by the removal of water have an effect on the stress resistance of D. radiodurans, we compared the survival capacity of dried cells with that of hydrated cells after exposure to mono-and polychromatic UV radiation, -radiation, and heat shock (85C). In all cases, resistance was enhanced in dried cells. It is suggested that these effects are mainly due to a reduced oxidative stress in dried cells, as the metabolism is shut down and radical diffusion is very limited. Hence, desiccating conditions as encountered in space vacuum or on arid planets such as Mars may be beneficial instead of detrimental to the survival of some polyextremophilic microbes. Ongoing experiments aim to evaluate damage at a subcellular level in dried and hydrated cells after exposure to irradiation or heat shock.

  3. The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence by Enhancing Resistance to Neutrophil Extracellular Traps.

    Directory of Open Access Journals (Sweden)

    Mark J Lee

    2015-10-01

    Full Text Available Of the over 250 Aspergillus species, Aspergillus fumigatus accounts for up to 80% of invasive human infections. A. fumigatus produces galactosaminogalactan (GAG, an exopolysaccharide composed of galactose and N-acetyl-galactosamine (GalNAc that mediates adherence and is required for full virulence. Less pathogenic Aspergillus species were found to produce GAG with a lower GalNAc content than A. fumigatus and expressed minimal amounts of cell wall-bound GAG. Increasing the GalNAc content of GAG of the minimally pathogenic A. nidulans, either through overexpression of the A. nidulans epimerase UgeB or by heterologous expression of the A. fumigatus epimerase Uge3 increased the amount of cell wall bound GAG, augmented adherence in vitro and enhanced virulence in corticosteroid-treated mice to levels similar to A. fumigatus. The enhanced virulence of the overexpression strain of A. nidulans was associated with increased resistance to NADPH oxidase-dependent neutrophil extracellular traps (NETs in vitro, and was not observed in neutropenic mice or mice deficient in NADPH-oxidase that are unable to form NETs. Collectively, these data suggest that cell wall-bound GAG enhances virulence through mediating resistance to NETs.

  4. Enhanced adherence of methicillin-resistant Staphylococcus pseudintermedius sequence type 71 to canine and human corneocytes

    DEFF Research Database (Denmark)

    Latronico, Francesca; Moodley, Arshnee; Nielsen, Søren Saxmose;

    2014-01-01

    adherence properties between MRSP and methicillin-susceptible (MSSP) strains. Four MRSP, including a human and a canine strain belonging to ST71 and two canine non-ST71 strains, and three genetically unrelated MSSP were tested on corneocytes collected from five dogs and six humans. All strains were fully......The recent worldwide spread of methicillin-resistant Staphylococcus pseudintermedius (MRSP) in dogs is a reason for concern due to the typical multidrug resistance patterns displayed by some MRSP lineages such as sequence type (ST) 71. The objective of this study was to compare the in vitro....... pseudintermedius adherence to canine corneocytes was significantly higher compared to human corneocytes (p human origin adhered equally well to canine and human corneocytes, suggesting that MRSP ST71 may be able to adapt to human skin. The genetic basis of the enhanced...

  5. Corrosion resistance enhancement of WC-Co hard metal in NaOH solution

    International Nuclear Information System (INIS)

    SiC is a useful non-oxide ceramic material having unique physicochemical and mechanical properties such as high strength, excellent wear, and oxidation and corrosion resistance. These properties originate from the very strong covalent bond between silicon and carbon and its tetrahedral coordination. However, adhesion between the materials is a serious obstacle to the application of a SiC coating to WC-Co. Several techniques are used to improve the adhesion, such as sputtering, ion beam mixing (IBM), dynamic ion mixing and ion beam assisted deposition. Among those, IBM is a powerful tool. This paper demonstrates that SiC can be successfully coated on WC-Co through the IBM technique. The corrosion resistance of WC-Co in alkali solutions is greatly enhanced by the ion mixed SiC coating, as proven by potentiodynamic electrochemical experiments

  6. Corrosion resistance enhancement of WC-Co hard metal in NaOH solution

    Energy Technology Data Exchange (ETDEWEB)

    Yeo, Sun Mog; Park, Jae Won [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2011-05-15

    SiC is a useful non-oxide ceramic material having unique physicochemical and mechanical properties such as high strength, excellent wear, and oxidation and corrosion resistance. These properties originate from the very strong covalent bond between silicon and carbon and its tetrahedral coordination. However, adhesion between the materials is a serious obstacle to the application of a SiC coating to WC-Co. Several techniques are used to improve the adhesion, such as sputtering, ion beam mixing (IBM), dynamic ion mixing and ion beam assisted deposition. Among those, IBM is a powerful tool. This paper demonstrates that SiC can be successfully coated on WC-Co through the IBM technique. The corrosion resistance of WC-Co in alkali solutions is greatly enhanced by the ion mixed SiC coating, as proven by potentiodynamic electrochemical experiments

  7. Insecticide Mixtures Could Enhance the Toxicity of Insecticides in a Resistant Dairy Population of Musca domestica L

    OpenAIRE

    Hafiz Azhar Ali Khan; Waseem Akram; Sarfraz Ali Shad; Jong-Jin Lee

    2013-01-01

    House flies, Musca domestica L., are important pests of dairy operations worldwide, with the ability to adapt wide range of environmental conditions. There are a number of insecticides used for their management, but development of resistance is a serious problem. Insecticide mixtures could enhance the toxicity of insecticides in resistant insect pests, thus resulting as a potential resistance management tool. The toxicity of bifenthrin, cypermethrin, deltamethrin, chlorpyrifos, profenofos, em...

  8. Testicular germ cell sensitivity to TRAIL-induced apoptosis is dependent upon p53 expression and is synergistically enhanced by DR5 agonistic antibody treatment.

    Science.gov (United States)

    McKee, Chad M; Ye, Yang; Richburg, John H

    2006-12-01

    The ability of the TRAIL/DR5 signaling pathway to induce apoptosis has generally been limited to tumor cells. Here we report that in primary testis explants, addition of TRAIL (0.5 mug/ml) caused a three-fold increase in germ cell apoptosis. Furthermore, exposure of C57BL/6 mice to the testicular toxicant, mono-(2-ethylhexyl) phthalate (MEHP), caused an increased p53 stability and elevated DR5 mRNA levels coincident with increases in the levels of apoptosis in spermatocytes. To further assess the mechanisms responsible for the sensitivity of germ cells to undergo TRAIL/DR5-mediated apoptosis, we used the germ cell lines GC-1spg and GC-2spd(ts) (a temperature sensitive spermatocyte-like cell line that allows for p53 nuclear localization at 32 degrees C but not 37 degrees C). Addition of TRAIL and the anti-DR5 monoclonal antibody, MD5-1, triggered a robust synergistic increase of apoptosis in p53 permissive GC-2 cells (32 degrees C) but not in GC-1 cells. In addition, DR5 levels on the plasma membrane of permissive cells were considerably enhanced concomitant with p53 expression and after MD5-1 treatment. These data represent the first indication that testicular germ cells, specifically spermatocytes, can undergo TRAIL-mediated apoptosis and the clinically relevant observation that pretreatment with a DR5 monoclonal antibody can greatly sensitize their apoptotic response to TRAIL.

  9. Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells

    Institute of Scientific and Technical Information of China (English)

    Zhi-Kun Qiu; Dong Shen; Yin-Sheng Chen; Qun-Ying Yang; Cheng-Cheng Guo; Bing-Hong Feng; Zhong-Ping Chen

    2014-01-01

    O6-methylguanine DNA methyltransferase (MGMT) can remove DNA alkylation adducts, thereby repairing damaged DNA and contributing to the drug resistance of gliomas to alkylating agents. In addition, glioma stem-like cells (GSCs) have been demonstrated to be involved in the recurrence and treatment resistance of gliomas. In this study, we aimed to investigate MGMT expression and regulatory mechanisms in GSCs and the association of MGMT with temozolomide (TMZ) sensitivity. GSCs were enriched from one MGMT-positive cellline (SF-767) and 7 MGMT-negative celllines (U251, SKMG-4, SKMG-1, SF295, U87, MGR1, and MGR2) through serum-free clone culture. GSCs from the U251G, SKMG-4G, SF295G, and SKMG-1G cell lines became MGMT-positive, but those from the U87G, MGR1G, and MGR2G cell lines remained MGMT-negative. However, al the GSCs and their parental glioma celllines were positive for nuclear factor-κB (NF-κB). In addition, GSCs were more resistant to TMZ than their parental glioma cell lines (P 0.05). When we treated the MGMT-positive GSCs with TMZ plus MG-132 (an NF-κB inhibitor), the antitumor activity was significantly enhanced compared to that of GSCs treated with TMZ alone (P < 0.05). Furthermore, we found that MGMT expression decreased through the down-regulation of NF-κB expression by MG-132. Our results show that MG-132 may inhibit NF-κB expression and further decrease MGMT expression, resulting in a synergistic effect on MGMT-positive GSCs. These results indicate that enhanced MGMT expression contributes to TMZ resistance in MGMT-positive GSCs.

  10. Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells

    Science.gov (United States)

    Qiu, Zhi-Kun; Shen, Dong; Chen, Yin-Sheng; Yang, Qun-Ying; Guo, Cheng-Cheng; Feng, Bing-Hong; Chen, Zhong-Ping

    2014-01-01

    O6-methylguanine DNA methyltransferase (MGMT) can remove DNA alkylation adducts, thereby repairing damaged DNA and contributing to the drug resistance of gliomas to alkylating agents. In addition, glioma stem-like cells (GSCs) have been demonstrated to be involved in the recurrence and treatment resistance of gliomas. In this study, we aimed to investigate MGMT expression and regulatory mechanisms in GSCs and the association of MGMT with temozolomide (TMZ) sensitivity. GSCs were enriched from one MGMT-positive cell line (SF-767) and 7 MGMT-negative cell lines (U251, SKMG-4, SKMG-1, SF295, U87, MGR1, and MGR2) through serum-free clone culture. GSCs from the U251G, SKMG-4G, SF295G, and SKMG-1G cell lines became MGMT-positive, but those from the U87G, MGR1G, and MGR2G cell lines remained MGMT-negative. However, all the GSCs and their parental glioma cell lines were positive for nuclear factor-κB (NF-κB). In addition, GSCs were more resistant to TMZ than their parental glioma cell lines (P 0.05). When we treated the MGMT-positive GSCs with TMZ plus MG-132 (an NF-κB inhibitor), the antitumor activity was significantly enhanced compared to that of GSCs treated with TMZ alone (P < 0.05). Furthermore, we found that MGMT expression decreased through the down-regulation of NF-κB expression by MG-132. Our results show that MG-132 may inhibit NF-κB expression and further decrease MGMT expression, resulting in a synergistic effect on MGMT-positive GSCs. These results indicate that enhanced MGMT expression contributes to TMZ resistance in MGMT-positive GSCs. PMID:23958055

  11. A potent class of GPR40 full agonists engages the enteroinsular axis to promote glucose control in rodents.

    Directory of Open Access Journals (Sweden)

    Jian Luo

    Full Text Available Type 2 diabetes is characterized by impaired glucose homeostasis due to defects in insulin secretion, insulin resistance and the incretin response. GPR40 (FFAR1 or FFA1 is a G-protein-coupled receptor (GPCR, primarily expressed in insulin-producing pancreatic β-cells and incretin-producing enteroendocrine cells of the small intestine. Several GPR40 agonists, including AMG 837 and TAK-875, have been disclosed, but no GPR40 synthetic agonists have been reported that engage both the insulinogenic and incretinogenic axes. In this report we provide a molecular explanation and describe the discovery of a unique and potent class of GPR40 full agonists that engages the enteroinsular axis to promote dramatic improvement in glucose control in rodents. GPR40 full agonists AM-1638 and AM-6226 stimulate GLP-1 and GIP secretion from intestinal enteroendocrine cells and increase GSIS from pancreatic islets, leading to enhanced glucose control in the high fat fed, streptozotocin treated and NONcNZO10/LtJ mouse models of type 2 diabetes. The improvement in hyperglycemia by AM-1638 was reduced in the presence of the GLP-1 receptor antagonist Ex(9-39NH(2.

  12. Marked enhancement of the immune response to BioThrax® (Anthrax Vaccine Adsorbed) by the TLR9 agonist CPG 7909 in healthy volunteers.

    Science.gov (United States)

    Rynkiewicz, Dianna; Rathkopf, Melinda; Sim, Iain; Waytes, A Thomas; Hopkins, Robert J; Giri, Lallan; DeMuria, Deborah; Ransom, Janet; Quinn, James; Nabors, Gary S; Nielsen, Carl J

    2011-08-26

    Immunization with BioThrax(®) (Anthrax Vaccine Adsorbed) is a safe and effective means of preventing anthrax. Animal studies have demonstrated that the addition of CpG DNA adjuvants to BioThrax can markedly increase the immunogenicity of the vaccine, increasing both serum anti-protective antigen (PA) antibody and anthrax toxin-neutralizing antibody (TNA) concentrations. The immune response to CpG-adjuvanted BioThrax in animals was not only stronger, but was also more rapid and led to higher levels of protection in spore challenge models. The B-class CpG DNA adjuvant CPG 7909, a 24-base synthetic, single-strand oligodeoxynucleotide, was evaluated for its safety profile and adjuvant properties in a Phase 1 clinical trial. A double-blind study was performed in which 69 healthy subjects, age 18-45 years, were randomized to receive three doses of either: (1) BioThrax alone, (2) 1 mg of CPG 7909 alone or (3) BioThrax plus 1 mg of CPG 7909, all given intramuscularly on study days 0, 14 and 28. Subjects were monitored for IgG to PA by ELISA and for TNA titers through study day 56 and for safety through month 6. CPG 7909 increased the antibody response by 6-8-fold at peak, and accelerated the response by 3 weeks compared to the response seen in subjects vaccinated with BioThrax alone. No serious adverse events related to study agents were reported, and the combination was considered to be reasonably well tolerated. The marked acceleration and enhancement of the immune response seen by combining BioThrax and CPG 7909 offers the potential to shorten the course of immunization and reduce the time to protection, and may be particularly useful in the setting of post-exposure prophylaxis. PMID:21624418

  13. Smart doxorubicin nanoparticles with high drug payload for enhanced chemotherapy against drug resistance and cancer diagnosis

    Science.gov (United States)

    Yu, Caitong; Zhou, Mengjiao; Zhang, Xiujuan; Wei, Weijia; Chen, Xianfeng; Zhang, Xiaohong

    2015-03-01

    Considering the obvious advantages in efficacy and price, doxorubicin (DOX) has been widely used for a range of cancers, which is usually encapsulated in various nanocarriers for drug delivery. Although effective, in most nanocarrier-based delivery systems, the drug loading capacity of DOX is rather low; this can lead to undesired systemic toxicity and excretion concern. Herein, we report for the first time the usage of pure doxorubicin nanoparticles (DOX NPs) without addition of any carriers for enhanced chemotherapy against drug-resistance. The drug payload reaches as high as 90.47%, which largely surpassed those in previous reports. These PEG stabilized DOX NPs exhibit good biocompatibility and stability, long blood circulation time, fast release in an acidic environment and high accumulation in tumors. Compared with free DOX, DOX NPs display a dramatically enhanced anticancer therapeutic efficacy in the inhibition of cell and tumor growth. Moreover, they can also be readily incorporated with other anticancer drugs for synergistic chemotherapy to overcome the drug resistance of cancers. The fluorescence properties of DOX also endow these NPs with imaging capabilities, thus making it a multifunctional system for diagnosis and treatment. This work demonstrates great potential of DOX NPs for cancer diagnosis, therapy and overcoming drug tolerance.Considering the obvious advantages in efficacy and price, doxorubicin (DOX) has been widely used for a range of cancers, which is usually encapsulated in various nanocarriers for drug delivery. Although effective, in most nanocarrier-based delivery systems, the drug loading capacity of DOX is rather low; this can lead to undesired systemic toxicity and excretion concern. Herein, we report for the first time the usage of pure doxorubicin nanoparticles (DOX NPs) without addition of any carriers for enhanced chemotherapy against drug-resistance. The drug payload reaches as high as 90.47%, which largely surpassed those in

  14. SRPX2 Enhances the Epithelial-Mesenchymal Transition and Temozolomide Resistance in Glioblastoma Cells.

    Science.gov (United States)

    Tang, Haitao; Zhao, Jiaxin; Zhang, Liangyu; Zhao, Jiang; Zhuang, Yongzhi; Liang, Peng

    2016-10-01

    Glioblastoma (GBM) is the most common and most aggressive central nervous system tumor in adults. Due to GBM cell invasiveness and resistance to chemotherapy, current medical interventions are not satisfactory, and the prognosis for GBM is poor. It is necessary to investigate the underlying mechanism of GBM metastasis and drug resistance so that more effective treatments can be developed for GBM patients. sushi repeat-containing protein, X-linked 2 (SRPX2) is a prognostic biomarker in many different cancer cell lines and is associated with poor prognosis in cancer patients. SRPX2 overexpression promotes interactions between tumor and endothelial cells, leading to tumor progression and metastasis. We hypothesize that SRPX2 also contributes to GBM chemotherapy resistance and metastasis. Our results revealed that GBM tumor samples from 42 patients expressed higher levels of SRPX2 than the control normal brain tissue samples. High-SRPX2 expression levels are correlated with poor prognosis in those patients, as well as resistance to temozolomide in cultured GBM cells. Up-regulating SRPX2 expression in cultured GBM cell lines facilitated invasiveness and migration of GBM cells, while down-regulating SRPX2 through RNA interference was inhibitory. These results suggest that SRPX2 plays an important role in GBM metastasis. Epithelial to mesenchymal transition (EMT) is one of the processes that facilitate GBM metastasis and resistance to chemotherapy. EMT marker expression was decreased in SRPX2 down-regulated GBM cells, and MAPK signaling pathway marker expression was also decreased when SRPX2 is knocked down in GBM-cultured cells. Blocking the MAPK signaling pathway inhibited GBM metastasis but did not inhibit cell invasion and migration in SRPX2 down-regulated cells. Our results indicate that SRPX2 facilitates GBM metastasis by enhancing the EMT process via the MAPK signaling pathway.

  15. SRPX2 Enhances the Epithelial-Mesenchymal Transition and Temozolomide Resistance in Glioblastoma Cells.

    Science.gov (United States)

    Tang, Haitao; Zhao, Jiaxin; Zhang, Liangyu; Zhao, Jiang; Zhuang, Yongzhi; Liang, Peng

    2016-10-01

    Glioblastoma (GBM) is the most common and most aggressive central nervous system tumor in adults. Due to GBM cell invasiveness and resistance to chemotherapy, current medical interventions are not satisfactory, and the prognosis for GBM is poor. It is necessary to investigate the underlying mechanism of GBM metastasis and drug resistance so that more effective treatments can be developed for GBM patients. sushi repeat-containing protein, X-linked 2 (SRPX2) is a prognostic biomarker in many different cancer cell lines and is associated with poor prognosis in cancer patients. SRPX2 overexpression promotes interactions between tumor and endothelial cells, leading to tumor progression and metastasis. We hypothesize that SRPX2 also contributes to GBM chemotherapy resistance and metastasis. Our results revealed that GBM tumor samples from 42 patients expressed higher levels of SRPX2 than the control normal brain tissue samples. High-SRPX2 expression levels are correlated with poor prognosis in those patients, as well as resistance to temozolomide in cultured GBM cells. Up-regulating SRPX2 expression in cultured GBM cell lines facilitated invasiveness and migration of GBM cells, while down-regulating SRPX2 through RNA interference was inhibitory. These results suggest that SRPX2 plays an important role in GBM metastasis. Epithelial to mesenchymal transition (EMT) is one of the processes that facilitate GBM metastasis and resistance to chemotherapy. EMT marker expression was decreased in SRPX2 down-regulated GBM cells, and MAPK signaling pathway marker expression was also decreased when SRPX2 is knocked down in GBM-cultured cells. Blocking the MAPK signaling pathway inhibited GBM metastasis but did not inhibit cell invasion and migration in SRPX2 down-regulated cells. Our results indicate that SRPX2 facilitates GBM metastasis by enhancing the EMT process via the MAPK signaling pathway. PMID:26643178

  16. Overexpressing CYP71Z2 enhances resistance to bacterial blight by suppressing auxin biosynthesis in rice.

    Directory of Open Access Journals (Sweden)

    Wenqi Li

    Full Text Available The hormone auxin plays an important role not only in the growth and development of rice, but also in its defense responses. We've previously shown that the P450 gene CYP71Z2 enhances disease resistance to pathogens through regulation of phytoalexin biosynthesis in rice, though it remains unclear if auxin is involved in this process or not.The expression of CYP71Z2 was induced by Xanthomonas oryzae pv. oryzae (Xoo inoculation was analyzed by qRT-PCR, with GUS histochemical staining showing that CYP71Z2 expression was limited to roots, blades and nodes. Overexpression of CYP71Z2 in rice durably and stably increased resistance to Xoo, though no significant difference in disease resistance was detected between CYP71Z2-RNA interference (RNAi rice and wild-type. Moreover, IAA concentration was determined using the HPLC/electrospray ionization/tandem mass spectrometry system. The accumulation of IAA was significantly reduced in CYP71Z2-overexpressing rice regardless of whether plants were inoculated or not, whereas it was unaffected in CYP71Z2-RNAi rice. Furthermore, the expression of genes related to IAA, expansin and SA/JA signaling pathways was suppressed in CYP71Z2-overexpressing rice with or without inoculation.These results suggest that CYP71Z2-mediated resistance to Xoo may be via suppression of IAA signaling in rice. Our studies also provide comprehensive insight into molecular mechanism of resistance to Xoo mediated by IAA in rice. Moreover, an available approach for understanding the P450 gene functions in interaction between rice and pathogens has been provided.

  17. Dopaminergic agonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C

    2004-01-01

    Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy....

  18. Emerging GLP-1 receptor agonists

    DEFF Research Database (Denmark)

    Lund, Asger; Knop, Filip K; Vilsbøll, Tina

    2011-01-01

    Introduction: Recently, glucagon-like peptide-1 receptor (GLP-1R) agonists have become available for the treatment of type 2 diabetes. These agents exploit the physiological effects of GLP-1, which is able to address several of the pathophysiological features of type 2 diabetes. GLP-1R agonists...... presently available are administered once or twice daily, but several once-weekly GLP-1R agonists are in late clinical development. Areas covered: The present review aims to give an overview of the clinical data on the currently available GLP-1R agonists used for treatment of type 2 diabetes, exenatide and...... liraglutide, as well as the emerging GLP-1R agonists including the long-acting compounds. Expert opinion: An emerging therapeutic trend toward initial or early combination therapy with metformin- and incretin-based therapy is anticipated for patients with type 2 diabetes. GLP-1-based therapy has so far proven...

  19. Emerging GLP-1 receptor agonists

    DEFF Research Database (Denmark)

    Lund, Asger; Knop, Filip K; Vilsbøll, Tina

    2011-01-01

    Introduction: Recently, glucagon-like peptide-1 receptor (GLP-1R) agonists have become available for the treatment of type 2 diabetes. These agents exploit the physiological effects of GLP-1, which is able to address several of the pathophysiological features of type 2 diabetes. GLP-1R agonists...... presently available are administered once or twice daily, but several once-weekly GLP-1R agonists are in late clinical development. Areas covered: The present review aims to give an overview of the clinical data on the currently available GLP-1R agonists used for treatment of type 2 diabetes, exenatide...... and liraglutide, as well as the emerging GLP-1R agonists including the long-acting compounds. Expert opinion: An emerging therapeutic trend toward initial or early combination therapy with metformin- and incretin-based therapy is anticipated for patients with type 2 diabetes. GLP-1-based therapy has so far proven...

  20. Loss of RASSF2 Enhances Tumorigencity of Lung Cancer Cells and Confers Resistance to Chemotherapy

    Directory of Open Access Journals (Sweden)

    Jennifer Clark

    2012-01-01

    Full Text Available RASSF2 is a novel pro-apoptotic effector of K-Ras that is frequently inactivated in a variety of primary tumors by promoter methylation. Inactivation of RASSF2 enhances K-Ras-mediated transformation and overexpression of RASSF2 suppresses tumor cell growth. In this study, we confirm that RASSF2 and K-Ras form an endogenous complex, validating that RASSF2 is a bona fide K-Ras effector. We adopted an RNAi approach to determine the effects of inactivation of RASSF2 on the transformed phenotype of lung cancer cells containing an oncogenic K-Ras. Loss of RASSF2 expression resulted in a more aggressive phenotype that was characterized by enhanced cell proliferation and invasion, decreased cell adhesion, the ability to grow in an anchorage-independent manner and cell morphological changes. This enhanced transformed phenotype of the cells correlated with increased levels of activated AKT, indicating that RASSF2 can modulate Ras signaling pathways. Loss of RASSF2 expression also confers resistance to taxol and cisplatin, two frontline therapeutics for the treatment of lung cancer. Thus we have shown that inactivation of RASSF2, a process that occurs frequently in primary tumors, enhances the transforming potential of activated K-Ras and our data suggests that RASSF2 may be a novel candidate for epigenetic-based therapy in lung cancer.

  1. Toll-like receptor 2 agonists inhibit human fibrocyte differentiation

    Directory of Open Access Journals (Sweden)

    Maharjan Anu S

    2010-11-01

    Full Text Available Abstract Background In healing wounds, some monocytes enter the wound and differentiate into fibroblast-like cells called fibrocytes. Since Toll-like receptors (TLRs are present on monocytes, and pathogens that can infect a wound have and/or release TLR agonists, we examined whether TLR agonists affect fibrocyte differentiation. Results When human peripheral blood mononuclear cells (PBMCs were cultured with TLR3, TLR4, TLR5, TLR7, TLR8 or TLR9 agonists, there was no significant effect on fibrocyte differentiation, even though enhanced extracellular tumor necrosis factor (TNF-α accumulation and/or increased cell surface CD86 or major histocompatibility complex (MHC class II levels were observed. However, all TLR2 agonists tested inhibited fibrocyte differentiation without any significant effect on cell survival. Adding TLR2 agonists to purified monocytes had no effect on fibrocyte differentiation. However, some TLR2 agonists caused PBMCs to secrete a factor that inhibits the differentiation of purified monocytes into fibrocytes. This factor is not interferon (IFN-α, IFN-γ, interleukin (IL-12, aggregated immunoglobulin G (IgG or serum amyloid P (SAP, factors known to inhibit fibrocyte differentiation. TLR2 agonist-treated PBMCs secrete low levels of IL-6, TNF-α, IFN-γ, granulocyte colony-stimulating factor and tumor growth factor β1, but combinations of these factors had no effect on fibrocyte differentiation from purified monocytes. Conclusions Our results indicate that TLR2 agonists indirectly inhibit fibrocyte differentiation and that, for some TLR2 agonists, this inhibition involves other cell types in the PBMC population secreting an unknown factor that inhibits fibrocyte differentiation. Together, these data suggest that the presence of some bacterial signals can inhibit fibrocyte differentiation and may thus slow wound closure.

  2. Enhanced microwave absorbing properties and heat resistance of carbonyl iron by electroless plating Co

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongyu, E-mail: wanghongyu07010310@163.com; Zhu, Dongmei; Zhou, Wancheng; Luo, Fa

    2015-11-01

    Co coated carbonyl iron particles (Co (CI)) are fabricated through electroless plating method, and the electromagnetic microwave absorbing properties are investigated in the frequencies during 8.2–12.4 GHz. The complex permittivity of CI particles after electroless plating Co is higher than that of raw CI particles due to improvment of the polarization process. Furthermore, according to the XRD and TG results, the Co layer can enhance the heat resistance of CI particles. The bandwidth below −10 dB can reach 3.9 GHz for the Co(CI) absorbent. The results indicate that the electroless plating Co not only enhances the absorbing properties but also improves the heat resistance of CI. - Highlights: • The Co-coated carbonyl iron Co(CI) particles were prepared by electroless plating. • The electromagnetic wave absorbing properties of Co(CI) particles were studied. • The heat treatment on the absorbing property of Co(CI) particles was studied. • The Co(CI) particles have good absorbing property when compared with CI.

  3. Bitter melon extracts enhance the activity of chemotherapeutic agents through the modulation of multiple drug resistance.

    Science.gov (United States)

    Kwatra, Deep; Venugopal, Anand; Standing, David; Ponnurangam, Sivapriya; Dhar, Animesh; Mitra, Ashim; Anant, Shrikant

    2013-12-01

    Recently, we demonstrated that extracts of bitter melon (BME) can be used as a preventive/therapeutic agent in colon cancers. Here, we determined BME effects on anticancer activity and bioavailability of doxorubicin (DOX) in colon cancer cells. BME enhanced the effect of DOX on cell proliferation and sensitized the cells toward DOX upon pretreatment. Furthermore, there was both increased drug uptake and reduced drug efflux. We also observed a reduction in the expression of multidrug resistance conferring proteins (MDRCP) P-glycoprotein, MRP-2, and BCRP. Further BME suppressed DOX efflux in MDCK cells overexpressing the three efflux proteins individually, suggesting that BME is a potent inhibitor of MDR function. Next, we determined the effect of BME on PXR, a xenobiotic sensing nuclear receptor and a transcription factor that controls the expression of the three MDR genes. BME suppressed PXR promoter activity thereby suppressing its expression. Finally, we determined the effect of AMPK pathway on drug efflux because we have previously demonstrated that BME affects the pathway. However, inhibiting AMPK did not affect drug resistance, suggesting that BME may use different pathways for the anticancer and MDR modulating activities. Together, these results suggest that BME can enhance the bioavailability and efficacy of conventional chemotherapy.

  4. EXPRESSION OF BACTERIAL PROTEIN-A IN TOBACCO LEADS TO ENHANCED RESISTANCE TO STRESS CONDITIONS

    Directory of Open Access Journals (Sweden)

    Chaitali Roy

    2014-08-01

    Full Text Available Tobacco is the most commonly used plant for expression of transgenes from a variety of organisms because it can be easily grown and transformed, it provides abundant amounts of fresh tissue and has a well-established cell culture system. As bacterial enzymes can be synthesized in tobacco, here we explore the possibility of in planta expression of staphylococcal protein-A(PA which is an antibody, an important group among biopharmaceuticals. In our study we have shown that the tobacco plants harboring PA gene could combat the crown gall infection and also effective in resisting abiotic stress conditions. Transgenic plants when subjected to interact with wild variety of Agrobacterium shows its enhanced capability to resist the gall formation. And when transgenic tobacco plants were grown in presence of 200mM NaCl and/or MG(Methylglyoxal solution, shows their increased tolerance towards salinity stress and high MG stress. So far transgenic tobacco plants are concerned, improvements in the expression of recombinant proteins and their recovery from tobacco may also enhance production and commercial use of this protein.

  5. Transgenic rice homozygous lines expressing GNA showed enhanced resistance to rice brown planthopper

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Mature seed-derived calli from two elite Chinese japonica rice (Oryza sativa L.) cultivars Eyi 105 and Ewan 5 were co-transformed with two plasmids, pWRG1515 and pRSSGNA1, containing the selectable marker hygromycin phosphotransferase gene (hpt), the reporter β-glucuronidase gene (gusA) and the snowdrop (Galanthus nivalis)lectin gene (gna) via particle bombardment. 61 independent transgenic rice plants were regenerated from 329 bombarded calli. 79% transgenic plants contained all the three genes, revealed by PCR/Southern blot analysis. Western blot analysis revealed that 36 out of 48 gna-containing transgenic plants expressed GNA (75 %) at various levels with the highest expression being approximately 0.5% of total soluble protein. Genetic analysis confirmed Mendelian segregation of transgenes in progeny. From the R2 generations whose R1 parent plants showing 3:1 Mendelian segregation patterns,we identified five independent homozygous lines containing and expressing all the three transgenes. Insect bioassay and feeding tests showed that these homozygous lines had significant inhibition to rice brown planthopper (Nilaparvata lugens, BPH) by decreasing BPH survival and overall fecundity, retarding BPH development and declining BPH feeding.These BPH-resistant lines have been incorporated into rice insect resistance breeding program. This is the first report that homozygous transgenic rice lines expressing GNA, developed by genetic transformation and through genetic analysis-based selection, conferred enhanced resistance to BPH, one of the most damaging insect pests in rice.

  6. Pack Aluminide Coatings Formed at 650℃ for Enhancing Oxidation Resistance of Low Alloy Steels

    Institute of Scientific and Technical Information of China (English)

    Z.D.Xiang; S.R.Rose; P.K.Datta

    2004-01-01

    This study aims to investigate the feasibility of forming iron aluminide coatings on a commercial 9Cr-1Mo (wt.%) alloy steel by pack cementation at 650℃ in an attempt to improve its high temperature oxidation resistance. Pack powders containing Al, Al2O3 and a series of halide salts were used to carry out the coating deposition experiments, which enabled identification of the most suitable activator for the pack aluminising process at the intended temperature. The effect of pack aluminium content on the growth kinetics and microstructure of the coatings was then studied by keeping deposition conditions and pack activator content constant while increasing the pack aluminium content from 1.4 wt.% to 6 wt.%. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) techniques were used to analyse the phases and microstructures of the coatings formed and to determine depth profiles of coating elements in the coating layer. Oxidation resistance of the coating was studied at 650 ~C in air by intermittent weight measurement at room temperature. It was observed that the coating could substantially enhance the oxidation resistance of the steel under these testing conditions, which was attributed to the capability of the iron aluminide phases to form alumina scale on the coating surface through preferential A1 oxidation.

  7. Pack Aluminide Coatings Formed at 650 ℃ for Enhancing Oxidation Resistance of Low Alloy Steels

    Institute of Scientific and Technical Information of China (English)

    Z. D. Xiang; S. R. Rose; P. K. Datta

    2004-01-01

    This study aims to investigate the feasibility of forming iron aluminide coatings on a commercial 9Cr-lMo (wt.%)alloy steel by pack cementation at 650 ℃ in an attempt to improve its high temperature oxidation resistance. Pack powders containing Al, Al2O3 and a series of halide salts were used to carry out the coating deposition experiments, which enabled identification of the most suitable activator for the pack aluminising process at the intended temperature. The effect of pack aluminium content on the growth kinetics and microstructure of the coatings was then studied by keeping deposition conditions and pack activator content constant while increasing the pack aluminium content from 1.4 wt.% to 6 wt.%. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) techniques were used to analyse the phases and microstructures of the coatings formed and to determine depth profiles of coating elements in the coating layer. Oxidation resistance of the coating was studied at 650 ℃ in air by intermittent weight measurement at room temperature. It was observed that the coating could substantially enhance the oxidation resistance of the steel under these testing conditions, which was attributed to the capability of the iron aluminide phases to form alumina scale on the coating surface through preferential Al oxidation.

  8. Enhanced corrosion resistance of magnesium alloy AM60 by cerium(III) in chloride solution

    Energy Technology Data Exchange (ETDEWEB)

    Heakal, F. El-Taib, E-mail: fakihaheakal@yahoo.com [Chemistry Department, Faculty of Science, Cairo University, Giza 12613 (Egypt); Shehata, O.S. [Physical Chemistry Department, National Research Centre, Dokki, Giza (Egypt); Tantawy, N.S. [Girl' s College of Arts, Science and Education, Ain Shams University, Asma Fahmi Street, Cairo (Egypt)

    2012-03-15

    Highlights: Black-Right-Pointing-Pointer Corrosion rate of AM60 in Cl{sup -} solution decreases with increasing [Ce{sup 3+}] up to 1 mM. Black-Right-Pointing-Pointer Beyond that level the corrosion rate increases and then stabilizes. Black-Right-Pointing-Pointer The spontaneously formed film characterises by increasing resistance with time. Black-Right-Pointing-Pointer The converted film after 10 d immersion exhibits self-healing in plain Cl{sup -} solution. Black-Right-Pointing-Pointer Ce(III) should be present in the corrodent to form a more compact surface coating. - Abstract: Cerium(III) was utilised to enhance the corrosion resistance of AM60 in NaCl solution. Ce{sup 3+} can suppress corrosion deterioration up to 1.0 mM. Beyond that level corrosion rate increases till a steady value. Surface film resistance increases with time evolution until 24 h, then decreases and stabilizes. The converted film after 240 h immersion exhibits self-healing and thickening when re-exposed to plain chloride solution. SEM and EDX confirmed that when Ce is present as additive in solution, more compact coating is formed better than its presence as a post coating on the alloy surface before being immersed in the corrosive environment.

  9. MiR-145 expression accelerates esophageal adenocarcinoma progression by enhancing cell invasion and anoikis resistance.

    Directory of Open Access Journals (Sweden)

    Mathieu Francois Derouet

    Full Text Available BACKGROUND: Carcinoma of the esophagus has a high case fatality ratio and is now the 6th most common cause of cancer deaths in the world. We previously conducted a study to profile the expression of miRNAs in esophageal adenocarcinoma (EAC pre and post induction therapy. Of the miRNAs differentially expressed post induction chemoradiation, miR-145, a known tumor suppressor miRNA, was upregulated 8-fold following induction therapy, however, its expression was associated with shorter disease-free survival. This unexpected result was explored in this current study. METHODS: In order to study the role of miR-145 in EAC, miRNA-145 was overexpressed in 3 EAC cell lines (OE33, FLO-1, SK-GT-4 and one ESCC cell line (KYSE-410. After validation of the expression of miR-145, hallmarks of cancer such as cell proliferation, resistance to chemotherapy drugs or anoikis, and cell invasion were analyzed. RESULTS: There were no differences in cell proliferation and 5 FU resistance between miR145 cell lines and the control cell lines. miR-145 expression also had no effect on cisplatin resistance in two of three cell lines (OE33 and FLO-1, but miR-145 appeared to protect SK-GT-4 cells against cisplatin treatment. However, there was a significant difference in cell invasion, cell adhesion and resistance to anoikis. All three EAC miR-145 cell lines invaded more than their respective controls. Similarly, OE33 and SK-GT-4 miR-145 cell lines were able to survive longer in a suspension state. DISCUSSION: While expression of miR-145 in ESCC stopped proliferation and invasion, expression of miR-145 in EAC cells enhanced invasion and anoikis resistance. Although more work is required to understand how miR-145 conveys these effects, expression of miR-145 appears to promote EAC progression by enhancing invasion and protection against anoikis, which could in turn facilitate distant metastasis.

  10. Association with Soil Bacteria Enhances p38-Dependent Infection Resistance in Caenorhabditis elegans

    Science.gov (United States)

    Montalvo-Katz, Sirena; Huang, Hao; Appel, Michael David; Berg, Maureen

    2013-01-01

    The importance of our inner microbial communities for proper immune responses against invading pathogens is now well accepted, but the mechanisms underlying this protection are largely unknown. In this study, we used Caenorhabditis elegans to investigate such mechanisms. Since very little is known about the microbes interacting with C. elegans in its natural environment, we began by taking the first steps to characterize the C. elegans microbiota. We established a natural-like environment in which initially germfree, wild-type larvae were grown on enriched soil. Bacterial members of the adult C. elegans microbiota were isolated by culture and identified using 16S rRNA gene sequencing. Using pure cultures of bacterial isolates as food, we identified two, Bacillus megaterium and Pseudomonas mendocina, that enhanced resistance to a subsequent infection with the Gram-negative pathogen Pseudomonas aeruginosa. Whereas protection by B. megaterium was linked to impaired egg laying, corresponding to a known trade-off between fecundity and resistance, the mechanism underlying protection conferred by P. mendocina depended on weak induction of immune genes regulated by the p38 MAPK pathway. Disruption of the p38 ortholog, pmk-1, abolished protection. P. mendocina enhanced resistance to P. aeruginosa but not to the Gram-positive pathogen Enterococcus faecalis. Furthermore, protection from P. aeruginosa was similarly induced by a P. aeruginosa gacA mutant with attenuated virulence but not by a different C. elegans-associated Pseudomonas sp. isolate. Our results support a pivotal role for the conserved p38 pathway in microbiota-initiated immune protection and suggest that similarity between microbiota members and pathogens may play a role in such protection. PMID:23230286

  11. Alternating current electrical stimulation enhanced chemotherapy: a novel strategy to bypass multidrug resistance in tumor cells

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    Dini Gabriele

    2006-03-01

    Full Text Available Abstract Background Tumor burden can be pharmacologically controlled by inhibiting cell division and by direct, specific toxicity to the cancerous tissue. Unfortunately, tumors often develop intrinsic pharmacoresistance mediated by specialized drug extrusion mechanisms such as P-glycoprotein. As a consequence, malignant cells may become insensitive to various anti-cancer drugs. Recent studies have shown that low intensity very low frequency electrical stimulation by alternating current (AC reduces the proliferation of different tumor cell lines by a mechanism affecting potassium channels while at intermediate frequencies interfere with cytoskeletal mechanisms of cell division. The aim of the present study is to test the hypothesis that permeability of several MDR1 over-expressing tumor cell lines to the chemotherapic agent doxorubicin is enhanced by low frequency, low intensity AC stimulation. Methods We grew human and rodent cells (C6, HT-1080, H-1299, SKOV-3 and PC-3 which over-expressed MDR1 in 24-well Petri dishes equipped with an array of stainless steel electrodes connected to a computer via a programmable I/O board. We used a dedicated program to generate and monitor the electrical stimulation protocol. Parallel cultures were exposed for 3 hours to increasing concentrations (1, 2, 4, and 8 μM of doxorubicin following stimulation to 50 Hz AC (7.5 μA or MDR1 inhibitor XR9576. Cell viability was assessed by determination of adenylate kinase (AK release. The relationship between MDR1 expression and the intracellular accumulation of doxorubicin as well as the cellular distribution of MDR1 was investigated by computerized image analysis immunohistochemistry and Western blot techniques. Results By the use of a variety of tumor cell lines, we show that low frequency, low intensity AC stimulation enhances chemotherapeutic efficacy. This effect was due to an altered expression of intrinsic cellular drug resistance mechanisms. Immunohistochemical

  12. Mild electrical stimulation with heat shock ameliorates insulin resistance via enhanced insulin signaling.

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    Saori Morino

    Full Text Available Low-intensity electrical current (or mild electrical stimulation; MES influences signal transduction and activates phosphatidylinositol-3 kinase (PI3K/Akt pathway. Because insulin resistance is characterized by a marked reduction in insulin-stimulated PI3K-mediated activation of Akt, we asked whether MES could increase Akt phosphorylation and ameliorate insulin resistance. In addition, it was also previously reported that heat shock protein 72 (Hsp72 alleviates hyperglycemia. Thus, we applied MES in combination with heat shock (HS to in vitro and in vivo models of insulin resistance. Here we show that 10-min treatment with MES at 5 V (0.1 ms pulse duration together with HS at 42 degrees C increased the phosphorylation of insulin signaling molecules such as insulin receptor substrate (IRS and Akt in HepG2 cells maintained in high-glucose medium. MES (12 V+mild HS treatment of high fat-fed mice also increased the phosphorylation of insulin receptor beta subunit (IRbeta and Akt in mice liver. In high fat-fed mice and db/db mice, MES+HS treatment for 10 min applied twice a week for 12-15 weeks significantly decreased fasting blood glucose and insulin levels and improved insulin sensitivity. The treated mice showed significantly lower weight of visceral and subcutaneous fat, a markedly improved fatty liver and decreased size of adipocytes. Our findings indicated that the combination of MES and HS alleviated insulin resistance and improved fat metabolism in diabetes mouse models, in part, by enhancing the insulin signaling pathway.

  13. Longer Interset Rest Periods Enhance Muscle Strength and Hypertrophy in Resistance-Trained Men.

    Science.gov (United States)

    Schoenfeld, Brad J; Pope, Zachary K; Benik, Franklin M; Hester, Garrett M; Sellers, John; Nooner, Josh L; Schnaiter, Jessica A; Bond-Williams, Katherine E; Carter, Adrian S; Ross, Corbin L; Just, Brandon L; Henselmans, Menno; Krieger, James W

    2016-07-01

    Schoenfeld, BJ, Pope, ZK, Benik, FM, Hester, GM, Sellers, J, Nooner, JL, Schnaiter, JA, Bond-Williams, KE, Carter, AS, Ross, CL, Just, BL, Henselmans, M, and Krieger, JW. Longer interset rest periods enhance muscle strength and hypertrophy in resistance-trained men. J Strength Cond Res 30(7): 1805-1812, 2016-The purpose of this study was to investigate the effects of short rest intervals normally associated with hypertrophy-type training versus long rest intervals traditionally used in strength-type training on muscular adaptations in a cohort of young, experienced lifters. Twenty-one young resistance-trained men were randomly assigned to either a group that performed a resistance training (RT) program with 1-minute rest intervals (SHORT) or a group that employed 3-minute rest intervals (LONG). All other RT variables were held constant. The study period lasted 8 weeks with subjects performing 3 total body workouts a week comprised 3 sets of 8-12 repetition maximum (RM) of 7 different exercises per session. Testing was performed prestudy and poststudy for muscle strength (1RM bench press and back squat), muscle endurance (50% 1RM bench press to failure), and muscle thickness of the elbow flexors, triceps brachii, and quadriceps femoris by ultrasound imaging. Maximal strength was significantly greater for both 1RM squat and bench press for LONG compared to SHORT. Muscle thickness was significantly greater for LONG compared to SHORT in the anterior thigh, and a trend for greater increases was noted in the triceps brachii (p = 0.06) as well. Both groups saw significant increases in local upper body muscle endurance with no significant differences noted between groups. This study provides evidence that longer rest periods promote greater increases in muscle strength and hypertrophy in young resistance-trained men.

  14. Chloroquine enhances gefitinib cytotoxicity in gefitinib-resistant nonsmall cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Mei-Chuan Tang

    Full Text Available Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs, including gefitinib, are effective for non-small cell lung cancer (NSCLC patients with EGFR mutations. However, these patients eventually develop resistance to EGFR-TKI. The goal of the present study was to investigate the involvement of autophagy in gefitinib resistance. We developed gefitinib-resistant cells (PC-9/gef from PC-9 cells (containing exon 19 deletion EGFR after long-term exposure in gefitinib. PC-9/gef cells (B4 and E3 were 200-fold more resistant to gefitinib than PC-9/wt cells. Compared with PC-9/wt cells, both PC-9/gefB4 and PC-9/gefE3 cells demonstrated higher basal LC3-II levels which were inhibited by 3-methyladenine (3-MA, an autophagy inhibitor and potentiated by chloroquine (CQ, an inhibitor of autophagolysosomes formation, indicating elevated autophagy in PC-9/gef cells. 3-MA and CQ concentration-dependently inhibited cell survival of both PC-9wt and PC-9/gef cells, suggesting that autophagy may be pro-survival. Furthermore, gefitinib increased LC3-II levels and autolysosome formation in both PC-9/wt cells and PC-9/gef cells. In PC-9/wt cells, CQ potentiated the cytotoxicity by low gefitinib (3 nM. Moreover, CQ overcame the acquired gefitinib resistance in PC-9/gef cells by enhancing gefitinib-induced cytotoxicity, activation of caspase 3 and poly (ADP-ribose polymerase cleavage. Using an in vivo model xenografting with PC-9/wt and PC-9/gefB4 cells, oral administration of gefitinib (50 mg/kg completely inhibited the tumor growth of PC-9/wt but not PC-9/gefB4cells. Combination of CQ (75 mg/kg, i.p. and gefitinib was more effective than gefitinib alone in reducing the tumor growth of PC-9/gefB4. Our data suggest that inhibition of autophagy may be a therapeutic strategy to overcome acquired resistance of gefitinib in EGFR mutation NSCLC patients.

  15. Bipolar resistive switching properties of AlN films deposited by plasma-enhanced atomic layer deposition

    Science.gov (United States)

    Zhang, Jian; Zhang, Qilong; Yang, Hui; Wu, Huayu; Zhou, Juehui; Hu, Liang

    2014-10-01

    AlN thin films deposited by plasma-enhanced atomic layer deposition (PEALD) have been used to investigate the resistive switching (RS) behavior. The bipolar RS properties were observed in the Cu/PEALD-AlN/Pt devices, which are induced upon the formation/disruption of Cu conducting filaments, as confirmed by the temperature dependent resistances relationships at different resistance states. The resistance ratio of the high and low resistance states (HRS/LRS) is 102-105. The dominant conduction mechanisms at HRS and LRS are trap-controlled space charge limited current and Ohmic behavior, respectively. This study demonstrated that the PEALD-AlN films have a great potential for the applications in high-density resistance random access memory.

  16. Enhanced horizontal transfer of antibiotic resistance genes in freshwater microcosms induced by an ionic liquid.

    Directory of Open Access Journals (Sweden)

    Qing Wang

    Full Text Available The spread and propagation of antibiotic resistance genes (ARGs is a worldwide public health concern. Ionic liquids (ILs, considered as "environmentally friendly" replacements for industrial organic solvents, have been widely applied in modern industry. However, few data have been collected regarding the potential ecological and environmental risks of ILs, which are important for preparing for their potential discharge into the environment. In this paper, the IL 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIm][PF6] (0.001-5.0 g/L was tested for its effects on facilitating ARGs horizontal transfer mediated by plasmid RP4 in freshwater microcosms. In the horizontal transfer microcosms, the transfer frequency of plasmid RP4 was significantly enhanced (60-fold higher than untreated groups by the IL [BMIm][PF6] (1.0 g/L. Meanwhile, two strains of opportunistic pathogen Acinetobacter spp. and Salmonella spp. were isolated among the transconjugants, illustrating plasmid RP4 mediated horizontal transfer of ARGs occurred in pathogen. This could increase the risk of ARGs dissemination to human pathogens and pose great threat to public health. The cause that [BMIm[PF6] enhanced the transfer frequency of plasmid RP4 was proposed by suppressed cell membrane barrier and enhanced cell membrane permeability, which was evidenced by flow cytometry (FCM. This is the first report that some ILs facilitate horizontal transfer of plasmid RP4 which is widely distributed in the environment and thus add the adverse effects of the environmental risk of ILs.

  17. Enhanced chemosensitization in multidrug-resistant human breast cancer cells by inhibition of IL-6 and IL-8 production.

    Science.gov (United States)

    Shi, Zhi; Yang, Wei-Min; Chen, Li-Pai; Yang, Dong-Hua; Zhou, Qi; Zhu, Jin; Chen, Jun-Jiang; Huang, Ruo-Chun; Chen, Zhe-Sheng; Huang, Ruo-Pan

    2012-10-01

    Drug resistance remains a major hurdle to successful cancer treatment. Many mechanisms such as overexpression of multidrug-resistance related proteins, increased drug metabolism, decreased apoptosis, and impairment of signal transduction pathway can contribute multidrug resistance (MDR). Recent studies strongly suggest a close link between cytokines and drug resistance. To identify new targets involved in drug resistance, we established a multidrug-resistant human breast cancer cell line MCF-7/R and examined the cytokine profile using cytokine antibody array technology. Among 120 cytokines/chemokines screened, IL-6, IL-8, and 13 other proteins were found to be markedly increased in drug-resistant MCF-7/R cell line as compared to sensitive MCF-7/S cell line, while 7 proteins were specifically reduced in drug-resistant MCF-7/R cells. Neutralizing antibodies against IL-6 and IL-8 partially reversed the drug resistance of MCF-7/R to paclitaxel and doxorubicin, while a neutralizing antibody against MCP-1 had no significant effect. Inhibition of endogenous IL-6 or IL-8 by siRNA technology significantly enhanced drug sensitivity of MCF-7/R cells. Furthermore, overexpression of IL-6 or IL-8 expression by transfection increased the ADM resistance in MCF-7/S cells. Our data suggest that increased expression levels of IL-6 and IL-8 may contribute to MDR in human breast cancer cells.

  18. Insecticide mixtures could enhance the toxicity of insecticides in a resistant dairy population of Musca domestica L [corrected].

    Directory of Open Access Journals (Sweden)

    Hafiz Azhar Ali Khan

    Full Text Available House flies, Musca domestica L., are important pests of dairy operations worldwide, with the ability to adapt wide range of environmental conditions. There are a number of insecticides used for their management, but development of resistance is a serious problem. Insecticide mixtures could enhance the toxicity of insecticides in resistant insect pests, thus resulting as a potential resistance management tool. The toxicity of bifenthrin, cypermethrin, deltamethrin, chlorpyrifos, profenofos, emamectin benzoate and fipronil were assessed separately, and in mixtures against house flies. A field-collected population was significantly resistant to all the insecticides under investigation when compared with a laboratory susceptible strain. Most of the insecticide mixtures like one pyrethroid with other compounds evaluated under two conditions (1∶1-"A" and LC50: LC50-"B" significantly increased the toxicity of pyrethroids in the field population. Under both conditions, the combination indices of pyrethroids with other compounds, in most of the cases, were significantly below 1, suggesting synergism. The enzyme inhibitors, PBO and DEF, when used in combination with insecticides against the resistant population, toxicities of bifenthrin, cypermethrin, deltamethrin and emamectin were significantly increased, suggesting esterase and monooxygenase based resistance mechanism. The toxicities of bifenthrin, cypermethrin and deltamethrin in the resistant population of house flies could be enhanced by the combination with chlorpyrifos, profenofos, emamectin and fipronil. The findings of the present study might have practical significance for resistance management in house flies.

  19. l-Arginine Enhances Resistance against Oxidative Stress and Heat Stress in Caenorhabditis elegans

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    Heran Ma

    2016-09-01

    Full Text Available The antioxidant properties of l-arginine (l-Arg in vivo, and its effect on enhancing resistance to oxidative stress and heat stress in Caenorhabditis elegans were investigated. C. elegans, a worm model popularly used in molecular and developmental biology, was used in the present study. Here, we report that l-Arg, at a concentration of 1 mM, prolonged C. elegans life by 26.98% and 37.02% under oxidative and heat stress, respectively. Further experiments indicated that the longevity-extending effects of l-Arg may be exerted by its free radical scavenging capacity and the upregulation of aging-associated gene expression in worms. This work is important in the context of numerous recent studies that concluded that environment stresses are associated with an increased population death rate.

  20. Enhanced ethylene separation and plasticization resistance in polymer membranes incorporating metal-organic framework nanocrystals

    Science.gov (United States)

    Bachman, Jonathan E.; Smith, Zachary P.; Li, Tao; Xu, Ting; Long, Jeffrey R.

    2016-08-01

    The implementation of membrane-based separations in the petrochemical industry has the potential to reduce energy consumption significantly relative to conventional separation processes. Achieving this goal, however, requires the development of new membrane materials with greater selectivity, permeability and stability than available at present. Here, we report composite materials consisting of nanocrystals of metal-organic frameworks dispersed within a high-performance polyimide, which can exhibit enhanced selectivity for ethylene over ethane, greater ethylene permeability and improved membrane stability. Our results suggest that framework-polymer interactions reduce chain mobility of the polymer while simultaneously boosting membrane separation performance. The increased stability, or plasticization resistance, is expected to improve membrane utility under real process conditions for petrochemical separations and natural gas purification. Furthermore, this approach can be broadly applied to numerous polymers that encounter aggressive environments, potentially making gas separations possible that were previously inaccessible to membranes.

  1. Chitosan and oligochitosan enhance the resistance of peach fruit to brown rot.

    Science.gov (United States)

    Ma, Zengxin; Yang, Lingyu; Yan, Haixia; Kennedy, John F; Meng, Xianghong

    2013-04-15

    The effects of chitosan and oligachitosan on resistance induction of peach fruit against brown rot caused by Monilinia fructicola were investigated. Both chitosan and oligochitosan showed significant effect on controlling this disease. Moreover, chitosan and oligochitosan delayed fruit softening and senescence. The two antifungal substances enhanced antioxidant and defense-related enzymes, such as catalase (CAT), peroxidase (POD), β-1,3-glucanase (GLU) and chitinase (CHI), and they also stimulated the transcript expression of POD and GLU. These findings suggest that the effects of chitosan and oligochitosan on disease control and quality maintenance of peach fruit may be associated with their antioxidant property and the elicitation of defense responses in fruit. PMID:23544538

  2. CCBE1 promotes GIST development through enhancing angiogenesis and mediating resistance to imatinib.

    Science.gov (United States)

    Tian, Guang-Ang; Zhu, Chun-Chao; Zhang, Xiao-Xin; Zhu, Lei; Yang, Xiao-Mei; Jiang, Shu-Heng; Li, Rong-Kun; Tu, Lin; Wang, Yang; Zhuang, Chun; He, Ping; Li, Qing; Cao, Xiao-Yan; Cao, Hui; Zhang, Zhi-Gang

    2016-01-01

    Gastrointestinal stromal tumor (GIST) is the most major mesenchymal neoplasm of the digestive tract. Up to now, imatinib mesylate has been used as a standard first-line treatment for irresectable and metastasized GIST patients or adjuvant treatment for advanced GIST patients who received surgical resection. However, secondary resistance to imatinib usually happens, resulting in a major obstacle in GIST successful therapy. In this study, we first found that collagen and calcium binding EGF domains 1 (CCBE1) expression gradually elevated along with the risk degree of NIH classification, and poor prognosis emerged in the CCBE1-positive patients. In vitro experiments showed that recombinant CCBE1 protein can enhance angiogenesis and neutralize partial effect of imatinib on the GIST-T1 cells. In conclusion, these data indicated that CCBE1 may be served as a new predictor of prognosis in post-operative GIST patients and may play an important role in stimulating GIST progression. PMID:27506146

  3. Indomethacin Analogues that Enhance Doxorubicin Cytotoxicity in Multidrug Resistant Cells without Cox Inhibitory Activity.

    Science.gov (United States)

    Arisawa, Mitsuhiro; Kasaya, Yayoi; Obata, Tohru; Sasaki, Takuma; Ito, Mika; Abe, Hiroshi; Ito, Yoshihiro; Yamano, Akihito; Shuto, Satoshi

    2011-05-12

    Conformationally restricted indomethacin analogues were designed and prepared from the corresponding 2-substituted indoles, which were synthesized by a one-pot isomerization/enamide-ene metathesis as the key reaction. Conformational analysis by calculations, NMR studies, and X-ray crystallography suggested that these analogues were conformationally restricted in the s-cis or the s-trans form due to the 2-substituent as expected. Their biological activities on cyclooxygenase-1 (COX-1) inhibition, cyclooxygenase-2 (COX-2) inhibition, and modulation of MRP-1-mediated multidrug resistance (MDR) are described. Some of these indomethacin analogues enhanced doxorubicin cytotoxicity, although they do not have any COX inhibitory activity, which suggests that the MDR-modulating effect of an NSAID can be unassociated with its COX-inhibitory activity. This may be an entry into the combination chemotherapy of doxorubicin with a MDR modulator. PMID:24900317

  4. Enhanced ethylene separation and plasticization resistance in polymer membranes incorporating metal-organic framework nanocrystals.

    Science.gov (United States)

    Bachman, Jonathan E; Smith, Zachary P; Li, Tao; Xu, Ting; Long, Jeffrey R

    2016-08-01

    The implementation of membrane-based separations in the petrochemical industry has the potential to reduce energy consumption significantly relative to conventional separation processes. Achieving this goal, however, requires the development of new membrane materials with greater selectivity, permeability and stability than available at present. Here, we report composite materials consisting of nanocrystals of metal-organic frameworks dispersed within a high-performance polyimide, which can exhibit enhanced selectivity for ethylene over ethane, greater ethylene permeability and improved membrane stability. Our results suggest that framework-polymer interactions reduce chain mobility of the polymer while simultaneously boosting membrane separation performance. The increased stability, or plasticization resistance, is expected to improve membrane utility under real process conditions for petrochemical separations and natural gas purification. Furthermore, this approach can be broadly applied to numerous polymers that encounter aggressive environments, potentially making gas separations possible that were previously inaccessible to membranes.

  5. Enhancing the formation and shear resistance of nitrifying biofilms on membranes by surface modification

    DEFF Research Database (Denmark)

    Lackner, Susanne; Holmberg, Maria; Terada, Akihiko;

    2009-01-01

    Polypropylene (PP) membranes and polyethylene (PE) surfaces were modified to enhance formation and shear resistance of nitrifying biofilms for wastewater treatment applications. A combination of plasma polymerization and wet chemistry was employed to ultimately introduce poly(ethyleneglycol) (PEG......) chains with two different functional groups (-PEG-NH2 and -PEG-CH3). Biofilm growth experiments using a mixed nitrifying bacterial culture revealed that the specific combination of PEG chains with amino groups resulted in most biofilm formation on both PP and PE samples. Detachment experiments showed...... similar trends: biofilms on -PEG-NH2 modified surfaces were much stronger compared to the other modifications and the unmodified reference surfaces. Electrostatic interactions between the protonated amino group and negatively charged bacteria as well as PEG chain density which can affect the surface...

  6. Enhancing Fracture and Wear Resistance of Dentures/Overdentures Utilizing Digital Technology: A Case Series Report.

    Science.gov (United States)

    Afify, Ahmed; Haney, Stephan

    2016-08-01

    Since it was first introduced into the dental world, computer-aided design/computer-aided manufacturing (CAD/CAM) technology has improved dramatically in regards to both data acquisition and fabrication abilities. CAD/CAM is capable of providing well-fitting intra- and extraoral prostheses when sound guidelines are followed. As CAD/CAM technology encompasses both surgical and prosthetic dental applications as well as fixed and removable aspects, it could improve the average quality of dental prostheses compared with the results obtained by conventional manufacturing methods. The purpose of this article is to provide an introduction into the methods in which this technology may be used to enhance the wear and fracture resistance of dentures and overdentures. This article will also showcase two clinical reports in which CAD/CAM technology has been implemented. PMID:26916680

  7. Enhancement of host resistance against Listeria infection by Lactobacillus casei: Role of macrophages

    International Nuclear Information System (INIS)

    Among the 10 species of the genus Lactobacillus, L. casei showed the strongest protective action against Listeria monocytogenes infection in mice. The activity of L. casei differed with regard to the dose of administration. The anti-L. monocytogenes resistance in mice intravenously administered 5.5 X 10(7), 2.8 X 10(8), or 1.1 X 10(9) L. casei cells was most manifest at ca. 2, 2 and 13, and 3 to 21 days after its administration, respectively. The growth of L. monocytogenes in the liver of mice injected with L. casei (10(7), 10(8), or 10(9) cells) 48 h after infection was suppressed, particularly when 10(8) or 10(9) L. casei cells were given 2 or 13 days before the induced infection, respectively. This suppression of L. monocytogenes growth was overcome by carrageenan treatment or X-ray irradiation. [3H]thymidine incorporation into the liver DNA increased 13 days after administration of L. casei, and augmentation of [3H]thymidine incorporation during 6 to 48 h after infection was dependent on the dose of L. casei. Peritoneal macrophage accumulation observed 1 to 5 days after intraperitoneal injection of UV-killed L. monocytogenes was markedly enhanced when the mice were treated with L. casei cells 13 days before macrophage elicitation. Therefore, the enhanced host resistance by L. casei to L. monocytogenes infection may be mediated by macrophages migrating from the blood stream to the reticuloendothelial system in response to L. casei injection before or after L. monocytogenes infection

  8. A Novel Peptide from Soybean Protein Isolate Significantly Enhances Resistance of the Organism under Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Heran Ma

    Full Text Available Recent studies have indicated that protein hydrolysates have broad biological effects. In the current study we describe a novel antioxidative peptide, FDPAL, from soybean protein isolate (SPI. The aim of this study was to purify and characterize an antioxidative peptide from SPI and determine its antioxidative mechanism. LC-MS/MS was used to isolate and identify the peptide from SPI. The sequence of the peptide was determined to be Phe-Asp-Pro-Ala-Leu (FDPAL, 561 Da. FDPAL can cause significant enhancement of resistance to oxidative stress both in cells as well as simple organisms. In Caenorhabditis elegans (C. elegans, FDPAL can up-regulate the expression of certain genes associated with resistance. The antioxidant activity of this peptide can be attributed to the presence of a specific amino acid sequence. Results from our work suggest that FDPAL can facilitate potential applications of proteins carrying this sequence in the nutraceutical, bioactive material and clinical medicine areas, as well as in cosmetics and health care products.

  9. Enhanced oscillatory rectification and negative differential resistance in pentamantane diamondoid-cumulene systems.

    Science.gov (United States)

    Tawfik, Sherif Abdulkader; Cui, X Y; Ringer, S P; Stampfl, C

    2016-02-14

    We propose a new functionality for diamondoids in nanoelectronics. Based on the nonequilibrium Green's function formalism and density functional theory, we reveal that when attached to gold electrodes, the pentamantane-cumulene molecular junction exhibits large and oscillatory rectification and negative differential resistance (NDR) - depending on the number of carbon atoms in cumulene (Cn). When n is odd rectification is greatly enhanced where the rectification ratio can reach ∼180 and a large negative differential resistance peak current of ∼3 μA. This oscillatory behavior is well rationalised in terms of the occupancy of the carbon 2p states in Cn. Interestingly, different layers of C atoms in the pentamantane molecule have different contributions to transmission. The first and third layers of C atoms in pentamantane have a slight contribution to rectification, and the fifth and sixth layers have a stronger contribution to both rectification and NDR. Thus, our results suggest potential avenues for controlling their functions by chemically manipulating various parts of the diamondoid molecule, thus extending the applications of diamondoids in nanoscale integrated circuits.

  10. Enhanced oscillatory rectification and negative differential resistance in pentamantane diamondoid-cumulene systems

    Science.gov (United States)

    Tawfik, Sherif Abdulkader; Cui, X. Y.; Ringer, S. P.; Stampfl, C.

    2016-02-01

    We propose a new functionality for diamondoids in nanoelectronics. Based on the nonequilibrium Green's function formalism and density functional theory, we reveal that when attached to gold electrodes, the pentamantane-cumulene molecular junction exhibits large and oscillatory rectification and negative differential resistance (NDR) - depending on the number of carbon atoms in cumulene (Cn). When n is odd rectification is greatly enhanced where the rectification ratio can reach ~180 and a large negative differential resistance peak current of ~3 μA. This oscillatory behavior is well rationalised in terms of the occupancy of the carbon 2p states in Cn. Interestingly, different layers of C atoms in the pentamantane molecule have different contributions to transmission. The first and third layers of C atoms in pentamantane have a slight contribution to rectification, and the fifth and sixth layers have a stronger contribution to both rectification and NDR. Thus, our results suggest potential avenues for controlling their functions by chemically manipulating various parts of the diamondoid molecule, thus extending the applications of diamondoids in nanoscale integrated circuits.

  11. Tobacco OPBP1 Enhances Salt Tolerance and Disease Resistance of Transgenic Rice

    Directory of Open Access Journals (Sweden)

    Xujun Chen

    2008-12-01

    Full Text Available Osmotin promoter binding protein 1 (OPBP1, an AP2/ERF transcription factor of tobacco, has been demonstrated to function in disease resistance and salt tolerance in tobacco. To increase stress tolerant capability of rice, we generated rice plants with an OPBP1 overexpressing construct. Salinity shock treatment with 250 mM NaCl indicated that most of the OPBP1 transgenic plants can survive, whereas the control seedlings cannot. Similar recovery was found by using the seedlings grown in 200 mM NaCl for two weeks. The OPBP1 transgenic and control plants were also studied for oxidative stress tolerance by treatment with paraquat, showing the transgenic lines were damaged less in comparison with the control plants. Further, the OPBP1 overexpression lines exhibited enhanced resistance to infections of Magnaporthe oryzae and Rhizoctonia solani pathogens. Gene expressing analysis showed increase in mRNA accumulation of several stress related genes. These results suggest that expression of OPBP1 gene increase the detoxification capability of rice.

  12. The white barley mutant albostrians shows enhanced resistance to the biotroph Blumeria graminis f. sp. hordei.

    Science.gov (United States)

    Jain, Sanjay Kumar; Langen, Gregor; Hess, Wolfgang; Börner, Thomas; Hückelhoven, Ralph; Kogel, Karl-Heinz

    2004-04-01

    We performed cytological and molecular analyses of the interaction between the biotrophic barley powdery mildew fungus Blumeria graminis f. sp. hordei and white and green leaves of the barley albostrians mutant. The leaves have the same nuclear genotype but differ from each other in respect to plastid differentiation. White leaves showed enhanced penetration resistance to B. graminis f. sp. hordei, associated with higher epidermal H2O2 accumulation beneath the appressorial germ tubes and protein cross-linking in papillae. Very low basal salicylic acid content was found in white leaves, which further confirmed that H2O2 accumulation and penetration resistance in barley are independent of salicylic acid. Expression analysis of stress and defense-related genes, including such being involved in reactive oxygen species production and cell death regulation, revealed stronger constitutive or pathogen-induced transcript accumulation in white leaves. We discuss the data on the basis of the finding that white albostrians leaves exhibit a supersusceptible interaction phenotype with the hemibiotrophic fungus Bipolaris sorokiniana.

  13. Enhancing alkylating agent resistance through ERCC2 gene transfection in human glioma cell line

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhongping 陈忠平; ZHANG Junying 张俊英; Gérard MOHR

    2003-01-01

    Objective To confirm the enhancing effect of excision repair cross complementing rodent repair deficiency gene 2 (ERCC2) on alkylating agents resistance. Methods The authors constructed a pcDNA3-ERCC2 plasmid. The pcDNA3-ERCC2 was transfected into a selected ERCC2 negative human glioma cell line, SKMG-4, using liposome-mediated transfection. After G418 selection, a stable transfected cell line was obtained and tested for cytotoxicity of several alkylating agents. Results The stable transfectant was obtained and confirmed by RT-PCR as well as Western blot analysis to be strongly expressing ERCC2 at both mRNA and protein levels. The IC90 (μmol/L) of two alkylating agents, cisplatin and melphalan, increased from 1.0 to 1.75 (75%) and 5.6 to 9.0 (61%), respectively, compared with control cell line. Conclusion The present data provided evidences and confirmed the authors' previous results that ERCC2 contributes, at least partially, to alkylating agent resistance in human glioma cell line.

  14. A Novel Peptide from Soybean Protein Isolate Significantly Enhances Resistance of the Organism under Oxidative Stress.

    Science.gov (United States)

    Ma, Heran; Liu, Rui; Zhao, Ziyuan; Zhang, Zhixian; Cao, Yue; Ma, Yudan; Guo, Yi; Xu, Li

    2016-01-01

    Recent studies have indicated that protein hydrolysates have broad biological effects. In the current study we describe a novel antioxidative peptide, FDPAL, from soybean protein isolate (SPI). The aim of this study was to purify and characterize an antioxidative peptide from SPI and determine its antioxidative mechanism. LC-MS/MS was used to isolate and identify the peptide from SPI. The sequence of the peptide was determined to be Phe-Asp-Pro-Ala-Leu (FDPAL, 561 Da). FDPAL can cause significant enhancement of resistance to oxidative stress both in cells as well as simple organisms. In Caenorhabditis elegans (C. elegans), FDPAL can up-regulate the expression of certain genes associated with resistance. The antioxidant activity of this peptide can be attributed to the presence of a specific amino acid sequence. Results from our work suggest that FDPAL can facilitate potential applications of proteins carrying this sequence in the nutraceutical, bioactive material and clinical medicine areas, as well as in cosmetics and health care products. PMID:27455060

  15. Siliceous spicules enhance fracture-resistance and stiffness of pre-colonial Amazonian ceramics

    Science.gov (United States)

    Natalio, Filipe; Corrales, Tomas P.; Wanka, Stephanie; Zaslansky, Paul; Kappl, Michael; Lima, Helena Pinto; Butt, Hans-Jürgen; Tremel, Wolfgang

    2015-08-01

    Pottery was a traditional art and technology form in pre-colonial Amazonian civilizations, widely used for cultural expression objects, utensils and as cooking vessels. Abundance and workability of clay made it an excellent choice. However, inferior mechanical properties constrained their functionality and durability. The inclusion of reinforcement particles is a possible route to improve its resistance to mechanical and thermal damage. The Amazonian civilizations incorporated freshwater tree sponge spicules (cauixí) into the clay presumably to prevent shrinkage and crack propagation during drying, firing and cooking. Here we show that isolated siliceous spicules are almost defect-free glass fibres with exceptional mechanical stability. After firing, the spicule Young’s modulus increases (from 28 ± 5 GPa to 46 ± 8 GPa) inferring a toughness increment. Laboratory-fabricated ceramic models containing different inclusions (sand, glass-fibres, sponge spicules) show that mutually-oriented siliceous spicule inclusions prevent shrinkage and crack propagation leading to high stiffness clays (E = 836 ± 3 MPa). Pre-colonial amazonian potters were the first civilization known to employ biological materials to generate composite materials with enhanced fracture resistance and high stiffness in the history of mankind.

  16. Pipecolic acid enhances resistance to bacterial infection and primes salicylic acid and nicotine accumulation in tobacco.

    Science.gov (United States)

    Vogel-Adghough, Drissia; Stahl, Elia; Návarová, Hana; Zeier, Juergen

    2013-11-01

    Distinct amino acid metabolic pathways constitute integral parts of the plant immune system. We have recently identified pipecolic acid (Pip), a lysine-derived non-protein amino acid, as a critical regulator of systemic acquired resistance (SAR) and basal immunity to bacterial infection in Arabidopsis thaliana. In Arabidopsis, Pip acts as an endogenous mediator of defense amplification and priming. For instance, Pip conditions plants for effective biosynthesis of the phenolic defense signal salicylic acid (SA), accumulation of the phytoalexin camalexin, and expression of defense-related genes. Here, we show that tobacco plants respond to leaf infection by the compatible bacterial pathogen Pseudomonas syringae pv tabaci (Pstb) with a significant accumulation of several amino acids, including Lys, branched-chain, aromatic, and amide group amino acids. Moreover, Pstb strongly triggers, alongside the biosynthesis of SA and increases in the defensive alkaloid nicotine, the production of the Lys catabolites Pip and α-aminoadipic acid. Exogenous application of Pip to tobacco plants provides significant protection to infection by adapted Pstb or by non-adapted, hypersensitive cell death-inducing P. syringae pv maculicola. Pip thereby primes tobacco for rapid and strong accumulation of SA and nicotine following bacterial infection. Thus, our study indicates that the role of Pip as an amplifier of immune responses is conserved between members of the rosid and asterid groups of eudicot plants and suggests a broad practical applicability for Pip as a natural enhancer of plant disease resistance.

  17. Enhancement of stress resistance of the guppy Poecilia reticulata through feeding with vitamin C supplement

    OpenAIRE

    Lim, L C; Dhert, P.; Chew, W.Y.; Dermaux, V.; Nelis, H.; Sorgeloos, P.

    2002-01-01

    This study investigated the use of vitamin C supplement in formulated diets and live Artemia juveniles to enhance the stress resistance of the guppy Poecilia reticulata. To evaluate the stress resistance, fish were subjected to osmotic shock in pre-aerated water containing 35 ppt sodium chloride. Ascorbyl acid-poly phosphate and ascorbyl palmitate were used as vitamin C sources for formulated diets and live Artemia juveniles, respectively. Results showed that guppies fed moist formulated diet...

  18. Enhanced Locomotor Activity Is Required to Exert Dietary Restriction-Dependent Increase of Stress Resistance in Drosophila

    Directory of Open Access Journals (Sweden)

    Saurav Ghimire

    2015-01-01

    Full Text Available Dietary restriction (DR is known to be one of the most effective interventions to increase stress resistance, yet the mechanisms remain elusive. One of the most obvious DR-induced changes in phenotype is an increase in locomotor activity. Although it is conceptually perceivable that nutritional scarcity should prompt enhanced foraging behavior to garner additional dietary resources, the significance of enhanced movement activity has not been associated with the DR-dependent increase of stress resistance. In this study, we confirmed that flies raised on DR exhibited enhanced locomotive activity and increased stress resistance. Excision of fly wings minimized the DR-induced increase in locomotive activity, which resulted in attenuation of the DR-dependent increase of stress resistance. The possibility that wing clipping counteracts the DR by coercing flies to have more intake was ruled out since it did not induce any weight gain. Rather it was found that elimination of reactive oxygen species (ROS that is enhanced by DR-induced upregulation of expression of antioxidant genes was significantly reduced by wing clipping. Collectively, our data suggests that DR increased stress resistance by increasing the locomotor activity, which upregulated expression of protective genes including, but not limited to, ROS scavenger system.

  19. Enhanced Locomotor Activity Is Required to Exert Dietary Restriction-Dependent Increase of Stress Resistance in Drosophila.

    Science.gov (United States)

    Ghimire, Saurav; Kim, Man Su

    2015-01-01

    Dietary restriction (DR) is known to be one of the most effective interventions to increase stress resistance, yet the mechanisms remain elusive. One of the most obvious DR-induced changes in phenotype is an increase in locomotor activity. Although it is conceptually perceivable that nutritional scarcity should prompt enhanced foraging behavior to garner additional dietary resources, the significance of enhanced movement activity has not been associated with the DR-dependent increase of stress resistance. In this study, we confirmed that flies raised on DR exhibited enhanced locomotive activity and increased stress resistance. Excision of fly wings minimized the DR-induced increase in locomotive activity, which resulted in attenuation of the DR-dependent increase of stress resistance. The possibility that wing clipping counteracts the DR by coercing flies to have more intake was ruled out since it did not induce any weight gain. Rather it was found that elimination of reactive oxygen species (ROS) that is enhanced by DR-induced upregulation of expression of antioxidant genes was significantly reduced by wing clipping. Collectively, our data suggests that DR increased stress resistance by increasing the locomotor activity, which upregulated expression of protective genes including, but not limited to, ROS scavenger system.

  20. Resistant starch and protein intake enhances fat oxidation and feelings of fullness in lean and overweight/obese women

    DEFF Research Database (Denmark)

    Gentile, Christopher L; Ward, Emery; Holst, Jens Juul;

    2015-01-01

    BACKGROUND: Diets high in either resistant starch or protein have been shown to aid in weight management. We examined the effects of meals high in non-resistant or resistant starch with and without elevated protein intake on substrate utilization, energy expenditure, and satiety in lean...... and overweight/obese women. METHODS: Women of varying levels of adiposity consumed one of four pancake test meals in a single-blind, randomized crossover design: 1) waxy maize (control) starch (WMS); 2) waxy maize starch and whey protein (WMS+WP); 3) resistant starch (RS); or 4) RS and whey protein (RS...... factors were not different among any of the test meals. However, peptide YY (PYY) was significantly elevated at 180 min following RS+WP meal. CONCLUSIONS: The combined consumption of dietary resistant starch and protein increases fat oxidation, PYY, and enhances feelings of satiety and fullness to levels...

  1. Enhanced resistance of the Pamirs high-mountain strain of Cryptococcus albidus to UV radiation of an ecological range

    Energy Technology Data Exchange (ETDEWEB)

    Strakhovskaya, M.G.; Lavrukhina, O.G.; Fraikin, G.Y. [Moscow State Univ. (Russian Federation)

    1995-07-01

    The results of a comparative analysis of the resistance of Pamirs high-mountain and lowland strains of the yeast Cryptococcus albidus to UV radiation of an ecological range are presented. A high-mountain strain, adapted to elevated UV radiation in its habitat, was found to be more resistant to UV light of a total ecorange (290-400 nm), including medium-wave (290-320 nm) and long-wave (320-400 nm) UV ranges. The enhanced UV light resistance of the high-mountain strain can be explained by efficient functioning of the excision DNA repair system. 7 refs., 3 tabs.

  2. Ultralow specific on-resistance high voltage trench SOI LDMOS with enhanced RESURF effect

    International Nuclear Information System (INIS)

    A RESURF-enhanced high voltage SOI LDMOS (ER-LDMOS) with an ultralow specific on-resistance (Ron, sp) is proposed. The device features an oxide trench in the drift region, a P-pillar at the sidewall of the trench, and a buried P-layer (BPL) under the trench. First, the P-pillar adjacent to the P-body not only acts as a vertical junction termination extension (JTE), but also forms a vertical reduced surface field (RESURF) structure with the N-drift region. Both of them optimize the bulk electric field distributions and increase the doping concentration of the drift region. Second, the BPL together with the N-drift region and the buried oxide layer (BOX) exhibits a triple-RESURF effect, which further improves the bulk field distributions and the doping concentration. Additionally, multiple-directional depletion is induced owing to the P-pillar, the BPL, and two MIS-like structures consisting of the N-drift region combined with the oxide trench and the BOX. As a result, a significantly enhanced-RESURF effect is achieved, leading to a high breakdown voltage (BV) and a low Ron, sp. Moreover, the oxide trench folds the drift region in the vertical direction, resulting in a reduced cell pitch and thus Ron, sp. Simulated results show that the ER-LDMOS improves BV by 67% and reduces Ron, sp by 91% compared with the conventional trench LDMOS at the same cell pitch. (semiconductor devices)

  3. Enhanced Cadmium (Cd Phytoextraction from Contaminated Soil using Cd-Resistant Bacterium

    Directory of Open Access Journals (Sweden)

    Kunchaya Setkit

    2014-01-01

    Full Text Available A cadmium (Cd-resistant bacterium, Micrococcus sp. MU1, is able to produce indole-3-acetic acid and promotes root elongation and plant growth. The potential of this bacterium on enhancement of Cd uptake and bioaccumulation of Cd in Helianthus annuus L. planted in Cd-contaminated soil was evaluated in greenhouse condition. The results showed that Micrococcus sp. MU1promoted the growth of H. annuus L. by increasing the root length, stem height, dry biomass, root to shoot ratio and also significantly increased Cd accumulation in the root and above-ground tissues of H. annuus L. compared to uninoculated control. Re-inoculation with Micrococcus sp. MU1in contaminated soil helped in promoting plant growth and Cd phytoextraction throughout the cultivation period. In addition, phytoextraction coefficient and translocation factor (TF of H. annuus L. inoculated with Micrococcus sp. MU1were higher than that of uninoculated control and TF continuously increased with time. Our results suggested that Micrococcus sp. MU1 has an ability to enhance plant growth and Cd uptake in H. annuus L. Synergistic interaction between Micrococcus sp. MU1 and H. annuus L. could be further applied for Cd phytoextraction in polluted areas.

  4. Expression of rabbit IL-4 by recombinant myxoma viruses enhances virulence and overcomes genetic resistance to myxomatosis.

    Science.gov (United States)

    Kerr, P J; Perkins, H D; Inglis, B; Stagg, R; McLaughlin, E; Collins, S V; Van Leeuwen, B H

    2004-06-20

    Rabbit IL-4 was expressed in the virulent standard laboratory strain (SLS) and the attenuated Uriarra (Ur) strain of myxoma virus with the aim of creating a Th2 cytokine environment and inhibiting the development of an antiviral cell-mediated response to myxomatosis in infected rabbits. This allowed testing of a model for genetic resistance to myxomatosis in wild rabbits that have undergone 50 years of natural selection for resistance to myxomatosis. Expression of IL-4 significantly enhanced virulence of both virulent and attenuated virus strains in susceptible (laboratory) and resistant (wild) rabbits. SLS-IL-4 completely overcame genetic resistance in wild rabbits. The pathogenesis of SLS-IL-4 was compared in susceptible and resistant rabbits. The results support a model for resistance to myxomatosis of an enhanced innate immune response controlling virus replication and allowing an effective antiviral cell-mediated immune response to develop in resistant rabbits. Expression of IL-4 did not overcome immunity to myxomatosis induced by immunization. PMID:15183059

  5. Overexpression of phosphomimic mutated OsWRKY53 leads to enhanced blast resistance in rice.

    Directory of Open Access Journals (Sweden)

    Tetsuya Chujo

    Full Text Available WRKY transcription factors and mitogen-activated protein kinase (MAPK cascades have been shown to play pivotal roles in the regulation of plant defense responses. We previously reported that OsWRKY53-overexpressing rice plants showed enhanced resistance to the rice blast fungus. In this study, we identified OsWRKY53 as a substrate of OsMPK3/OsMPK6, components of a fungal PAMP-responsive MAPK cascade in rice, and analyzed the effect of OsWRKY53 phosphorylation on the regulation of basal defense responses to a virulence race of rice blast fungus Magnaporthe oryzae strain Ina86-137. An in vitro phosphorylation assay revealed that the OsMPK3/OsMPK6 activated by OsMKK4 phosphorylated OsWRKY53 recombinant protein at its multiple clustered serine-proline residues (SP cluster. When OsWRKY53 was coexpressed with a constitutively active mutant of OsMKK4 in a transient reporter gene assay, the enhanced transactivation activity of OsWRKY53 was found to be dependent on phosphorylation of the SP cluster. Transgenic rice plants overexpressing a phospho-mimic mutant of OsWRKY53 (OsWRKY53SD showed further-enhanced disease resistance to the blast fungus compared to native OsWRKY53-overexpressing rice plants, and a substantial number of defense-related genes, including pathogenesis-related protein genes, were more upregulated in the OsWRKY53SD-overexpressing plants compared to the OsWRKY53-overexpressing plants. These results strongly suggest that the OsMKK4-OsMPK3/OsMPK6 cascade regulates transactivation activity of OsWRKY53, and overexpression of the phospho-mimic mutant of OsWRKY53 results in a major change to the rice transcriptome at steady state that leads to activation of a defense response against the blast fungus in rice plants.

  6. Enhanced non-volatile resistive switching in suspended single-crystalline ZnO nanowire with controllable multiple states

    Science.gov (United States)

    Zhang, Rui; Pang, Wei; Zhang, Qing; Chen, Yan; Chen, Xuejiao; Feng, Zhihong; Yang, Jianhua; Zhang, Daihua

    2016-08-01

    Resistive switching nanostructures are a promising candidate for next-generation non-volatile memories. In this report, we investigate the switching behaviors of single-crystalline ZnO nanowires suspended in air. They exhibit significantly higher current density, lower switching voltage, and more pronounced multiple conductance states compared to nanowires in direct contact with substrate. We attribute the effect to enhanced Joule heating efficiency, reduced surface scattering, and more significantly, the positive feedback established between the current density and local temperature in the suspended nanowires. The proposed mechanism has been quantitatively examined by finite element simulations. We have also demonstrated an innovative approach to initiating the current–temperature mutual enhancement through illumination by ultraviolet light, which further confirmed our hypothesis and enabled even greater enhancement. Our work provides further insight into the resistive switching mechanism of single-crystalline one-dimensional nanostructures, and suggests an effective means of performance enhancement and device optimization.

  7. Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen

    DEFF Research Database (Denmark)

    Baldwin, Susan L; Roeffen, Will; Singh, Susheel K;

    2016-01-01

    , liposomes, and alum) in C57BL/6 mice. Some, but not all, formulations containing either the synthetic TLR4 agonist GLA or SLA elicited the highest parasite-specific antibody titers, the greatest IFN-γ responses in CD4+ TH1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN...

  8. Antibacterial Activity and Antibiotic-Enhancing Effects of Honeybee Venom against Methicillin-Resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Sang Mi Han

    2016-01-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA, along with other antibiotic resistant bacteria, has become a significant social and clinical problem. There is thus an urgent need to develop naturally bioactive compounds as alternatives to the few antibiotics that remain effective. Here we assessed the in vitro activities of bee venom (BV, alone or in combination with ampicillin, penicillin, gentamicin or vancomycin, on growth of MRSA strains. The antimicrobial activity of BV against MRSA strains was investigated using minimum inhibitory concentrations (MIC, minimum bactericidal concentrations (MBC and a time-kill assay. Expression of atl which encodes murein hydrolase, a peptidoglycan-degrading enzyme involved in cell separation, was measured by reverse transcription-polymerase chain reaction. The MICs of BV were 0.085 µg/mL and 0.11 µg/mL against MRSA CCARM 3366 and MRSA CCARM 3708, respectively. The MBC of BV against MRSA 3366 was 0.106 µg/mL and that against MRSA 3708 was 0.14 µg/mL. The bactericidal activity of BV corresponded to a decrease of at least 3 log CFU/g cells. The combination of BV with ampicillin or penicillin yielded an inhibitory concentration index ranging from 0.631 to 1.002, indicating a partial and indifferent synergistic effect. Compared to ampicillin or penicillin, both MRSA strains were more susceptible to the combination of BV with gentamicin or vancomycin. The expression of atl gene was increased in MRSA 3366 treated with BV. These results suggest that BV exhibited antibacterial activity and antibiotic-enhancing effects against MRSA strains. The atl gene was increased in MRSA exposed to BV, suggesting that cell division was interrupted. BV warrants further investigation as a natural antimicrobial agent and synergist of antibiotic activity.

  9. Antibacterial Activity and Antibiotic-Enhancing Effects of Honeybee Venom against Methicillin-Resistant Staphylococcus aureus.

    Science.gov (United States)

    Han, Sang Mi; Kim, Joung Min; Hong, In Pyo; Woo, Soon Ok; Kim, Se Gun; Jang, He Rye; Pak, Sok Cheon

    2016-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA), along with other antibiotic resistant bacteria, has become a significant social and clinical problem. There is thus an urgent need to develop naturally bioactive compounds as alternatives to the few antibiotics that remain effective. Here we assessed the in vitro activities of bee venom (BV), alone or in combination with ampicillin, penicillin, gentamicin or vancomycin, on growth of MRSA strains. The antimicrobial activity of BV against MRSA strains was investigated using minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC) and a time-kill assay. Expression of atl which encodes murein hydrolase, a peptidoglycan-degrading enzyme involved in cell separation, was measured by reverse transcription-polymerase chain reaction. The MICs of BV were 0.085 µg/mL and 0.11 µg/mL against MRSA CCARM 3366 and MRSA CCARM 3708, respectively. The MBC of BV against MRSA 3366 was 0.106 µg/mL and that against MRSA 3708 was 0.14 µg/mL. The bactericidal activity of BV corresponded to a decrease of at least 3 log CFU/g cells. The combination of BV with ampicillin or penicillin yielded an inhibitory concentration index ranging from 0.631 to 1.002, indicating a partial and indifferent synergistic effect. Compared to ampicillin or penicillin, both MRSA strains were more susceptible to the combination of BV with gentamicin or vancomycin. The expression of atl gene was increased in MRSA 3366 treated with BV. These results suggest that BV exhibited antibacterial activity and antibiotic-enhancing effects against MRSA strains. The atl gene was increased in MRSA exposed to BV, suggesting that cell division was interrupted. BV warrants further investigation as a natural antimicrobial agent and synergist of antibiotic activity. PMID:26771592

  10. Chitosan and oligochitosan enhance ginger (Zingiber officinale Roscoe) resistance to rhizome rot caused by Fusarium oxysporum in storage

    Science.gov (United States)

    The ability of chitosan and oligochitosan to enhance the resistance of ginger (Zingiber officinale) to rhizome rot, caused by Fusarium oxysporum, in storage was investigated. Both chitosan and oligochitosan at 1 and 5 g/L significantly inhibited rhizome rot, relative to the untreated control, with...

  11. Agonists and inverse agonists for the herpesvirus 8-encoded constitutively active seven-transmembrane oncogene product, ORF-74

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Kledal, T N; Bräuner-Osborne, Hans;

    1999-01-01

    , whereas IP-10 and stromal cell-derived factor-1alpha surprisingly acted as inverse agonists. These peptides had similar pharmacological properties with regard to enhancing or inhibiting, respectively, the stimulatory effect of ORF-74 on NIH-3T3 cell proliferation. Construction of a high affinity zinc...... as demonstrated by the effect of Zn2+ on the metal ion site-engineered receptor....

  12. Targeted nanoparticles for enhanced X-ray radiation killing of multidrug-resistant bacteria

    Science.gov (United States)

    Luo, Yang; Hossain, Mainul; Wang, Chaoming; Qiao, Yong; An, Jincui; Ma, Liyuan; Su, Ming

    2012-12-01

    This paper describes a nanoparticle enhanced X-ray irradiation based strategy that can be used to kill multidrug resistant (MDR) bacteria. In the proof-of-concept experiment using MDR Pseudomonas aeruginosa (P. aeruginosa) as an example, polyclonal antibody modified bismuth nanoparticles are introduced into bacterial culture to specifically target P. aeruginosa. After washing off uncombined bismuth nanoparticles, the bacteria are irradiated with X-rays, using a setup that mimics a deeply buried wound in humans. Results show that up to 90% of MDR P. aeruginosa are killed in the presence of 200 μg ml-1 bismuth nanoparticles, whereas only ~6% are killed in the absence of bismuth nanoparticles when exposed to 40 kVp X-rays for 10 min. The 200 μg ml-1 bismuth nanoparticles enhance localized X-ray dose by 35 times higher than the control with no nanoparticles. In addition, no significant harmful effects on human cells (HeLa and MG-63 cells) have been observed with 200 μg ml-1 bismuth nanoparticles and 10 min 40 kVp X-ray irradiation exposures, rendering the potential for future clinical use. Since X-rays can easily penetrate human tissues, this bactericidal strategy has the potential to be used in effectively killing deeply buried MDR bacteria in vivo.This paper describes a nanoparticle enhanced X-ray irradiation based strategy that can be used to kill multidrug resistant (MDR) bacteria. In the proof-of-concept experiment using MDR Pseudomonas aeruginosa (P. aeruginosa) as an example, polyclonal antibody modified bismuth nanoparticles are introduced into bacterial culture to specifically target P. aeruginosa. After washing off uncombined bismuth nanoparticles, the bacteria are irradiated with X-rays, using a setup that mimics a deeply buried wound in humans. Results show that up to 90% of MDR P. aeruginosa are killed in the presence of 200 μg ml-1 bismuth nanoparticles, whereas only ~6% are killed in the absence of bismuth nanoparticles when exposed to 40 kVp X

  13. CO2 fertilization and enhanced drought resistance in Greek firs from Cephalonia Island, Greece.

    Science.gov (United States)

    Koutavas, Athanasios

    2013-02-01

    Growth-climate relationships were investigated in Greek firs from Ainos Mountain on the island of Cephalonia in western Greece, using dendrochronology. The goal was to test whether tree growth is sensitive to moisture stress, whether such sensitivity has been stable through time, and whether changes in growth-moisture relationships support an influence of atmospheric CO2 on growth. Regressions of tree-ring indices (ad 1820-2007) with instrumental temperature, precipitation, and Palmer Drought Severity Index (PDSI) indicate that growth is fundamentally limited by growing-season moisture in late spring/early summer, most critically during June. However, this simple picture obscures a pattern of sharply evolving growth-climate relationships during the 20th century. Correlations between growth and June temperature, precipitation, and PDSI were significantly greater in the early 20th century but later degraded and disappeared. By the late 20th-early 21st century, there remains no statistically significant relationship between moisture and growth implying markedly enhanced resistance to drought. Moreover, growth experienced a net increase over the last half-century culminating with a sharp spike in ad 1988-1990. This recent growth acceleration is evident in the raw ring-width data prior to standardization, ruling out artifacts from statistical detrending. The vanishing relationship with moisture and parallel enhancement of growth are all the more notable because they occurred against a climatic backdrop of increasing aridity. The results are most consistent with a significant CO2 fertilization effect operating through restricted stomatal conductance and improved water-use efficiency. If this interpretation is correct, atmospheric CO2 is now overcompensating for growth declines anticipated from drier climate, suggesting its effect is unusually strong and likely to be detectable in other up-to-date tree-ring chronologies from the Mediterranean.

  14. TaCPK2-A, a calcium-dependent protein kinase gene that is required for wheat powdery mildew resistance enhances bacterial blight resistance in transgenic rice.

    Science.gov (United States)

    Geng, Shuaifeng; Li, Aili; Tang, Lichuan; Yin, Lingjie; Wu, Liang; Lei, Cailin; Guo, Xiuping; Zhang, Xin; Jiang, Guanghuai; Zhai, Wenxue; Wei, Yuming; Zheng, Youliang; Lan, Xiujin; Mao, Long

    2013-08-01

    Calcium-dependent protein kinases (CPKs) are important Ca2+ signalling components involved in complex immune and stress signalling networks; but the knowledge of CPK gene functions in the hexaploid wheat is limited. Previously, TaCPK2 was shown to be inducible by powdery mildew (Blumeria graminis tritici, Bgt) infection in wheat. Here, its functions in disease resistance are characterized further. This study shows the presence of defence-response and cold-response cis-elements on the promoters of the A subgenome homoeologue (TaCPK2-A) and D subgenome homoeologue (TaCPK2-D), respectively. Their expression patterns were then confirmed by quantitative real-time PCR (qRT-PCR) using genome-specific primers, where TaCPK2-A was induced by Bgt treatment while TaCPK2-D mainly responded to cold treatment. Downregulation of TaCPK2-A by virus-induced gene silencing (VIGS) causes loss of resistance to Bgt in resistant wheat lines, indicating that TaCPK2-A is required for powdery mildew resistance. Furthermore, overexpression of TaCPK2-A in rice enhanced bacterial blight (Xanthomonas oryzae pv. oryzae, Xoo) resistance. qRT-PCR analysis showed that overexpression of TaCPK2-A in rice promoted the expression of OsWRKY45-1, a transcription factor involved in both fungal and bacterial resistance by regulating jasmonic acid and salicylic acid signalling genes. The opposite effect was found in wheat TaCPK2-A VIGS plants, where the homologue of OsWRKY45-1 was significantly repressed. These data suggest that modulation of WRKY45-1 and associated defence-response genes by CPK2 genes may be the common mechanism for multiple disease resistance in grass species, which may have undergone subfunctionalization in promoters before the formation of hexaploid wheat. PMID:23918959

  15. Are Dopamine Agonists Neuroprotective in Parkinson′s Disease?

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Dopamine (DA) agonists are playing increasingly important role in the treatment of not only advanced Parkinson′s disease (PD) and in PD patient with levodopa (L-DOPA)-induced motor fluctuations,but also in early treatment of the disease.This shift has been largely due to the demonstrated L-DOPA-sparing effect of DA agonists and their putative neuroprotective effect,based largely on experimental in vitro and in vivo studies.In this article we review the evidence of neuroprotection by DA agonists pramipexole,ropinirole,pergolide,bromocriptine and apomorphine in cell cultures and animal models of nigral injury.Most of the studies suggest that DA agonists exert their neuroprotection via directly scavenging free radicals or increasing the activities of radical-scavenging enzymes,and enhancing neurotrophic activity.The finding that pramipexole can normalize mitochondrial membrane potential and inhibit activity of caspase-3 in cytoplasmic hybrid cells made from mitochondrial DNA of nonfamilial Alzheimer′s disease patients,however,suggests even a broader implication for the neuroprotective role of DA agonists.Although the clinical evidence for neuroprotection by DA agonists is still limited,the preliminary results from several on-going clinical trials are promising.Several longitudinal studies are currently in progress designed to demonstrate a delay or slowing of progresion of PD using various surrogate markers of neuronal degeneration such as 18 F-L-DOPA PET and 123 I β-CIT SPECT.The results of these experimental and clinical studies will improve our understanding of the action of DA agonists and provide critical information needed for planning future therapeutic strategies in PD and related neurodegenerative disorders.``

  16. Are Dopamine Agonists Neuroprotective in Parkinson‘s disease?

    Institute of Scientific and Technical Information of China (English)

    乐卫东; Jank.J

    2002-01-01

    Dopamine(DA) agonists are playing increasingly important role in the treatment of not only advanced Parkinson's disease(PD) and in PD patient with levodopa(L-DO-PA)-induced motor fluctuations,but also in early treatment of the disease.This shift has been largely due to the demonstrated L-DOPA-sparing effect of DA agonists and their putative neuroprotective effect,based largely on experimental in vitro and in vivo studies.In this article we review the evidence of neuroprotection by DA agonists pramipexole,ropinirole,pergolide,bromocriptine and apomorphine in cell cultures and animal models of nigral injury.Most of the studies suggest that DA agonists exert their neuroprotection via directly scavenging free radicals or increasing the activities of radical-scavenging enzymes,and enhancing neurotrophic activity.The finding that pramipexole can normalize mitochondrial membrane potential and inhibit activity of caspase-3 in cytoylasmic hybrid cells made from mitochondrial DNA of nonfamilial Alzheimer's disease patients,however,suggests even a broader implication for the neuroprotective role of DA agonists.Although the clinical evidence for neuroprotection by DA agonists is still limited,the preliminary results from several on-going clinal trials are promising.Several longitudinal studies are currently in progress designed to demonstrate a delay or slowing of progresion of PD using various surrogate markers of neuronal degeneration such as18F-L-DOPA PET and123I β-CIT SPECT.The results of these experimental and clinical studies will improve our understanding of the action of DA agonists and provide critical information needed for planning future therapeutic strategies in PD and related neurodegenerative disorders.

  17. 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.

  18. Enhancement of oxidation resistance via a self-healing boron carbide coating on diamond particles

    Science.gov (United States)

    Sun, Youhong; Meng, Qingnan; Qian, Ming; Liu, Baochang; Gao, Ke; Ma, Yinlong; Wen, Mao; Zheng, Weitao

    2016-02-01

    A boron carbide coating was applied to diamond particles by heating the particles in a powder mixture consisting of H3BO3, B and Mg. The composition, bond state and coverage fraction of the boron carbide coating on the diamond particles were investigated. The boron carbide coating prefers to grow on the diamond (100) surface than on the diamond (111) surface. A stoichiometric B4C coating completely covered the diamond particle after maintaining the raw mixture at 1200 °C for 2 h. The contribution of the boron carbide coating to the oxidation resistance enhancement of the diamond particles was investigated. During annealing of the coated diamond in air, the priory formed B2O3, which exhibits a self-healing property, as an oxygen barrier layer, which protected the diamond from oxidation. The formation temperature of B2O3 is dependent on the amorphous boron carbide content. The coating on the diamond provided effective protection of the diamond against oxidation by heating in air at 1000 °C for 1 h. Furthermore, the presence of the boron carbide coating also contributed to the maintenance of the static compressive strength during the annealing of diamond in air.

  19. 25-Hydroxyvitamin D3-deficiency enhances oxidative stress and corticosteroid resistance in severe asthma exacerbation.

    Directory of Open Access Journals (Sweden)

    Nan Lan

    Full Text Available Oxidative stress plays a significant role in exacerbation of asthma. The role of vitamin D in oxidative stress and asthma exacerbation remains unclear. We aimed to determine the relationship between vitamin D status and oxidative stress in asthma exacerbation. Severe asthma exacerbation patients with 25-hydroxyvitamin D3-deficiency (V-D deficiency or 25-hydroxyvitamin D-sufficiency (V-D sufficiency were enrolled. Severe asthma exacerbation with V-D-deficiency showed lower forced expiratory volume in one second (FEV1 compared to that with V-D-sufficiency. V-D-deficiency intensified ROS release and DNA damage and increased TNF-α, OGG1 and NFκB expression and NFκB phosphorylation in severe asthma exacerbation. Supplemental vitamin D3 significantly increased the rates of FEV1 change and decreased ROS and DNA damage in V-D-deficiency. Vitamin D3 inhibited LPS-induced ROS and DNA damage and were associated with a decline in TNF-α and NFκB in epithelial cells. H2O2 reduces nuclear translocation of glucocorticoid receptors in airway epithelial cell lines. V-D pretreatment enhanced the dexamethasone-induced nuclear translocation of glucocorticoid receptors in airway epithelial cell lines and monocytes from 25-hydroxyvitamin D3-deficiency asthma patients. These findings indicate that V-D deficiency aggravates oxidative stress and DNA damage, suggesting a possible mechanism for corticosteroid resistance in severe asthma exacerbation.

  20. 25-Hydroxyvitamin D3-deficiency enhances oxidative stress and corticosteroid resistance in severe asthma exacerbation.

    Science.gov (United States)

    Lan, Nan; Luo, Guangyan; Yang, Xiaoqiong; Cheng, Yuanyuan; Zhang, Yun; Wang, Xiaoyun; Wang, Xing; Xie, Tao; Li, Guoping; Liu, Zhigang; Zhong, Nanshan

    2014-01-01

    Oxidative stress plays a significant role in exacerbation of asthma. The role of vitamin D in oxidative stress and asthma exacerbation remains unclear. We aimed to determine the relationship between vitamin D status and oxidative stress in asthma exacerbation. Severe asthma exacerbation patients with 25-hydroxyvitamin D3-deficiency (V-D deficiency) or 25-hydroxyvitamin D-sufficiency (V-D sufficiency) were enrolled. Severe asthma exacerbation with V-D-deficiency showed lower forced expiratory volume in one second (FEV1) compared to that with V-D-sufficiency. V-D-deficiency intensified ROS release and DNA damage and increased TNF-α, OGG1 and NFκB expression and NFκB phosphorylation in severe asthma exacerbation. Supplemental vitamin D3 significantly increased the rates of FEV1 change and decreased ROS and DNA damage in V-D-deficiency. Vitamin D3 inhibited LPS-induced ROS and DNA damage and were associated with a decline in TNF-α and NFκB in epithelial cells. H2O2 reduces nuclear translocation of glucocorticoid receptors in airway epithelial cell lines. V-D pretreatment enhanced the dexamethasone-induced nuclear translocation of glucocorticoid receptors in airway epithelial cell lines and monocytes from 25-hydroxyvitamin D3-deficiency asthma patients. These findings indicate that V-D deficiency aggravates oxidative stress and DNA damage, suggesting a possible mechanism for corticosteroid resistance in severe asthma exacerbation.

  1. Feasibility study of enhancing earthquake resistance of the nuclear power plant Dukovany structures

    International Nuclear Information System (INIS)

    The paper deals with the seismic analysis of safety related structures of an operating nuclear power plant. This analysis represents a basic step in the assessment of the general reliability of an upgraded nuclear plant as a whole. At present time nuclear power plants of the VVER-400/213 type operate for over thirty years and there are arising justified requirements to verify the actual state of the structures in order to assess their residual life. The up-to-date computing means allow performing an advanced seismic response analysis of the structures considering the newly postulated earthquake loads. Recently a detailed stress analysis of nuclear structures operated and loaded for decades has been performed. Consequently feasible ways of enhancing the earthquake resistance of structures have been proposed. A sophisticated computation model has been developed for the seismic structural analysis using the ANSYS program package. The model involves the complex of all constrained structures of two main production blocks with equipment. Solid finite elements have been applied to model reinforced concrete structures, mainly beam elements have been used in modeling steel structures. In order to get a general view at the seismic load effects, seismic response analysis has been performed using linear response spectrum method. Site-specific response spectra been applied. Combinations of dead loads and seismic loads have been considered in the stress assessment of the structures. The results of the performed analyses form a base for residual life prediction of selected structures.. (authors)

  2. Overexpression of Soybean Isoflavone Reductase (GmIFR) Enhances Resistance to Phytophthora sojae in Soybean.

    Science.gov (United States)

    Cheng, Qun; Li, Ninghui; Dong, Lidong; Zhang, Dayong; Fan, Sujie; Jiang, Liangyu; Wang, Xin; Xu, Pengfei; Zhang, Shuzhen

    2015-01-01

    Isoflavone reductase (IFR) is an enzyme involved in the biosynthetic pathway of isoflavonoid phytoalexin in plants. IFRs are unique to the plant kingdom and are considered to have crucial roles in plant response to various biotic and abiotic environmental stresses. Here, we report the characterization of a novel member of the soybean isoflavone reductase gene family GmIFR. Overexpression of GmIFR transgenic soybean exhibited enhanced resistance to Phytophthora sojae. Following stress treatments, GmIFR was significantly induced by P. sojae, ethephon (ET), abscisic acid (placeCityABA), salicylic acid (SA). It is located in the cytoplasm when transiently expressed in soybean protoplasts. The daidzein levels reduced greatly for the seeds of transgenic plants, while the relative content of glyceollins in transgenic plants was significantly higher than that of non-transgenic plants. Furthermore, we found that the relative expression levels of reactive oxygen species (ROS) of transgenic soybean plants were significantly lower than those of non-transgenic plants after incubation with P. sojae, suggesting an important role of GmIFR might function as an antioxidant to reduce ROS in soybean. The enzyme activity assay suggested that GmIFR has isoflavone reductase activity.

  3. [Photosynthetic responses of wheat and pea seedlings to enhanced UV-C radiation and their resistances].

    Science.gov (United States)

    Li, Xue-Mei; Zhang, Li-Hong; He, Xing-Yuan; Hao, Lin

    2007-03-01

    With wheat and pea seedlings as test materials, this paper studied the effects of UV-C radiation on their leaf photosynthetic characteristics and antioxidant enzyme activities. The results showed that enhanced UV-C radiation could markedly decrease the photosynthetic rate (Pn) , stomatal conductance (Gs), intercellular CO2 concentration (Ci), transpiration rate (Tr) and carboxylation efficiency (CE) of pea leaves, but for wheat leaves, these parameters were increased first and decreased then. Under UV-C condition, the CO2 compensation point of leaf was increased for pea, but decreased first and increased then for wheat. With the increasing duration of UV-C radiation, the antioxidant enzyme activities of both test plants increased first and decreased then, except that the POD activity of pea and SOD activity of wheat decreased gradually. All of these suggested that wheat had a stronger resistance to short-time UV-C radiation than pea, but, with the prolonged duration of UV-C radiation, the photosynthesis and antioxidant enzyme activities of wheat and pea were all decreased.

  4. Overexpression of soybean isoflavone reductase (GmIFR enhances resistance to Phytophthora sojae in soybean

    Directory of Open Access Journals (Sweden)

    Qun eCheng

    2015-11-01

    Full Text Available Isoflavone reductase (IFR is an enzyme involved in the biosynthetic pathway of isoflavonoid phytoalexin in plants. IFRs are unique to the plant kingdom and are considered to have crucial roles in plant response to various biotic and abiotic environmental stresses. Here, we report the characterization of a novel member of the soybean isoflavone reductase gene family GmIFR. The cDNA of GmIFR was 1199 bp containing a 939 bp open reading frame encoding a polypeptide of 312 amino acids. Sequence analysis suggested that GmIFR contained a NAD(P domain of 107 amino acids. Overexpression of GmIFR transgenic soybean exhibited enhanced resistance to Phytophthora sojae. Following stress treatments, GmIFR was significantly induced by P. sojae, ethephon (ET, abscisic acid (ABA, salicylic acid (SA. It is located in the cytoplasmic when transiently expressed in Arabidopsis protoplasts. The daidzein levels reduced greatly for the seeds of transgenic plants, while levels of genistein and glycitein had little change compared to that of control plants. Furthermore, we also found that the reactive oxygen species (ROS content of transgenic soybean plants was significantly lower than that of control plants, suggesting an important role of GmIFR might function as an antioxidant to reduce ROS in soybean.

  5. Enhancement of oxidation resistance via a self-healing boron carbide coating on diamond particles.

    Science.gov (United States)

    Sun, Youhong; Meng, Qingnan; Qian, Ming; Liu, Baochang; Gao, Ke; Ma, Yinlong; Wen, Mao; Zheng, Weitao

    2016-02-02

    A boron carbide coating was applied to diamond particles by heating the particles in a powder mixture consisting of H3BO3, B and Mg. The composition, bond state and coverage fraction of the boron carbide coating on the diamond particles were investigated. The boron carbide coating prefers to grow on the diamond (100) surface than on the diamond (111) surface. A stoichiometric B4C coating completely covered the diamond particle after maintaining the raw mixture at 1200 °C for 2 h. The contribution of the boron carbide coating to the oxidation resistance enhancement of the diamond particles was investigated. During annealing of the coated diamond in air, the priory formed B2O3, which exhibits a self-healing property, as an oxygen barrier layer, which protected the diamond from oxidation. The formation temperature of B2O3 is dependent on the amorphous boron carbide content. The coating on the diamond provided effective protection of the diamond against oxidation by heating in air at 1000 °C for 1 h. Furthermore, the presence of the boron carbide coating also contributed to the maintenance of the static compressive strength during the annealing of diamond in air.

  6. FG020326 Sensitized Multidrug Resistant Cancer Cells to Docetaxel-Mediated Apoptosis via Enhancement of Caspases Activation

    Directory of Open Access Journals (Sweden)

    Li-Wu Fu

    2012-05-01

    Full Text Available Apoptotic resistance is the main obstacle for treating cancer patients with chemotherapeutic drugs. Multidrug resistance (MDR is often characterized by the expression of P-glycoprotein (P-gp, a 170-KD ATP-dependent drug efflux protein. Functional P-gp can confer resistance to activate caspase-8 and -3 dependent apoptosis induced by a range of different stimuli, including tumor necrosis and chemotherapeutic drugs such as docetaxel and vincristine. We demonstrated here that comparison of sensitive KB cells, P-gp positive (P-gp+ve KBv200 cells were extremely resistant to apoptosis induced by docetaxel. FG020326, a pharmacological inhibitor of P-gp function, could enhance concentration-dependently the effect of docetaxel on cell apoptosis and sensitize caspase-8, -9 and -3 activation in P-gp overexpressing KBv200 cells, but not in KB cells. Therefore, the enhancement of caspase-8, -9 and -3 activation induced by docetaxel may be one of the key mechanisms of the reversal of P-gp mediated docetaxel resistance by FG020326.

  7. Acute caffeine ingestion enhances strength performance and reduces perceived exertion and muscle pain perception during resistance exercise.

    Science.gov (United States)

    Duncan, Michael J; Stanley, Michelle; Parkhouse, Natalie; Cook, Kathryn; Smith, Mike

    2013-01-01

    The efficacy of caffeine ingestion in enhancing aerobic performance is well established. However, despite suggestions that caffeine may enhance resistance exercise performance, research is equivocal on the effect of acute caffeine ingestion on resistance exercise performance. It has also been suggested that dampened perception of perceived exertion and pain perception might be an explanation for any possible enhancement of resistance exercise performance due to caffeine ingestion. Therefore, the aim of this study was to examine the acute effect of caffeine ingestion on repetitions to failure, rating of perceived exertion (RPE) and muscle pain perception during resistance exercise to failure. Eleven resistance trained individuals (9 males, 2 females, mean age±SD=26.4±6.4 years), took part in this double-blind, randomised cross-over experimental study whereby they ingested a caffeinated (5 mg kg(-1)) or placebo solution 60 minutes before completing a bout of resistance exercise. Experimental conditions were separated by at least 48 hours. Resistance exercise sessions consisted of bench press, deadlift, prone row and back squat exercise to failure at an intensity of 60% 1 repetition maximum. Results indicated that participants completed significantly greater repetitions to failure, irrespective of exercise, in the presence of caffeine (p=0.0001). Mean±S.D of repetitions to failure was 19.6±3.7 and 18.5±4.1 in caffeine and placebo conditions, respectively. There were no differences in peak heart rate or peak blood lactate values across conditions (both p >0.05). RPE was significantly lower in the caffeine compared to the placebo condition (p=0.03) and was significantly higher during lower body exercises compared to upper body exercises irrespective of substance ingested (p=0.0001). For muscle pain perception, a significant condition by exercise interaction (p=0.027) revealed that muscle pain perception was lower in the caffeine condition, irrespective of exercise

  8. Strategies for designing synthetic immune agonists.

    Science.gov (United States)

    Wu, Tom Y-H

    2016-08-01

    Enhancing the immune system is a validated strategy to combat infectious disease, cancer and allergy. Nevertheless, the development of immune adjuvants has been hampered by safety concerns. Agents that can stimulate the immune system often bear structural similarities with pathogen-associated molecular patterns found in bacteria or viruses and are recognized by pattern recognition receptors (PRRs). Activation of these PRRs results in the immediate release of inflammatory cytokines, up-regulation of co-stimulatory molecules, and recruitment of innate immune cells. The distribution and duration of these early inflammatory events are crucial in the development of antigen-specific adaptive immunity in the forms of antibody and/or T cells capable of searching for and destroying the infectious pathogens or cancer cells. However, systemic activation of these PRRs is often poorly tolerated. Hence, different strategies have been employed to modify or deliver immune agonists in an attempt to control the early innate receptor activation through temporal or spatial restriction. These approaches include physicochemical manipulation, covalent conjugation, formulation and conditional activation/deactivation. This review will describe recent examples of discovery and optimization of synthetic immune agonists towards clinical application. PMID:27213842

  9. Enhancing rice resistance to fungal pathogens by transformation with cell wall degrading enzyme genes from Trichoderma atroviride

    Institute of Scientific and Technical Information of China (English)

    刘梅; 孙宗修; 朱洁; 徐同; HARMANGaryE; LORITOMatteo

    2004-01-01

    Three genes encoding for fungal cell wall degrading enzymes (CWDEs), ech42, nag70 and gluc78 from the biocontrol fungus Trichoderma atroviride were inserted into the binary vector pCAMBIA1305.2 singly and in all possible combinations and transformed to rice plants. More than 1800 independently regenerated plantlets in seven different populations (for each of the three genes and each of the four gene combinations) were obtained. The ech42 gene encoding for an endochitinase increased resistance to sheath blight caused by Rhizoctonia solani, while the exochitinase-encoding gene, nag70, had lesser effect. The expression level of endochitinase but exochitinase was correlated with disease resistance. Nevertheless, exochitinase enhanced the effect of endochitinase on disease resistance when the two genes co-expressed in transgenics. Resistance to Magnaporthe grisea was found in all kinds of regenerated plants including that with single gluc78. A few lines expressing either ech42 or nag70 gene were immune to the disease. Transgenic plants are being tested to further evaluate disease resistance at field level. This is the first report of multiple of expression of genes encoding CWDEs from Trichoderma atroviride that result in resistance to blast and sheath blight in rice.

  10. Antitumor effect of 5-fluorouracil is enhanced by rosemary extract in both drug sensitive and resistant colon cancer cells.

    Science.gov (United States)

    González-Vallinas, Margarita; Molina, Susana; Vicente, Gonzalo; de la Cueva, Ana; Vargas, Teodoro; Santoyo, Susana; García-Risco, Mónica R; Fornari, Tiziana; Reglero, Guillermo; Ramírez de Molina, Ana

    2013-06-01

    5-Fluorouracil (5-FU) is the most used chemotherapeutic agent in colorectal cancer. However, resistance to this drug is relatively frequent, and new strategies to overcome it are urgently needed. The aim of this work was to determine the antitumor properties of a supercritical fluid rosemary extract (SFRE), alone and in combination with 5-FU, as a potential adjuvant therapy useful for colon cancer patients. This extract has been recognized as a healthy component by the European Food Safety Authority (EFSA). The effects of SFRE both alone and in combination with 5-FU were evaluated in different human colon cancer cells in terms of cell viability, cytotoxicity, and cell transformation. Additionally, colon cancer cells resistant to 5-FU were used to assay the effects of SFRE on drug resistance. Finally, qRT-PCR was performed to ascertain the mechanism by which SFRE potentiates the effect of 5-FU. Our results show that SFRE displays dose-dependent antitumor activities and exerts a synergistic effect in combination with 5-FU on colon cancer cells. Furthermore, SFRE sensitizes 5-FU-resistant cells to the therapeutic activity of this drug, constituting a beneficial agent against both 5-FU sensitive and resistant tumor cells. Gene expression analysis indicates that the enhancement of the effect of 5-FU by SFRE might be explained by the downregulation of TYMS and TK1, enzymes related to 5-FU resistance. PMID:23557932

  11. Suppression of the homeobox gene HDTF1 enhances resistance to Verticillium dahliae and Botrytis cinerea in cotton

    Institute of Scientific and Technical Information of China (English)

    Wei Gao; Lu Long; Li Xu; Keith Lindsey; Xianlong Zhang; Longfu Zhu

    2016-01-01

    Development of pathogen-resistant crops, such as fungus-resistant cotton, has significantly reduced chemical application and improved crop yield and quality. However, the mechanism of resistance to cotton pathogens such as Verticillium dahliae is still poorly understood. In this study, we characterized a cotton gene (HDTF1) that was isolated following transcriptome profiling during the resistance response of cotton to V. dahliae. HDTF1 putatively encodes a homeodomain transcription factor, and its expression was found to be down-regulated in cotton upon inoculation with V. dahliae and Botrytis cinerea. To characterise the involvement of HDTF1 in the response to these pathogens, we used virus-induced gene silencing (VIGS) to generate HDTF1-silenced cotton. VIGS reduction in HDTF1 expression significantly enhanced cotton plant resistance to both pathogens. HDTF1 silencing resulted in activation of jasmonic acid (JA)-mediated signaling and JA accumulation. However, the silenced plants were not altered in the accumulation of salicylic acid (SA) or the expression of marker genes associated with SA signaling. These results suggest that HDTF1 is a negative regulator of the JA pathway, and resistance to V. dahliae and B. cinerea can be engineered by activation of JA signaling.

  12. Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase.

    Science.gov (United States)

    Victor, Victor M; Rovira-Llopis, Susana; Bañuls, Celia; Diaz-Morales, Noelia; Martinez de Marañon, Arantxa; Rios-Navarro, Cesar; Alvarez, Angeles; Gomez, Marcelino; Rocha, Milagros; Hernández-Mijares, Antonio

    2016-01-01

    Cardiovascular diseases and oxidative stress are related to polycystic ovary syndrome (PCOS) and insulin resistance (IR). We have evaluated the relationship between myeloperoxidase (MPO) and leukocyte activation in PCOS patients according to homeostatic model assessment of IR (HOMA-IR), and have explored a possible correlation between these factors and endocrine and inflammatory parameters. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 101 PCOS subjects and 105 control subjects. We divided PCOS subjects into PCOS non-IR (HOMA-IRPCOS IR (HOMA-IR>2.5). Metabolic and anthropometric parameters, total and mitochondrial reactive oxygen species (ROS) production, MPO levels, interactions between human umbilical vein endothelial cells and leukocytes, adhesion molecules (E-selectin, ICAM-1 and VCAM-1) and proinflammatory cytokines (IL-6 and TNF-α) were evaluated. Oxidative stress was observed in PCOS patients, in whom there was an increase in total and mitochondrial ROS production and MPO levels. Enhanced rolling flux and adhesion, and a decrease in polymorphonuclear cell rolling velocity were also detected in PCOS subjects. Increases in IL-6 and TNF-α and adhesion molecules (E-selectin, ICAM-1 and VCAM-1) were also observed, particularly in the PCOS IR group, providing evidence that inflammation and oxidative stress are related in PCOS patients. HOMA-IR was positively correlated with hsCRP (pPCOS patients in general, and particularly in those with IR. Inflammation in PCOS induces leukocyte-endothelium interactions and a simultaneous increase in IL-6, TNF-α, E-selectin, ICAM-1 and VCAM-1. These conditions are aggravated by the presence of IR.

  13. Enhanced resistive switching performance for bilayer HfO2/TiO2 resistive random access memory

    Science.gov (United States)

    Ye, Cong; Deng, Tengfei; Zhang, Junchi; Shen, Liangping; He, Pin; Wei, Wei; Wang, Hao

    2016-10-01

    We prepared bilayer HfO2/TiO2 resistive random accessory memory (RRAM) using magnetron sputtering on an ITO/PEN flexible substrate. The switching voltages (V SET and V RESET) were smaller for the Pt/HfO2/TiO2/ITO device than for a Pt/HfO2/ITO memory device. The insertion of a TiO2 layer in the switching layer was inferred to act as an oxygen reservoir to reduce the switching voltages. In addition, greatly improved uniformity was achieved, which showed the coefficient of the variations of V SET and V RESET to be 9.90% and 6.35% for the bilayer structure RRAM. We deduced that occurrence of conductive filament connection/rupture at the interface of the HfO2 and TiO2, in combination with the HfO2 acting as a virtual cathode, led to the improved uniformity. A multilevel storage capability can be obtained by varying the stop voltage in the RESET process for bilayer HfO2/TiO2 RRAM. By analyzing the current conduction mechanism, we demonstrated that the multilevel high resistance state (HRS) was attributable to the increased barrier height when the stop voltage was increased.

  14. Endurance training in Wistar rats decreases receptor sensitivity to a serotonin agonist.

    Science.gov (United States)

    Dwyer, D; Browning, J

    2000-11-01

    There is mounting evidence that increased brain serotonin during exercise is associated with the onset of CNS-mediated fatigue. Serotonin receptor sensitivity is likely to be an important determinant of this fatigue. Alterations in brain serotonin receptor sensitivity were examined in Wistar rats throughout 6 weeks of endurance training, running on a treadmill four times a week with two exercise tests per week to exhaustion. Receptor sensitivity was determined indirectly as the reduction in exercise time in response to a dose of a serotonin (1A) agonist, m-chlorophenylpiperazine (m-CPP). The two groups of controls were used to examine (i) the effect of the injection per se on exercise performance and (ii) changes in serotonin receptor sensitivity associated with maturation. In the test group, undrugged exercise performance significantly improved by 47% after 6 weeks of training (4518 +/- 729 to 6640 +/- 903 s, P=0.01). Drugged exercise performance also increased significantly from week 1 to week 6 (306 +/- 69-712 +/- 192 s, P = 0.04). Control group results indicated that the dose of m-CPP alone caused fatigue during exercise tests and that maturation was not responsible for any decrease in receptor sensitivity. Improved resistance to the fatiguing effects of the serotonin agonist suggests desensitization of central serotonin receptors, probably the 5-HT1A receptors. Endurance training appears to stimulate an adaptive response to the fatiguing effects of increased brain serotonin, which may enhance endurance exercise performance. PMID:11167306

  15. Bulgecin A as a β-lactam enhancer for carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii clinical isolates containing various resistance mechanisms

    Directory of Open Access Journals (Sweden)

    Skalweit MJ

    2016-09-01

    Full Text Available Marion J Skalweit,1–5 Mei Li2 1Department of Medicine, 2Research Section, 3Infectious Diseases Section, Louis Stokes Cleveland Department of Veterans, 4Department of Medicine, 5Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH, USA Abstract: Genetic screening of Pseudomonas aeruginosa (PSDA and Acinetobacter ­baumannii (ACB reveals genes that confer increased susceptibility to β-lactams when disrupted, suggesting novel drug targets. One such target is lytic transglycosylase. Bulgecin A (BlgA is a natural product of Pseudomonas mesoacidophila and a lytic transglycosolase inhibitor that works synergistically with β-lactams targeting PBP3 for Enterobacteriaceae. BlgA also weakly inhibits di-Zn2+ metallo-β-lactamases like L1 of Stenotrophomonas maltophilia. We hypothesized that because of its unique mechanism of action, BlgA could restore susceptibility to carbapenems in carbapenem-resistant PSDA (CR-PSDA and carbapenem-resistant ACB, as well as ACB resistant to sulbactam. A BlgA-containing extract was prepared using a previously published protocol. CR-PSDA clinical isolates demonstrating a variety of carbapenem resistance mechanisms (VIM-2 carbapenemases, efflux mechanisms, and AmpC producer expression were characterized with agar dilution minimum inhibitory concentration (MIC testing and polymerase chain reaction. Growth curves using these strains were prepared using meropenem, BlgA extract, and meropenem plus BlgA extract. A concentrated Blg A extract combined with low concentrations of meropenem, was able to inhibit the growth of clinical strains of CR-PSDA for strains that had meropenem MICs ≥8 mg/L by agar dilution, and a clinical strain of an OXA-24 producing ACB that had a meropenem MIC >32 mg/L and intermediate ampicillin/sulbactam susceptibility. Similar experiments were conducted on a TEM-1 producing ACB strain resistant to sulbactam. BlgA with ampicillin/sulbactam inhibited the growth

  16. Resistance to bio-insecticides or how to enhance their sustainability: a review

    OpenAIRE

    Myriam eSIEGWART; Benoit eGraillot; Christine eBlachère-Lopez; Samantha eBesse; Marc eBardin; Philippe eNicot; Miguel eLopez-Ferber

    2015-01-01

    After more than 70 years of chemical pesticide use, modern agriculture is increasingly using biological control products. Resistances to conventional insecticides are wide spread, while those to bio-insecticides have raised less attention, and resistance management is frequently neglected. However, a good knowledge of the limitations of a new technique often provides greater sustainability. In this review, we compile cases of resistance to widely used bio-insecticides and describe the associa...

  17. CNX-011-67, a novel GPR40 agonist, enhances glucose responsiveness, insulin secretion and islet insulin content in n-STZ rats and in islets from type 2 diabetic patients

    OpenAIRE

    Sunil, Venkategowda; Verma, Mahesh Kumar; Oommen, Anup M; Sadasivuni, ManojKumar; Singh, Jaideep; Vijayraghav, Dasarahalli N; Chandravanshi, Bhawna; Shetty, Jayalaxmi; Biswas, Sanghamitra; Dandu, Anilkumar; Moolemath, Yoganand; Venkataranganna, Marikunte V.; Somesh, Baggavalli P; Jagannath, Madanahalli R

    2014-01-01

    Background GPR40 is a G-protein coupled receptor regulating free fatty acid induced and also glucose induced insulin secretion. We generated neonatally-streptozotocin-treated female rats (n-STZ) and treated them with CNX-011-67, a GPR40 agonist to examine the role of GPR40 in modulation of glucose metabolism, insulin secretion and content. Methods Female n-STZ animals were orally administered with CNX-011-67 (15 mg/kg body weight, twice daily) or with vehicle for 8 weeks (n = 8 per group). Gl...

  18. Deposition of TiC film on titanium for abrasion resistant implant material by ion-enhanced triode plasma CVD

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Yuhe, E-mail: zyh1120@hotmail.co.jp [School of Stomatology, China Medical University, Shen Yang (China); Wang Wei; Jia Xingya [School of Stomatology, China Medical University, Shen Yang (China); Akasaka, Tsukasa [Department of Health Science, School of Dental Medicine Hokkaido University, Sapporo (Japan); Liao, Susan [School of Materials Science and Engineering, Nanyang Technological University (Singapore); Watari, Fumio [Department of Health Science, School of Dental Medicine Hokkaido University, Sapporo (Japan)

    2012-12-01

    Highlights: Black-Right-Pointing-Pointer Deposition of Titanium Carbide (TiC) layer on titanium (Ti) surface has been demonstrated by an ion-enhanced triode plasma chemical vapor deposition (CVD) method. Black-Right-Pointing-Pointer The Vickers hardness of surface carbide was more than 2000, which confirmed its high abrasion resistance. Black-Right-Pointing-Pointer Physical and mechanical properties of the deposited TiC film on Ti were investigated to examine its potential application as an abrasion resistant implant material. - Abstract: Deposition of titanium carbide (TiC) layer on titanium (Ti) surface has been demonstrated by an ion-enhanced triode plasma chemical vapor deposition (CVD) method using a TiCl{sub 4} + CH{sub 4} + H{sub 2} gas mixture. Physical and mechanical properties of the deposited TiC film on Ti were investigated to examine its potential application as an abrasion resistant implant material. X-ray diffraction (XRD) showed that the specimen was consisted of TiC and Ti. Carbide layer of about 6 {mu}m thickness was observed on the cross section of the specimen by scanning electron microscopy (SEM). The Vickers hardness of surface carbide was more than 2000, which confirmed its high abrasion resistance.

  19. Deposition of TiC film on titanium for abrasion resistant implant material by ion-enhanced triode plasma CVD

    International Nuclear Information System (INIS)

    Highlights: ► Deposition of Titanium Carbide (TiC) layer on titanium (Ti) surface has been demonstrated by an ion-enhanced triode plasma chemical vapor deposition (CVD) method. ► The Vickers hardness of surface carbide was more than 2000, which confirmed its high abrasion resistance. ► Physical and mechanical properties of the deposited TiC film on Ti were investigated to examine its potential application as an abrasion resistant implant material. - Abstract: Deposition of titanium carbide (TiC) layer on titanium (Ti) surface has been demonstrated by an ion-enhanced triode plasma chemical vapor deposition (CVD) method using a TiCl4 + CH4 + H2 gas mixture. Physical and mechanical properties of the deposited TiC film on Ti were investigated to examine its potential application as an abrasion resistant implant material. X-ray diffraction (XRD) showed that the specimen was consisted of TiC and Ti. Carbide layer of about 6 μm thickness was observed on the cross section of the specimen by scanning electron microscopy (SEM). The Vickers hardness of surface carbide was more than 2000, which confirmed its high abrasion resistance.

  20. Cefditoren and ceftriaxone enhance complement-mediated immunity in the presence of specific antibodies against antibiotic-resistant pneumococcal strains.

    Directory of Open Access Journals (Sweden)

    Elisa Ramos-Sevillano

    Full Text Available BACKGROUND: Specific antibodies mediate humoral and cellular protection against invading pathogens such as Streptococcus pneumoniae by activating complement mediated immunity, promoting phagocytosis and stimulating bacterial clearance. The emergence of pneumococcal strains with high levels of antibiotic resistance is of great concern worldwide and a serious threat for public health. METHODOLOGY/PRINCIPAL FINDINGS: Flow cytometry was used to determine whether complement-mediated immunity against three antibiotic-resistant S. pneumoniae clinical isolates is enhanced in the presence of sub-inhibitory concentrations of cefditoren and ceftriaxone. The binding of acute phase proteins such as C-reactive protein and serum amyloid P component, and of complement component C1q, to pneumococci was enhanced in the presence of serum plus either of these antibiotics. Both antibiotics therefore trigger the activation of the classical complement pathway against S. pneumoniae. C3b deposition was also increased in the presence of specific anti-pneumococcal antibodies and sub-inhibitory concentrations of cefditoren and ceftriaxone confirming that the presence of these antibiotics enhances complement-mediated immunity to S. pneumoniae. CONCLUSIONS/SIGNIFICANCE: Using cefditoren and ceftriaxone to promote the binding of acute phase proteins and C1q to pneumococci, and to increase C3b deposition, when anti-pneumococcal antibodies are present, might help reduce the impact of antibiotic resistance in S. pneumoniae infections.

  1. Water soluble fraction of Tinospora cordifolia leaves enhanced the non-specific immune mechanisms and disease resistance in Oreochromis mossambicus.

    Science.gov (United States)

    Alexander, Catherine P; Kirubakaran, C John Wesly; Michael, R Dinakaran

    2010-11-01

    The present paper describes the effect of water-soluble fraction of the leaves of the Indian medicinal plant, Tinospora cordifolia (Miers) on the non-specific immunity and disease resistance in Oreochromis mossambicus (Peters). Fish were intraperitoneally injected with 0, 6, 60 or 600 mg kg(-1) body weight, of the water soluble fraction. The non-specific humoral (lysozyme, antiprotease and complement) and cellular (production of reactive oxygen and nitrogen species and myeloperoxidase) responses and disease resistance against Aeromonas hydrophila were tested. All the doses of water-soluble fraction tested, significantly enhanced the serum lysozyme, antiprotease and natural haemolytic complement activities on most of the days tested. Similarly, all the doses of water-soluble fraction used, enhanced the cellular myeloperoxidase activity on all the days tested. The enhancement in the ROS and RNI production by peripheral blood leucocytes was observed on almost all the days tested, in most of the treated groups. All the doses of water-soluble fraction when administered as a single or double dose gave protection in terms of reduced percent mortality which is reflected in the increased Relative Percent Survival (RPS) values. The results clearly indicate the immunostimulatory and disease resistance properties of T. cordifolia leaf fraction and so its potential to be used as an immunoprophylactic in finfish aquaculture. PMID:20624469

  2. Enhanced radiation resistance through interface modification of nano-structured steels for Gen IV in-core applications

    International Nuclear Information System (INIS)

    This project is to increase radiation tolerance of candidate alloys for Gen IV core component through the optimization of grain size and grain boundary characteristics. The focus is on nanocrystalline metal alloys with a fcc crystal structure. The long-term goal is to design and develop bulk nanostructured austenitic steels with enhanced void swelling resistance and substantial ductility, and to enhance their creep resistance at elevated temperatures via grain boundary engineering. An austenitic stainless steel, HT-UPS (high temperature ultra-fine precipitates strengthened) was developed at ORNL, and is expected to show enhanced void swelling resistance through the trapping of point defects at nanometer-sized carbides. Reducing the grain size and increasing the fraction-induced point defects (due to the increased sink area of the grain boundaries), to make bubble nucleation at the boundaries less likely (by reducing the fraction of high-energy boundaries), and to improve the strength and ductility under radiation by producing a higher density of nanometer sized carbides on the boundaries

  3. Emancipatory Sexuality Education and Sexual Assault Resistance: Does the Former Enhance the Latter?

    Science.gov (United States)

    Senn, Charlene Y.; Gee, Stephanie S.; Thake, Jennifer

    2011-01-01

    The current study examined whether adding emancipatory sexuality education, which encourages the exploration of women's own sexual values and desires, to a sexual assault resistance program would improve women's resistance to sexual assault by known men. The participants were 214 first-year university students. A randomized experimental design…

  4. GnRH agonist triggering

    DEFF Research Database (Denmark)

    Kol, Shahar; Humaidan, Peter; Al Humaidan, Peter Samir Heskjær

    2013-01-01

    The concept that a bolus of gonadotrophin-releasing hormone agonist (GnRHa) can replace human chorionic gonadotrophin (HCG) as a trigger of final oocyte maturation was introduced several years ago. Recent developments in the area strengthen this premise. GnRHa trigger offers important advantages...... triggering concept should be challenged and that the GnRHa trigger is the way to move forward with thoughtful consideration of the needs, safety and comfort of our patients. Routinely, human chorionic gonadotrophin (HCG) is used to induce ovulation in fertility treatments. This approach deviates...... significantly from physiology and often results in insufficient hormonal support in early pregnancy and in ovarian hyperstimulation syndrome (OHSS). An alternative approach is to use a gonadotrophin-releasing hormone (GnRH) agonist which allows a more physiological trigger of ovulation and, most importantly...

  5. Enhanced Earthquake-Resistance on the High Level Radioactive Waste Canister

    International Nuclear Information System (INIS)

    In this paper, the earthquake-resistance type buffer was developed with the method protecting safely about the earthquake. The main parameter having an effect on the earthquake-resistant performance was analyzed and the earthquake-proof type buffer material was designed. The shear analysis model was developed and the performance of the earthquake-resistance buffer material was evaluated. The dynamic behavior of the radioactive waste disposal canister was analyzed in case the earthquake was generated. In the case, the disposal canister gets the serious damage. In this paper, the earthquake-resistance buffer material was developed in order to prevent this damage. By putting the buffer in which the density is small between the canister and buffer, the earthquake-resistant performance was improved about 80%

  6. A synthetic TLR4 agonist formulated in an emulsion enhances humoral and Type 1 cellular immune responses against GMZ2 - A GLURP-MSP3 fusion protein malaria vaccine candidate

    DEFF Research Database (Denmark)

    Lousada-Dietrich, Susana; Jogdand, Prajakta S; Jepsen, Søren;

    2011-01-01

    GMZ2 adjuvanted by aluminum hydroxide is a candidate malaria vaccine that has successfully passed phase 1 clinical testing in adult German and Gabonese volunteers and Gabonese children under five. Here we report a preclinical study screening a series of adjuvant vehicles and Toll-like receptor (TLR......) agonists in CB6F1 mice to identify an improved formulation of GMZ2 suitable for further human clinical studies. GMZ2 formulated in an oil-in-water emulsion plus the synthetic TLR4 agonist GLA elicits the highest (a) vaccine-specific IgG2a and total IgG titers, (b) parasite-specific IFA titers, (c) levels...... of Type 1 cytokine responses (IFN-¿), and (d) number of long-lived-plasma cells (LLPC) secreting antibodies against both the GMZ2 fusion and its two components. Thus, GLA helps to elicit a vaccine-specific Type 1 antibody profile together with high levels of LLPC, both of which are thought to be essential...

  7. Cytokine-induced loss of glucocorticoid function: effect of kinase inhibitors, long-acting β(2-adrenoceptor [corrected] agonist and glucocorticoid receptor ligands.

    Directory of Open Access Journals (Sweden)

    Christopher F Rider

    expression by TNF. Finally, formoterol-enhanced 2×GRE reporter activity was also proportional to agonist efficacy and functionally reversed repression by TNF. As similar effects were apparent on glucocorticoid-induced gene expression, the most effective strategy to overcome glucocorticoid resistance in this model was addition of formoterol to high efficacy NR3C1 agonists.

  8. Enhanced late blight resistance of transgenic potato expressing glucose oxidase under the control of pathogen-inducible promoter

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To engineer crop disease resistance by utilizing natural defense mechanism that was expressed in the incompatible host-pathogen interactions is expected to result in a durable and broad-spectrum resistance. In order to prove this viewpoint, we amplified the coding region of the glucose oxidase (GO) gene from Aspergillus niger via PCR and fused it to the pathogen-inducible promoter, Prp1-1. The chimeric gene was cloned into a plant expression vector and conjugated into Agrobacterium. Twenty-three transgenic potato plants were obtained by Agrobacterium-mediated transformation. The integration of GO gene was confirmed by Southern hybridization and the GO gene expression was identified with KI-starch color reaction. Phytophthora infestans inoculation revealed that the expression of the chimeric transgene was induced by pathogen infection. Most of the transgenic plants exhibited various degrees of enhanced disease resistance. Four of them had lesion sizes reduced to less than half of the non-transgenic controls. One plant showed disease resistance of the hypersensitive response. These results testified the feasibility of our strategy of expressing GO transgene under the control of the disease-inducible promoter in engineering crop disease resistance.

  9. Enhanced resistance to Botrytis cinerea and Rhizoctonia solani in transgenic broccoli with a Trichoderma viride endochitinase gene

    Institute of Scientific and Technical Information of China (English)

    YU Ya; REN Shu-xin; GUO Yang-dong; ZHANG Lei; LIAN Wei-ran; XU Feng-feng; LI Shuang-tao; XIANG Juan; ZHANG Guo-zhen; HU Zan-min; ZHAO Bing

    2015-01-01

    A endochitinase gene (Tch ) from the fungus Trichoderma viride was introduced into broccoli (Brassica oleracea var. italica) by Agrobacterium-mediated transformation. Sixty-eight putative transformants were obtained and the presence of the Tch gene was conifrmed by both PCR and Southern blot analysis. RT-PCR analysis showed an accumulation of the transcript encoding the endochitinase protein in the transgenic plants. Using real-time quantitative PCR, the expression proifling of endochitinase gene was analyzed. Primary transformants and selfed progeny were examined for expression of the endo-chitinase using a lfuorometric assay and for their resistance to the pathogenic fungi Botrytis cinerea and Rhizoctonia solani. The endochitinase activities in T0 in vitro plants, T0 mature plants and T1 mature plants were correlated with leaf lesions, and the transgenic line T618 had high endochitinse activities of 102.68, 114.53 and 120.27 nmol L–1 MU min–1 mg–1 protein in the three kinds of plants, respectively. The endochitinase activity showed a positive correlation with the resistance to the pathogens. Most transgenic T0 broccoli had increased resistance to the pathogens of B. cinerea and R. solani in leaf assays and this resistance was conifrmed to be inheritable. These ifndings suggested that expression of the Tch gene from T. viride could enhance resistance to pathogenic fungi in Brassica species.

  10. Allosteric coupling from G protein to the agonist-binding pocket in GPCRs.

    Science.gov (United States)

    DeVree, Brian T; Mahoney, Jacob P; Vélez-Ruiz, Gisselle A; Rasmussen, Soren G F; Kuszak, Adam J; Edwald, Elin; Fung, Juan-Jose; Manglik, Aashish; Masureel, Matthieu; Du, Yang; Matt, Rachel A; Pardon, Els; Steyaert, Jan; Kobilka, Brian K; Sunahara, Roger K

    2016-07-01

    G-protein-coupled receptors (GPCRs) remain the primary conduit by which cells detect environmental stimuli and communicate with each other. Upon activation by extracellular agonists, these seven-transmembrane-domain-containing receptors interact with heterotrimeric G proteins to regulate downstream second messenger and/or protein kinase cascades. Crystallographic evidence from a prototypic GPCR, the β2-adrenergic receptor (β2AR), in complex with its cognate G protein, Gs, has provided a model for how agonist binding promotes conformational changes that propagate through the GPCR and into the nucleotide-binding pocket of the G protein α-subunit to catalyse GDP release, the key step required for GTP binding and activation of G proteins. The structure also offers hints about how G-protein binding may, in turn, allosterically influence ligand binding. Here we provide functional evidence that G-protein coupling to the β2AR stabilizes a ‘closed’ receptor conformation characterized by restricted access to and egress from the hormone-binding site. Surprisingly, the effects of G protein on the hormone-binding site can be observed in the absence of a bound agonist, where G-protein coupling driven by basal receptor activity impedes the association of agonists, partial agonists, antagonists and inverse agonists. The ability of bound ligands to dissociate from the receptor is also hindered, providing a structural explanation for the G-protein-mediated enhancement of agonist affinity, which has been observed for many GPCR–G-protein pairs. Our data also indicate that, in contrast to agonist binding alone, coupling of a G protein in the absence of an agonist stabilizes large structural changes in a GPCR. The effects of nucleotide-free G protein on ligand-binding kinetics are shared by other members of the superfamily of GPCRs, suggesting that a common mechanism may underlie G-protein-mediated enhancement of agonist affinity. PMID:27362234

  11. Prolonging survival of corneal transplantation by selective sphingosine-1-phosphate receptor 1 agonist.

    Directory of Open Access Journals (Sweden)

    Min Gao

    Full Text Available Corneal transplantation is the most used therapy for eye disorders. Although the cornea is somewhat an immune privileged organ, immune rejection is still the major problem that reduces the success rate. Therefore, effective chemical drugs that regulate immunoreactions are needed to improve the outcome of corneal transplantations. Here, a sphingosine-1-phosphate receptor 1 (S1P1 selective agonist was systematically evaluated in mouse allogeneic corneal transplantation and compared with the commonly used immunosuppressive agents. Compared with CsA and the non-selective sphingosine 1-phosphate (S1P receptor agonist FTY720, the S1P1 selective agonist can prolong the survival corneal transplantation for more than 30 days with a low immune response. More importantly, the optimal dose of the S1P1 selective agonist was much less than non-selective S1P receptor agonist FTY720, which would reduce the dose-dependent toxicity in drug application. Then we analyzed the mechanisms of the selected S1P1 selective agonist on the immunosuppression. The results shown that the S1P1 selective agonist could regulate the distribution of the immune cells with less CD4+ T cells and enhanced Treg cells in the allograft, moreover the expression of anti-inflammatory cytokines TGF-β1 and IL-10 unregulated which can reduce the immunoreactions. These findings suggest that S1P1 selective agonist may be a more appropriate immunosuppressive compound to effectively prolong mouse allogeneic corneal grafts survival.

  12. Enhanced corrosion resistance and biocompatibility of β-type Ti–25Nb–25Zr alloy by electrochemical anodization

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Her-Hsiung [Department of Dentistry, National Yang-Ming University, Taipei, 112 Taiwan (China); Graduate Institute of Basic Medical Science, China Medical University, Taichung, 404 Taiwan (China); Department of Biomedical Informatics, Asia University, Taichung, 413 Taiwan (China); Department of Stomatology, Taipei Veterans General Hospital, Taipei, 112 Taiwan (China); Wu, Chia-Ping; Sun, Ying-Sui; Huang, Hsun-Miao [Institute of Oral Biology, National Yang-Ming University, Taipei, 112 Taiwan (China); Lee, Tzu-Hsin, E-mail: biomaterials@hotmail.com [School of Dentistry, Chung Shan Medical University, Taichung, 402 Taiwan (China); Oral Medicine Center, Chung Shan Medical University Hospital, Taichung, 402 Taiwan (China)

    2013-12-31

    The biocompatibility of implants is largely determined by their surface characteristics. This study presents a novel method for performing electrochemical anodization on β-type Ti–25Nb–25Zr alloy with a low elastic modulus (approximately 70 GPa). This method results in a thin hybrid layer capable of enhancing the surface characteristics of the implants. We investigated the surface topography and microstructure of the resulting Ti–25Nb–25Zr alloy. The corrosion resistance was evaluated using potentiodynamic polarization curve measurements in simulated body fluid. The cytotoxicity was evaluated according to International Organization for Standardization 10993–5 specification. Cell adhesion of human bone marrow mesenchymal stem cells on the test specimens was observed using scanning electron microscopy and fluorescence microscopy. The anodization produced a thin (approximately 40 nm-thick) hybrid oxide layer with a nanoporous outer sublayer (pore size < 15 nm) and a dense inner layer. The thin hybrid oxide layer increased the corrosion resistance of the Ti–25Nb–25Zr alloy by increasing the corrosion potential and decreasing both the corrosion rate and passive current. Ti–25Nb–25Zr alloys with and without anodization treatment were non-toxic. Surface nanotopography on the anodized Ti–25Nb–25Zr alloy enhanced protein adsorption and cell adhesion. Our results demonstrate that electrochemical anodization increases the corrosion resistance and cell adhesion of β-type Ti–25Nb–25Zr alloy while providing a lower elastic modulus suitable for implant applications. - Highlights: • An electrochemical anodization was applied to β-type Ti–25Nb–25Zr alloy surface. • Anodized surface had nanoscale hybrid oxide layer. • Anodized surface increased corrosion resistance due to dense inner sublayer. • Anodized surface enhanced cell adhesion due to nanoporous outer sublayer. • Electrochemical anodization has potential as implant surface treatment.

  13. Enhanced corrosion resistance and biocompatibility of β-type Ti–25Nb–25Zr alloy by electrochemical anodization

    International Nuclear Information System (INIS)

    The biocompatibility of implants is largely determined by their surface characteristics. This study presents a novel method for performing electrochemical anodization on β-type Ti–25Nb–25Zr alloy with a low elastic modulus (approximately 70 GPa). This method results in a thin hybrid layer capable of enhancing the surface characteristics of the implants. We investigated the surface topography and microstructure of the resulting Ti–25Nb–25Zr alloy. The corrosion resistance was evaluated using potentiodynamic polarization curve measurements in simulated body fluid. The cytotoxicity was evaluated according to International Organization for Standardization 10993–5 specification. Cell adhesion of human bone marrow mesenchymal stem cells on the test specimens was observed using scanning electron microscopy and fluorescence microscopy. The anodization produced a thin (approximately 40 nm-thick) hybrid oxide layer with a nanoporous outer sublayer (pore size < 15 nm) and a dense inner layer. The thin hybrid oxide layer increased the corrosion resistance of the Ti–25Nb–25Zr alloy by increasing the corrosion potential and decreasing both the corrosion rate and passive current. Ti–25Nb–25Zr alloys with and without anodization treatment were non-toxic. Surface nanotopography on the anodized Ti–25Nb–25Zr alloy enhanced protein adsorption and cell adhesion. Our results demonstrate that electrochemical anodization increases the corrosion resistance and cell adhesion of β-type Ti–25Nb–25Zr alloy while providing a lower elastic modulus suitable for implant applications. - Highlights: • An electrochemical anodization was applied to β-type Ti–25Nb–25Zr alloy surface. • Anodized surface had nanoscale hybrid oxide layer. • Anodized surface increased corrosion resistance due to dense inner sublayer. • Anodized surface enhanced cell adhesion due to nanoporous outer sublayer. • Electrochemical anodization has potential as implant surface treatment

  14. Niobium addition enhancing the corrosion resistance of nanocrystalline Ti5Si3 coating in H2SO4 solution

    International Nuclear Information System (INIS)

    In this paper, novel Nb-containing Ti5Si3 (i.e., Ti56.2Nb6.3Si37.5 and Ti50.0Nb12.5Si37.5) nanocrystalline coatings were deposited onto Ti–6Al–4V substrates by a double glow discharge plasma technique. The effects of Nb alloying on the electrochemical behavior of the Ti5Si3 nanocrystalline coatings were systematically investigated in a naturally aerated 5 wt.% H2SO4 solution, for which various electrochemical techniques, including potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), potentiostatic polarization and Mott–Schottky analysis, were employed. Moreover, to evaluate the corrosion performance of the as-deposited coatings over an extended period, their corrosion resistance was analyzed after 7 days’ immersion in a 5 wt.% H2SO4 solution by EIS measurements and observations of corroded surface morphologies. The results showed that the Ti62.5−xNbxSi37.5 (x = 0, 6.3, 12.5) nanocrystalline coatings exhibit superior corrosion resistance compared with Ti–6Al–4V, and their corrosion resistance is enhanced with increasing Nb content, suggesting that Nb alloying is an effective strategy for improving the corrosion protection ability of the Ti5Si3 nanocrystalline coating. The roles of Nb additions in enhancing the corrosion resistance of the Ti5Si3 nanocrystalline coatings can be summarized as: (a) reducing the residual tensile stresses of the as-deposited coatings and (b) tailoring the composition, compactness and electronic structure of the passive films formed. These findings are expected to broaden the application of Ti5Si3 as a highly corrosion-resistant coating for engineering components operating under aggressive conditions

  15. Cancer stem cell overexpression of nicotinamide N-methyltransferase enhances cellular radiation resistance

    DEFF Research Database (Denmark)

    D’Andrea, Filippo P.; Safwat, Akmal; Kassem, Moustapha;

    2011-01-01

    found the genes involved in cancer, proliferation, DNA repair and cell death. ConclusionsThe higher radiation resistance in clone CE8 is likely due to NNMT overexpression. The higher levels of NNMT could affect the cellular damage resistance through depletion of the accessible amounts of nicotinamide...... that could explain cancer stem cell radiation resistance. MethodsTumorigenic mesenchymal cancer stem cell clones BB3 and CE8 were irradiated at varying doses and assayed for clonogenic surviving fraction. Altered gene expression before and after 2Gy was assessed by Affymetric exon chip analysis and further...... validated with q-RT-PCR using TaqMan probes. ResultsThe CE8 clone was more radiation resistant than the BB3 clone. From a pool of 15 validated genes with altered expression in the CE8 clone, we found the enzyme nicotinamide N-methyltransferase (NNMT) more than 5-fold upregulated. In-depth pathway analysis...

  16. Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells

    OpenAIRE

    Zhi-Kun Qiu; Dong Shen; Yin-Sheng Chen; Qun-Ying Yang; Cheng-Cheng Guo; Bing-Hong Feng; Zhong-Ping Chen

    2014-01-01

    O6-methylguanine DNA methyltransferase (MGMT) can remove DNA alkylation adducts, thereby repairing damaged DNA and contributing to the drug resistance of gliomas to alkylating agents. In addition, glioma stem-like cells (GSCs) have been demonstrated to be involved in the recurrence and treatment resistance of gliomas. In this study, we aimed to investigate MGMT expression and regulatory mechanisms in GSCs and the association of MGMT with temozolomide (TMZ) sensitivity. GSC...

  17. Enhancing integrated pest management in GM cotton systems using host plant resistance

    Directory of Open Access Journals (Sweden)

    Carlos eTrapero

    2016-04-01

    Full Text Available Cotton has lost many ancestral defensive traits against key invertebrate pests. This is suggested by the levels of resistance to some pests found in wild cotton genotypes as well as in cultivated landraces and is a result of domestication and a long history of targeted breeding for yield and fibre quality, along with the capacity to control pests with pesticides. Genetic modification (GM allowed integration of toxins from a bacteria into cotton to control key Lepidopteran pests. Since the mid-1990’s, use of GM cotton cultivars has greatly reduced the amount of pesticides used in many cotton systems. However, pests not controlled by the GM traits have usually emerged as problems, especially the sucking bug complex. Control of this complex with pesticides often causes a reduction in beneficial invertebrate populations, allowing other secondary pests to increase rapidly and require control. Control of both sucking bug complex and secondary pests is problematic due to the cost of pesticides and/or high risk of selecting for pesticide resistance. Deployment of host plant resistance provides an opportunity to manage these issues in GM cotton systems. Cotton cultivars resistant to the sucking bug complex and/or secondary pests would require fewer pesticide applications, reducing costs and risks to beneficial invertebrate populations and pesticide resistance. Incorporation of host plant resistance traits into elite cotton cultivars with high yield and fibre quality offers the potential to further reduce pesticide use and increase the durability of pest management in GM cotton systems. We review the challenges that the identification and use of host plant resistance against invertebrate pests brings to cotton breeding. We explore sources of resistance to the sucking bug complex and secondary pests, the mechanisms that control them and the approaches to incorporate these defence traits to commercial cultivars.

  18. Nighttime warming enhances drought resistance of plant communities in a temperate steppe

    OpenAIRE

    Zhongling Yang; Lin Jiang; Fanglong Su; Qian Zhang; Jianyang Xia; Shiqiang Wan

    2016-01-01

    Drought events could have profound influence on plant community structure and ecosystem function, and have subsequent impacts on community stability, but we know little about how different climate warming scenarios affect community resistance and resilience to drought. Combining a daytime and nighttime warming experiment in the temperate steppe of north China with a natural drought event during the study period, we tested how daytime and nighttime warming influences drought resistance and res...

  19. DBC2 resistance is achieved by enhancing 26S proteasome-mediated protein degradation.

    Science.gov (United States)

    Collado, Denise; Yoshihara, Takashi; Hamaguchi, Masaaki

    2007-08-31

    Tumor suppressor gene DBC2 stops growth of tumor cells through regulation of CCND1. Interference of CCND1 down-regulation prevented growth arrest caused by DBC2 [T. Yoshihara, D. Collado, M. Hamaguchi, Cyclin D1 down-regulation is essential for DBC2's tumor suppressor function, Biochemical and biophysical research communications 358 (2007) 1076-1079]. It was also noted that DBC2 resistant cells eventually arose after repeated induction of DBC2 with muristerone A treatment [M. Hamaguchi, J.L. Meth, C. Von Klitzing, W. Wei, D. Esposito, L. Rodgers, T. Walsh, P. Welcsh, M.C. King, M.H. Wigler, DBC2, a candidate for a tumor suppressor gene involved in breast cancer, Proc. Natl. Acad. Sci. USA 99 (2002) 13647-13652]. In order to elucidate the mechanism of resistance acquisition, we analyzed DBC2 sensitive and resistant cells derived from the same progenitor cells (T-47D). We discovered that DBC2 protein was abundantly expressed in the sensitive cells when DBC2 was induced. In contrast, it was undetectable by western blot analysis in the resistant cells. We confirmed that the inducible gene expression system was responsive in both cells by detecting induced GFP. Additionally, inhibition of 26S proteasome by MG132 revealed production of DBC2 protein in the resistant cells. These findings indicate that the resistant T-47D cells survive DBC2 induction by rapid destruction of DBC2 through 26S proteasome-mediated protein degradation.

  20. Elimination of Enhanced Thermal Resistance of Spheroid Culture Model of Prostate Carcinoma Cell Line by Inhibitors of Hsp70 Induction

    Directory of Open Access Journals (Sweden)

    Samideh Khoei

    2010-01-01

    Full Text Available AbstractObjective: The purpose of this study was to investigate the enhanced thermal resistancemechanism of the DU145 tumor spheroid cultures as compared to the prostate carcinomacell line's monolayer cultures.Materials and Methods: DU145 cells were cultured either as spheroids or monolayers.Cultures were treated with hyperthermia in a precision water bath (at 43°C for 60 minutesand/or quercetin (50 and 500 μM for monolayer and spheroid cultures respectively. Afterhyperthermic treatment, the cell viability colony forming ability, and the expression of heatshock protein 70 (Hsp70 were examined in both culture systems. Hsp70 expression wasstudied using the western blot method.Results: Our results showed that the DU145 monolayer and spheroid cell culture treatmentwith hyperthermia alone resulted in a marked survival inhibition. Furthermore, thespheroids showed a more significant resistance to hyperthermia compared to the monolayercultures (p = 0.01. They also produced more Hsp70 than the monolayer cultures.Treatment of cells with quercetin reduced the Hsp70 level in both culture systems. However,with the reduced Hsp70 levels, thermal resistance of the spheroids showed a greaterdecrease in relation to that of the monolayers.Conclusion: The results suggest that the enhanced hyperthermia resistance mechanismof the spheroid cultures compared to that of the monolayer cultures can be attributed tospheroids' Hsp70 production.

  1. Enhancing the corrosion resistance of dentistry drills by plasma immersion nitrogen in implantation of AISI 434-based SS

    Energy Technology Data Exchange (ETDEWEB)

    Munoz C, A.E.; Lopez C, R.; Fuentes G, D.; Valencia A, R. [UAEM, Facultad de Quimica, Instituto Literario 100, Toluca (Mexico)]. e-mail: rlc@nuclear.inin.mx

    2007-07-01

    In order to enhance the resistance to the pitting corrosion due to asepsis processes and to avoid structural fractures in dentistry drills, a plasma immersion ion implantation (PIII) treatment using nitrogen has been performed. The selected drill samples, made of AISI 434 based stainless steel with a 0.670 mm diameter, were treated at a -1kV bias between 350 C and 450 C, this temperature being controlled by both a 20-50 {mu}s pulse width and a 200-1000 Hz repetition rate in the bias. The drills were analysed by cyclic potentiodynamic tests showing a good pitting corrosion resistance when treated at around 400 C, as follows from a resulting very low hysteresis loop. Yet, the resistance appears somehow diminished by the presence of sputtering when processed at temperatures near 450 C. It is also found that the PIII nitriding effectiveness appears to be limited by the appearance of uniform corrosion. Finally, X-ray diffraction of the samples has revealed the presence of two new phases, namely {epsilon}-Fe{sub 2}N and Fe{sub 4.4}N, while scanning electron microscopy of the treated surfaces has suggested a sputtering enhancement at the highest temperatures. (Author)

  2. Low-Frequency Ultrasound Enhances Antimicrobial Activity of Colistin-Vancomycin Combination against Pan-Resistant Biofilm of Acinetobacter baumannii.

    Science.gov (United States)

    Liu, Xu; Yin, Hong; Weng, Chun-Xiao; Cai, Yun

    2016-08-01

    Acinetobacter baumannii biofilms in catheters are very difficult to treat. Low-frequency ultrasound (LFU) may improve bactericidal or bacteriostatic activity. However, no previous studies have been reported on its efficacy against pan-resistant biofilms of A. baumannii. This study was designed to investigate whether LFU can enhance the activity of colistin, vancomycin and colistin-vancomycin combinations against pan-resistant biofilms of A. baumannii. The efficacy of colistin combinations was determined using the fractional inhibitory concentration index (FICI). The antibacterial effect was determined from bacteria counts in biofilms and the establishment of 24-h time-kill curves. A significantly synergistic effect was detected between colistin and vancomycin (FICI colistin in the combination treatments resulted in a better ultrasound-enhanced antibacterial effect. In 24-h time-kill curves, the combination of colistin (8 μg/mL) plus vancomycin (4 μg/mL) with LFU caused a significant reduction in bacteria counts in biofilms after 8 h and a continuing decline until 24 h. Bacterial counts were reduced by 3.77 log(CFU/mL) by LFU plus combinations, compared with combinations without LFU at 24 h. Our results indicate that LFU in combination with colistin plus vancomycin may be useful in treating pan-resistant A. baumannii infections. PMID:27131840

  3. Glycine propionyl-L-carnitine produces enhanced anaerobic work capacity with reduced lactate accumulation in resistance trained males

    Directory of Open Access Journals (Sweden)

    Orem Ihsan

    2009-04-01

    Full Text Available Abstract Background Recent research has indicated that short term administration of glycine propionyl-L-carnitine (GPLC significantly elevates levels of nitric oxide metabolites at rest and in response to reactive hyperaemia. However, no scientific evidence exists that suggests such supplementation enhances exercise performance in healthy, trained individuals. The purpose of this study was to examine the effects of GPLC on the performance of repeated high intensity stationary cycle sprints with limited recovery periods in resistance trained male subjects. Methods In a double-blind, placebo-controlled, cross-over design, twenty-four male resistance trained subjects (25.2 ± 3.6 years participated in two test sessions separated by one week. Testing was performed 90 minutes following oral ingestion of either 4.5 grams GPLC or 4.5 grams cellulose (PL, in randomized order. The exercise testing protocol consisted of five 10-second Wingate cycle sprints separated by 1-minute active recovery periods. Peak (PP and mean values (MP of sprint power output and percent decrement of power (DEC were determined per bout and standardized relative to body masss. Heart rate (HR and blood lactate (LAC were measured prior to, during and following the five sprint bouts. Results Significant main effects (p Conclusion These findings indicate that short-term oral supplementation of GPLC can enhance peak power production in resistance trained males with significantly less LAC accumulation.

  4. Enhancing the corrosion resistance of dentistry drills by plasma immersion nitrogen in implantation of AISI 434-based SS

    International Nuclear Information System (INIS)

    In order to enhance the resistance to the pitting corrosion due to asepsis processes and to avoid structural fractures in dentistry drills, a plasma immersion ion implantation (PIII) treatment using nitrogen has been performed. The selected drill samples, made of AISI 434 based stainless steel with a 0.670 mm diameter, were treated at a -1kV bias between 350 C and 450 C, this temperature being controlled by both a 20-50 μs pulse width and a 200-1000 Hz repetition rate in the bias. The drills were analysed by cyclic potentiodynamic tests showing a good pitting corrosion resistance when treated at around 400 C, as follows from a resulting very low hysteresis loop. Yet, the resistance appears somehow diminished by the presence of sputtering when processed at temperatures near 450 C. It is also found that the PIII nitriding effectiveness appears to be limited by the appearance of uniform corrosion. Finally, X-ray diffraction of the samples has revealed the presence of two new phases, namely ε-Fe2N and Fe4.4N, while scanning electron microscopy of the treated surfaces has suggested a sputtering enhancement at the highest temperatures. (Author)

  5. Exosomal miR-221/222 enhances tamoxifen resistance in recipient ER-positive breast cancer cells.

    Science.gov (United States)

    Wei, Yifang; Lai, Xiaofeng; Yu, Shentong; Chen, Suning; Ma, Yongzheng; Zhang, Yuan; Li, Huichen; Zhu, Xingmei; Yao, Libo; Zhang, Jian

    2014-09-01

    Recent studies have demonstrated that specific miRNAs, such as miR-221/222, may be responsible for tamoxifen resistance in breast cancer. Secreted miRNAs enclosed in exosomes can act as intercellular bio-messengers. Our objective is to investigate the role of secreted miR-221/222 in tamoxifen resistance of ER-positive breast cancer cells. Transmission electron microscopy analysis and nanoparticle tracking analysis were performed to determine the exosomes difference between MCF-7(TamR) (tamoxifen resistant) and MCF-7(wt) (tamoxifen sensitive) cells. PKH67 fluorescent labeling assay was used to detect exosomes derived from MCF-7(TamR) cells entering into MCF-7(wt) cells. The potential function of exosomes on tamoxifen resistance transmission was analyzed with cell viability, apoptosis ,and colony formation. MiRNA microarrays and qPCR were used to detect and compare the miRNAs expression levels in the two cells and exosomes. As the targets of miR-221/222, p27 and ERα were analyzed with western blot and qPCR. Compared with the MCF-7(wt) exosomes, there were significant differences in the concentration and size distribution of MCF-7(TamR) exosomes. MCF-7(wt) cells had an increased amount of exosomal RNA and proteins compared with MCF-7(TamR) cells. MCF-7(TamR) exosomes could enter into MCF-7(wt) cells, and then released miR-221/222. And the elevated miR-221/222 effectively reduced the target genes expression of P27 and ERα, which enhanced tamoxifen resistance in recipient cells. Our results are the first to show that secreted miR-221/222 serves as signaling molecules to mediate communication of tamoxifen resistance. PMID:25007959

  6. Resistance training enhances insulin suppression of endogenous glucose production in elderly women.

    Science.gov (United States)

    Honka, Miikka-Juhani; Bucci, Marco; Andersson, Jonathan; Huovinen, Ville; Guzzardi, Maria Angela; Sandboge, Samuel; Savisto, Nina; Salonen, Minna K; Badeau, Robert M; Parkkola, Riitta; Kullberg, Joel; Iozzo, Patricia; Eriksson, Johan G; Nuutila, Pirjo

    2016-03-15

    An altered prenatal environment during maternal obesity predisposes offspring to insulin resistance, obesity, and their consequent comorbidities, type 2 diabetes and cardiovascular disease. Telomere shortening and frailty are additional risk factors for these conditions. The aim of this study was to evaluate the effects of resistance training on hepatic metabolism and ectopic fat accumulation. Thirty-five frail elderly women, whose mothers' body mass index (BMI) was known, participated in a 4-mo resistance training program. Endogenous glucose production (EGP) and hepatic and visceral fat glucose uptake were measured during euglycemic hyperinsulinemia with [(18)F]fluorodeoxyglucose and positron emission tomography. Ectopic fat was measured using magnetic resonance spectroscopy and imaging. We found that the training intervention reduced EGP during insulin stimulation [from 5.4 (interquartile range 3.0, 7.0) to 3.9 (-0.4, 6.1) μmol·kg body wt(-1)·min(-1), P = 0.042] in the whole study group. Importantly, the reduction was higher among those whose EGP was more insulin resistant at baseline (higher than the median) [-5.6 (7.1) vs. 0.1 (5.4) μmol·kg body wt(-1)·min(-1), P = 0.015]. Furthermore, the decrease in EGP was associated with telomere elongation (r = -0.620, P = 0.001). The resistance training intervention did not change either hepatic or visceral fat glucose uptake or the amounts of ectopic fat. Maternal obesity did not influence the studied measures. In conclusion, resistance training improves suppression of EGP in elderly women. The finding of improved insulin sensitivity of EGP with associated telomere lengthening implies that elderly women can reduce their risk for type 2 diabetes and cardiovascular disease with resistance training. PMID:26744506

  7. A compensatory mutation provides resistance to disparate HIV fusion inhibitor peptides and enhances membrane fusion.

    Directory of Open Access Journals (Sweden)

    Matthew P Wood

    Full Text Available Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations.

  8. Bisphosphocins: novel antimicrobials for enhanced killing of drug-resistant and biofilm-forming bacteria.

    Science.gov (United States)

    Wong, Jonathan P; DiTullio, Paul; Parkinson, Steve

    2015-01-01

    The global prevalence of antibiotic resistance and the threat posed by drug-resistant superbugs are a leading challenge confronting modern medicine in the 21st century. However, the progress on the development of novel antibiotics to combat this problem is severely lagging. A more concerted effort to develop novel therapeutic agents with robust activity and unique mechanisms of action will be needed to overcome the problem of drug resistance. Furthermore, biofilm forming bacteria are known to be increasingly resistant to the actions of antibiotics and are a leading cause of mortality or morbidity in nosocomial infections. Bisphosphocins (also scientifically known as nubiotics) are novel small protonated deoxynucleotide molecules, and exert their antibacterial activity by depolarization of the bacterial cell membrane, causing bacterial cell death. Bisphosphocins may represent an effective weapon against antibiotic-resistant and biofilm-forming pathogenic bacteria. Preclinical efficacy studies in animals have shown that the compounds are safe and, efficacious against various bacterial infections, including drug-resistant pathogens. In vitro biochemical analysis confirmed that the bactericidal activity of bisphosphocins is mediated by depolarization of the bacterial cell membrane, and these compounds are better able to penetrate through bacterial biofilm and kill the biofilm encased bacteria. This article will cover the structure, mode of action, safety, efficacy and the current state of development of bisphosphocins. Together, the information presented here will present a strong case for bisphosphocins to be considered for use as new weapons to complement the existing arsenal of antimicrobial drugs and as a first line defence against drug-resistant and biofilm-forming bacteria. PMID:26597426

  9. Deficiency of p110δ isoform of the phosphoinositide 3 kinase leads to enhanced resistance to Leishmania donovani.

    Directory of Open Access Journals (Sweden)

    Forough Khadem

    2014-06-01

    Full Text Available Visceral leishmaniasis is the most clinically relevant and dangerous form of human leishmaniasis. Most traditional drugs for treatment of leishmaniasis are toxic, possess many adverse reactions and drug resistance is emerging. Therefore, there is urgent need for identification of new therapeutic targets. Recently, we found that mice with an inactivating knock-in mutation in the p110δ isoform of pi3k, (p110δ(d910a are hyper resistant to L. major, develop minimal cutaneous lesion and rapidly clear their parasite. Here, we investigated whether pi3k signaling also regulates resistance to L. donovani, one of the causative agents of visceral leishmaniasis.WT and p110δ(D910A mice (on a BALB/c background were infected with L. donovani. At different time points, parasite burden and granuloma formation were assessed. T and B cell responses in the liver and spleen were determined. In addition, Tregs were expanded in vivo and its impact on resistance was assessed. We found that p110δ(D910A mice had significantly reduced splenomegaly and hepatomegaly and these organs harbored significantly fewer parasites than those of WT mice. Interestingly, infected p110δ(D910A mice liver contains fewer and less organized granulomas than their infected WT counterparts. Cells from p110δ(D910A mice were significantly impaired in their ability to produce cytokines compared to WT mice. The percentage and absolute numbers of Tregs in infected p110δ(D910A mice were lower than those in WT mice throughout the course of infection. In vivo expansion of Tregs in infected p110δ(D910A mice abolished their enhanced resistance to L. donovani infection.Our results indicate that the enhanced resistance of p110δ(D910A mice to L. donovani infection is due to impaired activities of Tregs. They further show that resistance to Leishmania in the absence of p110δ signaling is independent of parasite species, suggesting that targeting the PI3K signaling pathway may be useful for

  10. Dual Agent Loaded PLGA Nanoparticles Enhanced Antitumor Activity in a Multidrug-Resistant Breast Tumor Eenograft Model

    Directory of Open Access Journals (Sweden)

    Yan Chen

    2014-02-01

    Full Text Available Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed strong synergism with the reversal index of approximately 130 in the multidrug-resistant MCF-7/ADR cells compared to drug-sensitive MCF-7 cells. The lyophilized nanoparticles could get dispersed quickly with the similar size distribution, zeta potential and encapsulation efficiency to the pre-lyophilized nanoparticles suspension, and maintain the synergistic in vitro release ratio of drugs. The co-encapsulated nanoparticle formulation had lower toxicity than free vincristine/verapamil combinations according to the acute-toxicity test. Furthermore, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free vincristine, free vincristine/verapamil combinations and single-drug nanoparticle combinations. All the data demonstrated that PLGANPs simultaneously loaded with chemotherapeutic drug and chemosensitizer might be one of the most potential formulations in the treatment of multidrug-resistant breast cancer in clinic.

  11. Identification of Fusarium virguliforme FvTox1-Interacting Synthetic Peptides for Enhancing Foliar Sudden Death Syndrome Resistance in Soybean.

    Directory of Open Access Journals (Sweden)

    Bing Wang

    Full Text Available Soybean is one of the most important crops grown across the globe. In the United States, approximately 15% of the soybean yield is suppressed due to various pathogen and pests attack. Sudden death syndrome (SDS is an emerging fungal disease caused by Fusarium virguliforme. Although growing SDS resistant soybean cultivars has been the main method of controlling this disease, SDS resistance is partial and controlled by a large number of quantitative trait loci (QTL. A proteinacious toxin, FvTox1, produced by the pathogen, causes foliar SDS. Earlier, we demonstrated that expression of an anti-FvTox1 single chain variable fragment antibody resulted in reduced foliar SDS development in transgenic soybean plants. Here, we investigated if synthetic FvTox1-interacting peptides, displayed on M13 phage particles, can be identified for enhancing foliar SDS resistance in soybean. We screened three phage-display peptide libraries and discovered four classes of M13 phage clones displaying FvTox1-interacting peptides. In vitro pull-down assays and in vivo interaction assays in yeast were conducted to confirm the interaction of FvTox1 with these four synthetic peptides and their fusion-combinations. One of these peptides was able to partially neutralize the toxic effect of FvTox1 in vitro. Possible application of the synthetic peptides in engineering SDS resistance soybean cultivars is discussed.

  12. GmPGIP3 enhanced resistance to both take-all and common root rot diseases in transgenic wheat.

    Science.gov (United States)

    Wang, Aiyun; Wei, Xuening; Rong, Wei; Dang, Liang; Du, Li-Pu; Qi, Lin; Xu, Hui-Jun; Shao, Yanjun; Zhang, Zengyan

    2015-05-01

    Take-all (caused by the fungal pathogen Gaeumannomyces graminis var. tritici, Ggt) and common root rot (caused by Bipolaris sorokiniana) are devastating root diseases of wheat (Triticum aestivum L.). Development of resistant wheat cultivars has been a challenge since no resistant wheat accession is available. GmPGIP3, one member of polygalacturonase-inhibiting protein (PGIP) family in soybean (Glycine max), exhibited inhibition activity against fungal endopolygalacturonases (PGs) in vitro. In this study, the GmPGIP3 transgenic wheat plants were generated and used to assess the effectiveness of GmPGIP3 in protecting wheat from the infection of Ggt and B. sorokiniana. Four independent transgenic lines were identified by genomic PCR, Southern blot, and reverse transcription PCR (RT-PCR). The introduced GmPGIP3 was integrated into the genomes of these transgenic lines and could be expressed. The expressing GmPGIP3 protein in these transgenic wheat lines could inhibit the PGs produced by Ggt and B. sorokiniana. The disease response assessments postinoculation showed that the GmPGIP3-expressing transgenic wheat lines displayed significantly enhanced resistance to both take-all and common root rot diseases caused by the infection of Ggt and B. sorokiniana. These data suggested that GmPGIP3 is an attractive gene resource in improving resistance to both take-all and common root rot diseases in wheat.

  13. Loss of Scribble Promotes Snail Translation through Translocation of HuR and Enhances Cancer Drug Resistance.

    Science.gov (United States)

    Zhou, Yi; Chang, Renxu; Ji, Weiwei; Wang, Na; Qi, Meiyan; Xu, Yi; Guo, Jingyu; Zhan, Lixing

    2016-01-01

    Drug resistance of cancer cells to various therapeutic agents and molecular targets is a major problem facing current cancer research. The tumor suppressor gene Scribble encodes a polarity protein that is conserved between Drosophila and mammals; loss of the locus disrupts cell polarity, inhibits apoptosis, and mediates cancer process. However, the role of Scribble in drug resistance remains unknown. We show here that knockdown of Scribble enhances drug resistance by permitting accumulation of Snail, which functions as a transcription factor during the epithelial-mesenchymal transition. Then, loss of Scribble activates the mRNA-binding protein human antigen R (HuR) by facilitating translocation of HuR from the nucleus to the cytoplasm. Furthermore, we demonstrate HuR can recognize AU-rich elements of the Snail-encoding mRNA, thereby regulating Snail translation. Moreover, loss of Scribble-induced HuR translocation mediates the accumulation of Snail via activation of the p38 MAPK pathway. Thus, this work clarifies the role of polarity protein Scribble, which is directly implicated in the regulation of developmental transcription factor Snail, and suggesting a mechanism for Scribble mediating cancer drug resistance. PMID:26527679

  14. Enhancement of Corrosion Resistance of Type 304 Stainless Steel Through a Novel Thermo-mechanical Surface Treatment

    Science.gov (United States)

    Toppo, Anita; Kaul, R.; Pujar, M. G.; Kamachi Mudali, U.; Kukreja, L. M.

    2013-02-01

    The paper describes a novel thermo-mechanical surface treatment approach, involving conventional shot blasting followed by laser surface heating, to engineer microstructural modification in type 304 austenitic stainless steel for enhancing its corrosion resistance. Thermo-mechanical surface treatment resulted in the formation of fine recrystallized grains with some strain-induced martensite on the modified surface. Surface treatment of type 304 stainless steel brought about significant improvement in its resistance against uniform as well as pitting corrosion. Electrochemical impedance spectroscopic studies showed improved polarization resistance ( R p) value for thermo-mechanically treated surface indicating formation of a more protective passive film than that formed on the untreated surface. In contrast to untreated type 304 stainless steel specimens where pits preferentially initiated at the site of Al2O3 inclusions, thermo-mechanically treated specimen exhibited only general dissolution with a few repassivated and shallow pits. Grain refinement and dispersion of alumina inclusions on the modified surface are considered to be the key factors responsible for improvement in uniform and pitting corrosion resistance of type 304SS.

  15. Focusing and sustaining the antitumor CTL effector killer response by agonist anti-CD137 mAb

    Science.gov (United States)

    Weigelin, Bettina; Bolaños, Elixabet; Teijeira, Alvaro; Martinez-Forero, Ivan; Labiano, Sara; Azpilikueta, Arantza; Morales-Kastresana, Aizea; Quetglas, José I.; Wagena, Esther; Sánchez-Paulete, Alfonso Rodríguez; Chen, Lieping; Friedl, Peter; Melero, Ignacio

    2015-01-01

    Cancer immunotherapy is undergoing significant progress due to recent clinical successes by refined adoptive T-cell transfer and immunostimulatory monoclonal Ab (mAbs). B16F10-derived OVA-expressing mouse melanomas resist curative immunotherapy with either adoptive transfer of activated anti-OVA OT1 CTLs or agonist anti-CD137 (4-1BB) mAb. However, when acting in synergistic combination, these treatments consistently achieve tumor eradication. Tumor-infiltrating lymphocytes that accomplish tumor rejection exhibit enhanced effector functions in both transferred OT-1 and endogenous cytotoxic T lymphocytes (CTLs). This is consistent with higher levels of expression of eomesodermin in transferred and endogenous CTLs and with intravital live-cell two-photon microscopy evidence for more efficacious CTL-mediated tumor cell killing. Anti-CD137 mAb treatment resulted in prolonged intratumor persistence of the OT1 CTL-effector cells and improved function with focused and confined interaction kinetics of OT-1 CTL with target cells and increased apoptosis induction lasting up to six days postadoptive transfer. The synergy of adoptive T-cell therapy and agonist anti-CD137 mAb thus results from in vivo enhancement and sustainment of effector functions. PMID:26034288

  16. Enhancement of wear resistance of ductile iron surface alloyed by stellite 6

    International Nuclear Information System (INIS)

    Research highlights: → This paper deals with the improvement of the wear resistance of ductile iron surface alloyed by stellite 6 hardfacing alloy. → The microstructure of the surface alloyed layer consisted of carbides dispersed in a Co-based solid solution matrix with dendritic structure. → The higher wear resistance of the coated sample than that of uncoated sample attributed to the hardness of the surface alloyed layer. → The dominant mechanism of the wear in the coated and uncoated samples was delamination wear. -- Abstract: This paper deals with the improvement of the wear resistance of ductile iron surface alloyed by a hypoeutectic stellite 6 alloy. In this regard, the surface alloyed layer with 3 mm thickness deposited on ductile iron using tungsten inert gas (TIG) surface processing. The microstructure, hardness and wear resistance of surface alloyed layer were investigated using optical microscopy, scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction analysis, Vickers hardness (HV0.3) and pin-on-plate tests. The results showed that the microstructure of the surface alloyed layer consisted of carbides dispersed in a Co-based solid solution matrix with dendritic structure. This microstructure was responsible for the improvement of the hardness and wear resistance of the coating. Further investigations showed that the dominant mechanism of the wear in the coated and uncoated samples was delamination wear.

  17. Low-load resistance training during step-reduction attenuates declines in muscle mass and strength and enhances anabolic sensitivity in older men

    OpenAIRE

    Devries, Michaela C; Breen, Leigh; Von Allmen, Mark; MacDonald, Maureen J; Moore, Daniel R.; Offord, Elizabeth A; Horcajada, Marie-Noëlle; Breuillé, Denis; Phillips, Stuart M.

    2015-01-01

    Step-reduction (SR) in older adults results in muscle atrophy and an attenuated rise in postprandial muscle protein synthesis (MPS): anabolic resistance. Knowing that resistance exercise (RT) can enhance MPS, we examined whether RT could enhance MPS following 2 weeks of SR. In addition, as we postulated that SR may impair feeding-induced vasodilation limiting nutrient delivery to muscle, we also examined whether citrulline (CIT), as an arginine and nitric oxide precursor, could attenuate musc...

  18. Transformation of Arabidopsis thaliana via Agrobacterium tumefacience with an endochitinase gene from Trichoderma, and enhanced resistance to Sclerotinia sclerotiorum

    Institute of Scientific and Technical Information of China (English)

    DAI Fu-ming; XU Tong

    2004-01-01

    @@ Sclerotinia sclerotiorum is an important pathogen to many crops and is especially damaging to rape in China. As a model plant Arabidopsis thaliana (ColO) was transformed by spraying Agrobacterium tumefacience with Trichoderma endochitinase gene ThEn-42 at initial bud stage. Eleven seedlings (corresponding to about 0.22 percent transformation) exhibited resistance to hygromycin. The DNA fragment unique to endochitinase ( ThEn-42 ) was amplified by Arabidopsis leaf-PCR or genomic DNA PCR. Unfertile, dwarf and normal phenotypes appeared in the T1 generation. In addition, an enhanced resistance to S. sclerotiorum was observed. The mortality percentage (7.7% to 33.3%) in transgenic plants was significantly lower than in non-transgenic plants (86. 7%) 10 days after inoculation with the pathogen.

  19. Nitric oxide donor seed priming enhances defense responses and induces resistance against pearl millet downy mildew disease

    DEFF Research Database (Denmark)

    Manjunatha, G.; Raj, S. Niranjan; Shetty, Nandini Prasad;

    2008-01-01

    experiments with NO donors showed no adverse effect either on the host or pathogen. Aqueous SNP seed treatment with or without polyethylene glycol (PEG) priming was the most effective in inducing the host resistance against downy mildew both under greenhouse and field conditions. Potassium Ferrocyanide...... between the inducer treatment and subsequent pathogen inoculation was necessary for maximum resistance development. Disease protection ability of NO donors was also validated as durable in nature. Conversely, prior-treatment with NO scavenger 2-4-carboxyphenyl-4,4,5,5 tetrazoline-1-oxyl-3-oxide potassium...... salt (C-PTIO) rendered the pearl millet plants relatively susceptible for pathogen infection. Expression of primary defense responses like hypersensitive response, lignin deposition and defense related enzyme phenylalanine ammonialyase -EC 4.3.1.5 (PAL) were enhanced by NO donor treatments....

  20. Enhanced resistance of plasma-sprayed TiC coatings to thermal shocks

    International Nuclear Information System (INIS)

    In previous tests the maximum observed TiC coating thickness which showed good resistance to 0.7 s thermal shocks was 400 μm. For this thickness, only microcracks perpendicular to the surface (segmentation) were observed, whereas for thicker ones, spalling inside the coatings occured. With a combination of substrate surface modification (macroroughening or spraying a bondcoat) and preheating to 375deg C before the thermal shocks, it has been possible to completely avoid the delamination during heating and to promote the resistance to delamination on cooling. This allows a doubling at the thickness of thermal shock resistant coatings up to 1mm. Hemispherical coated limiters were tested in TdeV (Tokamak de Varennes) with plasma currents of 210 kA and have absorbed 20 kW during 1.2 s associated with a power deposition factor of about 10 MW m-2 s0.5. (orig.)

  1. Plasma surface alloying of titanium alloy for enhancing burn-resistant property

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ping-ze; XU Zhong; ZHANG Gao-hui; HE Zhi-yong; YAO Zheng-jun

    2006-01-01

    Conventional titanium alloy may be ignited and burnt under high temperature, high pressure and high gas flow velocity condition. In order to avoid this problem, burn-resistant alloying layers were made on the surface of Ti-6Al-4V and Ti-6.5Al-0.3Mo-1.5Zr-0.25Si titanium alloys by using double glow plasma surface alloying technology (DG Technology). Two typical burn-resistant layers Ti-Cr and Ti-Mo were made by DG plasma chromizing and DG plasma molybdenizing, respectively. Burn-resistant properties were tested by layer ignition method using 2 kW laser machine. Ignition experiments result reveals that the ignition temperature of alloyed layer with Mo and Cr concentration above 10% is about 200℃ higher than ignition temperature of Ti-6Al-4V substrate.

  2. Enhancing Integrated Pest Management in GM Cotton Systems Using Host Plant Resistance.

    Science.gov (United States)

    Trapero, Carlos; Wilson, Iain W; Stiller, Warwick N; Wilson, Lewis J

    2016-01-01

    Cotton has lost many ancestral defensive traits against key invertebrate pests. This is suggested by the levels of resistance to some pests found in wild cotton genotypes as well as in cultivated landraces and is a result of domestication and a long history of targeted breeding for yield and fiber quality, along with the capacity to control pests with pesticides. Genetic modification (GM) allowed integration of toxins from a bacteria into cotton to control key Lepidopteran pests. Since the mid-1990s, use of GM cotton cultivars has greatly reduced the amount of pesticides used in many cotton systems. However, pests not controlled by the GM traits have usually emerged as problems, especially the sucking bug complex. Control of this complex with pesticides often causes a reduction in beneficial invertebrate populations, allowing other secondary pests to increase rapidly and require control. Control of both sucking bug complex and secondary pests is problematic due to the cost of pesticides and/or high risk of selecting for pesticide resistance. Deployment of host plant resistance (HPR) provides an opportunity to manage these issues in GM cotton systems. Cotton cultivars resistant to the sucking bug complex and/or secondary pests would require fewer pesticide applications, reducing costs and risks to beneficial invertebrate populations and pesticide resistance. Incorporation of HPR traits into elite cotton cultivars with high yield and fiber quality offers the potential to further reduce pesticide use and increase the durability of pest management in GM cotton systems. We review the challenges that the identification and use of HPR against invertebrate pests brings to cotton breeding. We explore sources of resistance to the sucking bug complex and secondary pests, the mechanisms that control them and the approaches to incorporate these defense traits to commercial cultivars. PMID:27148323

  3. GABAA receptor partial agonists and antagonists

    DEFF Research Database (Denmark)

    Krall, Jacob; Balle, Thomas; Krogsgaard-Larsen, Niels;

    2015-01-01

    antagonists and describes the development of potent antagonists from partial agonists originally derived from the potent GABAAR agonist muscimol. In this process, several heterocyclic aromatic systems have been used in combination with structural models in order to map the orthosteric binding site...... and to reveal structural details to be used for obtaining potency and subtype selectivity. The challenges connected to functional characterization of orthosteric GABAAR partial agonists and antagonists, especially with regard to GABAAR stoichiometry and alternative binding sites are discussed. GABAAR...

  4. Ectopic Expression in Arabidopsis thaliana of an NB-ARC Encoding Putative Disease Resistance Gene from Wild Chinese Vitis pseudoreticulata Enhances Resistance to Phytopathogenic Fungi and Bacteria

    Directory of Open Access Journals (Sweden)

    Zhifeng eWen

    2015-12-01

    Full Text Available Plant resistance proteins mediate pathogen recognition and activate innate immune responses to restrict pathogen proliferation. One common feature of these proteins is an NB-ARC domain. In this study, we characterized a gene encoding a protein with an NB-ARC domain from wild Chinese grapevine Vitis pseudoreticulata accession Baihe-35-1, which was identified in a transcriptome analysis of the leaves following inoculation with Erysiphe necator (Schw., a causal agent of powdery mildew. Transcript levels of this gene, designated VpCN (GenBank accession number KT265084, increased strongly after challenge of grapevine leaves with E. necator. The deduced amino acid sequence was predicted to contain an NB-ARC domain in the C-terminus and an RxCC-like domain similar to CC domain of Rx protein in the N-terminus. Ectopic expression of VpCN in Arabidopsis thaliana resulted in either a wild-type phenotype or a dwarf phenotype. The phenotypically normal transgenic A. thaliana showed enhance resistance to A. thaliana powdery mildew Golovinomyces cichoracearum, as well as to a virulent bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Moreover, promoter::GUS (β-glucuronidase analysis revealed that powdery mildew infection induced the promoter activity of VpCN in grapevine leaves. Finally, a promoter deletion analysis showed that TC rich repeat elements likely play an important role in the response to E. necator infection. Taken together, our results suggest that VpCN contribute to powdery mildew disease resistant in grapevine.

  5. Impact ionization in high resistivity silicon induced by an intense terahertz field enhanced by an antenna array

    DEFF Research Database (Denmark)

    Tarekegne, Abebe Tilahun; Iwaszczuk, Krzysztof; Zalkovskij, Maksim;

    2015-01-01

    antenna array. The carrier multiplication is probed by the frequency shift of the resonance of the antenna array due to the change of the local refractive index of the substrate. Experimental results and simulations show that the carrier density in silicon increases by over seven orders of magnitude in......We report on the observation of ultrafast impact ionization and carrier generation in high resistivity silicon induced by intense subpicosecond terahertz transients. Local terahertz peak electric fields of several MV cm−1 are obtained by field enhancement in the near field of a resonant metallic...

  6. Chromosome engineering to enhance utility of alien-derived stem rust resistance

    Science.gov (United States)

    In the past 50 years, a number of stem rust (Sr) resistance genes identified from wild relatives of wheat have been incorporated into wheat genomes through chromosome engineering. Some of these genes, including Sr25, Sr26, Sr32, Sr37, Sr39, Sr40, Sr43, Sr44, SrR, and three unnamed novel Sr genes fr...

  7. Thermally oxidized titania nanotubes enhance the corrosion resistance of Ti6Al4V.

    Science.gov (United States)

    Grotberg, John; Hamlekhan, Azhang; Butt, Arman; Patel, Sweetu; Royhman, Dmitry; Shokuhfar, Tolou; Sukotjo, Cortino; Takoudis, Christos; Mathew, Mathew T

    2016-02-01

    The negative impact of in vivo corrosion of metallic biomedical implants remains a complex problem in the medical field. We aimed to determine the effects of electrochemical anodization (60V, 2h) and thermal oxidation (600°C) on the corrosive behavior of Ti-6Al-4V, with serum proteins, at physiological temperature. Anodization produced a mixture of anatase and amorphous TiO2 nanopores and nanotubes, while the annealing process yielded an anatase/rutile mixture of TiO2 nanopores and nanotubes. The surface area was analyzed by the Brunauer-Emmett-Teller method and was estimated to be 3 orders of magnitude higher than that of polished control samples. Corrosion resistance was evaluated on the parameters of open circuit potential, corrosion potential, corrosion current density, passivation current density, polarization resistance and equivalent circuit modeling. Samples both anodized and thermally oxidized exhibited shifts of open circuit potential and corrosion potential in the noble direction, indicating a more stable nanoporous/nanotube layer, as well as lower corrosion current densities and passivation current densities than the smooth control. They also showed increased polarization resistance and diffusion limited charge transfer within the bulk oxide layer. The treatment groups studied can be ordered from greatest corrosion resistance to least as Anodized+Thermally Oxidized > Anodized > Smooth > Thermally Oxidized for the conditions investigated. This study concludes that anodized surface has a potential to prevent long term implant failure due to corrosion in a complex in-vivo environment.

  8. Expression of a synthetic Bacillus thuringiensis endotoxin to enhance resistance against fall armyworm in bahiagrass

    Science.gov (United States)

    Bahiagrass is a low input, drought tolerant and disease resistant warm season turfgrass used for forage and turf in the southeastern U.S. and other subtropical regions of the world. Fall armyworm, Spodoptera frugiperda (J. E. Smith) is a destructive migratory pest of many tropical and subtropical g...

  9. Enhancing the wear resistance of case carburized steel (En 353) by cryogenic treatment

    Science.gov (United States)

    Bensely, A.; Prabhakaran, A.; Mohan Lal, D.; Nagarajan, G.

    2005-12-01

    All mechanical components that undergo sliding or rolling contact are subject to some degree of wear. So wear is an important tribological phenomenon while studying the failure of components. The observed frequent failure of crown and pinion due to wear and fatigue lead to this study on effect of cryogenic treatment on the wear resistance of case carburized steel (En 353). This paper deals with the pin on disk wear test without lubrication as per ASTM standard, designation: G 99-95A. The test was carried out for three different load conditions and seven sliding speeds for the samples, which has undergone three different treatment conditions namely conventional heat treatment (CHT), shallow cryogenic treatment (SCT) and deep cryogenic treatment (DCT). It has been found that the wear resistance has been considerably increased due to shallow cryogenic treatment and deep cryogenic treatment includes much more improvement in wear resistance when compared to conventional heat treatment. Also it is concluded that for better wear resistance, it is advisable to go for deep cryogenic treatment. The results are consistent with the previous studies reported in the literature on cryogenic treatments for other materials.

  10. Nematicides Enhance Growth and Yield of Rotylenchulus Reniformis Resistant Cotton Genotypes

    Science.gov (United States)

    Schrimsher, Drew W.; Lawrence, Kathy S.; Sikkens, Roelof B.; Weaver, David B.

    2014-01-01

    Rotylenchulus reniformis resistant LONREN-1×FM966 breeding lines developed at Auburn University have demonstrated that the nematode resistance is accompanied by severe stunting, limited growth, and low yields. The objectives of this study were to evaluate the effects of applying nematicides to selected LONREN breeding lines on R. reniformis nematode populations, plant stunting, and yield. Four resistant breeding lines from the LONREN-1×FM966 cross, one susceptible line from the LONREN-1×FM966 cross, as well as LONREN-1, BARBREN-713, and the susceptible cultivar DP393 were evaluated with and without nematicides in the presence of R. reniformis. In the greenhouse, nematicides increased plant height across all genotypes compared with no nematicide. Rotylenchulus reniformis populations were 50% lower in the resistant lines compared with the susceptible lines at 45 days after planting (DAP). In microplot and field trials, the phenotypic stunting of all genotypes was reduced by aldicarb with increases in plant heights at 30 and 75 DAP. Increases in yields were evident across all genotypes treated with aldicarb. In all three trial environments, BARBREN-713 outperformed the LONREN-derived lines as well as ‘DP393’ in seed cotton yields, while having significantly lower R. reniformis egg densities than the susceptible genotypes. PMID:25580030

  11. Medical-grade honey enriched with antimicrobial peptides has enhanced activity against antibiotic-resistant pathogens

    NARCIS (Netherlands)

    Kwakman, P.H.S.; Boer, den L.; Ruyter-Spira, C.; Creemers-Molenaar, T.; Helsper, J.P.F.G.; Vandenbroucke-Grauls, C.M.J.E.; Zaat, S.A.J.; Velde, te A.A.

    2011-01-01

    Honey has potent activity against both antibioticsensitive and -resistant bacteria, and is an interesting agent for topical antimicrobial application to wounds. As honey is diluted by wound exudate, rapid bactericidal activity up to high dilution is a prerequisite for its successful application. We

  12. Medical-grade honey enriched with antimicrobial peptides has enhanced activity against antibiotic-resistant pathogens

    NARCIS (Netherlands)

    P.H.S. Kwakman; L. de Boer; C.P. Ruyter-Spira; T. Creemers-Molenaar; J.P.F.G. Helsper; C.M.J.E. Vandenbroucke-Grauls; S.A.J. Zaat; A.A. te Velde

    2011-01-01

    Honey has potent activity against both antibiotic-sensitive and -resistant bacteria, and is an interesting agent for topical antimicrobial application to wounds. As honey is diluted by wound exudate, rapid bactericidal activity up to high dilution is a prerequisite for its successful application. We

  13. Characterization of Arabidopsis enhanced disease susceptibility mutants that are affected in systemically induced resistance

    NARCIS (Netherlands)

    Ton, J.; Vos, M. de; Robben, C.; Buchala, Anthony; Métraux, Jean-Pierre; Loon, L.C. van; Pieterse, C.M.J.

    2002-01-01

    In Arabidopsis, the rhizobacterial strain Pseudomonas fluorescens WCS417r triggers jasmonate (JA)- and ethylene (ET)-dependent induced systemic resistance (ISR) that is effective against different pathogens. Arabidopsis genotypes unable to express rhizobacteria-mediated ISR against the bacterial pat

  14. A new low voltage level-shifted FVF current mirror with enhanced bandwidth and output resistance

    Science.gov (United States)

    Aggarwal, Bhawna; Gupta, Maneesha; Gupta, Anil Kumar; Sangal, Ankur

    2016-10-01

    This paper proposes a new high-performance level-shifted flipped voltage follower (LSFVF) based low-voltage current mirror (CM). The proposed CM utilises the low-supply voltage and low-input resistance characteristics of a flipped voltage follower (FVF) CM. In the proposed CM, level-shifting configuration is used to obtain a wide operating current range and resistive compensation technique is employed to increase the operating bandwidth. The peaking in frequency response is reduced by using an additional large MOSFET. Moreover, a very high output resistance (in GΩ range) along with low-current transfer error is achieved through super-cascode configuration for a wide current range (0-440 µA). Small signal analysis is carried out to show the improvements achieved at each step. The proposed CM is simulated by Mentor Graphics Eldospice in TSMC 0.18 µm CMOS, BSIM3 and Level 53 technology. In the proposed CM, a bandwidth of 6.1799 GHz, 1% settling time of 0.719 ns, input and output resistances of 21.43 Ω and 1.14 GΩ, respectively, are obtained with a single supply voltage of 1 V. The layout of the proposed CM has been designed and post-layout simulation results have been shown. The post-layout simulation results for Monte Carlo and temperature analysis have also been included to show the reliability of the CM against the variations in process parameters and temperature changes.

  15. Neuronal monoamine reuptake inhibitors enhance in vitro susceptibility to chloroquine in resistant Plasmodium falciparum.

    OpenAIRE

    Coutaux, A F; Mooney, J. J.; Wirth, D. F.

    1994-01-01

    Chloroquine resistance in Plasmodium falciparum was reversed in vitro by the neuronal monoamine reuptake inhibitors and antidepressants desipramine, sertraline, fluoxetine, and norfluoxetine but not by carbamazepine, an antiseizure and mood-stabilizing tricyclic drug resembling desipramine which only weakly inhibits neuronal monoamine reuptake. These findings have important clinical implications for drug combination therapy.

  16. Potent anti-diabetic effects of MHY908, a newly synthesized PPAR α/γ dual agonist in db/db mice.

    Directory of Open Access Journals (Sweden)

    Min Hi Park

    Full Text Available Peroxisome proliferator-activated receptor (PPAR α/γ dual agonists have been developed to alleviate metabolic disorders and have the potential to be used as therapeutic agents for the treatment of type 2 diabetes. In this study, we investigated the effects of a newly synthesized PPAR α/γ dual agonist, 2-[4-(5-chlorobenzo [d] thiazol-2-yl phenoxy]-2-methylpropanoic acid (MHY908 on type 2 diabetes in vitro and in vivo. To obtain initial evidence that MHY908 acts as a PPAR α/γ dual agonist, ChIP and reporter gene assays were conducted in AC2F rat liver cells, and to investigate the anti-diabetic effects and molecular mechanisms, eight-week-old, male db/db mice were allowed to eat ad libitum, placed on calorie restriction, or administered MHY908 (1 mg or 3 mg/kg/day mixed in food for 4 weeks. Age-matched male db/m lean mice served as non-diabetic controls. It was found that MHY908 enhanced the binding and transcriptional activity of PPAR α and γ in AC2F cells, and it reduced serum glucose, triglyceride, and insulin levels, however increased adiponectin levels without body weight gain. In addition, MHY908 significantly improved hepatic steatosis by enhancing CPT-1 levels. Remarkably, MHY908 reduced endoplasmic reticulum (ER stress and c-Jun N-terminal kinase (JNK activation in the livers of db/db mice, and subsequently reduced insulin resistance. The study shows MHY908 has beneficial effects on type 2 diabetes by simultaneously activating PPAR α/γ and improving ER stress, and suggests that MHY908 could have a potent anti-diabetic effect as a PPAR α/γ dual agonist, and potential for the treatment of type 2 diabetes.

  17. Overexpression of a Modified Plant Thionin Enhances Disease Resistance to Citrus Canker and Huanglongbing (HLB).

    Science.gov (United States)

    Hao, Guixia; Stover, Ed; Gupta, Goutam

    2016-01-01

    Huanglongbing (HLB or citrus greening disease) caused by Candidatus Liberibacter asiaticus (Las) is a great threat to the US citrus industry. There are no proven strategies to eliminate HLB disease and no cultivar has been identified with strong HLB resistance. Citrus canker is also an economically important disease associated with a bacterial pathogen (Xanthomonas citri). In this study, we characterized endogenous citrus thionins and investigated their expression in different citrus tissues. Since no HLB-resistant citrus cultivars have been identified, we attempted to develop citrus resistant to both HLB and citrus canker through overexpression of a modified plant thionin. To improve effectiveness for disease resistance, we modified and synthesized the sequence encoding a plant thionin and cloned into the binary vector pBinPlus/ARS. The construct was then introduced into Agrobacterium strain EHA105 for citrus transformation. Transgenic Carrizo plants expressing the modified plant thionin were generated by Agrobacterium-mediated transformation. Successful transformation and transgene gene expression was confirmed by molecular analysis. Transgenic Carrizo plants expressing the modified thionin gene were challenged with X. citri 3213 at a range of concentrations, and a significant reduction in canker symptoms and a decrease in bacterial growth were demonstrated compared to nontransgenic plants. Furthermore, the transgenic citrus plants were challenged with HLB via graft inoculation. Our results showed significant Las titer reduction in roots of transgenic Carrizo compared with control plants and reduced scion Las titer 12 months after graft inoculation. These data provide promise for engineering citrus disease resistance against HLB and canker. PMID:27499757

  18. Sputum containing zinc enhances carbapenem resistance, biofilm formation and virulence of Pseudomonas aeruginosa.

    Science.gov (United States)

    Marguerettaz, Mélanie; Dieppois, Guennaëlle; Que, Yok Ai; Ducret, Véréna; Zuchuat, Sandrine; Perron, Karl

    2014-12-01

    Pseudomonas aeruginosa chronic lung infections are the leading cause of mortality in cystic fibrosis patients, a serious problem which is notably due to the numerous P. aeruginosa virulence factors, to its ability to form biofilms and to resist the effects of most antibiotics. Production of virulence factors and biofilm formation by P. aeruginosa is highly coordinated through complex regulatory systems. We recently found that CzcRS, the zinc and cadmium-specific two-component system is not only involved in metal resistance, but also in virulence and carbapenem antibiotic resistance in P. aeruginosa. Interestingly, zinc has been shown to be enriched in the lung secretions of cystic fibrosis patients. In this study, we investigated whether zinc might favor P. aeruginosa pathogenicity using an artificial sputum medium to mimic the cystic fibrosis lung environment. Our results show that zinc supplementation triggers a dual P. aeruginosa response: (i) it exacerbates pathogenicity by a CzcRS two-component system-dependent mechanism and (ii) it stimulates biofilm formation by a CzcRS-independent mechanism. Furthermore, P. aeruginosa cells embedded in these biofilms exhibited increased resistance to carbapenems. We identified a novel Zn-sensitive regulatory circuit controlling the expression of the OprD porin and modifying the carbapenem resistance profile. Altogether our data demonstrated that zinc levels in the sputum of cystic fibrosis patients might aggravate P. aeruginosa infection. Targeting zinc levels in sputum would be a valuable strategy to curb the increasing burden of P. aeruginosa infections in cystic fibrosis patients. PMID:25448466

  19. Overexpression of a modified plant thionin enhances disease resistance to citrus canker and Huanglongbing (HLB

    Directory of Open Access Journals (Sweden)

    Guixia Hao

    2016-07-01

    Full Text Available Huanglongbing (HLB or citrus greening disease caused by Candidatus Liberibacter asiaticus (Las is a great threat to the US citrus industry. There are no proven strategies to eliminate HLB disease and no cultivar has been identified with strong HLB resistance. Citrus canker is also an economically important disease associated with a bacterial pathogen (Xanthomonas citri. In this study, we characterized endogenous citrus thionins and investigated their expression in different citrus tissues. Since no HLB-resistant citrus cultivars have been identified, we attempted to develop citrus resistant to both HLB and citrus canker through overexpression of a modified plant thionin. To improve effectiveness for disease resistance, we modified and synthesized the sequence encoding a plant thionin and cloned into the binary vector pBinPlus/ARS. The construct was then introduced into Agrobacterium strain EHA105 for citrus transformation. Transgenic Carrizo plants expressing the modified plant thionin were generated by Agrobacterium-mediated transformation. Successful transformation and transgene gene expression was confirmed by molecular analysis. Transgenic Carrizo plants expressing the modified thionin gene were challenged with X. citri 3213 at a range of concentrations, and a significant reduction in canker symptoms and a decrease in bacterial growth were demonstrated compared to nontransgenic plants. Furthermore the transgenic citrus plants were challenged with HLB via graft inoculation. Our results showed significant Las titer reduction in roots of transgenic Carrizo compared with control plants and reduced scion Las titer twelve months after graft inoculation. These data provide promise for engineering citrus disease resistance against HLB and canker.

  20. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    International Nuclear Information System (INIS)

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC50 values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC50 = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other

  1. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    Energy Technology Data Exchange (ETDEWEB)

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi, E-mail: kumamote@cc.saga-u.ac.jp

    2013-04-26

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

  2. The global status of insect resistance to neonicotinoid insecticides.

    Science.gov (United States)

    Bass, Chris; Denholm, Ian; Williamson, Martin S; Nauen, Ralf

    2015-06-01

    The first neonicotinoid insecticide, imidacloprid, was launched in 1991. Today this class of insecticides comprises at least seven major compounds with a market share of more than 25% of total global insecticide sales. Neonicotinoid insecticides are highly selective agonists of insect nicotinic acetylcholine receptors and provide farmers with invaluable, highly effective tools against some of the world's most destructive crop pests. These include sucking pests such as aphids, whiteflies, and planthoppers, and also some coleopteran, dipteran and lepidopteran species. Although many insect species are still successfully controlled by neonicotinoids, their popularity has imposed a mounting selection pressure for resistance, and in several species resistance has now reached levels that compromise the efficacy of these insecticides. Research to understand the molecular basis of neonicotinoid resistance has revealed both target-site and metabolic mechanisms conferring resistance. For target-site resistance, field-evolved mutations have only been characterized in two aphid species. Metabolic resistance appears much more common, with the enhanced expression of one or more cytochrome P450s frequently reported in resistant strains. Despite the current scale of resistance, neonicotinoids remain a major component of many pest control programmes, and resistance management strategies, based on mode of action rotation, are of crucial importance in preventing resistance becoming more widespread. In this review we summarize the current status of neonicotinoid resistance, the biochemical and molecular mechanisms involved, and the implications for resistance management.

  3. [Dissertations 25 years after date 21. Enhancing resistance to bacteria with chlorhexidine varnish and probiotics].

    Science.gov (United States)

    Schaeken, M J M

    2010-02-01

    The aim of the research described in 'Chemotherapy against Streptococcus mutans' was to increase colonization resistance against mutans streptococci by inoculating Actinomyces naeslundii on the dentition. Actinomyces naeslundii established better after chlorhexidine application than after dental cleansing only but did not exceed the 1% level of the total actinomyces population. This was insufficient to increase the colonization resistance against mutans streptococci. A 33% chlorhexidine varnish was developed. After a single short-term application of the varnish all plaque bacteria were erased. After several hours Streptococcus sanguinis, Streptococcus oralis, Streptococcus mitis and Streptococcus gordonii re-established on the surface. Actinomyces naeslundii recovered later, but often with higher numbers. Mutans streptococci remained suppressed for months. This led to less acid production in dental plaque and caries reduction. The combination of mechanical cleansing and varnish application resulted in additional pocket reduction. Recently, attention is also established for research on the application ofprobiotics in periodotology. PMID:20225702

  4. Hydrogen enhanced thermal donor formation in oxygen enriched high resistive float-zone silicon

    International Nuclear Information System (INIS)

    Hydrogen supported thermal donor (TD) formation was observed in oxygen enriched high resistive float zone (FZ) silicon being used as substrates for detectors in the Large Hadron Collider (CERN). TD formation was provided by a '2-step-process', consisting of a plasma hydrogenation at 250 deg. C (60 min) and subsequent annealing at 450 deg. C in air (typically for 20-30 min). The samples were analyzed by spreading resistance probe (SRP), C(V) and DLTS measurements. Doping by TDs in the oxygen enriched layers of FZ Si samples might be a promising method for the creation of very deep (∼100 μm) electrical field gradients for an improved performance of Si radiation detectors

  5. Enhancing Integrated Pest Management in GM Cotton Systems Using Host Plant Resistance

    OpenAIRE

    Trapero, Carlos; Wilson, Iain W; Stiller, Warwick N.; Lewis J Wilson

    2016-01-01

    Cotton has lost many ancestral defensive traits against key invertebrate pests. This is suggested by the levels of resistance to some pests found in wild cotton genotypes as well as in cultivated landraces and is a result of domestication and a long history of targeted breeding for yield and fiber quality, along with the capacity to control pests with pesticides. Genetic modification (GM) allowed integration of toxins from a bacteria into cotton to control key Lepidopteran pests. Since the mi...

  6. Enhancing integrated pest management in GM cotton systems using host plant resistance

    OpenAIRE

    Carlos eTrapero; Wilson, Iain W; Stiller, Warwick N.; Lewis J Wilson

    2016-01-01

    Cotton has lost many ancestral defensive traits against key invertebrate pests. This is suggested by the levels of resistance to some pests found in wild cotton genotypes as well as in cultivated landraces and is a result of domestication and a long history of targeted breeding for yield and fibre quality, along with the capacity to control pests with pesticides. Genetic modification (GM) allowed integration of toxins from a bacteria into cotton to control key Lepidopteran pests. Since the mi...

  7. ENHANCEMENT OF CHLORIDE RESISTANCE OF PRE-STRESSED CONCRETE SHEET PILE BY BLAST FURNACE SLAG

    OpenAIRE

    Irmawaty, Rita

    2012-01-01

    Chloride-induced corrosion is one of the main mechanisms of deterioration affecting the long-term performance of concrete structures. In Japan, a large majority of structures are built either near the costal or indirect contact with seawater. The durability of reinforced or pre-stressed concrete structure depends on the resistance of concrete to chloride penetration. Naturally concrete provides physical and chemical protection to the reinforcing steel from chloride penetrating. The chloride ...

  8. Metallised holographic diffraction gratings with the enhanced radiation resistance for laser pulse compression systems

    International Nuclear Information System (INIS)

    The methods for improving the radiation resistance and strength of metallised diffraction gratings for laser pulse compression systems are considered. It is shown that the modification of the method for applying gold on the holographic grating surface provides a substantial increase in the grating damage threshold. It is also shown that the use of additional dielectric coatings allows a further doubling of the damage threshold for nanosecond laser pulses. (laser applications and other topics in quantum electronics)

  9. Enhanced combination therapy effect on paclitaxel-resistant carcinoma by chloroquine co-delivery via liposomes

    Directory of Open Access Journals (Sweden)

    Gao MH

    2015-10-01

    Full Text Available Menghua Gao,1 Yuzhen Xu,1 Liyan Qiu2,3 1College of Pharmaceutical Sciences, 2Ministry of Education (MOE Key Laboratory of Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 3Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: A novel composite liposomal system co-encapsulating paclitaxel (PTX with chloroquine phosphate (CQ was designed for treating PTX-resistant carcinoma. It was confirmed that liposomal CQ can sensitize PTX by means of autophagy inhibition and competitively binding with multidrug-resistance transporters. Furthermore, according to the in vitro cytotoxicity and apoptosis assay, real-time observation of cellular uptake, and in vivo tissue distribution study, co-encapsulation of PTX and CQ in liposomes was validated as superior to the mixture of PTX liposome plus CQ liposome due to the simultaneous delivery and synergetic effect of the two drugs. Consequently, this composite liposome achieved significantly stronger anticancer efficacy in vivo than the PTX liposome plus CQ liposome mixture. This study helps to guide and enlighten ongoing and future clinical trials about the optimal administration modes for drug combination therapy. Keywords: paclitaxel, chloroquine, liposome, drug resistance, combination therapy

  10. CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo

    International Nuclear Information System (INIS)

    Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression

  11. CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.M.; Gao, S.J.; Guo, X.F.; Sun, W.J. [Department of Oncology, The Second Affiliated Hospital, Harbin Medical University, Harbin (China); Yan, Z.Q. [Department of Breast Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin (China); Wang, W.X.; Xu, Y.Q.; Lu, D. [Department of Oncology, The Second Affiliated Hospital, Harbin Medical University, Harbin (China)

    2014-03-21

    Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression.

  12. Enhancing the Scratch Resistance by Introducing Chemical Bonding in Highly Stretchable and Transparent Electrodes.

    Science.gov (United States)

    Guo, Chuan Fei; Chen, Yan; Tang, Lu; Wang, Feng; Ren, Zhifeng

    2016-01-13

    Stretchable transparent electrodes are key elements in flexible electronics and e-skins. However, existing stretchable transparent electrodes, including graphene sheets, carbon nanotube, and metal nanowire networks, weakly adheres to the substrate by van der Waals forces. Such electrodes suffer from poor scratch-resistance or poor durability, and this issue has been one of the biggest problems for their applications in industry. Here we show that, by introducing a Au-S bond between a Au nanomesh (AuNM) and the underlying elastomeric substrate, the AuNM strongly adheres to the substrate and can withstand scratches of a pressure of several megapascals. We find that the strong chemical bond, on the other hand, leads to a stiffening effect and localized rupture of the AuNM upon stretching; thus the stretchability is poor. A prestraining process is applied to suppress the localized rupture and has successfully improved the stretchability: electrical resistance of the prestrained AuNM exhibits modest change by one-time stretching to 160%, or repeated stretching to 50% for 25 000 cycles. This conductor is an ideal platform for robust stretchable photoelectronics. The idea of introducing a covalent bond to improve the scratch-resistance may also be applied to other systems including Ag nanowire films, carbon nanotube films, graphene, and so forth. PMID:26674364

  13. Nanocrystallization of aluminized surface of carbon steel for enhanced resistances to corrosion and corrosive wear

    Energy Technology Data Exchange (ETDEWEB)

    Chen, C. [Dept. of Materials Physical and Chemical, University of Science and Technology Beijing, Beijing 100083 (China); Dept. of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta, T6G 2V4 (Canada); Li, D.Y., E-mail: dongyang.li@ualberta.c [Dept. of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta, T6G 2V4 (Canada); Shang, C.J. [Dept. of Materials Physical and Chemical, University of Science and Technology Beijing, Beijing 100083 (China)

    2009-12-15

    Aluminizing is often used to improve steel's resistances to corrosion, oxidation and wear. This article reports our recent attempts to further improve aluminized carbon steel through surface nanocrystallization for higher resistances to corrosion and corrosive wear. The surface nanocrystallization was achieved using a process combining sandblasting and recovery heat treatment. The entire surface modification process includes dipping carbon steel specimens into a molten Al pool to form an Al coat, subsequent diffusion treatment at elevated temperature to form an aluminized layer, sandblasting to generate dislocation network or cells, and recovery treatment to turn the dislocation cells into nano-sized grains. The grain size of the nanocrystallized aluminized surface layer was in the range of 20-100 nm. Electrochemical properties, electron work function (EWF), and corrosive wear of the nanocrystalline alloyed surfaces were investigated. It was demonstrated that the nanocrystalline aluminized surface of carbon steel exhibited improved resistances to corrosion, wear and corrosive wear. The passive film developed on the nanocrystallized aluminized surface was also evaluated in terms of its mechanical properties and adherence to the substrate.

  14. Non-cytotoxic nanomaterials enhance antimicrobial activities of cefmetazole against multidrug-resistant Neisseria gonorrhoeae.

    Science.gov (United States)

    Li, Lan-Hui; Yen, Muh-Yong; Ho, Chao-Chi; Wu, Ping; Wang, Chien-Chun; Maurya, Pawan Kumar; Chen, Pai-Shan; Chen, Wei; Hsieh, Wan-Yu; Chen, Huei-Wen

    2013-01-01

    The emergence and spread of antibiotic-resistant Neisseria gonorrhoeae has led to difficulties in treating patients, and novel strategies to prevent and treat this infection are urgently needed. Here, we examined 21 different nanomaterials for their potential activity against N. gonorrhoeae (ATCC 49226). Silver nanoparticles (Ag NPs, 120 nm) showed the greatest potency for reducing N. gonorrhoeae colony formation (MIC: 12.5 µg/ml) and possessed the dominant influence on the antibacterial activity with their properties of the nanoparticles within a concentration range that did not induce cytotoxicity in human fibroblasts or epithelial cells. Electron microscopy revealed that the Ag NPs significantly reduced bacterial cell membrane integrity. Furthermore, the use of clinical isolates of multidrug-resistant N. gonorrhoeae showed that combined treatment with 120 nm Ag NPs and cefmetazole produced additive effects. This is the first report to screen the effectiveness of nanomaterials against N. gonorrhoeae, and our results indicate that 120 nm Ag NPs deliver low levels of toxicity to human epithelial cells and could be used as an adjuvant with antibiotic therapy, either for topical use or as a coating for biomaterials, to prevent or treat multidrug-resistant N. gonorrhoeae. PMID:23705013

  15. Non-cytotoxic nanomaterials enhance antimicrobial activities of cefmetazole against multidrug-resistant Neisseria gonorrhoeae.

    Directory of Open Access Journals (Sweden)

    Lan-Hui Li

    Full Text Available The emergence and spread of antibiotic-resistant Neisseria gonorrhoeae has led to difficulties in treating patients, and novel strategies to prevent and treat this infection are urgently needed. Here, we examined 21 different nanomaterials for their potential activity against N. gonorrhoeae (ATCC 49226. Silver nanoparticles (Ag NPs, 120 nm showed the greatest potency for reducing N. gonorrhoeae colony formation (MIC: 12.5 µg/ml and possessed the dominant influence on the antibacterial activity with their properties of the nanoparticles within a concentration range that did not induce cytotoxicity in human fibroblasts or epithelial cells. Electron microscopy revealed that the Ag NPs significantly reduced bacterial cell membrane integrity. Furthermore, the use of clinical isolates of multidrug-resistant N. gonorrhoeae showed that combined treatment with 120 nm Ag NPs and cefmetazole produced additive effects. This is the first report to screen the effectiveness of nanomaterials against N. gonorrhoeae, and our results indicate that 120 nm Ag NPs deliver low levels of toxicity to human epithelial cells and could be used as an adjuvant with antibiotic therapy, either for topical use or as a coating for biomaterials, to prevent or treat multidrug-resistant N. gonorrhoeae.

  16. Crosslinked and Dyed Chitosan Fiber Presenting Enhanced Acid Resistance and Bioactivities

    Directory of Open Access Journals (Sweden)

    Xiao-Qiong Li

    2016-04-01

    Full Text Available The application of biodegradable chitosan fiber for healthy and hygienic textiles is limited due to its poor acid resistance in wet processing and poor antioxidant activity. In order to prepare chitosan fiber with good acid resistance and high antioxidant activity, chitosan fiber was first crosslinked by a water-soluble aziridine crosslinker, and then dyed with natural lac dye consisting of polyphenolic anthraquinone compounds. The main application conditions and crosslinking mechanism of the aziridine crosslinker, the adsorption mechanism and building-up property of lac dye on the crosslinked fiber, and the effects of crosslinking and dyeing on the antioxidant and antibacterial activities of chitosan fiber were studied. The crosslinked fiber exhibited greatly reduced weight loss in acidic solution, and possessed excellent acid resistance. Lac dye displayed a very high adsorption capability on the crosslinked fiber and a high utilization rate under weakly acidic medium. The Langmuir–Nernst isotherm was the best model to describe the adsorption behavior of lac dye, and Langmuir adsorption had great contribution to total adsorption. Lac dyeing imparted good antioxidant activity to chitosan fiber. Crosslinking and dyeing had no impact on the good inherent antibacterial activity of chitosan fiber.

  17. Enhancement of wear and corrosion resistance of beta titanium alloy by laser gas alloying with nitrogen

    Science.gov (United States)

    Chan, Chi-Wai; Lee, Seunghwan; Smith, Graham; Sarri, Gianluca; Ng, Chi-Ho; Sharba, Ahmed; Man, Hau-Chung

    2016-03-01

    The relatively high elastic modulus coupled with the presence of toxic vanadium (V) in Ti6Al4V alloy has long been a concern in orthopaedic applications. To solve the problem, a variety of non-toxic and low modulus beta-titanium (beta-Ti) alloys have been developed. Among the beta-Ti alloy family, the quaternary Ti-Nb-Zr-Ta (TNZT) alloys have received the highest attention as a promising replacement for Ti6Al4V due to their lower elastic modulus and outstanding long term stability against corrosion in biological environments. However, the inferior wear resistance of TNZT is still a problem that must be resolved before commercialising in the orthopaedic market. In this work, a newly developed laser surface treatment technique was employed to improve the surface properties of Ti-35.3Nb-7.3Zr-5.7Ta alloy. The surface structure and composition of the laser-treated TNZT surface were examined by grazing incidence X-ray diffraction (GI-XRD) and X-ray photoelectron spectroscopy (XPS). The wear and corrosion resistance were evaluated by pin-on-plate sliding test and anodic polarisation test in Hanks' solution. The experimental results were compared with the untreated (or base) TNZT material. The research findings showed that the laser surface treatment technique reported in this work can effectively improve the wear and corrosion resistance of TNZT.

  18. Enhancement of memory windows in Pt/Ta{sub 2}O{sub 5−x}/Ta bipolar resistive switches via a graphene oxide insertion layer

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Je Bock; Bae, Yoon Cheol; Lee, Ah Rahm; Baek, Gwang Ho [Department of Nanoscale Semiconductor Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Min Yong [Department of Energy Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); R& D Division, SK Hynix, Kyoungki-do 467-701 (Korea, Republic of); Yoon, Hee Wook; Park, Ho Bum [Department of Energy Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Hong, Jin Pyo, E-mail: jphong@hanyang.ac.kr [Department of Nanoscale Semiconductor Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); The Research Institute for Natural Science, Novel Functional Materials and Devices Lab, Department of Physics, Hanyang University, Seoul 133-791 (Korea, Republic of)

    2015-07-31

    The influence of a graphene oxide (GO) layer on Pt/Ta{sub 2}O{sub 5−x}/Ta bipolar resistive switches, in which the GO layer is spin-coated on the Ta bottom electrode before the growth of a Ta{sub 2}O{sub 5−x} switching element was examined. Experimental observations suggest that the insertion of the GO layer is crucial for adjusting the low resistance states without changing the high resistance states. Controlling GO layer thickness represents the variation of the forming voltage and on/off ratio, demonstrating enhanced memory windows. The possible nature of the enhanced switching events is described by adapting the creation of strong conductive filaments driven by a greater resistive GO layer. - Highlights: • Graphene oxide (GO) layer functions as the strong conductive filaments. • The GO insertion layer controls the low resistance states of bipolar switching. • Memory windows of bipolar switching were intentionally manipulated.

  19. Enhanced immune response and resistance to white tail disease in chitin-diet fed freshwater prawn, Macrobrachium rosenbergii

    Directory of Open Access Journals (Sweden)

    B.T. Naveen Kumar

    2015-11-01

    Full Text Available Chitin is one of the natural biopolymer found abundantly in the shells of crustaceans, insects and in cell walls of fungi. In this study, we determined the effect of dietary administration of 0.5, 0.75 and 1% chitin on the immune response and disease resistance in freshwater prawn, challenged against Macrobrachium rosenbergii nodavirus (MrNV and extra small virus (XSV. We observed a significantly enhanced immune response, indicated as higher prophenoloxidase activity and respiratory burst of hemocytes, in 0.75% chitin-diet fed prawns compared to the chitin-free-diet fed prawns. Importantly, the relative percent survival (RPS following challenge with white muscle disease (WTD viruses was found relatively high in M. rosenbergii fed with diet containing 0.75% chitin (63.16%, suggesting an increased resistance to disease susceptibility. These results indicate that the incorporation of chitin in prawn diet would be beneficial in stimulating the immune response and thereby developing resistance against diseases.

  20. Down-regulation of Fusarium oxysporum endogenous genes by Host-Delivered RNA interference enhances disease resistance

    Directory of Open Access Journals (Sweden)

    Zongli eHu

    2015-01-01

    Full Text Available Fusarium oxysporum is a devastating pathogen causing extensive yield losses in a variety of crops and development of sustainable, environmentally friendly methods to improve crop resistance is crucial. We have used Host-Derived RNA interference (HD-RNAi technology to partially silence three different genes (FOW2, FRP1 and OPR in the hemi-biotrophic fungus Fusarium oxysporum f. sp. conglutinans. Expression of double stranded RNA molecules targeting fungal pathogen genes was achieved in a number of transgenic Arabidopsis lines. F. oxysporum infecting the transgenic lines displayed substantially reduced mRNA levels on all three targeted genes, with an average of 75%, 83% and 72% reduction for FOW2, FRP1 and OPR respectively. The silencing of pathogen genes had a clear positive effect on the ability of the transgenic lines to fight infection. All transgenic lines displayed enhanced resistance to F. oxysporum with delayed disease symptom development, especially FRP1 and OPR lines. Survival rates after fungal infection were higher in the transgenic lines compared to control wild type plants which consistently showed survival rates of 10%, with FOW2 lines showing 25% survival; FRP1 lines 30-50% survival and FOW2 between 45-70% survival. The down-regulation effect was specific for the targeted genes without unintended effects in related genes. In addition to producing resistant crops, HD-RNAi can provide a useful tool to rapidly screen candidate fungal pathogenicity genes without the need to produce fungal knockout mutants.

  1. Down-regulation of Fusarium oxysporum endogenous genes by Host-Delivered RNA interference enhances disease resistance

    Science.gov (United States)

    Hu, Zongli; Parekh, Urvi; Maruta, Natsumi; Trusov, Yuri; Botella, Jimmy

    2015-01-01

    Fusarium oxysporum is a devastating pathogen causing extensive yield losses in a variety of crops and development of sustainable, environmentally friendly methods to improve crop resistance is crucial. We have used Host-Derived RNA interference (HD-RNAi) technology to partially silence three different genes (FOW2, FRP1 and OPR) in the hemi-biotrophic fungus Fusarium oxysporum f. sp. conglutinans. Expression of double stranded RNA molecules targeting fungal pathogen genes was achieved in a number of transgenic Arabidopsis lines. F. oxysporum infecting the transgenic lines displayed substantially reduced mRNA levels on all three targeted genes, with an average of 75%, 83% and 72% reduction for FOW2, FRP1 and OPR respectively. The silencing of pathogen genes had a clear positive effect on the ability of the transgenic lines to fight infection. All transgenic lines displayed enhanced resistance to F. oxysporum with delayed disease symptom development, especially FRP1 and OPR lines. Survival rates after fungal infection were higher in the transgenic lines compared to control wild type plants which consistently showed survival rates of 10%, with FOW2 lines showing 25% survival; FRP1 lines 30-50% survival and FOW2 between 45-70% survival. The down-regulation effect was specific for the targeted genes without unintended effects in related genes. In addition to producing resistant crops, HD-RNAi can provide a useful tool to rapidly screen candidate fungal pathogenicity genes without the need to produce fungal knockout mutants.

  2. Hepatitis B virus enhancer Ⅰ in chronic carriers resistant to interferon treatment

    Institute of Scientific and Technical Information of China (English)

    SONG Jing-yu; H. W. Han

    2001-01-01

    OBJECTIVE To study the structural and preliminary functional characterization of the hepatitis B virus(HBV) enhancer Ⅰ in patients with chronic hepatitis B treated with interferon (IFN). METHODS The characteristics of the HBV enhancer Ⅰ in 12chronic carrier who were treated with alpha interferon was detected by the methods of molecular biology including PCR, cloning of PCR products, sequencing and cell culture.RESULTS Four of 6 patients cleared viral DNA; all 6 in this group also seroconverted from e antigen to antibody. Prior to therapy, the HBV enhancer Ⅰ region demonstrated many point mutations in all 6 patients who became nonresponders, compared to patients who responded to interferon. The mutated sequences, many of which were within regions of transcription factor binding, were significantly more active than the corresponding wild type sequences in reporter gene assays. CONCLUSION These results imply that the mutations found in nonresponders appear to render the virus less sensitive to interferon.

  3. Enhanced High Temperature Corrosion Resistance in Advanced Fossil Energy Systems by Nano-Passive Layer Formation

    Energy Technology Data Exchange (ETDEWEB)

    Arnold R. Marder

    2007-06-14

    Due to their excellent corrosion resistance, iron aluminum alloys are currently being considered for use as weld claddings in fossil fuel fired power plants. The susceptibility to hydrogen cracking of these alloys at higher aluminum concentrations has highlighted the need for research into the effect of chromium additions on the corrosion resistance of lower aluminum alloys. In the present work, three iron aluminum alloys were exposed to simulated coal combustion environments at 500 C and 700 C for both short (100 hours) and long (5,000 hours) isothermal durations. Scanning electron microscopy was used to analyze the corrosion products. All alloys exhibited excellent corrosion resistance in the short term tests. For longer exposures, increasing the aluminum concentration was beneficial to the corrosion resistance. The addition of chromium to the binary iron aluminum alloy prevented the formation iron sulfide and resulted in lower corrosion kinetics. A classification of the corrosion products that developed on these alloys is presented. Scanning transmission electron microscopy (STEM) of the as-corroded coupons revealed that chromium was able to form chromium sulfides only on the higher aluminum alloy, thereby preventing the formation of deleterious iron sulfides. When the aluminum concentration was too low to permit selective oxidation of only aluminum (upon initial exposure to the corrosion environment), the formation of chromium oxide alongside the aluminum oxide led to depletion of chromium beneath the oxide layer. Upon penetration of sulfur through the oxide into this depletion layer, iron sulfides (rather than chromium sulfides) were found to form on the low aluminum alloy. Thus, it was found in this work that the role of chromium on alloy corrosion resistance was strongly effected by the aluminum concentration of the alloy. STEM analysis also revealed the encapsulation of external iron sulfide products with a thin layer of aluminum oxide, which may provide a

  4. Enhanced NFκB and AP-1 transcriptional activity associated with antiestrogen resistant breast cancer

    International Nuclear Information System (INIS)

    Signaling pathways that converge on two different transcription factor complexes, NFκB and AP-1, have been identified in estrogen receptor (ER)-positive breast cancers resistant to the antiestrogen, tamoxifen. Two cell line models of tamoxifen-resistant ER-positive breast cancer, MCF7/HER2 and BT474, showing increased AP-1 and NFκB DNA-binding and transcriptional activities, were studied to compare tamoxifen effects on NFκB and AP-1 regulated reporter genes relative to tamoxifen-sensitive MCF7 cells. The model cell lines were treated with the IKK inhibitor parthenolide (PA) or the proteasome inhibitor bortezomib (PS341), alone and in combination with tamoxifen. Expression microarray data available from 54 UCSF node-negative ER-positive breast cancer cases with known clinical outcome were used to search for potential genes signifying upregulated NFκB and AP-1 transcriptional activity in association with tamoxifen resistance. The association of these genes with patient outcome was further evaluated using node-negative ER-positive breast cancer cases identified from three other published data sets (Rotterdam, n = 209; Amsterdam, n = 68; Basel, n = 108), each having different patient age and adjuvant tamoxifen treatment characteristics. Doses of parthenolide and bortezomib capable of sensitizing the two endocrine resistant breast cancer models to tamoxifen were capable of suppressing NFκB and AP-1 regulated gene expression in combination with tamoxifen and also increased ER recruitment of the transcriptional co-repressor, NCoR. Transcript profiles from the UCSF breast cancer cases revealed three NFκB and AP-1 upregulated genes – cyclin D1, uPA and VEGF – capable of dichotomizing node-negative ER-positive cases into early and late relapsing subsets despite adjuvant tamoxfien therapy and most prognostic for younger age cases. Across the four independent sets of node-negative ER-positive breast cancer cases (UCSF, Rotterdam, Amsterdam, Basel), high expression of

  5. Enhanced NFκB and AP-1 transcriptional activity associated with antiestrogen resistant breast cancer

    Directory of Open Access Journals (Sweden)

    Moore Dan H

    2007-04-01

    Full Text Available Abstract Background Signaling pathways that converge on two different transcription factor complexes, NFκB and AP-1, have been identified in estrogen receptor (ER-positive breast cancers resistant to the antiestrogen, tamoxifen. Methods Two cell line models of tamoxifen-resistant ER-positive breast cancer, MCF7/HER2 and BT474, showing increased AP-1 and NFκB DNA-binding and transcriptional activities, were studied to compare tamoxifen effects on NFκB and AP-1 regulated reporter genes relative to tamoxifen-sensitive MCF7 cells. The model cell lines were treated with the IKK inhibitor parthenolide (PA or the proteasome inhibitor bortezomib (PS341, alone and in combination with tamoxifen. Expression microarray data available from 54 UCSF node-negative ER-positive breast cancer cases with known clinical outcome were used to search for potential genes signifying upregulated NFκB and AP-1 transcriptional activity in association with tamoxifen resistance. The association of these genes with patient outcome was further evaluated using node-negative ER-positive breast cancer cases identified from three other published data sets (Rotterdam, n = 209; Amsterdam, n = 68; Basel, n = 108, each having different patient age and adjuvant tamoxifen treatment characteristics. Results Doses of parthenolide and bortezomib capable of sensitizing the two endocrine resistant breast cancer models to tamoxifen were capable of suppressing NFκB and AP-1 regulated gene expression in combination with tamoxifen and also increased ER recruitment of the transcriptional co-repressor, NCoR. Transcript profiles from the UCSF breast cancer cases revealed three NFκB and AP-1 upregulated genes – cyclin D1, uPA and VEGF – capable of dichotomizing node-negative ER-positive cases into early and late relapsing subsets despite adjuvant tamoxfien therapy and most prognostic for younger age cases. Across the four independent sets of node-negative ER-positive breast cancer cases

  6. Enhancement of wear and ballistic resistance of armour grade AA7075 aluminium alloy using friction stir processing

    Directory of Open Access Journals (Sweden)

    I. Sudhakar

    2015-03-01

    Full Text Available Industrial applications of aluminium and its alloys are restricted because of their poor tribological properties. Thermal spraying, laser surfacing, electron beam welding are the most widely used techniques to alter the surface morphology of base metal. Preliminary studies reveal that the coating and layering of aluminium alloys with ceramic particles enhance the ballistic resistance. Furthermore, among aluminium alloys, 7075 aluminium alloy exhibits high strength which can be compared to that of steels and has profound applications in the designing of lightweight fortification structures and integrated protection systems. Having limitations such as poor bond integrity, formation of detrimental phases and interfacial reaction between reinforcement and substrate using fusion route to deposit hard particles paves the way to adopt friction stir processing for fabricating surface composites using different sizes of boron carbide particles as reinforcement on armour grade 7075 aluminium alloy as matrix in the present investigation. Wear and ballistic tests were carried out to assess the performance of friction stir processed AA7075 alloy. Significant improvement in wear resistance of friction stir processed surface composites is attributed to the change in wear mechanism from abrasion to adhesion. It has also been observed that the surface metal matrix composites have shown better ballistic resistance compared to the substrate AA7075 alloy. Addition of solid lubricant MoS2 has reduced the depth of penetration of the projectile to half that of base metal AA7075 alloy. For the first time, the friction stir processing technique was successfully used to improve the wear and ballistic resistances of armour grade high strength AA7075 alloy.

  7. Enhancement of wear and ballistic resistance of armour grade AA7075 aluminium alloy using friction stir processing

    Institute of Scientific and Technical Information of China (English)

    I. SUDHAKAR; V. MADHU; G. MADHUSUDHAN REDDY; K. SRINIVASA RAO

    2015-01-01

    Industrial applications of aluminium and its alloys are restricted because of their poor tribological properties. Thermal spraying, laser surfacing, electron beam welding are the most widely used techniques to alter the surface morphology of base metal. Preliminary studies reveal that the coating and layering of aluminium alloys with ceramic particles enhance the ballistic resistance. Furthermore, among aluminium alloys, 7075 aluminium alloy exhibits high strength which can be compared to that of steels and has profound applications in the designing of lightweight fortification structures and integrated protection systems. Having limitations such as poor bond integrity, formation of detrimental phases and interfacial reaction between reinforcement and substrate using fusion route to deposit hard particles paves the way to adopt friction stir processing for fabricating surface composites using different sizes of boron carbide particles as reinforcement on armour grade 7075 aluminium alloy as matrix in the present investigation. Wear and ballistic tests were carried out to assess the performance of friction stir processed AA7075 alloy. Significant improvement in wear resistance of friction stir processed surface composites is attributed to the change in wear mechanism from abrasion to adhesion. It has also been observed that the surface metal matrix composites have shown better ballistic resistance compared to the substrate AA7075 alloy. Addition of solid lubricant MoS2 has reduced the depth of penetration of the projectile to half that of base metal AA7075 alloy. For the first time, the friction stir processing technique was successfully used to improve the wear and ballistic resistances of armour grade high strength AA7075 alloy.

  8. Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis.

    Science.gov (United States)

    Machado, Diana; Pires, David; Perdigão, João; Couto, Isabel; Portugal, Isabel; Martins, Marta; Amaral, Leonard; Anes, Elsa; Viveiros, Miguel

    2016-01-01

    resistance pattern. This work highlights the potential value ion channel blockers as adjuvants of tuberculosis chemotherapy, in particular for the development of new therapeutic strategies, with strong potential for treatment shortening against drug susceptible and resistant forms of tuberculosis. Medicinal chemistry studies are now needed to improve the properties of these compounds, increasing their M. tuberculosis efflux-inhibition and killing-enhancement activity and reduce their toxicity for humans, therefore optimizing their potential for clinical usage. PMID:26919135

  9. Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Diana Machado

    irrespective of their resistance pattern. This work highlights the potential value ion channel blockers as adjuvants of tuberculosis chemotherapy, in particular for the development of new therapeutic strategies, with strong potential for treatment shortening against drug susceptible and resistant forms of tuberculosis. Medicinal chemistry studies are now needed to improve the properties of these compounds, increasing their M. tuberculosis efflux-inhibition and killing-enhancement activity and reduce their toxicity for humans, therefore optimizing their potential for clinical usage.

  10. β2-agonist therapy in lung disease.

    Science.gov (United States)

    Cazzola, Mario; Page, Clive P; Rogliani, Paola; Matera, M Gabriella

    2013-04-01

    β2-Agonists are effective bronchodilators due primarily to their ability to relax airway smooth muscle (ASM). They exert their effects via their binding to the active site of β2-adrenoceptors on ASM, which triggers a signaling cascade that results in a number of events, all of which contribute to relaxation of ASM. There are some differences between β2-agonists. Traditional inhaled short-acting β2-agonists albuterol, fenoterol, and terbutaline provide rapid as-needed symptom relief and short-term prophylactic protection against bronchoconstriction induced by exercise or other stimuli. The twice-daily β2-agonists formoterol and salmeterol represent important advances. Their effective bronchodilating properties and long-term improvement in lung function offer considerable clinical benefits to patients. More recently, a newer β2-agonist (indacaterol) with a longer pharmacodynamic half-life has been discovered, with the hopes of achieving once-daily dosing. In general, β2-agonists have an acceptable safety profile, although there is still controversy as to whether long-acting β2-agonists may increase the risk of asthma mortality. In any case, they can induce adverse effects, such as increased heart rate, palpitations, transient decrease in PaO2, and tremor. Desensitization of β2-adrenoceptors that occurs during the first few days of regular use of β2-agonist treatment may account for the commonly observed resolution of the majority of these adverse events after the first few doses. Nevertheless, it can also induce tolerance to bronchoprotective effects of β2-agonists and has the potential to reduce bronchodilator sensitivity to them. Some novel once-daily β2-agonists (olodaterol, vilanterol, abediterol) are under development, mainly in combination with an inhaled corticosteroid or a long-acting antimuscarinic agent. PMID:23348973

  11. Laser alloyed Al-W coatings on aluminum for enhanced corrosion resistance

    Energy Technology Data Exchange (ETDEWEB)

    Rajamure, Ravi Shanker; Vora, Hitesh D.; Srinivasan, S.G.; Dahotre, Narendra B., E-mail: Narendra.Dahotre@unt.edu

    2015-02-15

    Highlights: • Al{sub 4}W intermetallic phase was formed after laser surface alloying. • Potential–time measurements show the stable behavior after laser surface alloying. • Cyclic polarization indicates increase in corrosion resistance after laser surface alloying. - Abstract: A tungsten precursor deposit was spray coated on aluminum 1100 substrate and was subsequently surface alloyed using a continuous wave diode-pumped ytterbium laser at varying laser energy densities. For the laser energy input of 21–32 J/mm{sup 2} the melt depth ranged between 135 and 150 μm. Scanning electron microscopy observations indicated the formation of uniform and continuously dense laser alloyed coatings with sound interface between the modified surface and substrate along with an equi-axed grain structure with second phase precipitates in the intergranular region. X-ray diffraction analysis confirmed that laser processing has resulted in the formation of Al{sub 4}W, as the major phase with retention of W in Al within the alloyed region. The corrosion resistance of laser alloyed coatings was evaluated in near natural chloride solution using ac and dc electrochemical techniques. After laser processing potential–time measurements has indicated the relatively stable and high potential values over the longer exposure times. Cyclic polarization results showed the reduction in the corrosion current density by a factor of 8, compared to untreated Al 1100. Besides, the electrochemical impedance spectroscopy confirmed the increase in the total resistance (47–70 kΩ cm{sup 2}) with the increase in the laser energy density.

  12. Overexpression of a defensin enhances resistance to a fruit-specific anthracnose fungus in pepper.

    Directory of Open Access Journals (Sweden)

    Hyo-Hyoun Seo

    Full Text Available Functional characterization of a defensin, J1-1, was conducted to evaluate its biotechnological potentiality in transgenic pepper plants against the causal agent of anthracnose disease, Colletotrichum gloeosporioides. To determine antifungal activity, J1-1 recombinant protein was generated and tested for the activity against C. gloeosporioides, resulting in 50% inhibition of fungal growth at a protein concentration of 0.1 mg·mL-1. To develop transgenic pepper plants resistant to anthracnose disease, J1-1 cDNA under the control of 35S promoter was introduced into pepper via Agrobacterium-mediated genetic transformation method. Southern and Northern blot analyses confirmed that a single copy of the transgene in selected transgenic plants was normally expressed and also stably transmitted to subsequent generations. The insertion of T-DNA was further analyzed in three independent homozygous lines using inverse PCR, and confirmed the integration of transgene in non-coding region of genomic DNA. Immunoblot results showed that the level of J1-1 proteins, which was not normally accumulated in unripe fruits, accumulated high in transgenic plants but appeared to differ among transgenic lines. Moreover, the expression of jasmonic acid-biosynthetic genes and pathogenesis-related genes were up-regulated in the transgenic lines, which is co-related with the resistance of J1-1 transgenic plants to anthracnose disease. Consequently, the constitutive expression of J1-1 in transgenic pepper plants provided strong resistance to the anthracnose fungus that was associated with highly reduced lesion formation and fungal colonization. These results implied the significance of the antifungal protein, J1-1, as a useful agronomic trait to control fungal disease.

  13. [The enhancement of human thermal resistance by the single use of bemitil and fenibut].

    Science.gov (United States)

    Makarov, V I; Tiurenkov, I N; Klauchek, S V; Nalivaĭko, I Iu; Antipova, A Iu

    1997-01-01

    The authors studied the effect of single intake of bymetil (0.5 g) and phenibut (0.25 g) on the thermal state, gas-energy exchange, blood oxygenation, working capacity, and the subjective status of man in intensive physical exertion in isolating means of individual protection. The drugs under study increased thermal resistance, promoted normal supply of the organism with oxygen, and provided the maintenance of man's high working capacity under conditions which lead to his overheating. The best protective effects was produced in this case with phenibut. PMID:9162292

  14. Negative Regulation-Resistant p53 Variant Enhances Oncolytic Adenoviral Gene Therapy

    OpenAIRE

    Koo, Taeyoung; Choi, Il-Kyu; Kim, Minjung; Lee, Jung-Sun; Oh, Eonju; Kim, Jungho; Yun, Chae-Ok

    2012-01-01

    Intact p53 function is essential for responsiveness to cancer therapy. However, p53 activity is attenuated by the proto-oncoprotein Mdm2, the adenovirus protein E1B 55kD, and the p53 C-terminal domain. To confer resistance to Mdm2, E1B 55kD, and C-terminal negative regulation, we generated a p53 variant (p53VPΔ30) by deleting the N-terminal and C-terminal regions of wild-type p53 and inserting the transcriptional activation domain of herpes simplex virus VP16 protein. The oncolytic adenovirus...

  15. Overexpression of TiERF1 enhances resistance to sharp eyespot in transgenic wheat

    OpenAIRE

    Chen, Liang; Zhang, Zengyan; Liang, Hongxia; Liu, Hongxia; Du, Lipu; Xu, Huijun; Xin, ZhiYong

    2008-01-01

    Wheat sharp eyespot, primarily caused by a soil-borne fungus Rhizoctonia cerealis, has become one of the most serious diseases of wheat in China. In this study, an ethylene response factor (ERF) gene from a wheat relative Thinopyrum intermedium, TiERF1, was characterized further, transgenic wheat lines expressing TiERF1 were developed, and the resistance of the transgenic wheat lines against R. cerealis was investigated. Southern blotting analysis indicated that at least two copies of the TiE...

  16. Phosphatidic acid enhances mTOR signaling and resistance exercise induced hypertrophy

    OpenAIRE

    Joy, Jordan M; Gundermann, David M.; Ryan P. Lowery; Jäger, Ralf; McCleary, Sean A; Purpura, Martin; Roberts, Michael D.; Wilson, Stephanie MC; Hornberger, Troy A.; Wilson, Jacob M.

    2014-01-01

    Introduction The lipid messenger phosphatidic acid (PA) plays a critical role in the stimulation of mTOR signaling. However, the mechanism by which PA stimulates mTOR is currently unknown. Therefore, the purpose of this study was to compare the effects of various PA precursors and phospholipids on their ability to stimulate mTOR signaling and its ability to augment resistance training-induced changes in body composition and performance. Methods In phase one, C2C12 myoblasts cells were stimula...

  17. Polyamide desalination membrane characterization and surface modification to enhance fouling resistance.

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Mukul M. (Univeristy of Texas at Austin, Austin, TX); Freeman, Benny D. (Univeristy of Texas at Austin, Austin, TX); Van Wagner, Elizabeth M. (Univeristy of Texas at Austin, Austin, TX); Hickner, Michael A. (Pennsylvania State University, University Park, PA); Altman, Susan Jeanne

    2010-08-01

    The market for polyamide desalination membranes is expected to continue to grow during the coming decades. Purification of alternative water sources will also be necessary to meet growing water demands. Purification of produced water, a byproduct of oil and gas production, is of interest due to its dual potential to provide water for beneficial use as well as to reduce wastewater disposal costs. However, current polyamide membranes are prone to fouling, which decreases water flux and shortens membrane lifetime. This research explored surface modification using poly(ethylene glycol) diglycidyl ether (PEGDE) to improve the fouling resistance of commercial polyamide membranes. Characterization of commercial polyamide membrane performance was a necessary first step before undertaking surface modification studies. Membrane performance was found to be sensitive to crossflow testing conditions. Concentration polarization and feed pH strongly influenced NaCl rejection, and the use of continuous feed filtration led to higher water flux and lower NaCl rejection than was observed for similar tests performed using unfiltered feed. Two commercial polyamide membranes, including one reverse osmosis and one nanofiltration membrane, were modified by grafting PEGDE to their surfaces. Two different PEG molecular weights (200 and 1000) and treatment concentrations (1% (w/w) and 15% (w/w)) were studied. Water flux decreased and NaCl rejection increased with PEGDE graft density ({micro}g/cm{sup 2}), although the largest changes were observed for low PEGDE graft densities. Surface properties including hydrophilicity, roughness and charge were minimally affected by surface modification. The fouling resistance of modified and unmodified membranes was compared in crossflow filtration studies using model foulant solutions consisting of either a charged surfactant or an oil in water emulsion containing n-decane and a charged surfactant. Several PEGDE-modified membranes demonstrated improved

  18. Immunotherapy with Agonistic Anti-CD137: Two Sides of a Coin

    Institute of Scientific and Technical Information of China (English)

    YonglianSun; JonathanH.Chen; YangxinFu

    2004-01-01

    CD137 (4-1BB), a member of the TNF receptor superfamily, is an inducible T cell costimulatory receptor primarily expressed on activated CD4+ and CD8+ T cells. Agonistic monoclonal antibodies (mAbs) against CD137 greatly enhance T cell-mediated immune responses against many types of tumors and viruses. Surprisingly, these agonists also showed therapeutic effects in several autoimmune diseases. These findings suggest that in different disease environments, CD137 engagement with agonist mAb in vivo can diametrically modulate immune response outcomes. Therefore, CD137 agonists represent a promising immunotherapeutic approach to a wide array of disparate immune disorders. However, CD137's potency in modulating immune response necessitates caution when targeting CD137 clinically. Cellular & Molecular Immunology. 2004;1(1):31-36.

  19. Immunotherapy with Agonistic Anti-CD137: Two Sides of a Coin

    Institute of Scientific and Technical Information of China (English)

    Yonglian Sun; Jonathan H.Chen; Yangxin Fu

    2004-01-01

    CD137 (4-1BB), a member of the TNF receptor superfamily, is an inducible T cell costimulatory receptor primarily expressed on activated CD4+ and CD8+ T cells. Agonistic monoclonal antibodies (mAbs) against CD137 greatly enhance T cell-mediated immune responses against many types of tumors and viruses. Surprisingly, these agonists also showed therapeutic effects in several autoimmune diseases. These findings suggest that in different disease environments, CD137 engagement with agonist mAb in vivo can diametrically modulate immune response outcomes. Therefore, CD137 agonists represent a promising immunotherapeutic approach to a wide array of disparate immune disorders. However, CD137's potency in modulating immune response necessitates caution when targeting CD137 clinically. Cellular & Molecular Immunology. 2004;1(1):31-36.

  20. Integrin beta 1 enhances the epithelial-mesenchymal transition in association with gefitinib resistance of non-small cell lung cancer.

    Science.gov (United States)

    Ju, Lixia; Zhou, Caicun

    2013-01-01

    We have previously shown that integrinβ1 associates with gefitinib resistance. As epithelial-mesenchymal transition (EMT) also induces gefitinib resistance in vitro, we wished to determine the relation of them in gefitinib resistance. In this study, we show that integrinβ1 induced epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in xenograft tumors and gefitinib-resistant NSCLC tumors acquired EMT phenotype. Furthermore, inhibition of integrinβ1 reverses EMT, meanwhile overexpression and activation of integrinβ1 aggravates EMT. Lastly, we further identified that integrinβ1 enhanced EMT via FAK-AKT signaling pathway. These findings highlight a novel relation of integrinβ1 and EMT in EGFR TKI resistant NSCLC. PMID:24440972

  1. A new layered nano hybrid perovskite film with enhanced resistance to moisture-induced degradation

    Science.gov (United States)

    Jiang, Wenlong; Ying, Jifei; Zhou, Wei; Shen, Kongchao; Liu, Xing; Gao, Xingyu; Guo, Fuqiang; Gao, Yanmin; Yang, Tieying

    2016-08-01

    In this paper, a new layered hybrid perovskite film ((EDA)(MA)2[Pb3I10]) was synthesized through one-step method. Ethylenediamine (EDA) cation was introduced into the perovskite lattice to synthesize a layered structure with improved resistance to degradation by humidity. The effects of humidity and time on crystal structure, composition, morphology and absorption spectra of (EDA)(MA)2[Pb3I10] were analyzed by in situ grazing incidence X-ray diffraction (GIXRD), scanning electron microscope (SEM), and UV-Vis spectroscope. The results reveal that a (EDA)(MA)2[Pb3I10] film is more moisture resistant than a CH3NH3PbI3 film which is widely used in the perovskite solar cell now. UV-Vis spectroscopy result also shows that the layered structure film is a suitable solar absorber with a bandgap (1.67 eV), which is close to the optimum value for solar photoelectric conversion. Compared to CH3NH3PbI3, the low-cost perovskite structure offers greater tunability on a molecular level for further material optimization and possibility for widely used in the future.

  2. Laser alloyed Al-W coatings on aluminum for enhanced corrosion resistance

    Science.gov (United States)

    Rajamure, Ravi Shanker; Vora, Hitesh D.; Srinivasan, S. G.; Dahotre, Narendra B.

    2015-02-01

    A tungsten precursor deposit was spray coated on aluminum 1100 substrate and was subsequently surface alloyed using a continuous wave diode-pumped ytterbium laser at varying laser energy densities. For the laser energy input of 21-32 J/mm2 the melt depth ranged between 135 and 150 μm. Scanning electron microscopy observations indicated the formation of uniform and continuously dense laser alloyed coatings with sound interface between the modified surface and substrate along with an equi-axed grain structure with second phase precipitates in the intergranular region. X-ray diffraction analysis confirmed that laser processing has resulted in the formation of Al4W, as the major phase with retention of W in Al within the alloyed region. The corrosion resistance of laser alloyed coatings was evaluated in near natural chloride solution using ac and dc electrochemical techniques. After laser processing potential-time measurements has indicated the relatively stable and high potential values over the longer exposure times. Cyclic polarization results showed the reduction in the corrosion current density by a factor of 8, compared to untreated Al 1100. Besides, the electrochemical impedance spectroscopy confirmed the increase in the total resistance (47-70 kΩ cm2) with the increase in the laser energy density.

  3. Hierarchically ordered self-lubricating superhydrophobic anodized aluminum surfaces with enhanced corrosion resistance.

    Science.gov (United States)

    Vengatesh, Panneerselvam; Kulandainathan, Manickam Anbu

    2015-01-28

    Herein, we report a facile method for the fabrication of self-lubricating superhydrophobic hierarchical anodic aluminum oxide (AAO) surfaces with improved corrosion protection, which is greatly anticipated to have a high impact in catalysis, aerospace, and the shipping industries. This method involves chemical grafting of as-formed AAO using low surface free energy molecules like long chain saturated fatty acids, perfluorinated fatty acid (perfluorooctadecanoic acid, PFODA), and perfluorosulfonicacid-polytetrafluoroethylene copolymer. The pre and post treatment processes in the anodization of aluminum (Al) play a vital role in the grafting of fatty acids. Wettability and surface free energy were analyzed using a contact angle meter and achieved 161.5° for PFODA grafted anodized aluminum (PFODA-Al). This study was also aimed at evaluating the surface for corrosion resistance by Tafel polarization and self-lubricating properties by tribological studies using a pin-on-disc tribometer. The collective results showed that chemically grafted AAO nanostructures exhibit high corrosion resistance toward seawater and low frictional coefficient due to low surface energy and self-lubricating property of fatty acids covalently linked to anodized Al surfaces. PMID:25529561

  4. Monascus-fermented dioscorea enhances oxidative stress resistance via DAF-16/FOXO in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Yeu-Ching Shi

    Full Text Available BACKGROUND: Monascus-fermented products are mentioned in an ancient Chinese pharmacopoeia of medicinal food and herbs. Monascus-fermented products offer valuable therapeutic benefits and have been extensively used in East Asia for several centuries. Several biological activities of Monascus-fermented products were recently described, and the extract of Monascus-fermented products showed strong antioxidant activity of scavenging DPPH radicals. To evaluate whether Monascus-fermented dioscorea products have potential as nutritional supplements, Monascus-fermented dioscorea's modulation of oxidative-stress resistance and associated regulatory mechanisms in Caenorhabditis elegans were investigated. PRINCIPAL FINDINGS: We examined oxidative stress resistance of the ethanol extract of red mold dioscorea (RMDE in C. elegans, and found that RMDE-treated wild-type C. elegans showed an increased survival during juglone-induced oxidative stress compared to untreated controls, whereas the antioxidant phenotype was absent from a daf-16 mutant. In addition, the RMDE reduced the level of intracellular reactive oxygen species in C. elegans. Finally, the RMDE affected the subcellular distribution of the FOXO transcription factor, DAF-16, in C. elegans and induced the expression of the sod-3 antioxidative gene. CONCLUSIONS: These findings suggest that the RMDE acts as an antioxidative stress agent and thus may have potential as a nutritional supplement. Further studies in C. elegans suggest that the antioxidant effect of RMDE is mediated via regulation of the DAF-16/FOXO-dependent pathway.

  5. Enhanced biocorrosion resistance and biocompatibility of degradable Mg-Nd-Zn-Zr alloy by brushite coating.

    Science.gov (United States)

    Niu, Jialin; Yuan, Guangyin; Liao, Yi; Mao, Lin; Zhang, Jian; Wang, Yongping; Huang, Feng; Jiang, Yao; He, Yaohua; Ding, Wenjiang

    2013-12-01

    To further improve the corrosion resistance and biocompatibility of Mg-Nd-Zn-Zr alloy (JDBM), a biodegradable calcium phosphate coating (Ca-P coating) with high bonding strength was developed using a novel chemical deposition method. The main composition of the Ca-P coating was brushite (CaHPO4·2H2O). The bonding strength between the coating and the JDBM substrate was measured to be over 10 MPa, and the thickness of the coating layer was about 10-30 μm. The in vitro corrosion tests indicated that the Ca-P treatment improved the corrosion resistance of JDBM alloy in Hank's solution. Ca-P treatment significantly reduced the hemolysis rate of JDBM alloy from 48% to 0.68%, and induced no toxicity to MC3T3-E1 cells. The in vivo implantation experiment in New Zealand's rabbit tibia showed that the degradation rate was reduced obviously by the Ca-P treatment and less gas was produced from Ca-P treated JDBM bone plates and screws in early stage of the implantation, and at least 10weeks degradation time can be prolonged by the present coating techniques. Both Ca-P treated and untreated JDBM Mg alloy induced bone growth. The primary results indicate that the present Ca-P treatment is a promising technique for the degradable Mg-based biomaterials for orthopedic applications.

  6. Enhanced Strain-Dependent Electrical Resistance of Polyurethane Composites with Embedded Oxidized Multiwalled Carbon Nanotube Networks

    Directory of Open Access Journals (Sweden)

    R. Benlikaya

    2013-01-01

    Full Text Available The effect of different chemical oxidation of multiwalled carbon nanotubes with H2O2, HNO3, and KMnO4 on the change of electrical resistance of polyurethane composites with embedded oxidized nanotube networks subjected to elongation and bending has been studied. The testing has shown about twenty-fold increase in the electrical resistance for the composite prepared from KMnO4 oxidized nanotubes in comparison to the composites prepared from the pristine and other oxidized nanotubes. The evaluated sensitivity of KMnO4 treated composite in terms of the gauge factor increases with strain to nearly 175 at the strain 11%. This is a substantial increase, which ranks the composite prepared from KMnO4 oxidized nanotubes among materials as strain gauges with the highest electromechanical sensitivity. The observed differences in electromechanical properties of the composites are discussed on basis of their structure which is examined by the measurements of Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and scanning electron microscope. The possible practical use of the composites is demonstrated by monitoring of elbow joint flexion during two different physical exercises.

  7. Changes of renal blood flow after ESWL: Assessment by ASL MR imaging, contrast enhanced MR imaging, and renal resistive index

    Energy Technology Data Exchange (ETDEWEB)

    Abd Ellah, Mohamed, E-mail: dr_m_hamdy2006@hotmail.co [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria); Kremser, Christian, E-mail: christian.kremser@i-med.ac.a [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria); Pallwein, Leo, E-mail: leo.pallwein-prettner@uki.a [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria); Aigner, Friedrich, E-mail: friedrich.Aigner@uki.a [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria); Schocke, Michael, E-mail: michael.schocke@i-med.ac.a [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria); Peschel, Reinhard, E-mail: reinhard.peschel@uki.a [Innsbruck Medical University, Urology Dept., Anich St. 35, 6020 Innsbruck (Austria); Pedross, Florian, E-mail: florian.pedross@i-med.ac.a [Innsbruck Medical University, Medical Statistics Dept., Anich St. 35, 6020 Innsbruck (Austria); Pinggera, Germar-Michael, E-mail: germar.pinggera@uki.a [Innsbruck Medical University, Urology Dept., Anich St. 35, 6020 Innsbruck (Austria); Wolf, Christian, E-mail: christian.wolf@bkh-reutte.a [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria); Alsharkawy, Mostafa A.M., E-mail: drmostafamri@yahoo.co [Assiut University, Radiology Dept., Assiut (Egypt); Jaschke, Werner, E-mail: werner.jaschke@i-med.ac.a [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria); Frauscher, Ferdinand, E-mail: ferdinand.frauscher@uki.a [Innsbruck Medical University, Radiology Dept., Anich St. 35, 6020 Innsbruck (Austria)

    2010-10-15

    The annual incidence of stone formation is increased in the industrialised world. Extracorporeal shockwave lithotripsy is a non-invasive effective treatment of upper urinary tract stones. This study is aimed to evaluate changes of renal blood flow in patients undergoing extracorporeal shock wave lithotripsy (ESWL) by arterial spin labeling (ASL) MR imaging, contrast enhanced dynamic MR imaging, and renal resistive index (RI). Thirteen patients with nephrolithiasis were examined using MR imaging and Doppler ultrasound 12 h before and 12 h after ESWL. ASL sequence was done for both kidneys and followed by contrast enhanced MR imaging. In addition RI Doppler ultrasound measurements were performed. A significant increase in RI (p < 0.001) was found in both treated and untreated kidneys. ASL MR imaging also showed significant changes in both kidneys (p < 0.001). Contrast enhanced dynamic MR imaging did not show significant changes in the kidneys. ESWL causes changes in RI and ASL MR imaging, which seem to reflect changes in renal blood flow.

  8. Changes of renal blood flow after ESWL: Assessment by ASL MR imaging, contrast enhanced MR imaging, and renal resistive index

    International Nuclear Information System (INIS)

    The annual incidence of stone formation is increased in the industrialised world. Extracorporeal shockwave lithotripsy is a non-invasive effective treatment of upper urinary tract stones. This study is aimed to evaluate changes of renal blood flow in patients undergoing extracorporeal shock wave lithotripsy (ESWL) by arterial spin labeling (ASL) MR imaging, contrast enhanced dynamic MR imaging, and renal resistive index (RI). Thirteen patients with nephrolithiasis were examined using MR imaging and Doppler ultrasound 12 h before and 12 h after ESWL. ASL sequence was done for both kidneys and followed by contrast enhanced MR imaging. In addition RI Doppler ultrasound measurements were performed. A significant increase in RI (p < 0.001) was found in both treated and untreated kidneys. ASL MR imaging also showed significant changes in both kidneys (p < 0.001). Contrast enhanced dynamic MR imaging did not show significant changes in the kidneys. ESWL causes changes in RI and ASL MR imaging, which seem to reflect changes in renal blood flow.

  9. Initial results from investigations to enhance the performance of high temperature irradiation-resistant thermocouples

    International Nuclear Information System (INIS)

    Several options have been identified that could further enhance the lifetime and reliability of INL-developed thermocouples for in-pile testing, allowing their use in higher temperature applications (up to at least 1700degC (3092degF)). A joint University of Idaho (UI) and INL University Nuclear Energy Research Initiative (UNERI) is underway to investigate these options and, ultimately, provide recommendations for an enhanced thermocouple design. This paper presents preliminary results from this UI/INL effort. Results are reported from tests completed to evaluate the ductility, temperature resolution, transient response, and stability of thermocouples made from non-commercially available alloys of molybdenum and niobium. In addition, this paper reports preliminary insights gained by comparing the performance of thermocouples fabricated with various diameters. (author)

  10. IS ENHANCED-ECCENTRIC RESISTANCE TRAINING SUPERIOR TO TRADITIONAL TRAINING FOR INCREASING ELBOW FLEXOR STRENGTH?

    Directory of Open Access Journals (Sweden)

    Thomas W. Kaminski

    2003-06-01

    Full Text Available Protocols for strengthening muscle are important for fitness, rehabilitation, and the prevention of myotendinous injuries. In trained individuals, the optimal method of increasing strength remains unclear. The purpose of this study was to compare the effects of a traditional method of strengthening with a method that allowed for enhanced-eccentric training, on changes in elbow flexor strength in trained subjects. Thirty-nine (8 male, 31 female trained subjects with normal elbow function participated in this study. Subjects were rank-ordered according to isometric force production and randomly assigned to one of three training groups: control (CONT, traditional concentric/eccentric (TRAD, and concentric/enhanced-eccentric (NEG. The training groups completed 24 training sessions. An evaluator blinded to training group performed all testing. Mixed model ANOVA techniques were used to determine if differences existed in concentric one repetition maximum strength, and isometric force production among groups. Changes in peak and average isokinetic force production were also compared. Type 1 error was maintained at 5%. While both groups improved concentric one repetition maximum (NEG = 15.5%, TRAD = 13.8% neither training group statistically differed from changes demonstrated by the CONT group. Nor did either training group show significant improvements in isometric or isokinetic force production over the CONT group. These results do not support the superiority of enhanced-eccentric training for increasing force production in trained subjects.

  11. Heat enhancement of radiation resistivity of evaporated CsI, KI and KBr photocathodes

    CERN Document Server

    Tremsin, A S

    2000-01-01

    The photoemissive stability of as-deposited and heat-treated CsI, KI and KBr evaporated thin films under UV radiation is examined in this paper. After the deposition, some photocathodes were annealed for several hours at 90 deg. C in vacuum and their performance was then compared to the performance of non-heated samples. We observed that the post-evaporation thermal treatment not only increases the photoyield of CsI and KI photocathodes in the spectral range of 115-190 nm, but also reduces CsI, KI and KBr photocurrent degradation that occurs after UV irradiation. KBr evaporated layers appeared to be more radiation-resistant than CsI and KI layers. Post-deposition heat treatment did not result in any significant variation of KBr UV sensitivity.

  12. The enhanced callose deposition in barley with ml-o powdery mildew resistance genes

    DEFF Research Database (Denmark)

    Skou, Jens-Peder

    1985-01-01

    Carborundum treatment of barley leaves induced a callose deposition which was detected as diffuse blotches in the epidermal cells of susceptible barleys and as deeply stained tracks along the scratches in barleys with the ml-o powdery mildew resistance gene. Subsequent inoculation with powdery...... mildew resulted in appositions that enlarged inversely to their size in the respective varieties when inoculated without carborundum treatment. Aphids sucking the leaves resulted in rows of callose containing spots along the anticlinal cell walls. The spots were larger in the ml-o mutant than...... in the mother variety. Callose was deposited in connection with the pleiotropic necrotic spotting in barleys with the ml-o gene. Modification of the necrotic spotting by crossing the ml-o gene into other gene backgrounds did not result in any change in the size of appositions upon inoculation with powdery...

  13. Caspase-resistant VirD2 protein provides enhanced gene delivery and expression in plants.

    Science.gov (United States)

    Reavy, Brian; Bagirova, Svetlana; Chichkova, Nina V; Fedoseeva, Svetlana V; Kim, Sang Hyon; Vartapetian, Andrey B; Taliansky, Michael E

    2007-08-01

    Agrobacterium tumefaciens VirD2 protein is one of the key elements of Agrobacterium-mediated plant transformation, a process of transfer of T-DNA sequence from the Agrobacterium tumour inducing plasmid into the nucleus of infected plant cells and its integration into the host genome. The VirD2 protein has been shown to be a substrate for a plant caspase-like protease activity (PCLP) in tobacco. We demonstrate here that mutagenesis of the VirD2 protein to prevent cleavage by PCLP increases the efficiency of reporter gene transfer and expression. These results indicate that PCLP cleavage of the Agrobacterium VirD2 protein acts to limit the effectiveness of T-DNA transfer and is a novel resistance mechanism that plants utilise to combat Agrobacterium infection. PMID:17370074

  14. Enhanced resistance of Portunus trituberculatus to Vibrio alginolyticus by selective breeding

    Science.gov (United States)

    Mu, Changkao; Liu, Shuai; Song, Weiwei; Li, Ronghua; Wang, Chunlin

    2012-07-01

    We established a line (screened) of Portunus trituberculatus by selectively breeding individuals that survived from challenge with Vibrio alginolyticus, and compared the response of screened and unscreened (control) P. trituberculatus challenged with V. alginolyticus. We measured superoxide dismutase, catalase, acid phosphatase, alkaline phosphatase, and peroxidase activity and the content of hemocyanin in the plasma and phenoloxidase activity in serum. The cumulative survival rate after 24-h challenge with V. alginolyticus was significantly higher in the screened crabs than in the unscreened crabs ( P <0.05). T-SOD and PO activity were significantly lower in the screened stock than in the unscreened stock ( P <0.05). POD, CAT, and ACP activity and hemocyanin content were significantly higher in the screened stock than in the unscreened stock. Our results suggest that the screened stock was more resistant to infection. Furthermore, the indices we measured may be used to evaluate the health state of P. trituberculatus.

  15. Enhanced satellite cell proliferation with resistance training in elderly men and women

    DEFF Research Database (Denmark)

    Mackey, Abigail; Esmarck, B; Kadi, F;

    2007-01-01

    In addition to the well-documented loss of muscle mass and strength associated with aging, there is evidence for the attenuating effects of aging on the number of satellite cells in human skeletal muscle. The aim of this study was to investigate the response of satellite cells in elderly men and...... women to 12 weeks of resistance training. Biopsies were collected from the m. vastus lateralis of 13 healthy elderly men and 16 healthy elderly women (mean age 76+/-SD 3 years) before and after the training period. Satellite cells were visualized by immunohistochemical staining of muscle cross......-sections with a monoclonal antibody against neural cell adhesion molecule (NCAM) and counterstaining with Mayer's hematoxylin. Compared with the pre-training values, there was a significant increase (P<0.05) in the number of NCAM-positively stained cells per fiber post-training in males (from 0.11+/-0.03 to 0...

  16. Two-phase mixed media dielectric with macro dielectric beads for enhancing resistivity and breakdown strength

    Science.gov (United States)

    Falabella, Steven; Meyer, Glenn A; Tang, Vincent; Guethlein, Gary

    2014-06-10

    A two-phase mixed media insulator having a dielectric fluid filling the interstices between macro-sized dielectric beads packed into a confined volume, so that the packed dielectric beads inhibit electro-hydrodynamically driven current flows of the dielectric liquid and thereby increase the resistivity and breakdown strength of the two-phase insulator over the dielectric liquid alone. In addition, an electrical apparatus incorporates the two-phase mixed media insulator to insulate between electrical components of different electrical potentials. And a method of electrically insulating between electrical components of different electrical potentials fills a confined volume between the electrical components with the two-phase dielectric composite, so that the macro dielectric beads are packed in the confined volume and interstices formed between the macro dielectric beads are filled with the dielectric liquid.

  17. Designing Multiagent Dental Materials for Enhanced Resistance to Biofilm Damage at the Bonded Interface.

    Science.gov (United States)

    Melo, Mary Anne; Orrego, Santiago; Weir, Michael D; Xu, Huakun H K; Arola, Dwayne D

    2016-05-11

    The oral environment is considered to be an asperous environment for restored tooth structure. Recurrent dental caries is a common cause of failure of tooth-colored restorations. Bacterial acids, microleakage, and cyclic stresses can lead to deterioration of the polymeric resin-tooth bonded interface. Research on the incorporation of cutting-edge anticaries agents for the design of new, long-lasting, bioactive resin-based dental materials is demanding and provoking work. Released antibacterial agents such as silver nanoparticles (NAg), nonreleased antibacterial macromolecules (DMAHDM, dimethylaminohexadecyl methacrylate), and released acid neutralizer amorphous calcium phosphate nanoparticles (NACP) have shown potential as individual and dual anticaries approaches. In this study, these agents were synthesized, and a prospective combination was incorporated into all the dental materials required to perform a composite restoration: dental primer, adhesive, and composite. We focused on combining different dental materials loaded with multiagents to improve the durability of the complex dental bonding interface. A combined effect of bacterial acid attack and fatigue on the bonding interface simulated the harsh oral environment. Human saliva-derived oral biofilm was grown on each sample prior to the cyclic loading. The oral biofilm viability during the fatigue performance was monitored by the live-dead assay. Damage of the samples that developed during the test was quantified from the fatigue life distributions. Results indicate that the resultant multiagent dental composite materials were able to reduce the acidic impact of the oral biofilm, thereby improving the strength and resistance to fatigue failure of the dentin-resin bonded interface. In summary, this study shows that dental restorative materials containing multiple therapeutic agents of different chemical characteristics can be beneficial toward improving resistance to mechanical and acidic challenges in oral

  18. Ethanol from lignocellulose - Fermentation inhibitors, detoxification and genetic engineering of Saccharomyces cerevisiae for enhanced resistance

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, Simona

    2000-07-01

    Ethanol can be produced from lignocellulose by first hydrolysing the material to sugars, and then fermenting the hydrolysate with the yeast Saccharomyces cerevisiae. Hydrolysis using dilute sulphuric acid has advantages over other methods, however, compounds which inhibit fermentation are generated during this kind of hydrolysis. The inhibitory effect of aliphatic acids, furans, and phenolic compounds was investigated. The generation of inhibitors during hydrolysis was studied using Norway spruce as raw material. It was concluded that the decrease in the fermentability coincided with increasing harshness of the hydrolysis conditions. The decrease in fermentability was not correlated solely to the content of aliphatic acids or furan derivatives. To increase the fermentability, detoxification is often employed. Twelve detoxification methods were compared with respect to the chemical composition of the hydrolysate and the fermentability after treatment. The most efficient detoxification methods were anion-exchange at pH 10.0, overliming and enzymatic detoxification with the phenol-oxidase laccase. Detailed analyses of ion exchange revealed that anion exchange and unspecific hydrophobic interactions greatly contributed to the detoxification effect, while cation exchange did not. The comparison of detoxification methods also showed that phenolic compounds are very important fermentation inhibitors, as their selective removal with laccase had a major positive effect on the fermentability. Selected compounds; aliphatic acids, furans and phenolic compounds, were characterised with respect to their inhibitory effect on ethanolic fermentation by S. cerevisiae. When aliphatic acids or furans were compared, the inhibitory effects were found to be in the same range, but the phenolic compounds displayed widely different inhibitory effects. The possibility of genetically engineering S. cerevisiae to achieve increased inhibitor resistance was explored by heterologous expression of

  19. Angiopoietin-2 enhances survival in experimental sepsis induced by multidrug-resistant Pseudomonas aeruginosa.

    Science.gov (United States)

    Tzepi, Ira-Maria; Giamarellos-Bourboulis, Evangelos J; Carrer, Dionyssia-Pinelopi; Tsaganos, Thomas; Claus, Ralf A; Vaki, Ilia; Pelekanou, Aimilia; Kotsaki, Antigone; Tziortzioti, Vassiliki; Topouzis, Stavros; Bauer, Michael; Papapetropoulos, Andreas

    2012-11-01

    Levels of circulating angiopoietin-2 (Ang-2) increase in sepsis, raising the possibility that Ang-2 acts as a modulator in the sepsis cascade. To investigate this, experimental sepsis was induced in male C57BL6 mice by a multidrug-resistant isolate of Pseudomonas aeruginosa; survival was determined along with neutrophil tissue infiltration and release of proinflammatory cytokines. Survival was significantly increased either by pretreatment with recombinant Ang-2 2 h before or treatment with recombinant Ang-2 30 min after bacterial challenge. Likewise, Ang-2 pretreatment protected against sepsis-related death elicited by Escherichia coli; however, Ang-2 failed to provide protection in lipopolysaccharide (LPS)-challenged mice. The survival advantage of Ang-2 in response to P. aeruginosa challenge was lost in tumor necrosis factor (TNF)-deficient mice or neutropenic mice. Infiltration of the liver by neutrophils was elevated in the Ang-2 group compared with saline-treated animals. Serum TNF-α levels were reduced by Ang-2, whereas those of interleukin (IL)-6 and IL-10 remained unchanged. This was accompanied by lower release of TNF-α by stimulated splenocytes. When applied to U937 cells in vitro, heat-killed P. aeruginosa induced the secretion of IL-6 and TNF-α; low levels of exogenous TNF-α synergized with P. aeruginosa. This synergistic effect was abolished after the addition of Ang-2. These results put in evidence a striking protective role of Ang-2 in experimental sepsis evoked by a multidrug-resistant isolate of P. aeruginosa attributed to modulation of TNF-α production and changes in neutrophil migration. The protective role of Ang-2 is shown when whole microorganisms are used and not LPS, suggesting complex interactions with the host immune response. PMID:22859861

  20. An L-shaped low on-resistance current path SOI LDMOS with dielectric field enhancement

    International Nuclear Information System (INIS)

    A low specific on-resistance (Ron,sp) SOI NBL TLDMOS (silicon-on-insulator trench LDMOS with an N buried layer) is proposed. It has three features: a thin N buried layer (NBL) on the interface of the SOI layer/buried oxide (BOX) layer, an oxide trench in the drift region, and a trench gate extended to the BOX layer. First, on the on-state, the electron accumulation layer forms beside the extended trench gate; the accumulation layer and the highly doping NBL constitute an L-shaped low-resistance conduction path, which sharply decreases the Ron,sp. Second, in the y-direction, the BOX's electric field (E-field) strength is increased to 154 V/μm from 48 V/μm of the SOI Trench Gate LDMOS (SOI TG LDMOS) owing to the high doping NBL. Third, the oxide trench increases the lateral E-field strength due to the lower permittivity of oxide than that of Si and strengthens the multiple-directional depletion effect. Fourth, the oxide trench folds the drift region along the y-direction and thus reduces the cell pitch. Therefore, the SOI NBL TLDMOS structure not only increases the breakdown voltage (BV), but also reduces the cell pitch and Ron,sp. Compared with the TG LDMOS, the NBL TLDMOS improves the BV by 105% at the same cell pitch of 6 μm, and decreases the Ron,sp by 80% at the same BV. (semiconductor devices)

  1. Enhanced uptake of antibiotic resistance genes in the presence of nanoalumina.

    Science.gov (United States)

    Ding, Chengshi; Pan, Jie; Jin, Min; Yang, Dong; Shen, Zhiqiang; Wang, Jingfeng; Zhang, Bin; Liu, Weili; Fu, Jialun; Guo, Xuan; Wang, Daning; Chen, Zhaoli; Yin, Jing; Qiu, Zhigang; Li, Junwen

    2016-10-01

    Nanomaterial pollution and the spread of antibiotic resistance genes (ARGs) are global public health and environmental concerns. Whether nanomaterials could aid the transfer of ARGs released from dead bacteria into live bacteria to cause spread of ARGs is still unknown. Here, we demonstrated that nano-Al2O3 could significantly promote plasmid-mediated ARGs transformation into Gram-negative Escherichia coli strains and into Gram-positive Staphylococcus aureus; however, bulk Al2O3 did not have this effect. Under suitable conditions, 7.4 × 10(6) transformants of E. coli and 2.9 × 10(5) transformants of S. aureus were obtained from 100 ng of a pBR322-based plasmid when bacteria were treated with nano-Al2O3. Nanoparticles concentrations, plasmid concentrations, bacterial concentrations, interaction time between the nanomaterial and bacterial cells and the vortexing time affected the transformation efficiency. We also explored the mechanisms underlying this phenomenon. Using fluorescence in situ hybridization and scanning electron microscopy, we found that nano-Al2O3 damaged the cell membrane to produce pores, through which plasmid could enter bacterial cells. Results from reactive oxygen species (ROS) assays, genome-wide expression microarray profiling and quantitative real-time polymerase chain reactions suggested that intracellular ROS damaged the cell membrane, and that an SOS response promoted plasmid transformation. Our results indicated the environmental and health risk resulting from nanomaterials helping sensitive bacteria to obtain antibiotic resistance. PMID:26946995

  2. Enhanced performance of electrostatic precipitators through chemical modification of particle resistivity and cohesion

    Energy Technology Data Exchange (ETDEWEB)

    Durham, M.D.; Baldrey, K.E.; Bustard, C.J. [ADA Technologies, Inc., Englewood, CO (United States)

    1995-11-01

    Control of fine particles, including particulate air toxics, from utility boilers is required near-term by state and federal air regulations. Electrostatic precipitators (ESP) serve as the primary air pollution control device for the majority of coal-fired utility boilers in the Eastern and Midwestern united States. Cost-effective retrofit technologies for fine particle control, including flue gas conditioning, are needed for the large base of existing ESPs. Flue has conditioning is an attractive option because it requires minimal structural changes and lower capital costs. For flue gas conditioning to be effective for fine particle control, cohesive and particle agglomerating agents are needed to reduce reentrainment losses, since a large percentage of particulate emissions from well-performing ESPs are due to erosion, rapping, and non-rapping reentrainment. A related and somewhat ironic development is that emissions reductions of SO{sub 2} from utility boilers, as required by the Title IV acid rain program of the 1990 Clean Air Act amendments, has the potential to substantially increase particulate air toxics from existing ESPs. The switch to low-sulfur coals as an SO{sub 2} control strategy by many utilities has exacerbated ESP performance problems associated with high resistivity flyash. The use of flue gas conditioning has increased in the past several years to maintain adequate performance in ESPs which were not designed for high resistivity ash. However, commercially available flue gas conditioning systems, including NH{sub 3}/SO{sub 3} dual gas conditioning systems, have problems and inherent drawbacks which create a need for alternative conditioning agents. in particular, NH{sub 3}/SO{sub 3} systems can create odor and ash disposal problems due to ammonia outgassing. In addition, there are concerns over chemical handling safety and the potential for accidental releases.

  3. Enhancement of resistive switching under confined current path distribution enabled by insertion of atomically thin defective monolayer graphene

    Science.gov (United States)

    Lee, Keundong; Hwang, Inrok; Lee, Sangik; Oh, Sungtaek; Lee, Dukhyun; Kim, Cheol Kyeom; Nam, Yoonseung; Hong, Sahwan; Yoon, Chansoo; Morgan, Robert B.; Kim, Hakseong; Seo, Sunae; Seo, David H.; Lee, Sangwook; Park, Bae Ho

    2015-07-01

    Resistive random access memory (ReRAM) devices have been extensively investigated resulting in significant enhancement of switching properties. However fluctuations in switching parameters are still critical weak points which cause serious failures during ‘reading’ and ‘writing’ operations of ReRAM devices. It is believed that such fluctuations may be originated by random creation and rupture of conducting filaments inside ReRAM oxides. Here, we introduce defective monolayer graphene between an oxide film and an electrode to induce confined current path distribution inside the oxide film, and thus control the creation and rupture of conducting filaments. The ReRAM device with an atomically thin interlayer of defective monolayer graphene reveals much reduced fluctuations in switching parameters compared to a conventional one. Our results demonstrate that defective monolayer graphene paves the way to reliable ReRAM devices operating under confined current path distribution.

  4. [Enhanced resistance to phytopathogenic bacteria in transgenic tobacco plants with synthetic gene of antimicrobial peptide cecropin P1].

    Science.gov (United States)

    Zakharchenko, N S; Rukavtsova, E B; Gudkov, A T; Bur'ianov, Ia I

    2005-11-01

    Plasmids with a synthetic gene of the mammalian antimicrobial peptide cecropin P1 (cecP1) controlled by the constitutive promoter 35S RNA of cauliflower mosaic virus were constructed. Agrobacterial transformation of tobacco plants was conducted using the obtained recombinant binary vector. The presence of gene cecP1 in the plant genome was confirmed by PCR. The expression of gene cecP1 in transgenic plants was shown by Northern blot analysis. The obtained transgenic plants exhibit enhanced resistance to phytopathogenic bacteria Pseudomonas syringae, P. marginata, and Erwinia carotovora. The ability of transgenic plants to express cecropin P1 was transmitted to the progeny. F1 and F2 plants had the normal phenotype (except for a changed coloration of flowers) and retained the ability to produce normal viable seeds upon self-pollination. Lines of F1 plants with Mendelian segregation of transgenic traits were selected.

  5. Enhancement of toughness and wear resistance in boron nitride nanoplatelet (BNNP) reinforced Si3N4 nanocomposites

    Science.gov (United States)

    Lee, Bin; Lee, Dongju; Lee, Jun Ho; Ryu, Ho Jin; Hong, Soon Hyung

    2016-06-01

    Ceramics have superior hardness, strength and corrosion resistance, but are also associated with poor toughness. Here, we propose the boron nitride nanoplatelet (BNNP) as a novel toughening reinforcement component to ceramics with outstanding mechanical properties and high-temperature stability. We used a planetary ball-milling process to exfoliate BNNPs in a scalable manner and functionalizes them with polystyrene sulfonate. Non-covalently functionalized BNNPs were homogeneously dispersed with Si3N4 powders using a surfactant and then consolidated by hot pressing. The fracture toughness of the BNNP/Si3N4 nanocomposite increased by as much as 24.7% with 2 vol.% of BNNPs. Furthermore, BNNPs enhanced strength (9.4%) and the tribological properties (26.7%) of the ceramic matrix. Microstructural analyzes have shown that the toughening mechanisms are combinations of the pull-out, crack bridging, branching and blunting mechanisms.

  6. Depth profiles for hydrogen-enhanced thermal donor formation in silicon: Spreading resistance probe measurements

    International Nuclear Information System (INIS)

    Hydrogen enhancement of formation rates for oxygen-related thermal donors in Si has been investigated for dependence on: the source of hydrogen, hydrogen isotope, and exposure time and temperature. Hydrogen injection efficiency is an important variable and depth profiles are dependent upon the surface preparation of samples exposed in an electron cyclotron resonance plasma where ion energies are ≤35 eV. Formation rates up to 2 x 1016 cm-3 at 400 C have been observed. A sublinear dependence of the donor formation rate on beam current under 50 keV ion implantation is interpreted as a competition between oxygen-hydrogen and hydrogen-hydrogen interactions. Dependence on isotope mass and on exposure time in the plasma indicates hydrogen is the diffusing species that determines the penetration depth for the enhanced donor formation. Peculiar box-like depth profiles and high formation rates near the advancing front produced in RF plasma exposures are suggestive of hydrogen accumulation near the advancing front. The temperature dependence for the penetration depth gives in activation energy of 1.5 ± 0.2 eV. This energy is attributed to trap-limited diffusion wherein hydrogen lowers the energy barrier for the oxygen motion necessary to form thermal donors

  7. Dopamine agonist activity of EMD 23,448

    Energy Technology Data Exchange (ETDEWEB)

    Martin, G.E.; Pettibone, D.J. (Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania (USA). Dept. of Pharmacology)

    1985-01-01

    EMD 23,448 was examined in tests of dopaminergic function and was found to be an atypical dopamine (DA) agonist. EMD 23,448 was a weak or inactive DA agonist when examined in tests of normal postsynaptic DA receptor function: production of stereotypy in the rat (ED/sub 50/ greater than sign 5.0 mg/kg.i.p.); production of emesis in beagles (minimum effective dose = 81..mu..g/kg i.v.); and, enhanced locomotor activity of the mouse (no excitation in doses <=50 mg/i.p.). Moreover, EMD 23,448 was relatively weak in competing for (/sup 3/H)-apomorphine binding to rat striatal membranes (Ki, 205 nM). On the other hand, this indolyl-3-butylamine did activate supersensitive postsynaptic DA receptors. Specifically, it elicited contralateral turning in rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra (ED/sub 50/ value = 0.9 mg/kg) and did elicit stereotypy in rats given chronic daily haloperidol treatments. EMD 23,448 also exerted pharmacological effects in tests designed to measure activation of dopamine autoreceptors. It inhibited the ..gamma..-butyrolactone-induced increase in striatal dopa levels (ED/sub 50/ = 1 mg/kg i.p.) and produced a dose-related fall in the locomotor activity of the mouse. The results are discussed and contrasted with data derived for apomorphine and the putatively selective autoreceptor agonist (+-)-3-PPP.

  8. Chromium picolinate enhances skeletal muscle cellular insulin signaling in vivo in obese, insulin-resistant JCR:LA-cp rats.

    Science.gov (United States)

    Wang, Zhong Q; Zhang, Xian H; Russell, James C; Hulver, Matthew; Cefalu, William T

    2006-02-01

    Chromium is one of the few trace minerals for which a specific cellular mechanism of action has not been identified. Recent in vitro studies suggest that chromium supplementation may improve insulin sensitivity by enhancing insulin receptor signaling, but this has not been demonstrated in vivo. We investigated the effect of chromium supplementation on insulin receptor signaling in an insulin-resistant rat model, the JCR:LA-corpulent rat. Male JCR:LA-cp rats (4 mo of age) were randomly assigned to receive chromium picolinate (CrPic) (obese n=6, lean n=5) or vehicle (obese n=5, lean n=5) for 3 mo. The CrPic was provided in the water, and based on calculated water intake, rats randomized to CrPic received 80 microg/(kg.d). At the end of the study, skeletal muscle (vastus lateralis) biopsies were obtained at baseline and at 5, 15, and 30 min postinsulin stimulation to assess insulin signaling. Obese rats treated with CrPic had significantly improved glucose disposal rates and demonstrated a significant increase in insulin-stimulated phosphorylation of insulin receptor substrate (IRS)-1 and phosphatidylinositol (PI)-3 kinase activity in skeletal muscle compared with obese controls. The increase in cellular signaling was not associated with increased protein levels of the IRS proteins, PI-3 kinase or Akt. However, protein tyrosine phosphatase 1B (PTP1B) levels were significantly lower in obese rats administered CrPic than obese controls. When corrected for protein content, PTP1B activity was also significantly lower in obese rats administered CrPic than obese controls. Our data suggest that chromium supplementation of obese, insulin-resistant rats may improve insulin action by enhancing intracellular signaling.

  9. Overexpression of Three Glucosinolate Biosynthesis Genes in Brassica napus Identifies Enhanced Resistance to Sclerotinia sclerotiorum and Botrytis cinerea.

    Science.gov (United States)

    Zhang, Yuanyuan; Huai, Dongxin; Yang, Qingyong; Cheng, Yan; Ma, Ming; Kliebenstein, Daniel J; Zhou, Yongming

    2015-01-01

    Sclerotinia sclerotiorum and Botrytis cinerea are notorious plant pathogenic fungi with an extensive host range including Brassica crops. Glucosinolates (GSLs) are an important group of secondary metabolites characteristic of the Brassicales order, whose degradation products are proving to be increasingly important in plant protection. Enhancing the defense effect of GSL and their associated degradation products is an attractive strategy to strengthen the resistance of plants by transgenic approaches. We generated the lines of Brassica napus with three biosynthesis genes involved in GSL metabolic pathway (BnMAM1, BnCYP83A1 and BnUGT74B1), respectively. We then measured the foliar GSLs of each transgenic lines and inoculated them with S. sclerotiorum and B. cinerea. Compared with the wild type control, over-expressing BnUGT74B1 in B. napus increased the aliphatic and indolic GSL levels by 1.7 and 1.5 folds in leaves respectively; while over-expressing BnMAM1 or BnCYP83A1 resulted in an approximate 1.5-fold higher only in the aliphatic GSL level in leaves. The results of plant inoculation demonstrated that BnUGT74B1-overexpressing lines showed less severe disease symptoms and tissue damage compared with the wild type control, but BnMAM1 or BnCYP83A1-overexpressing lines showed no significant difference in comparison to the controls. These results suggest that the resistance to S. sclerotiorum and B. cinerea in B. napus could be enhanced through tailoring the GSL profiles by transgenic approaches or molecular breeding, which provides useful information to assist plant breeders to design improved breeding strategies. PMID:26465156

  10. Overexpression of Three Glucosinolate Biosynthesis Genes in Brassica napus Identifies Enhanced Resistance to Sclerotinia sclerotiorum and Botrytis cinerea.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Zhang

    Full Text Available Sclerotinia sclerotiorum and Botrytis cinerea are notorious plant pathogenic fungi with an extensive host range including Brassica crops. Glucosinolates (GSLs are an important group of secondary metabolites characteristic of the Brassicales order, whose degradation products are proving to be increasingly important in plant protection. Enhancing the defense effect of GSL and their associated degradation products is an attractive strategy to strengthen the resistance of plants by transgenic approaches. We generated the lines of Brassica napus with three biosynthesis genes involved in GSL metabolic pathway (BnMAM1, BnCYP83A1 and BnUGT74B1, respectively. We then measured the foliar GSLs of each transgenic lines and inoculated them with S. sclerotiorum and B. cinerea. Compared with the wild type control, over-expressing BnUGT74B1 in B. napus increased the aliphatic and indolic GSL levels by 1.7 and 1.5 folds in leaves respectively; while over-expressing BnMAM1 or BnCYP83A1 resulted in an approximate 1.5-fold higher only in the aliphatic GSL level in leaves. The results of plant inoculation demonstrated that BnUGT74B1-overexpressing lines showed less severe disease symptoms and tissue damage compared with the wild type control, but BnMAM1 or BnCYP83A1-overexpressing lines showed no significant difference in comparison to the controls. These results suggest that the resistance to S. sclerotiorum and B. cinerea in B. napus could be enhanced through tailoring the GSL profiles by transgenic approaches or molecular breeding, which provides useful information to assist plant breeders to design improved breeding strategies.

  11. Upregulation of retinoic acid receptor-β reverses drug resistance in cholangiocarcinoma cells by enhancing susceptibility to apoptosis.

    Science.gov (United States)

    Ren, Hong-Yue; Chen, Bo; Huang, Gui-Li; Liu, Yu; Shen, Dong-Yan

    2016-10-01

    Retinoic acid receptor β (RARβ), a known tumor suppressor gene, is frequently silenced in numerous malignant types of tumor. Recent reports have demonstrated that loss of RARβ expression may be responsible, in part, for the drug resistance observed in clinical trials. However, little is known about the role of RARβ in regulating drug sensitivity in patients with cholangiocarcinoma (CCA) with a high risk of mortality and poor outcomes. In the present study, low RARβ expression was observed in the majority of CCA tissues investigated (28/33, 84.8%). In addition, the CCA cell line QBC939, which exhibits low RARβ expression, was found to be significantly resistant to chemotherapeutic agents compared with SK‑ChA‑1, MZ‑ChA‑1 and Hccc9810 CCA cell lines, which exhibit high RARβ expression. Furthermore, upregulation of RARβ significantly enhanced the sensitivity of QBC939 cells to common chemotherapeutic agents both in vitro and in vivo. Upregulation of RARβ was shown to increase the expression of proapoptotic genes bax, bak and bim, in addition to caspase‑3 activity, and decrease the expression of antiapoptotic genes bcl‑2, bcl‑xL and mcl‑1. As a result, CCA cells were more susceptible to caspase‑dependent apoptosis. Taken together, these data suggest that RARβ upregulation rendered CCA cells more sensitive to chemotherapeutic agents by increasing the susceptibility of cells to caspase-dependent apoptosis. These results support the hypothesis that RARβ may be an ideal chemosensitization target for the treatment of patients with drug-resistant CCA. PMID:27599527

  12. Arabidopsis ENHANCED DISEASE SUSCEPTIBILITY1 promotes systemic acquired resistance via azelaic acid and its precursor 9-oxo nonanoic acid.

    Science.gov (United States)

    Wittek, Finni; Hoffmann, Thomas; Kanawati, Basem; Bichlmeier, Marlies; Knappe, Claudia; Wenig, Marion; Schmitt-Kopplin, Philippe; Parker, Jane E; Schwab, Wilfried; Vlot, A Corina

    2014-11-01

    Systemic acquired resistance (SAR) is a form of inducible disease resistance that depends on salicylic acid and its upstream regulator ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). Although local Arabidopsis thaliana defence responses activated by the Pseudomonas syringae effector protein AvrRpm1 are intact in eds1 mutant plants, SAR signal generation is abolished. Here, the SAR-specific phenotype of the eds1 mutant is utilized to identify metabolites that contribute to SAR. To this end, SAR bioassay-assisted fractionation of extracts from the wild type compared with eds1 mutant plants that conditionally express AvrRpm1 was performed. Using high-performance liquid chromatography followed by mass spectrometry, systemic immunity was associated with the accumulation of 60 metabolites, including the putative SAR signal azelaic acid (AzA) and its precursors 9-hydroperoxy octadecadienoic acid (9-HPOD) and 9-oxo nonanoic acid (ONA). Exogenous ONA induced SAR in systemic untreated leaves when applied at a 4-fold lower concentration than AzA. The data suggest that in planta oxidation of ONA to AzA might be partially responsible for this response and provide further evidence that AzA mobilizes Arabidopsis immunity in a concentration-dependent manner. The AzA fragmentation product pimelic acid did not induce SAR. The results link the C9 lipid peroxidation products ONA and AzA with systemic rather than local resistance and suggest that EDS1 directly or indirectly promotes the accumulation of ONA, AzA, or one or more of their common precursors possibly by activating one or more pathways that either result in the release of these compounds from galactolipids or promote lipid peroxidation.

  13. Decreased abundance of type III secretion system-inducing signals in Arabidopsis mkp1 enhances resistance against Pseudomonas syringae

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Jeffrey C.; Wan, Ying; Kim, Young-Mo; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Peck, Scott C.

    2014-04-21

    Many phytopathogenic bacteria use a type III secretion system (T3SS) to inject defense-suppressing effector proteins into host cells. Genes encoding the T3SS are induced at the start of infection, yet host signals that initiate T3SS gene expression are poorly understood. Here we identify several plant-derived metabolites that induce the T3SS in the bacterial pathogen Pseudomonas syringae pv tomato DC3000. In addition, we report that mkp1 (mapk phosphatase 1), an Arabidopsis mutant that is more resistant to bacterial infection, produces decreased levels of these T3SS-inducing metabolites. Consistent with the observed decrease in these metabolites, T3SS effector delivery by DC3000 was impaired in mkp1. Addition of the bioactive metabolites to the mkp1-DC3000 interaction fully restored T3SS effector delivery and suppressed enhanced resistance in mkp1. Together, these results demonstrate that DC3000 perceives multiple signals derived from plants to initiate their virulence program, and reveal a new layer of molecular communication between plants and these pathogenic bacteria.

  14. Inonotus obliquus containing diet enhances the innate immune mechanism and disease resistance in olive flounder Paralichythys olivaceus against Uronema marinum.

    Science.gov (United States)

    Harikrishnan, Ramasamy; Balasundaram, Chellam; Heo, Moon-Soo

    2012-06-01

    The present study describes the effect of diet supplementation with Chaga mushroom, Inonotus obliquus extract at 0%, 0.01%, 0.1%, and 1.0% levels on the innate humoral (lysozyme, antiprotease, and complement), cellular responses (production of reactive oxygen and nitrogen species and myeloperoxidase), and disease resistance in olive flounder, Paralichythys olivaceus against Uronema marinum. The lysozyme activity and complement activity significantly increased in each diet on weeks 2 and 4 against pathogen. The serum antiprotease activity and reactive nitrogen intermediates production significantly increased in fish fed with 0.1% and 1.0% diets from weeks 1-4. However, reactive oxygen species production and myeloperoxidase activity significantly increased in 1.0% and 2.0% diets on weeks 2 and 4. In fish fed with 0.1% and 1.0% diets and challenged with U. marinum the cumulative mortality was 50% and 40% while in 0% and 0.01% diets the mortality was 85% and 55%. The results clearly indicate that supplementation diet with I. obliquus at 0.1% and 1.0% level positively enhance the immune system and confer disease resistance which may be potentially used as an immunoprophylactic in finfish culture. PMID:22484608

  15. Electrostatic Assembly Preparation of High-Toughness Zirconium Diboride-Based Ceramic Composites with Enhanced Thermal Shock Resistance Performance.

    Science.gov (United States)

    Zhang, Baoxi; Zhang, Xinghong; Hong, Changqing; Qiu, Yunfeng; Zhang, Jia; Han, Jiecai; Hu, PingAn

    2016-05-11

    The central problem of using ceramic as a structural material is its brittleness, which associated with rigid covalent or ionic bonds. Whiskers or fibers of strong ceramics such as silicon carbide (SiC) or silicon nitride (Si3N4) are widely embedded in a ceramic matrix to improve the strength and toughness. The incorporation of these insulating fillers can impede the thermal flow in ceramic matrix, thus decrease its thermal shock resistance that is required in some practical applications. Here we demonstrate that the toughness and thermal shock resistance of zirconium diboride (ZrB2)/SiC composites can be improved simultaneously by introducing graphene into composites via electrostatic assembly and subsequent sintering treatment. The incorporated graphene creates weak interfaces of grain boundaries (GBs) and optimal thermal conductance paths inside composites. In comparison to pristine ZrB2-SiC composites, the toughness of (2.0%) ZrB2-SiC/graphene composites exhibited a 61% increasing (from 4.3 to 6.93 MPa·m(1/2)) after spark plasma sintering (SPS); the retained strength after thermal shock increased as high as 74.8% at 400 °C and 304.4% at 500 °C. Present work presents an important guideline for producing high-toughness ceramic-based composites with enhanced thermal shock properties.

  16. PROX1 promotes hepatocellular carcinoma proliferation and sorafenib resistance by enhancing β-catenin expression and nuclear translocation.

    Science.gov (United States)

    Liu, Y; Ye, X; Zhang, J-B; Ouyang, H; Shen, Z; Wu, Y; Wang, W; Wu, J; Tao, S; Yang, X; Qiao, K; Zhang, J; Liu, J; Fu, Q; Xie, Y

    2015-10-29

    Aberrant activation of the Wnt/β-catenin pathway is frequent in hepatocellular carcinoma (HCC) and contributes to HCC initiation and progression. This abnormal activation may result from somatic mutations in the genes of the Wnt/β-catenin pathway and/or dysregulation of the Wnt/β-catenin pathway. The mechanism for the latter remains poorly understood. Prospero-related homeobox 1 (PROX1) is a downstream target of the Wnt/β-catenin pathway in human colorectal cancer and elevated PROX1 expression promotes malignant progression. However, the Wnt/β-catenin pathway does not regulate PROX1 expression in the liver and HCC cells. Here we report that PROX1 promotes HCC cell proliferation in vitro and tumor growth in HCC xenograft mice. PROX1 and β-catenin levels are positively correlated in tumor tissues as well as in cultured HCC cells. PROX1 can upregulate β-catenin transcription by stimulating the β-catenin promoter and enhance the nuclear translocation of β-catenin in HCC cells, which leads to the activation of the Wnt/β-catenin pathway. Moreover, we show that increase in PROX1 expression renders HCC cells more resistant to sorafenib treatment, which is the standard therapy for advanced HCC. Overall, we have pinpointed PROX1 as a critical factor activating the Wnt/β-catenin pathway in HCC, which promotes HCC proliferation and sorafenib resistance.

  17. Investigate the Metabolic Reprogramming of Saccharomyces cerevisiae for Enhanced Resistance to Mixed Fermentation Inhibitors via 13C Metabolic Flux Analysis

    Science.gov (United States)

    Guo, Weihua; Chen, Yingying; Wei, Na; Feng, Xueyang

    2016-01-01

    The fermentation inhibitors from the pretreatment of lignocellulosic materials, e.g., acetic acid and furfural, are notorious due to their negative effects on the cell growth and chemical production. However, the metabolic reprogramming of the cells under these stress conditions, especially metabolic response for resistance to mixed inhibitors, has not been systematically investigated and remains mysterious. Therefore, in this study, 13C metabolic flux analysis (13C-MFA), a powerful tool to elucidate the intracellular carbon flux distributions, has been applied to two Saccharomyces cerevisiae strains with different tolerances to the inhibitors under acetic acid, furfural, and mixed (i.e., acetic acid and furfural) stress conditions to unravel the key metabolic responses. By analyzing the intracellular carbon fluxes as well as the energy and cofactor utilization under different conditions, we uncovered varied metabolic responses to different inhibitors. Under acetate stress, ATP and NADH production was slightly impaired, while NADPH tended towards overproduction. Under furfural stress, ATP and cofactors (including both NADH and NADPH) tended to be overproduced. However, under dual-stress condition, production of ATP and cofactors was severely impaired due to synergistic stress caused by the simultaneous addition of two fermentation inhibitors. Such phenomenon indicated the pivotal role of the energy and cofactor utilization in resisting the mixed inhibitors of acetic acid and furfural. Based on the discoveries, valuable insights are provided to improve the tolerance of S. cerevisiae strain and further enhance lignocellulosic fermentation. PMID:27532329

  18. In situ surface chemical modification of thin-film composite forward osmosis membranes for enhanced organic fouling resistance.

    Science.gov (United States)

    Lu, Xinglin; Romero-Vargas Castrillón, Santiago; Shaffer, Devin L; Ma, Jun; Elimelech, Menachem

    2013-01-01

    Forward osmosis (FO) is an emerging membrane-based water separation process with potential applications in a host of environmental and industrial processes. Nevertheless, membrane fouling remains a technical obstacle affecting this technology, increasing operating costs and decreasing membrane life. This work presents the first fabrication of an antifouling thin-film composite (TFC) FO membrane by an in situ technique without postfabrication treatment. The membrane was fabricated and modified in situ, grafting Jeffamine, an amine-terminated poly(ethylene glycol) derivative, to dangling acyl chloride surface groups on the nascent polyamide active layer. Surface characterization by contact angle, Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), zeta potential, atomic force microscopy (AFM), and fluorescence microscopy, confirms the presence of Jeffamine on the membrane surface. We demonstrate the improved fouling resistance of the in situ modified membranes through accelerated dynamic fouling FO experiments using a synthetic wastewater feed solution at high concentration (250 mg/L) of alginate, a model macromolecule for the hydrophilic fraction of wastewater effluent organic matter. Our results show a significantly lower flux decline for the in situ modified membranes compared to pristine polyamide (14.3 ± 2.7% vs 2.8 ± 1.4%, respectively). AFM adhesion force measurements between the membrane and a carboxylate-modified latex particle, a surrogate for the organic (alginate) foulant, show weaker foulant-membrane interactions, further confirming the enhanced fouling resistance of the in situ modified membranes. PMID:24066902

  19. Huge magnetic enhancement of the out-of-plane resistivity and depression of Tc onset in Bi-2212 single crystal

    International Nuclear Information System (INIS)

    During magnetoresistance measurement of Bi-2212 single crystals, we found the resistance in the c-axis direction exhibited a huge magnetic enhancement (H perpendicular to the a-b-plane) while the onset transition temperature along the c-axis showed a large depression when the magnetic fields were over a certain value (H > 180 Oe). No such phenomena were observed in small applied magnetic fields (H ≤ 180 Oe) and in a-b-plane magnetoresistance measurements. By changing different probes (eight probes being attached to the sample, each side having four probes) for the measurement of the magnetoresistance along the c-axis with H = 2000 Oe, we found that the resistance along the c-axis in the temperature region T/Tc > 0.90 was only related to the measuring dimensions and Tc onset remained unchanged. Our results provided evidence that both Lorentz-force-independent fluctuation-induced dissipation and Lorentz-force-dependent vortex motion dissipation exist in the mixed state. (author)

  20. A Resistive Boundary Condition Enhanced DGTD Scheme for the Transient Analysis of Graphene

    KAUST Repository

    Li, Ping

    2015-04-24

    In this paper, the electromagnetic (EM) features of graphene are characterized by a discontinuous Galerkin timedomain (DGTD) algorithm with a resistive boundary condition (RBC). The atomically thick graphene is equivalently modeled using a RBC by regarding the graphene as an infinitesimally thin conductive sheet. To incorporate RBC into the DGTD analysis, the surface conductivity of the graphene composed of contributions from both intraband and interband terms is firstly approximated by rational basis functions using the fastrelaxation vector-fitting (FRVF) method in the Laplace-domain. Next, through the inverse Laplace transform, the corresponding time-domain matrix equations in integral can be obtained. Finally, these matrix equations are solved by time-domain finite integral technique (FIT). For elements not touching the graphene sheet, however, the well-known Runge-Kutta (RK) method is employed to solve the two first-order time-derivative Maxwell’s equations. The application of the surface boundary condition significantly alleviates the memory consuming and the limitation of time step size required by Courant-Friedrichs-Lewy (CFL) condition. To validate the proposed algorithm, various numerical examples are presented and compared with available references.

  1. Enhanced resistance of Portunus trituberculatus to Vibrio alginolyticus by selective breeding

    Institute of Scientific and Technical Information of China (English)

    MU Changkao; LIU Shuai; SONG Weiwei; LI Ronghua; WANG Chunlin

    2012-01-01

    We established a line (screened) of Portunus trituberculatus by selectively breeding individuals that survived from challenge with Vibrio alginolyticus,and compared the response of screened and unscreened (control) P.trituberculatus challenged with V.alginolyticus.We measured superoxide dismutase,catalase,acid phosphatase,alkaline phosphatase,and peroxidase activity and the content of hemocyanin in the plasma and phenoloxidase activity in serum.The cumulative survival rate after 24-h challenge with V.alginolyticus was significantly higher in the screened crabs than in the unscreened crabs (P<0.05).T-SOD and PO activity were significantly lower in the screened stock than in the unscreened stock (P<0.05).POD,CAT,and ACP activity and hemocyanin content were significantly higher in the screened stock than in the unscreened stock.Our results suggest that the screened stock was more resistant to infection.Furthermore,the indices we measured may be used to evaluate the health state of P.trituberculatus.

  2. Corrosion resistance enhancement of Ni-P-nano SiO2 composite coatings on aluminum

    International Nuclear Information System (INIS)

    In this study, the influences of different concentrations of SiO2 nano sized particles in the bath on deposition rate, surface morphology and corrosion behavior of Ni-P-SiO2 Composite coatings were investigated. The deposition rate of coating was influenced by incorporation of SiO2 particles. The microstructure was investigated with field emission scanning electron microscopy (FESEM). The amount of SiO2 was examined by Energy Dispersive Analysis of X-Ray (EDX) and amount of SiO2 nanoparticles co-deposited reached a maximum value at 4.5 %wt. Corrosion behavior of coated aluminum was evaluated by electrochemical impedance spectroscopy (EIS) and polarization techniques. The results illustrated that the corrosion rate decreases (6.5–0.6 μA/cm2) and the corrosion potential increases (−0.64 to −0.3) with increasing the quantity of the SiO2 nanoparticles in the bath. Moreover, Ni-p-SiO2 nano-composite coating possesses less porosity than that in Ni-P coating, resulting in improving corrosion resistance.

  3. Enhanced UV resistance and improved killing of malaria mosquitoes by photolyase transgenic entomopathogenic fungi.

    Directory of Open Access Journals (Sweden)

    Weiguo Fang

    Full Text Available The low survival of microbial pest control agents exposed to UV is the major environmental factor limiting their effectiveness. Using gene disruption we demonstrated that the insect pathogenic fungus Metarhizium robertsii uses photolyases to remove UV-induced cyclobutane pyrimidine dimers (CPD and pyrimidine (6-4 photoproducts [(6-4PPs] from its DNA. However, this photorepair is insufficient to fix CPD lesions and prevent the loss of viability caused by seven hours of solar radiation. Expression of a highly efficient archaeal (Halobacterium salinarum CPD photolyase increased photorepair >30-fold in both M. robertsii and Beauveria bassiana. Consequently, transgenic strains were much more resistant to sunlight and retained virulence against the malaria vector Anopheles gambiae. In the field this will translate into much more efficient pest control over a longer time period. Conversely, our data shows that deleting native photolyase genes will strictly contain M. robertsii to areas protected from sunlight, alleviating safety concerns that transgenic hypervirulent Metarhizium spp will spread from mosquito traps or houses. The precision and malleability of the native and transgenic photolyases allows design of multiple pathogens with different strategies based on the environments in which they will be used.

  4. Topological design of all-ceramic dental bridges for enhancing fracture resistance.

    Science.gov (United States)

    Zhang, Zhongpu; Chen, Junning; Li, Eric; Li, Wei; Swain, Michael; Li, Qing

    2016-06-01

    Layered all-ceramic systems have been increasingly adopted in major dental prostheses. However, ceramics are inherently brittle, and they often subject to premature failure under high occlusion forces especially in the posterior region. This study aimed to develop mechanically sound novel topological designs for all-ceramic dental bridges by minimizing the fracture incidence under given loading conditions. A bi-directional evolutionary structural optimization (BESO) technique is implemented within the extended finite element method (XFEM) framework. Extended finite element method allows modeling crack initiation and propagation inside all-ceramic restoration systems. Following this, BESO searches the optimum distribution of two different ceramic materials, namely porcelain and zirconia, for minimizing fracture incidence. A performance index, as per a ratio of peak tensile stress to material strength, is used as a design objective. In this study, the novel XFEM based BESO topology optimization significantly improved structural strength by minimizing performance index for suppressing fracture incidence in the structures. As expected, the fracture resistance and factor of safety of fixed partial dentures structure increased upon redistributing zirconia and porcelain in the optimal topological configuration. Dental CAD/CAM systems and the emerging 3D printing technology were commercially available to facilitate implementation of such a computational design, exhibiting considerable potential for clinical application in the future. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26444905

  5. [Enhanced Resistance of Pea Plants to Oxidative: Stress Caused by Paraquat during Colonization by Aerobic Methylobacteria].

    Science.gov (United States)

    Agafonova, N V; Doronina, N Y; Trotsenko, Yu A

    2016-01-01

    The influence of colonization of the pea (Pisum sativum L.) by aerobic methylobacteria of five different species (Methylophilus flavus Ship, Methylobacterium extorquens G10, Methylobacillus arboreus Iva, Methylopila musalis MUSA, Methylopila turkiensis Sidel) on plant resistance to paraquat-induced stresses has been studied. The normal conditions of pea colonization by methylobacteria were characterized by a decrease in the activity of antioxidant enzymes (superoxide dismutase, catalase, and peroxidases) and in the concentrations of endogenous H2O2, proline, and malonic dialdehyde, which is a product of lipid peroxidation and indicator of damage to plant cell membranes, and an increase in the activity of the photosynthetic apparatus (the content of chlorophylls a, b and carotenoids). In the presence of paraquat, the colonized plants had higher activities of antioxidant enzymes, stable photosynthetic indices, and a less intensive accumulation of the products of lipid peroxidation as compared to noncolonized plants. Thus, colonization by methylobacteria considerably increased the adaptive protection of pea plants to the paraquat-induced oxidative stress.

  6. Field enhanced charge carrier reconfiguration in electronic and ionic coupled dynamic polymer resistive memory

    Energy Technology Data Exchange (ETDEWEB)

    Zhao Junhui; Thomson, Douglas J; Freund, Michael S [Department of Electrical and Computer Engineering, University of Manitoba, Winnipeg, MB (Canada); Pilapil, Matt; Pillai, Rajesh G; Aminur Rahman, G M, E-mail: thomson@ee.umanitoba.ca, E-mail: michael_freund@umanitoba.ca [Department of Chemistry, University of Manitoba, Winnipeg, MB (Canada)

    2010-04-02

    Dynamic resistive memory devices based on a conjugated polymer composite (PPy{sup 0}DBS{sup -}Li{sup +} (PPy: polypyrrole; DBS{sup -}: dodecylbenzenesulfonate)), with field-driven ion migration, have been demonstrated. In this work the dynamics of these systems has been investigated and it has been concluded that increasing the applied field can dramatically increase the rate at which information can be 'written' into these devices. A conductance model using space charge limited current coupled with an electric field induced ion reconfiguration has been successfully utilized to interpret the experimentally observed transient conducting behaviors. The memory devices use the rising and falling transient current states for the storage of digital states. The magnitude of these transient currents is controlled by the magnitude and width of the write/read pulse. For the 500 nm length devices used in this work an increase in 'write' potential from 2.5 to 5.5 V decreased the time required to create a transient conductance state that can be converted into the digital signal by 50 times. This work suggests that the scaling of these devices will be favorable and that 'write' times for the conjugated polymer composite memory devices will decrease rapidly as ion driving fields increase with decreasing device size.

  7. A Sorghum MYB Transcription Factor Induces 3-Deoxyanthocyanidins and Enhances Resistance against Leaf Blights in Maize

    Directory of Open Access Journals (Sweden)

    Farag Ibraheem

    2015-01-01

    Full Text Available Sorghum responds to the ingress of the fungal pathogen Colletotrichum sublineolum through the biosynthesis of 3-deoxyanthocyanidin phytoalexins at the site of primary infection. Biosynthesis of 3-deoxyanthocyanidins in sorghum requires a MYB transcription factor encoded by yellow seed1 (y1, an orthologue of the maize gene pericarp color1 (p1. Maize lines with a functional p1 and flavonoid structural genes do not produce foliar 3-deoxyanthocyanidins in response to fungal ingress. To perform a comparative metabolic analysis of sorghum and maize 3-deoxyanthocyanidin biosynthetic pathways, we developed transgenic maize lines expressing the sorghum y1 gene. In maize, the y1 transgene phenocopied p1-regulated pigment accumulation in the pericarp and cob glumes. LC-MS profiling of fungus-challenged Y1-maize leaves showed induction of 3-deoxyanthocyanidins, specifically luteolinidin. Y1-maize plants also induced constitutive and higher levels of flavonoids in leaves. In response to Colletotrichum graminicola, Y1-maize showed a resistance response.

  8. Female scent signals enhance the resistance of male mice to influenza.

    Directory of Open Access Journals (Sweden)

    Ekaterina A Litvinova

    Full Text Available BACKGROUND: The scent from receptive female mice functions as a signal, which stimulates male mice to search for potential mating partners. This searching behavior is coupled with infection risk due to sniffing both scent marks as well as nasal and anogenital areas of females, which harbor bacteria and viruses. Consideration of host evolution under unavoidable parasitic pressures, including helminthes, bacteria, viruses, etc., predicts adaptations that help protect hosts against the parasites associated with mating. METHODS AND FINDINGS: We propose that the perception of female signals by BALB/c male mice leads to adaptive redistribution of the immune defense directed to protection against respiratory infection risks. Our results demonstrate migration of macrophages and neutrophils to the upper airways upon exposure to female odor stimuli, which results in an increased resistance of the males to experimental influenza virus infection. This moderate leukocyte intervention had no negative effect on the aerobic performance in male mice. CONCLUSIONS: Our data provide the first demonstration of the adaptive immunological response to female odor stimuli through induction of nonspecific immune responses in the upper respiratory tract.

  9. K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism.

    Directory of Open Access Journals (Sweden)

    Atsuko Hachiya

    Full Text Available HIV-1 carrying the "Q151M complex" reverse transcriptase (RT mutations (A62V/V75I/F77L/F116Y/Q151M, or Q151Mc is resistant to many FDA-approved nucleoside RT inhibitors (NRTIs, but has been considered susceptible to tenofovir disoproxil fumarate (TFV-DF or TDF. We have isolated from a TFV-DF-treated HIV patient a Q151Mc-containing clinical isolate with high phenotypic resistance to TFV-DF. Analysis of the genotypic and phenotypic testing over the course of this patient's therapy lead us to hypothesize that TFV-DF resistance emerged upon appearance of the previously unreported K70Q mutation in the Q151Mc background. Virological analysis showed that HIV with only K70Q was not significantly resistant to TFV-DF. However, addition of K70Q to the Q151Mc background significantly enhanced resistance to several approved NRTIs, and also resulted in high-level (10-fold resistance to TFV-DF. Biochemical experiments established that the increased resistance to tenofovir is not the result of enhanced excision, as K70Q/Q151Mc RT exhibited diminished, rather than enhanced ATP-based primer unblocking activity. Pre-steady state kinetic analysis of the recombinant enzymes demonstrated that addition of the K70Q mutation selectively decreases the binding of tenofovir-diphosphate (TFV-DP, resulting in reduced incorporation of TFV into the nascent DNA chain. Molecular dynamics simulations suggest that changes in the hydrogen bonding pattern in the polymerase active site of K70Q/Q151Mc RT may contribute to the observed changes in binding and incorporation of TFV-DP. The novel pattern of TFV-resistance may help adjust therapeutic strategies for NRTI-experienced patients with multi-drug resistant (MDR mutations.

  10. Elevated STAT3 Signaling-Mediated Upregulation of MMP-2/9 Confers Enhanced Invasion Ability in Multidrug-Resistant Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Fei Zhang

    2015-10-01

    Full Text Available The development of multidrug resistance greatly impedes effective cancer therapy. Recent advances in cancer research have demonstrated that acquisition of multidrug resistance by cancer cells is usually accompanied by enhanced cell invasiveness. Several lines of evidence indicated that cross activation of other signaling pathways during development of drug resistance may increase invasive potential of multidrug-resistant (MDR cancer cells. However, the accurate mechanism of this process is largely undefined. In this study, to better understand the associated molecular pathways responsible for cancer progression induced by drug resistance, a MDR human breast cancer cell line SK-BR-3/EPR with P-glycoprotein overexpression was established using stepwise long-term exposure to increasing concentration of epirubicin. The SK-BR-3/EPR cell line exhibited decreased cell proliferative activity, but enhanced cell invasive capacity. We showed that the expression of metastasis-related matrix metalloproteinase (MMP-2/9 was elevated in SK-BR-3/EPR cells. Moreover, SK-BR-3/EPR cells showed elevated activation of STAT3. Activation of STAT3 signaling is responsible for enhanced invasiveness of SK-BR-3/EPR cells through upregulation of MMP-2/9. STAT3 is a well-known oncogene and is frequently implicated in tumorigenesis and chemotherapeutic resistance. Our findings augment insight into the mechanism underlying the functional association between MDR and cancer invasiveness.

  11. Expression of multiple resistance genes enhances tolerance to environmental stressors in transgenic poplar (Populus × euramericana 'Guariento'.

    Directory of Open Access Journals (Sweden)

    Xiaohua Su

    Full Text Available Commercial and non-commercial plants face a variety of environmental stressors that often cannot be controlled. In this study, transgenic hybrid poplar (Populus × euramericana 'Guariento' harboring five effector genes (vgb, SacB, JERF36, BtCry3A and OC-I were subjected to drought, salinity, waterlogging and insect stressors in greenhouse or laboratory conditions. Field trials were also conducted to investigate long-term effects of transgenic trees on insects and salt tolerance in the transformants. In greenhouse studies, two transgenic lines D5-20 and D5-21 showed improved growth, as evidenced by greater height and basal diameter increments and total biomass relative to the control plants after drought or salt stress treatments. The improved tolerance to drought and salt was primarily attributed to greater instantaneous water use efficiency (WUEi in the transgenic trees. The chlorophyll concentrations tended to be higher in the transgenic lines under drought or saline conditions. Transformed trees in drought conditions accumulated more fructan and proline and had increased Fv/Fm ratios (maximum quantum yield of photosystem II under waterlogging stress. Insect-feeding assays in the laboratory revealed a higher total mortality rate and lower exuviation index of leaf beetle [Plagiodera versicolora (Laicharting] larvae fed with D5-21 leaves, suggesting enhanced insect resistance in the transgenic poplar. In field trials, the dominance of targeted insects on 2-year-old D5-21 transgenic trees was substantially lower than that of the controls, indicating enhanced resistance to Coleoptera. The average height and DBH (diameter at breast height of 2.5-year-old transgenic trees growing in naturally saline soil were 3.80% and 4.12% greater than those of the control trees, but these increases were not significant. These results suggested that multiple stress-resistance properties in important crop tree species could be simultaneously improved, although

  12. Negative cooperativity in binding of muscarinic receptor agonists and GDP as a measure of agonist efficacy

    OpenAIRE

    Jakubík, J; Janíčková, H; El-Fakahany, EE; Doležal, V

    2011-01-01

    BACKGROUND AND PURPOSE Conventional determination of agonist efficacy at G-protein coupled receptors is measured by stimulation of guanosine-5′-γ−thiotriphosphate (GTPγS) binding. We analysed the role of guanosine diphosphate (GDP) in the process of activation of the M2 muscarinic acetylcholine receptor and provide evidence that negative cooperativity between agonist and GDP binding is an alternative measure of agonist efficacy. EXPERIMENTAL APPROACH Filtration and scintillation proximity ass...

  13. Lipocalin 2 Enhances Migration and Resistance against Cisplatin in Endometrial Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Tsutomu Miyamoto

    Full Text Available Lipocalin 2 (LCN2 is a secretory protein that is involved in various physiological processes including iron transport. We previously identified LCN2 as an up-regulated gene in endometrial carcinoma, and found that the overexpression of LCN2 and its receptor, SLC22A17, was associated with a poor prognosis. However, the functions and mechanism of action of LCN2 currently remain unclear.The LCN2-overexpressing endometrial carcinoma cell lines, HHUA and RL95-2, and LCN2-low-expressing one, HEC1B, were used. The effects of LCN2 on cell migration, cell viability, and apoptosis under various stresses, including ultraviolet (UV irradiation and cisplatin treatment, were examined using the scratch wound healing assay, WST-1 assay, and Apostrand assay, respectively.LCN2-silencing using shRNA method significantly reduced the migration ability of cells (p<0.05. Cytotoxic stresses significantly decreased the viability of LCN2-silenced cells more than that of control cells. In contrast, LCN2 overexpression was significantly increased cisplatin resistance. These effects were canceled by the addition of the iron chelator, deferoxamine. After UV irradiation, the expression of phosphorylated Akt (pAkt was decreased in LCN2-silenced cells, and the PI3K inhibitor canceled the difference induced in UV sensitivity by LCN2. The cisplatin-induced expression of pAkt was not affected by LCN2; however, the expression of p53 and p21 was increased by LCN2-silencing.These results indicated that LCN2 was involved in the migration and survival of endometrial carcinoma cells under various stresses in an iron-dependent manner. The survival function of LCN2 may be exerted through the PI3K pathway and suppression of the p53-p21 pathway. These functions of LCN2 may increase the malignant potential of endometrial carcinoma cells.

  14. Associative conditioning with leg cycling and inspiratory resistance enhances the early exercise ventilatory response in humans.

    Science.gov (United States)

    Turner, Duncan; Stewart, Jamie D

    2004-12-01

    Repeated trials of hypercapnic exercise [deltaPET CO2 = 7 (1) mmHg] augment the increase in inspired minute ventilation and tidal volume (V(T)) in the early phase of subsequent trials of unencumbered exercise alone. The increase in V(T) in the first 20 s of exercise was correlated to the increase in V(T) evoked during hypercapnic exercise trials, suggesting that the evoked increase in V(T) during conditioning may be a factor in mediating associative conditioning. To test this hypothesis, inspiratory resistive loading (IRL) was employed to evoke an increase in V(T) [deltaV(T) = 0.4 (0.1) I(BTPS)] during conditioning exercise trials [IRL + EX; deltaP(ET)CO2 = 2 (l) mmHg]. IRL + EX associative conditioning elicited a significant augmentation of the early minute ventilation (+46%) and V(T) (+100%) responses to subsequent unencumbered exercise. The latter was correlated to the evoked increase in V(T) during associative conditioning with IRL + EX. The results support the hypothesis that an evoked increase in V(T) during associative conditioning could be a factor in eliciting long-term modulation of minute ventilation in subsequent unencumbered exercise. The results further indicated that the modulation of ventilation early in exercise is not due to sensitisation to repeated trials of either IRL or exercise alone. Associative conditioning may shape the ventilatory response to exercise through a process of motor learning. Data are presented as mean (SEM) unless otherwise stated.

  15. On The Enhancement of Wear Resistance of Hardened Carbon Tool Steel (AISI 1095) With Cryogenic Quenching

    Institute of Scientific and Technical Information of China (English)

    V.Soundararajan; N.Alagurmurthi; K.Palaniradja

    2004-01-01

    Many experimental investigations reveal that it is very difficult to have a completely martensitic structure by any hardening process. Some amount of austenite is generally present in the hardened steel. This austenite existing along with martensite is normally referred as the retained austenite. The presence of retained austenite greatly reduces the mechanical properties and such steels do not develop maximum hardness even after cooling at rates higher than the critical cooling rates.Strength can be improved in hardened steels containing retained austenite by a process known as cryogenic quenching.Untransformed austenite is converted into martensite by this treatment. This conversion of retained austenite into martensite results in increased hardness, wear resistance and dimensional stability of steel. Wear can be defined as the progressive loss of materials from the operating surface of a body occurring as a result of relative motion at the surface. Hardness, load,speed, surface roughness, temperature are the major factors which influences wear. Many studies on wear indicate that increasing hardness decreases the wear of a material. With this in mind, to study the surface wear on a surface modified(Cryogenic treated) steel material an attempt has been made in this paper. In this study as a Part -I Hardening was carried out on carbon tool steel (AISI 1095) of different L/D ratio with conventional quenchants like purified water, aqueous solution and Hot mineral oil. As a Part -Ⅱ hardening was followed by quenching was carried out as said in Part- I and the hardened specimen were quenched in liquid Nitrogen which is at sub zero condition. The specimens were tested for its microstructure, hardness and wear loss. The results were compared and analyzed. The alloying elements increases the content of retained austenite hence the material used was AISI1095 (Carbon 0.9%, Si 0.2%, Mn0.4% and the rest Iron)

  16. A Designed Experiments Approach to Optimizing MALDI-TOF MS Spectrum Processing Parameters Enhances Detection of Antibiotic Resistance in Campylobacter jejuni.

    Science.gov (United States)

    Penny, Christian; Grothendick, Beau; Zhang, Lin; Borror, Connie M; Barbano, Duane; Cornelius, Angela J; Gilpin, Brent J; Fagerquist, Clifton K; Zaragoza, William J; Jay-Russell, Michele T; Lastovica, Albert J; Ragimbeau, Catherine; Cauchie, Henry-Michel; Sandrin, Todd R

    2016-01-01

    MALDI-TOF MS has been utilized as a reliable and rapid tool for microbial fingerprinting at the genus and species levels. Recently, there has been keen interest in using MALDI-TOF MS beyond the genus and species levels to rapidly identify antibiotic resistant strains of bacteria. The purpose of this study was to enhance strain level resolution for Campylobacter jejuni through the optimization of spectrum processing parameters using a series of designed experiments. A collection of 172 strains of C. jejuni were collected from Luxembourg, New Zealand, North America, and South Africa, consisting of four groups of antibiotic resistant isolates. The groups included: (1) 65 strains resistant to cefoperazone (2) 26 resistant to cefoperazone and beta-lactams (3) 5 strains resistant to cefoperazone, beta-lactams, and tetracycline, and (4) 76 strains resistant to cefoperazone, teicoplanin, amphotericin, B and cephalothin. Initially, a model set of 16 strains (three biological replicates and three technical replicates per isolate, yielding a total of 144 spectra) of C. jejuni was subjected to each designed experiment to enhance detection of antibiotic resistance. The most optimal parameters were applied to the larger collection of 172 isolates (two biological replicates and three technical replicates per isolate, yielding a total of 1,031 spectra). We observed an increase in antibiotic resistance detection whenever either a curve based similarity coefficient (Pearson or ranked Pearson) was applied rather than a peak based (Dice) and/or the optimized preprocessing parameters were applied. Increases in antimicrobial resistance detection were scored using the jackknife maximum similarity technique following cluster analysis. From the first four groups of antibiotic resistant isolates, the optimized preprocessing parameters increased detection respective to the aforementioned groups by: (1) 5% (2) 9% (3) 10%, and (4) 2%. An additional second categorization was created from the

  17. A Designed Experiments Approach to Optimizing MALDI-TOF MS Spectrum Processing Parameters Enhances Detection of Antibiotic Resistance in Campylobacter jejuni

    Directory of Open Access Journals (Sweden)

    Christian ePenny

    2016-05-01

    Full Text Available MALDI-TOF MS has been utilized as a reliable and rapid tool for microbial fingerprinting at the genus and species levels. Recently, there has been keen interest in using MALDI-TOF MS beyond the genus and species levels to rapidly identify antibiotic resistant strains of bacteria. The purpose of this study was to enhance strain level resolution for Campylobacter jejuni through the optimization of spectrum processing parameters using a series of designed experiments. A collection of 172 strains of C. jejuni were collected from Luxembourg, New Zealand, North America, and South Africa, consisting of four groups of antibiotic resistant isolates. The groups included: 1 65 strains resistant to cefoperazone 2 26 resistant to cefoperazone and beta-lactams 3 5 strains resistant to cefoperazone, beta-lactams, and tetracycline, and 4 76 strains resistant to cefoperazone, teicoplanin, amphotericin B and cephalothin. Initially, a model set of 16 strains (three biological replicates and three technical replicates per isolate, yielding a total of 144 spectra of C. jejuni was subjected to each designed experiment to enhance detection of antibiotic resistance. The most optimal parameters were applied to the larger collection of 172 isolates (two biological replicates and three technical replicates per isolate, yielding a total of 1,031 spectra. We observed an increase in antibiotic resistance detection whenever either a curve based similarity coefficient (Pearson or ranked Pearson was applied rather than a peak based (Dice and/or the optimized preprocessing parameters were applied. Increases in antimicrobial resistance detection were scored using the jackknife maximum similarity technique following cluster analysis. From the first four groups of antibiotic resistant isolates, the optimized preprocessing parameters increased detection respective to the aforementioned groups by: 1 five percent 2 nine percent 3 ten percent, and 4 two percent. An additional second

  18. Dihydrocodeine / Agonists for Alcohol Dependents

    Directory of Open Access Journals (Sweden)

    Albrecht eUlmer

    2012-03-01

    Full Text Available Objective: Alcohol addiction too often remains insufficiently treated. It shows the same profile as severe chronic diseases, but no comparable, effective basic treatment has been established up to now. Especially patients with repeated relapses, despite all therapeutic approaches, and patients who are not able to attain an essential abstinence to alcohol, need a basic medication. It seems necessary to acknowledge that parts of them need any agonistic substance, for years, possibly lifelong. For >14 years, we have prescribed such substances with own addictive character for these patients.Methods: We present a documented best possible practice, no designed study. Since 1997, we prescribed Dihydrocodeine (DHC to 102 heavily alcohol addict-ed patients, later, also Buprenorphine, Clomethiazole (>6 weeks, Baclofen and in one case Amphetamine, each on individual indication. This paper focuses on the data with DH, especially. The Clomethiazole-data has been submitted to a German journal. The number of treatments with the other substances is still low. Results: The 102 patients with the DHC-treatment had 1367 medically assisted detoxifications and specialized therapies before! The 4 years-retention rate was 26.4%, including 2.8% successfully terminated treatments. In our 12-step scale on clinical impression, we noticed a significant improvement from mean 3.7 to 8.4 after 2 years. The demand for medically assisted detoxifications in the 2 years remaining patients was reduced by 65.5%. Mean GGT improved from 206.6 U/l at baseline to 66.8 U/l after 2 years. Experiences with the other substances are similar but different in details.Conclusions: Similar to the Italian studies with GHB and Baclofen, we present a new approach, not only with new substances, but also with a new setting and much more trusting attitude. We observe a huge improvement, reaching an almost optimal, stable, long term status in around ¼ of the patients already. Many further

  19. Enhancement of oxidation resistance of NBD 200 silicon nitride ceramics by aluminum implantation

    Science.gov (United States)

    Mukundhan, Priya

    reduced by up to two orders of magnitude, the surface morphology and the phase characteristics of the oxides are enhanced as well. We have shown that aluminum implantation retards the outward diffusion of Mg2+ and lends a degree of protectiveness to the otherwise non-protective oxide layer. Diffusion studies using Mg-, Na- and Al-implanted silica model specimens have confirmed the effectiveness of Al in inhibiting the diffusion of Mg2+.

  20. Acute and Chronic Effects of ß2-Adrenoceptor Agonists in Relation to Exercise Performance and Doping with Emphasis on Terbutaline

    DEFF Research Database (Denmark)

    Hostrup, Morten

    This thesis addresses the performance enhancing effects of β2-agonists (asthma medication) with emphasis on terbutaline in the context of doping. Given the high prevalence of asthma in the athletic population, β2-agonists are among the most used drugs in competitive sport. While there is consensus...

  1. Expression of a wheat MYB gene in transgenic tobacco enhances resistance to Ralstonia solanacearum, and to drought and salt stresses.

    Science.gov (United States)

    Liu, Hongxia; Zhou, Xianyao; Dong, Na; Liu, Xin; Zhang, Huaiyu; Zhang, Zengyan

    2011-09-01

    MYB transcription factors play diverse roles in plant growth, developmental processes and stress responses. A full-length cDNA sequence of a MYB gene, namely TaPIMP1, was isolated from wheat (Triticum aestivum L.). The TaPIMP1 transcript level was significantly up-regulated by inoculation with a fungal pathogen Bipolaris sorokiniana and by drought treatment. TaPIMP1 encodes the MYB protein TaPIMP1 consisting of 323 amino acids. TaPIMP1 contains two MYB DNA binding domains (R2, R3), two putative nuclear localization sites and two putative transcription activation domains. TaPIMP1 is a new member of the R2R3-MYB transcription factor subfamily. Transient expression in onion epidermal cells of GFP fused with TaPIMP1 proved that subcellular localization of TaPIMP1 occurred in the nucleus. The TaPIMP1 gene was transferred into tobacco (Nicotiana tabacum L.) cultivar W38 by Agrobacterium-mediated transformation. After screening through PCR and RT-PCR analyses, transgenic tobacco lines expressing TaPIMP1 were identified and evaluated for pathogen resistance, and drought and salt tolerance. Compared to untransformed tobacco host plants, TaPIMP1 expressing plants displayed significantly enhanced resistance to Ralstonia solanacearum and exhibited improved tolerances to drought and salt stresses. In these transgenic lines, the activities of phenylalanine ammonia-lyase (PAL) and superoxide dismutase (SOD) were significantly increased relative to wild-type tobacco plants. The results suggested that the wheat R2R3-MYB transcription factor plays an important role in modulating responses to biotic and abiotic stresses.

  2. Chromate Reductase YieF from Escherichia coli Enhances Hexavalent Chromium Resistance of Human HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Xuan Liu

    2015-05-01

    Full Text Available Hexavalent chromium (Cr(VI is a serious environmental pollutant and human toxicant. Mammalian cells are very sensitive to chromate as they lack efficient chromate detoxifying strategy, e.g., chromate-reducing genes that are widely present in prokaryotes. To test whether introduction of prokaryotic chromate-reducing gene into mammalian cells could render higher chromate resistance, an Escherichia coli chromate-reducing gene yieF was transfected into human HepG2 cells. The expression of yieF was measured in stably transfected cells HepG2-YieF by quantitative RT-PCR and found up-regulated by 3.89-fold upon Cr(VI induction. In chromate-reducing ability test, HepG2-YieF cells that harbored the reductase showed significantly higher reducing ability of Cr(VI than HepG2 control cells. This result was further supported by the evidence of increased Cr(VI-removing ability of crude cell extract of HepG2-YieF. Moreover, HepG2-YieF demonstrated 10% higher viability and decreased expression of GSH synthesizing enzymes under Cr(VI stress. Subcellular localization of YieF was determined by tracing GFP-YieF fusion protein that was detected in both nucleus and cytoplasm by laser confocal microscopy. Altogether, this study successfully demonstrated that the expression of a prokaryotic Cr(VI-reducing gene yieF endowed mammalian cell HepG2 with enhanced chromate resistance, which brought new insight of Cr(VI detoxification in mammalian cells.

  3. Oseltamivir-resistant pandemic A(H1N1) 2009 influenza viruses detected through enhanced surveillance in the Netherlands, 2009-2010

    NARCIS (Netherlands)

    Meijer, Adam; Jonges, Marcel; Abbink, Floor; Ang, Wim; van Beek, Janko; Beersma, Matthias; Bloembergen, Peter; Boucher, Charles; Claas, Eric; Donker, Ge; van Gageldonk-Lafeber, Rianne; Isken, Leslie; Kroes, Aloys; Leenders, Sander; van der Lubben, Mariken; Mascini, Ellen; Niesters, Bert; Oosterheert, Jan Jelrik; Osterhaus, Albert; Riesmeijer, Rob; Riezebos-Brilman, Annelies; Schutten, Martin; Sebens, Fre; Stelma, Foekje; Swaan, Corien; Timen, Aura; van 't Veen, Annemarie; van der Vries, Erhard; Wierik, Margreet Te; Koopmans, Marion; de Jong, A

    2011-01-01

    Enhanced surveillance of infections due to the pandemic A(H1N1) influenza virus, which included monitoring for antiviral resistance, was carried out in the Netherlands from late April 2009 through late May 2010. More than 1100 instances of infection with the pandemic A(H1N1) influenza virus from 200

  4. Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability.

    Science.gov (United States)

    Christiansen, Elisabeth; Due-Hansen, Maria E; Urban, Christian; Grundmann, Manuel; Schmidt, Johannes; Hansen, Steffen V F; Hudson, Brian D; Zaibi, Mohamed; Markussen, Stine B; Hagesaether, Ellen; Milligan, Graeme; Cawthorne, Michael A; Kostenis, Evi; Kassack, Matthias U; Ulven, Trond

    2013-02-14

    The free fatty acid receptor 1 (FFA1, also known as GPR40) mediates enhancement of glucose-stimulated insulin secretion and is emerging as a new target for the treatment of type 2 diabetes. Several FFA1 agonists are known, but the majority of these suffer from high lipophilicity. We have previously reported the FFA1 agonist 3 (TUG-424). We here describe the continued structure-activity exploration and optimization of this compound series, leading to the discovery of the more potent agonist 40, a compound with low lipophilicity, excellent in vitro metabolic stability and permeability, complete oral bioavailability, and appreciable efficacy on glucose tolerance in mice. PMID:23294321

  5. GENETICS OF STEM RUST RESISTANCE IN THE SPRING WHEAT CULTIVAR THATCHER AND THE ENHANCEMENT OF STEM RUST RESISTANCE BY LR34

    Science.gov (United States)

    Three recombinant inbred line populations from the crosses RL6071/Thatcher, RL6071/RL6058 (Thatcher Lr34), and Thatcher/RL6058, were used to study the genetics of stem rust resistance in Thatcher. Segregation of stem rust resistance in each population was used to determine the number of genes confer...

  6. Thalidomide enhances both primary and secondary host resistances to Listeria monocytogenes infection by a neutrophil-related mechanism in female B6C3F1 mice

    International Nuclear Information System (INIS)

    Previously, we have reported that thalidomide can modulate the immune responses in female B6C3F1 mice. Furthermore, thalidomide immunomodulation increased primary host resistance to intravenously infected Listeria monocytogenes. The present study was intended to evaluate the mechanisms underlying the enhanced host resistance to L. monocytogenes by focusing on the neutrophils. Female B6C3F1 mice were treated intraperitoneally with thalidomide (100 mg/kg) for 15 days. Exposure to thalidomide increased the numbers of neutrophils in the spleens and livers of L. monocytogenes-infected mice when compared to the L. monocytogenes-infected control mice. Additionally, the percentage of neutrophils was also significantly increased after Thd treatment in L. monocytogenes-infected mice. Further studies using antibodies to deplete corresponding cells indicated that thalidomide-mediated increase in primary host resistance (both the moribundity and colony counts in the liver and spleen) to L. monocytogenes infection was due to its effect on neutrophils but not CD8+ T cells or NK cells. Finally, Thd exposure also increased host resistance to secondary host resistance to L. monocytogenes infection, and depletion of neutrophils abolished the protective effect. In conclusion, thalidomide enhanced host resistance to both primary and secondary L. monocytogenes infections by a neutrophil-related mechanism in female B6C3F1 mice

  7. Overexpression of TaPIEP1, a pathogen-induced ERF gene of wheat, confers host-enhanced resistance to fungal pathogen Bipolaris sorokiniana.

    Science.gov (United States)

    Dong, Na; Liu, Xin; Lu, Yan; Du, Lipu; Xu, Huijun; Liu, Hongxia; Xin, Zhiyong; Zhang, Zengyan

    2010-05-01

    Bipolaris sorokiniana is an economically important phytopathogen of wheat and other cereal species. In this paper, a novel pathogen-induced ethylene-responsive factor (ERF) gene of wheat, TaPIEP1, was isolated and characterized. The transcript of TaPIEP1 was significantly and rapidly induced by treatments with B. sorokiniana, and with ethylene (ET), jasmonate (JA), and abscisic acid. Molecular and biochemical assays demonstrated that TaPIEP1 is a new ERF transcription activator belonging to B-3c subgroup of the ERF family. Transgenic wheat lines overexpressing TaPIEP1 were generated by biolistic bombardment and molecular screening. Compared with the host wheat Yangmai12, six stable transgenic wheat lines overexpressing TaPIEP1 that exhibited significantly increased resistance to B. sorokiniana were identified by molecular detection in the T(0)-T(4) generations and by disease resistance tests. The degree of the enhanced resistance was correlated with an accumulation of the transcript level of TaPIEP1. Furthermore, the transcript levels of certain defense-related genes in the ET/JA pathways were markedly increased in the transgenic wheat plants with enhanced resistance. These results reveal that TaPIEP1 overexpression in wheat could obviously improve resistance to B. sorokiniana via activation of some defense genes, and TaPIEP1 gene may be useful in improving crop resistance to the pathogen.

  8. KP4 to control Ustilago tritici in wheat: Enhanced greenhouse resistance to loose smut and changes in transcript abundance of pathogen related genes in infected KP4 plants

    Directory of Open Access Journals (Sweden)

    Carolina Diaz Quijano

    2016-09-01

    Full Text Available Ustilago tritici causes loose smut, which is a seed-borne fungal disease of wheat, and responsible for yield losses up to 40%. Loose smut is a threat to seed production in developing countries where small scale farmers use their own harvest as seed material. The killer protein 4 (KP4 is a virally encoded toxin from Ustilago maydis and inhibits growth of susceptible races of fungi from the Ustilaginales. Enhanced resistance in KP4 wheat to stinking smut, which is caused by Tilletia caries, had been reported earlier. We show that KP4 in genetically engineered wheat increased resistance to loose smut up to 60% compared to the non-KP4 control under greenhouse conditions. This enhanced resistance is dose and race dependent. The overexpression of the transgene kp4 and its effect on fungal growth have indirect effects on the expression of endogenous pathogen defense genes.

  9. Maize peroxidase Px5 has a highly conserved sequence in inbreds resistant to mycotoxin producing fungi which enhances fungal and insect resistance.

    Science.gov (United States)

    Dowd, Patrick F; Johnson, Eric T

    2016-01-01

    Mycotoxin presence in maize causes health and economic issues for humans and animals. Although many studies have investigated expression differences of genes putatively governing resistance to producing fungi, few have confirmed a resistance role, or examined putative resistance gene structure in more than a couple of inbreds. The pericarp expression of maize Px5 has previously been associated with resistance to Aspergillus flavus growth and insects in a set of inbreds. Genes from 14 different inbreds that included ones with resistance and susceptibility to A. flavus, Fusarium proliferatum, F. verticillioides and F. graminearum and/or mycotoxin production were cloned using high fidelity enzymes, and sequenced. The sequence of Px5 from all resistant inbreds was identical, except for a single base change in two inbreds, only one of which affected the amino acid sequence. Conversely, the Px5 sequence from several susceptible inbreds had several base variations, some of which affected amino acid sequence that would potentially alter secondary structure, and thus enzyme function. The sequence of the maize peroxidase Px5 common to inbreds resistant to mycotoxigenic fungi was overexpressed in maize callus. Callus transformants overexpressing the gene caused significant reductions in growth for fall armyworms, corn earworms, and F. graminearum compared to transformant callus with a β-glucuronidase gene. This study demonstrates rarer transcripts of potential resistance genes overlooked by expression screens can be identified by sequence comparisons. A role in pest resistance can be verified by callus expression of the candidate genes, which can thereby justify larger scale transformation and regeneration of transgenic plants expressing the resistance gene for further evaluation. PMID:26659597

  10. The Multifarious PGPR Serratia marcescens CDP-13 Augments Induced Systemic Resistance and Enhanced Salinity Tolerance of Wheat (Triticum aestivum L..

    Directory of Open Access Journals (Sweden)

    Rajnish Prakash Singh

    Full Text Available The present study demonstrates the plant growth promoting (PGP potential of a bacterial isolate CDP-13 isolated from 'Capparis decidua' plant, and its ability to protect plants from the deleterious effect of biotic and abiotic stressors. Based on 16S rRNA gene sequence analysis, the isolate was identified as Serratia marcescens. Among the PGP traits, the isolate was found to be positive for ACC deaminase activity, phosphate solubilization, production of siderophore, indole acetic acid production, nitrogen fixation, and ammonia production. CDP-13 showed growth at an increased salt (NaCl concentration of up to 6%, indicating its potential to survive and associate with plants growing in saline soil. The inoculation of S. marcescens enhanced the growth of wheat plant under salinity stress (150-200 mM. It significantly reduced inhibition of plant growth (15 to 85% caused by salt stressors. Application of CDP-13 also modulated concentration (20 to 75% of different osmoprotectants (proline, malondialdehyde, total soluble sugar, total protein content, and indole acetic acid in plants suggesting its role in enabling plants to tolerate salt stressors. In addition, bacterial inoculation also reduced the disease severity caused by fungal infection, which illustrated its ability to confer induced systemic resistance (ISR in host plants. Treatment of wheat plants with the test organism caused alteration in anti-oxidative enzymes activities (Superoxide dismutase, Catalase, and Peroxidase under various salinity levels, and therefore minimizes the salinity-induced oxidative damages to the plants. Colonization efficiency of strain CDP-13 was confirmed by CFU count, epi-fluorescence microscopy, and ERIC-PCR-based DNA fingerprinting approach. Hence, the study indicates that bacterium CDP-13 enhances plant growth, and has potential for the amelioration of salinity stress in wheat plants. Likewise, the results also provide insights into biotechnological approaches to

  11. The Multifarious PGPR Serratia marcescens CDP-13 Augments Induced Systemic Resistance and Enhanced Salinity Tolerance of Wheat (Triticum aestivum L.).

    Science.gov (United States)

    Singh, Rajnish Prakash; Jha, Prabhat Nath

    2016-01-01

    The present study demonstrates the plant growth promoting (PGP) potential of a bacterial isolate CDP-13 isolated from 'Capparis decidua' plant, and its ability to protect plants from the deleterious effect of biotic and abiotic stressors. Based on 16S rRNA gene sequence analysis, the isolate was identified as Serratia marcescens. Among the PGP traits, the isolate was found to be positive for ACC deaminase activity, phosphate solubilization, production of siderophore, indole acetic acid production, nitrogen fixation, and ammonia production. CDP-13 showed growth at an increased salt (NaCl) concentration of up to 6%, indicating its potential to survive and associate with plants growing in saline soil. The inoculation of S. marcescens enhanced the growth of wheat plant under salinity stress (150-200 mM). It significantly reduced inhibition of plant growth (15 to 85%) caused by salt stressors. Application of CDP-13 also modulated concentration (20 to 75%) of different osmoprotectants (proline, malondialdehyde, total soluble sugar, total protein content, and indole acetic acid) in plants suggesting its role in enabling plants to tolerate salt stressors. In addition, bacterial inoculation also reduced the disease severity caused by fungal infection, which illustrated its ability to confer induced systemic resistance (ISR) in host plants. Treatment of wheat plants with the test organism caused alteration in anti-oxidative enzymes activities (Superoxide dismutase, Catalase, and Peroxidase) under various salinity levels, and therefore minimizes the salinity-induced oxidative damages to the plants. Colonization efficiency of strain CDP-13 was confirmed by CFU count, epi-fluorescence microscopy, and ERIC-PCR-based DNA fingerprinting approach. Hence, the study indicates that bacterium CDP-13 enhances plant growth, and has potential for the amelioration of salinity stress in wheat plants. Likewise, the results also provide insights into biotechnological approaches to using PGPR

  12. Modulation Effect of Peroxisome Proliferator-Activated Receptor Agonists on Lipid Droplet Proteins in Liver.

    Science.gov (United States)

    Zhu, Yun-Xia; Zhang, Ming-Liang; Zhong, Yuan; Wang, Chen; Jia, Wei-Ping

    2016-01-01

    Peroxisome proliferator-activated receptor (PPAR) agonists are used for treating hyperglycemia and type 2 diabetes. However, the mechanism of action of these agonists is still under investigation. The lipid droplet-associated proteins FSP27/CIDEC and LSDP5, regulated directly by PPARγ and PPARα, are associated with hepatic steatosis and insulin sensitivity. Here, we evaluated the expression levels of FSP27/CIDEC and LSDP5 and the regulation of these proteins by consumption of a high-fat diet (HFD) or administration of PPAR agonists. Mice with diet-induced obesity were treated with the PPARγ or PPARα agonist, pioglitazone or fenofibrate, respectively. Liver tissues from db/db diabetic mice and human were also collected. Interestingly, FSP27/CIEDC was expressed in mouse and human livers and was upregulated in obese C57BL/6J mice. Fenofibrate treatment decreased hepatic triglyceride (TG) content and FSP27/CIDEC protein expression in mice fed an HFD diet. In mice, LSDP5 was not detected, even in the context of insulin resistance or treatment with PPAR agonists. However, LSDP5 was highly expressed in humans, with elevated expression observed in the fatty liver. We concluded that fenofibrate greatly decreased hepatic TG content and FSP27/CIDEC protein expression in mice fed an HFD, suggesting a potential regulatory role for fenofibrate in the amelioration of hepatic steatosis.

  13. Resistant prolactinoma: Is it monoclonal or polyclonal?

    OpenAIRE

    K.V.S Hari Kumar; Pitambar Prusty

    2013-01-01

    Prolactinomas are solitary benign neoplasms and resistance to dopamine agonists occur in a small percentage of prolactinomas. Multiple pituitary adenomas are reported in less than 1% of pituitary adenomas and rarely result in resistant prolactinoma. We recently encountered an interesting patient of hyperprolactinemia with multiple pituitary microadenomas. Dopamine agonist use resulted in prolactin normalization and subsequent pregnancy resulted in drug withdrawal. Repeat evaluation after deli...

  14. p8/TTDA overexpression enhances UV-irradiation resistance and suppresses TFIIH mutations in a Drosophila trichothiodystrophy model.

    Directory of Open Access Journals (Sweden)

    Javier Aguilar-Fuentes

    2008-11-01

    Full Text Available Mutations in certain subunits of the DNA repair/transcription factor complex TFIIH are linked to the human syndromes xeroderma pigmentosum (XP, Cockayne's syndrome (CS, and trichothiodystrophy (TTD. One of these subunits, p8/TTDA, interacts with p52 and XPD and is important in maintaining TFIIH stability. Drosophila mutants in the p52 (Dmp52 subunit exhibit phenotypic defects similar to those observed in TTD patients with defects in p8/TTDA and XPD, including reduced levels of TFIIH. Here, we demonstrate that several Dmp52 phenotypes, including lethality, developmental defects, and sterility, can be suppressed by p8/TTDA overexpression. TFIIH levels were also recovered in rescued flies. In addition, p8/TTDA overexpression suppressed a lethal allele of the Drosophila XPB homolog. Furthermore, transgenic flies overexpressing p8/TTDA were more resistant to UV irradiation than were wild-type flies, apparently because of enhanced efficiency of cyclobutane-pyrimidine-dimers and 6-4 pyrimidine-pyrimidone photoproducts repair. This study is the first using an intact higher-animal model to show that one subunit mutant can trans-complement another subunit in a multi-subunit complex linked to human diseases.

  15. Methicillin-resistant Staphylococcus aureus colonization in HIV-infected outpatients is common and detection is enhanced by groin culture.

    Science.gov (United States)

    Peters, P J; Brooks, J T; Limbago, B; Lowery, H K; McAllister, S K; Mindley, R; Fosheim, G; Gorwitz, R J; Guest, J L; Hageman, J; Fridge, J; Rimland, D

    2011-07-01

    SUMMARYAlthough high rates of clinical infection with methicillin-resistant Staphylococcus aureus (MRSA) have been reported in HIV-infected adults, data on MRSA colonization are limited. We enrolled HIV-infected adults receiving care at the Atlanta VA Medical Center. Swabs from each participant's nares and groin were cultured with broth enrichment for S. aureus. Of 600 HIV-infected adults, 79 (13%) were colonized with MRSA and 180 (30%) with methicillin-susceptible S. aureus. MRSA pulsed-field gel electrophoresis types USA300 (n=44, 54%) and USA500/Iberian (n=29, 35%) predominated. Inclusion of groin swabs increased MRSA detection by 24% and USA300 detection by 38%. In multivariate analysis, MRSA colonization compared to no MRSA colonization was associated with a history of MRSA clinical infection, rarely or never using condoms, and contact with prisons and jails. In summary, the prevalence of MRSA colonization was high in this study of HIV-infected adults and detection of USA300 was enhanced by groin culture. PMID:20843384

  16. Enhanced Heat Resistance of Al-Cu-Mg Alloy by a Combination of Pre-stretching and Underaging

    Science.gov (United States)

    Wang, Xiaohu; Liu, Zhiyi; Bai, Song; Lin, Lianghua; Ye, Chengwu; Wang, Heng

    2016-06-01

    Enhanced heat resistance of Al-Cu-Mg alloy by employing a combined effect of pre-stretching and underaging has been characterized by thermal exposure, tensile testing, transmission electron microscopy (TEM) examination, and quantitative analysis. Tensile testing results showed that the samples subjected to both pre-stretching and underaging processing, presented a high tensile strength up to 440 MPa after thermal exposure at 200 °C for 500 h. This suggests that the long-time application temperature of Al-Cu-Mg alloys, which were normally applied at elevated temperature below 150 °C or even below 100 °C, can be raised to 200 °C by employing a combined effect of pre-stretching and underaging. TEM results showed that a fine and a narrow size distribution range of S' phase was formed by the combined processing of pre-stretching and underaging, as compared to that without pre-stretching. Quantitative analysis results indicated that this narrow range of size distribution greatly reduced the growth rate of S' phase during thermal exposure. It is suggested that this effect was ascribed to the Ostwald ripening mechanism.

  17. Cadmium resistance in transgenic tobacco plants enhanced by expressing bean heavy metal-responsive gene PvSR2

    Institute of Scientific and Technical Information of China (English)

    CHAI; Tuanyao; (柴团耀); CHEN; Qiong; (陈琼); ZHANG; Yuxiu; (张玉秀); DONG; Juan; (董娟); AN; Chengcai; (安成才)

    2003-01-01

    PvSR2 (Phaseolus vulgaris stress-related gene) has been cloned from French bean and shown to be expressed specifically upon heavy metal treatment. In order to investigate the role of PvSR2 in plant, PvSR2 gene under the control of cauliflower mosaic virus 35S promoter was introduced into tobacco mediated with Agrobacterium tumefaciens LBA4404. The regenerated plantlets were selected on medium with 100 mg/L kanamycin. PCR and Southern blot analysis showed PvSR2 gene was integrated in tobacco genome. Gus and Northern blot analysis indicated PvSR2 gene was expressed in transgenic seedling. The heavy metal resistance assay showed that the transgenic tobacco seedlings with the PvSR2 coding sequence exhibited higher tolerance to Cd compared with wild-type (WT) under Cd exposure. The Cd content accumulated in root between transgenic and WT seedlings had no obvious difference at lower Cd external concentration (0.05-0.075 mmol/L CdCl2), whereas transgenic plant showed a lower root Cd content than the control at higher external Cd concentration (0.1 mmol/L CdCl2). These results suggested that the expression of PvSR2 can enhance the Cd tolerance, and PvSR2 may be involved in Cd transportation and accumulation at the test concentration of 0.1 mmol/L Cd.

  18. Electrical resistivity tomography to monitor enhanced biodegradation of hydrocarbons with Rhodococcus erythropolis T902.1 at a pilot scale

    Science.gov (United States)

    Masy, Thibaut; Caterina, David; Tromme, Olivier; Lavigne, Benoît; Thonart, Philippe; Hiligsmann, Serge; Nguyen, Frédéric

    2016-01-01

    Petroleum hydrocarbons (HC) represent the most widespread contaminants and in-situ bioremediation remains a competitive treatment in terms of cost and environmental concerns. However, the efficiency of such a technique (by biostimulation or bioaugmentation) strongly depends on the environment affected and is still difficult to predict a priori. In order to overcome these uncertainties, Electrical Resistivity Tomography (ERT) appears as a valuable non-invasive tool to detect soil heterogeneities and to monitor biodegradation. The main objective of this study was to isolate an electrical signal linked to an enhanced bacterial activity with ERT, in an aged HC-contaminated clay loam soil. To achieve this, a pilot tank was built to mimic field conditions. Compared to a first insufficient biostimulation phase, bioaugmentation with Rhodococcus erythropolis T902.1 led to a HC depletion of almost 80% (6900 to 1600 ppm) in 3 months in the center of the contaminated zone, where pollutants were less bioavailable. In the meantime, lithological heterogeneities and microbial activities (growth and biosurfactant production) were successively discriminated by ERT images. In the future, this cost-effective technique should be more and more transferred to the field in order to monitor biodegradation processes and assist in selecting the most appropriate remediation technique.

  19. Chitosan and oligochitosan enhance ginger (Zingiber officinale Roscoe) resistance to rhizome rot caused by Fusarium oxysporum in storage.

    Science.gov (United States)

    Liu, Yiqing; Wisniewski, Michael; Kennedy, John F; Jiang, Yusong; Tang, Jianmin; Liu, Jia

    2016-10-20

    The ability of chitosan and oligochitosan to enhance ginger (Zingiber officinale) resistance to rhizome rot caused by Fusarium oxysporum in storage was investigated. Both chitosan and oligochitosan at 1 and 5g/L significantly inhibited rhizome rot, with the best control at 5g/L. Chitosan and oligochitosan applied at 5g/L also reduced weight loss, measured as a decrease in fresh weight, but did not affect soluble solids content or titratable acidity of rhizomes. The two compounds applied at 5g/L induced β-1,3-glucanase and phenylalanine ammonia-lyase enzyme activity and the transcript levels of their coding genes, as well as the total phenolic compounds in rhizome tissues. Therefore, the ability of chitosan and oligochitosan to reduce rot in stored rhizomes may be associated with their ability to induce defense responses in ginger. These results have practical implications for the application of chitosan and oligochitosan to harvested ginger rhizomes to reduce postharvest losses. PMID:27474591

  20. Constitutive production of nitric oxide leads to enhanced drought stress resistance and extensive transcriptional reprogramming in Arabidopsis.

    Science.gov (United States)

    Shi, Haitao; Ye, Tiantian; Zhu, Jian-Kang; Chan, Zhulong

    2014-08-01

    Nitric oxide (NO) is involved in plant responses to many environmental stresses. Transgenic Arabidopsis lines that constitutively express rat neuronal NO synthase (nNOS) were described recently. In this study, it is reported that the nNOS transgenic Arabidopsis plants displayed high levels of osmolytes and increased antioxidant enzyme activities. Transcriptomic analysis identified 601 or 510 genes that were differentially expressed as a consequence of drought stress or nNOS transformation, respectively. Pathway and gene ontology (GO) term enrichment analyses revealed that genes involved in photosynthesis, redox, stress, and phytohormone and secondary metabolism were greatly affected by the nNOS transgene. Several CBF genes and members of zinc finger gene families, which are known to regulate transcription in the stress response, were changed by the nNOS transgene. Genes regulated by both the nNOS transgene and abscisic acid (ABA) treatments were compared and identified, including those for two ABA receptors (AtPYL4 and AtPYL5). Moreover, overexpression of AtPYL4 and AtPYL5 enhanced drought resistance, antioxidant enzyme activity, and osmolyte levels. These observations increase our understanding of the role of NO in drought stress response in Arabidopsis. PMID:24868034

  1. Multifunctional substrate of Al alloy based on general hierarchical micro/nanostructures: superamphiphobicity and enhanced corrosion resistance

    Science.gov (United States)

    Li, Xuewu; Shi, Tian; Liu, Cong; Zhang, Qiaoxin; Huang, Xingjiu

    2016-01-01

    Aluminum alloys are vulnerable to penetrating and peeling failures in seawater and preparing a barrier coating to isolate the substrate from corrosive medium is an effective anticorrosion method. Inspired by the lotus leaves effect, a wetting alloy surface with enhanced anticorrosion behavior has been prepared via etch, deposition, and low-surface-energy modification. Results indicate that excellent superamphiphobicity has been achieved after the modification of the constructed hierarchical labyrinth-like microstructures and dendritic nanostructures. The as-prepared surface is also found with good chemical stability and mechanical durability. Furthermore, superior anticorrosion behaviors of the resultant samples in seawater are investigated by electrochemical measurements. Due to trapped air in micro/nanostructures, the newly presented solid-air-liquid contacting interface can help to resist the seawater penetration by greatly reducing the interface interaction between corrosive ions and the superamphiphobic surface. Finally, an optimized two-layer perceptron artificial neural network is set up to model and predict the cause-and-effect relationship between preparation conditions and the anticorrosion parameters. This work provides a great potential to extend the applications of aluminum alloys especially in marine engineering fields. PMID:27775053

  2. A study on improvement of low alloy steel for nuclear power plant through enhancement of fatigue resistance

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kwan Seon; Lee, H. C. [Seoul National University, Seoul (Korea, Republic of)

    1997-08-01

    The goal of this research project is to improve the low alloy steel for nuclear power plants made in Korea through enhancement of fatigue resistance. In order to achieve this goal, the characterization of SA508-3 steels used pressure vessel, YGN-3,4,5, UCN-3, 4 and JSW was carried out. The major difference of the different products was found to be the grain size. The domestic products showed thick interlath carbide layers which different from the JSW product. The fatigue crack propagation rates were found to be lower in aqueous solution than in air and the difference in the propagation rates increased in the near-threshold region. The fatigue crack propagation rates were significantly lower in vacuum than in other environments. In air and vacuum, the crack closure levels were higher in the near-threshold region and they decreased and reached to the constant values with increasing {delta}K. The crack closure level in aqueous solution was found to be higher than that in air and it increased initially with increasing the exposure time to the solution and reached to the maximum value with increasing {delta}K. 31 refs., 13 tabs., 63 figs. (author)

  3. Enhanced Heat Resistance of Al-Cu-Mg Alloy by a Combination of Pre-stretching and Underaging

    Science.gov (United States)

    Wang, Xiaohu; Liu, Zhiyi; Bai, Song; Lin, Lianghua; Ye, Chengwu; Wang, Heng

    2016-09-01

    Enhanced heat resistance of Al-Cu-Mg alloy by employing a combined effect of pre-stretching and underaging has been characterized by thermal exposure, tensile testing, transmission electron microscopy (TEM) examination, and quantitative analysis. Tensile testing results showed that the samples subjected to both pre-stretching and underaging processing, presented a high tensile strength up to 440 MPa after thermal exposure at 200 °C for 500 h. This suggests that the long-time application temperature of Al-Cu-Mg alloys, which were normally applied at elevated temperature below 150 °C or even below 100 °C, can be raised to 200 °C by employing a combined effect of pre-stretching and underaging. TEM results showed that a fine and a narrow size distribution range of S' phase was formed by the combined processing of pre-stretching and underaging, as compared to that without pre-stretching. Quantitative analysis results indicated that this narrow range of size distribution greatly reduced the growth rate of S' phase during thermal exposure. It is suggested that this effect was ascribed to the Ostwald ripening mechanism.

  4. Propolis and Herba Epimedii extracts enhance the non-specific immune response and disease resistance of Chinese sucker, Myxocyprinus asiaticus.

    Science.gov (United States)

    Zhang, Guobin; Gong, Shiyuan; Yu, Denghang; Yuan, Hanwen

    2009-03-01

    The effect of traditional Chinese medicine (TCM) formulated from propolis and Herba Epimedii extracts at the ratio of 3:1 (w/w) on non-specific immune response of Chinese sucker (Myxocyprinus asiaticus) was investigated. Fish were fed diets containing 0 (control), 0.1%, 0.5% or 1.0% TCM extracts for five weeks. The respiratory burst and phagocytic activities of blood leukocytes, lysozyme and natural haemolytic complement activities in plasma were measured weekly. After five weeks of feeding, fish were infected with Aeromonas hydrophila and mortalities were recorded. Results of this study showed that feeding Chinese sucker with different dosage of TCM extracts stimulated respiratory burst activity, phagocytosis of phagocytic cells in blood and lysozyme activity in plasma. They had no effect on plasma natural haemolytic complement activity. All dosage of treated groups showed reduced mortality following A. hydrophila infection. Feed containing 0.5% TCM extracts was the most effective with the mortality of the fish significantly reduced by 35% compared to the control. The results indicate that propolis and Herba Epimedii extracts in combination enhances the non-specific immune response and disease resistance of Chinese sucker against A. hydrophila. PMID:19185611

  5. Low sheet resistance titanium nitride films by low-temperature plasma-enhanced atomic layer deposition using design of experiments methodology

    Energy Technology Data Exchange (ETDEWEB)

    Burke, Micheal, E-mail: micheal.burke@tyndall.ie; Blake, Alan; Povey, Ian M.; Schmidt, Michael; Petkov, Nikolay; Carolan, Patrick; Quinn, Aidan J., E-mail: aidan.quinn@tyndall.ie [Tyndall National Institute, University College Cork, Cork (Ireland)

    2014-05-15

    A design of experiments methodology was used to optimize the sheet resistance of titanium nitride (TiN) films produced by plasma-enhanced atomic layer deposition (PE-ALD) using a tetrakis(dimethylamino)titanium precursor in a N{sub 2}/H{sub 2} plasma at low temperature (250 °C). At fixed chamber pressure (300 mTorr) and plasma power (300 W), the plasma duration and N{sub 2} flow rate were the most significant factors. The lowest sheet resistance values (163 Ω/sq. for a 20 nm TiN film) were obtained using plasma durations ∼40 s, N{sub 2} flow rates >60 standard cubic centimeters per minute, and purge times ∼60 s. Time of flight secondary ion mass spectroscopy data revealed reduced levels of carbon contaminants in the TiN films with lowest sheet resistance (163 Ω/sq.), compared to films with higher sheet resistance (400–600 Ω/sq.) while transmission electron microscopy data showed a higher density of nanocrystallites in the low-resistance films. Further significant reductions in sheet resistance, from 163 Ω/sq. to 70 Ω/sq. for a 20 nm TiN film (corresponding resistivity ∼145 μΩ·cm), were achieved by addition of a postcycle Ar/N{sub 2} plasma step in the PE-ALD process.

  6. Enhanced resistive switching and multilevel behavior in bilayered HfAlO/HfAlO{sub x} structures for non-volatile memory applications

    Energy Technology Data Exchange (ETDEWEB)

    Faita, F. L., E-mail: fabriciofaita@gmail.com [Centre of Physics, University of Minho, Campus de Gualtar, 4710-057 Braga (Portugal); Departamento de Física, Universidade Federal de Santa Catarina, Campus Trindade, 88040-900 Florianópolis, SC (Brazil); Silva, J. P. B., E-mail: josesilva@fisica.uminho.pt [Centre of Physics, University of Minho, Campus de Gualtar, 4710-057 Braga (Portugal); IFIMUP and IN-Institute of Nanoscience and Nanotechnology, Departamento de Física e Astronomia, Faculdade de Ciências da Universidade do Porto, 4169-007 Porto (Portugal); Pereira, M.; Gomes, M. J. M. [Centre of Physics, University of Minho, Campus de Gualtar, 4710-057 Braga (Portugal)

    2015-12-14

    In this work, hafnium aluminum oxide (HfAlO) thin films were deposited by ion beam sputtering deposition technique on Si substrate. The presence of oxygen vacancies in the HfAlO{sub x} layer deposited in oxygen deficient environment is evidenced from the photoluminescence spectra. Furthermore, HfAlO(oxygen rich)/HfAlO{sub x}(oxygen poor) bilayer structures exhibit multilevel resistive switching (RS), and the switching ratio becomes more prominent with increasing the HfAlO layer thickness. The bilayer structure with HfAlO/HfAlO{sub x} thickness of 30/40 nm displays the enhanced multilevel resistive switching characteristics, where the high resistance state/intermediate resistance state (IRS) and IRS/low resistance state resistance ratios are ≈10{sup 2} and ≈5 × 10{sup 5}, respectively. The switching mechanisms in the bilayer structures were investigated by the temperature dependence of the three resistance states. This study revealed that the multilevel RS is attributed to the coupling of ionic conduction and the metallic conduction, being the first associated to the formation and rupture of conductive filaments related to oxygen vacancies and the second with the formation of a metallic filament. Moreover, the bilayer structures exhibit good endurance and stability in time.

  7. Resistant prolactinoma: Is it monoclonal or polyclonal?

    Directory of Open Access Journals (Sweden)

    K. V. S. Hari Kumar

    2013-01-01

    Full Text Available Prolactinomas are solitary benign neoplasms and resistance to dopamine agonists occur in a small percentage of prolactinomas. Multiple pituitary adenomas are reported in less than 1% of pituitary adenomas and rarely result in resistant prolactinoma. We recently encountered an interesting patient of hyperprolactinemia with multiple pituitary microadenomas. Dopamine agonist use resulted in prolactin normalization and subsequent pregnancy resulted in drug withdrawal. Repeat evaluation after delivery showed a macroprolactinoma and dopamine agonist therapy resulted in biochemical cure without reduction in tumor size. We report the case for its presentation with multiple microadenomas progressing to macroprolactinoma suggesting polyclonal in origin.

  8. beta2-Agonists at the Olympic Games.

    Science.gov (United States)

    Fitch, Kenneth D

    2006-01-01

    The different approaches that the International Olympic Committee (IOC) had adopted to beta2-agonists and the implications for athletes are reviewed by a former Olympic team physician who later became a member of the Medical Commission of the IOC (IOC-MC). Steadily increasing knowledge of the effects of inhaled beta2-agonists on health, is concerned with the fact that oral beta2-agonists may be anabolic, and rapid increased use of inhaled beta2-agonists by elite athletes has contributed to the changes to the IOC rules. Since 2001, the necessity for athletes to meet IOC criteria (i.e., that they have asthma and/or exercise-induced asthma [EIA]) has resulted in improved management of athletes. The prevalence of beta2-agonist use by athletes mirrors the known prevalence of asthma symptoms in each country, although athletes in endurance events have the highest prevalence. The age-of-onset of asthma/EIA in elite winter athletes may be atypical. Of the 193 athletes at the 2006 Winter Olympics who met th IOC's criteria, only 32.1% had childhood asthma and 48.7% of athletes reported onset at age 20 yr or older. These findings lead to speculation that years of intense endurance training may be a causative factor in bronchial hyperreactivity. The distinction between oral (prohibited in sports) and inhaled salbutamol is possible, but athletes must be warned that excessive use of inhaled salbutamol can lead to urinary concentrations similar to those observed after oral administration. This article provides justification that athletes should provide evidence of asthma or EIA before being permitted to use inhaled beta2-agonists. PMID:17085798

  9. Reviews Related to the Techniques of Enhancing Microbial Stress Resistance%提高微生物抗逆性技术的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘玉萍; 唐鸿志; 许平

    2014-01-01

    Various stress resistant genes or mechanisms presented in microorganisms, and the discovery of these mechanisms laid a sound foundation for the directional enhancement of microbial stress tolerance. The main techniques of enhancing stress resistance of microorganisms contain over expression of stress-resistant genes, long-term adaptive evolution, genome shuffling, and heterologous expression of stress-resistant genes. These biological techniques can efficiently improve the stress resistance of industrial and environmental microorganisms, which surely benefited the bacteria based on industrial production and degradation of environmental pollutants.%微生物体内存在多种抗逆基因或机制,这些机制的发现为定向提高微生物的抗逆性奠定了基础。提高微生物抗逆性的技术主要有过表达抗逆基因,长期适应性进化, genome shuffling(基因组改组)和异源表达抗逆基因等。利用这几种技术增强微生物的抗逆性,在以微生物为主的工业生产和环境污染物降解方面有着广阔的应用前景。

  10. Enhanced Resistance of Snowdrop Lectin (Galanthus nivalis L. Agglutinin)-Expressing Maize to Asian Corn Borer (Ostrinia furnacalis Guenée)

    Institute of Scientific and Technical Information of China (English)

    Zhao-Yu WANG; Xiao-Fen SUN; Fei WANG; Ke-Xuan TANG; Ju-Ren ZHANG

    2005-01-01

    In order to enhance the resistance to pests, transgenic maize (Zea mays L.) plants from elite inbred lines containing the gene encoding snowdrop lectin (Galanthus nivalis L. agglutinin; GNA) under control of a phloem-specific promoter were generated through the Agrobacterium tumefaciens-mediated also studied. Thirty-six independently derived plants were subjected to molecular analyses. The level of GNA expression at 0.13%-0.28% of total soluble protein was observed in different transgenic plants. The progeny of three GNA-expressing independent transformants that were derived separately from the elite inbred lines DH4866, DH9942, and 8902, were selected for examination of resistance to ACB. These plants synthesized GNA at levels above 0.24% total soluble protein and enhanced resistance to ACB was demonstrated by exposing the plants to insects under greenhouse conditions. Semi-artificial diet bioassays also showed the toxic effect of GNA on ACB. Field evaluation of the transgenic plants supported the results from the artificial trial. In the present study, we have obtained new insect-resistant maize material for further breeding work and have found that GNA-expressing plants not only gained significant resistance to homopterans, but also showed toxicity to ACB, which is a type of Lepidoptera.

  11. Metabotropic glutamate receptor agonists potentiate a slow afterdepolarization in CNS neurons

    Science.gov (United States)

    Zheng, F.; Gallagher, J. P.

    1992-01-01

    We have previously reported that, in the rat dorsolateral septal nucleus (DLSN), metabotropic glutamate receptor (met-GluR) agonists evoked a slow depolarization accompanied by an increase in membrane conductance and burst firing. We have speculated that the burst firing elicited by met-GluR agonists may be due to activation or enhancement of a non-specific cation current, which exists in some DLSN neurons. Now we report that a slow afterdepolarization (sADP) mediated by a non-specific cation current was potentiated by both 1S,3R-ACPD and quisqualate. In addition, met-GluR agonists unmask a sADP in DLSN neurons which did not show a sADP under control conditions. Our data suggest that a non-specific cation current can be potentiated by activation of the met-GluR.

  12. Small Molecule Agonists of Cell Adhesion Molecule L1 Mimic L1 Functions In Vivo.

    Science.gov (United States)

    Kataria, Hardeep; Lutz, David; Chaudhary, Harshita; Schachner, Melitta; Loers, Gabriele

    2016-09-01

    Lack of permissive mechanisms and abundance of inhibitory molecules in the lesioned central nervous system of adult mammals contribute to the failure of functional recovery after injury, leading to severe disabilities in motor functions and pain. Peripheral nerve injury impairs motor, sensory, and autonomic functions, particularly in cases where nerve gaps are large and chronic nerve injury ensues. Previous studies have indicated that the neural cell adhesion molecule L1 constitutes a viable target to promote regeneration after acute injury. We screened libraries of known drugs for small molecule agonists of L1 and evaluated the effect of hit compounds in cell-based assays in vitro and in mice after femoral nerve and spinal cord injuries in vivo. We identified eight small molecule L1 agonists and showed in cell-based assays that they stimulate neuronal survival, neuronal migration, and neurite outgrowth and enhance Schwann cell proliferation and migration and myelination of neurons in an L1-dependent manner. In a femoral nerve injury mouse model, enhanced functional regeneration and remyelination after application of the L1 agonists were observed. In a spinal cord injury mouse model, L1 agonists improved recovery of motor functions, being paralleled by enhanced remyelination, neuronal survival, and monoaminergic innervation, reduced astrogliosis, and activation of microglia. Together, these findings suggest that application of small organic compounds that bind to L1 and stimulate the beneficial homophilic L1 functions may prove to be a valuable addition to treatments of nervous system injuries. PMID:26253722

  13. The increased expression of integrin α6 (ITGA6 enhances drug resistance in EVI1(high leukemia.

    Directory of Open Access Journals (Sweden)

    Norio Yamakawa

    Full Text Available Ecotropic viral integration site-1 (EVI1 is one of the candidate oncogenes for human acute myeloid leukemia (AML with chromosomal alterations at 3q26. High EVI1 expression (EVI1(high is a risk factor for AML with poor outcome. Using DNA microarray analysis, we previously identified that integrin α6 (ITGA6 was upregulated over 10-fold in EVI1(high leukemia cells. In this study, we determined whether the increased expression of ITGA6 is associated with drug-resistance and increased cell adhesion, resulting in poor prognosis. To this end, we first confirmed the expression pattern of a series of integrin genes using semi-quantitative PCR and fluorescence-activated cell sorter (FACS analysis and determined the cell adhesion ability in EVI1(high leukemia cells. We found that the adhesion ability of EVI1(high leukemia cells to laminin increased with the increased expression of ITGA6 and integrin β4 (ITGB4. The introduction of small-hairpin RNA against EVI1 (shEVI1 into EVI1(high leukemia cells reduced the cell adhesion ability and downregulated the expression of ITGA6 and ITGB4. In addition, the overexpression of EVI1 in EVI1(low leukemia cells enhanced their cell adhesion ability and increased the expression of ITGA6 and ITGB4. In a subsequent experiment, the introduction of shRNA against ITGA6 or ITGB4 into EVI1(high AML cells downregulated their cell adhesion ability; however, the EVI1(high AML cells transfected with shRNA against ITGA6 could not be maintained in culture. Moreover, treating EVI1(high leukemia cells with neutralizing antibodies against ITGA6 or ITGB4 resulted in an enhanced responsiveness to anti-cancer drugs and a reduction of their cell adhesion ability. The expression of ITGA6 is significantly elevated in cells from relapsed and EVI1(high AML cases; therefore, ITGA6 might represent an important therapeutic target for both refractory and EVI1(high AML.

  14. Computational Prediction and Biochemical Analyses of New Inverse Agonists for the CB1 Receptor.

    Science.gov (United States)

    Scott, Caitlin E; Ahn, Kwang H; Graf, Steven T; Goddard, William A; Kendall, Debra A; Abrol, Ravinder

    2016-01-25

    Human cannabinoid type 1 (CB1) G-protein coupled receptor is a potential therapeutic target for obesity. The previously predicted and experimentally validated ensemble of ligand-free conformations of CB1 [Scott, C. E. et al. Protein Sci. 2013 , 22 , 101 - 113 ; Ahn, K. H. et al. Proteins 2013 , 81 , 1304 - 1317] are used here to predict the binding sites for known CB1-selective inverse agonists including rimonabant and its seven known derivatives. This binding pocket, which differs significantly from previously published models, is used to identify 16 novel compounds expected to be CB1 inverse agonists by exploiting potential new interactions. We show experimentally that two of these compounds exhibit inverse agonist properties including inhibition of basal and agonist-induced G-protein coupling activity, as well as an enhanced level of CB1 cell surface localization. This demonstrates the utility of using the predicted binding sites for an ensemble of CB1 receptor structures for designing new CB1 inverse agonists.

  15. Enhancement of corrosion resistance for plasma nitrided AISI 4140 steel by plain air plasma post-oxidizing

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jiqiang; Liu, Han; Ye, Xuemei [Jiangsu Key Laboratory of Materials Surface Technology, Changzhou University, Changzhou 213164 (China); Chai, Yating [Materials Research and Education Center, Auburn University, AL 36849 (United States); Hu, Jing, E-mail: jinghoo@126.com [Jiangsu Key Laboratory of Materials Surface Technology, Changzhou University, Changzhou 213164 (China); Materials Research and Education Center, Auburn University, AL 36849 (United States)

    2015-05-25

    Highlights: • Plain air was primarily used for plasma post-oxidation for AISI 4140 steel. • A thin iron oxide layer composed of Fe{sub 3}O{sub 4} to Fe{sub 2}O{sub 3} was formed on top of the compound layer. • The ratio of Fe{sub 3}O{sub 4} to Fe{sub 2}O{sub 3} was closely related to the post-oxidizing conditions. • Post-oxidizing at 673 K for 60 min brought out highest ratio of Fe{sub 3}O{sub 4} to Fe{sub 2}O{sub 3} and optimum corrosion resistance. - Abstract: Plasma post-oxidizing was conducted immediately after plasma nitriding in the same equipment for AISI 4140 steel, and plain air was used as the oxygen bearing gas. The cross-sectional microstructures of the treated samples were observed by optical metallography and scanning electron microcopy (SEM), and the thickness of compound layer was measured accordingly. The phases were determined by X-ray diffraction (XRD), corrosion resistance was evaluated by electrochemical polarization, and the surface morphology before and after polarization test was also observed by SEM. Meanwhile, standard Gibbs free energy of the oxidation reactions existed in Fe–O system was calculated. The results show that a thin iron oxide layer composed of magnetite (Fe{sub 3}O{sub 4}) and hematite (Fe{sub 2}O{sub 3}) is formed on top of the compound layer during plasma post-oxidizing process, and the ratio of magnetite (Fe{sub 3}O{sub 4}) to hematite (Fe{sub 2}O{sub 3}) is depended on plasma post-oxidizing temperature and time. Highest ratio of Fe{sub 3}O{sub 4} to Fe{sub 2}O{sub 3} is obtained while post-oxidizing at 673 K for 60 min due to lower standard Gibbs free energy and appropriate forming rate for the formation of Fe{sub 3}O{sub 4} at this temperature. The thin oxide layer brings out significant enhancement of corrosion resistance, especially at higher ratios of Fe{sub 3}O{sub 4} to Fe{sub 2}O{sub 3}, due to the dense and adherent characteristic of Fe{sub 3}O{sub 4} oxide. Surface images of the post-oxidizing specimen

  16. Continuous intake of resistant maltodextrin enhanced intestinal immune response through changes in the intestinal environment in mice.

    Science.gov (United States)

    Miyazato, Shoko; Kishimoto, Yuka; Takahashi, Kyoko; Kaminogawa, Shuichi; Hosono, Akira

    2016-01-01

    We investigated the effect of resistant maltodextrin (RMD), a non-viscous soluble dietary fiber, on intestinal immune response and its mechanism in mice. Intestinal and fecal immunoglobulin A (IgA) were determined as indicators of intestinal immune response, and changes in the intestinal environment were focused to study the mechanism. BALB/c mice were fed one of three experimental diets, a control diet or a diet containing either 5% or 7.5% RMD, for two weeks. Continuous intake of RMD dose-dependently increased total IgA levels in the intestinal tract. Total IgA production from the cecal mucosa was significantly increased by RMD intake, while there were no significant differences in mucosal IgA production between the control group and experimental groups in the small intestine and colon. Continuous intake of RMD changed the composition of the cecal contents; that is, the composition of the cecal microbiota was changed, and short-chain fatty acids (SCFAs) were increased. There was an increased trend in Bacteroidales in the cecal microbiota, and butyrate, an SCFA, was significantly increased. Our study demonstrated that continuous intake of RMD enhanced the intestinal immune response by increasing the production of IgA in the intestinal tract. It suggested that the increase in total SCFAs and changes in the intestinal microbiota resulting from the fermentation of RMD orally ingested were associated with the induction of IgA production in intestinal immune cells, with the IgA production of the cecal mucosa in particular being significantly increased. PMID:26858925

  17. A synthetic antimicrobial peptide BTD-S expressed in Arabidopsis thaliana confers enhanced resistance to Verticillium dahliae.

    Science.gov (United States)

    Li, Feng; Shen, Hao; Wang, Ming; Fan, Kai; Bibi, Noreen; Ni, Mi; Yuan, Shuna; Wang, Xuede

    2016-08-01

    BTD-S is a synthetic non-cyclic θ-defensin derivative which was previously designed in our laboratory based on baboon θ-defensins (BTDs). It shows robust antimicrobial activity against economically important phytopathogen, Verticillium dahliae. Here, we deduced the coding nucleotide sequence of BTD-S and introduced the gene into wild-type (ecotype Columbia-0) Arabidopsis thaliana plants. Results demonstrated that BTD-S-transgenic lines displayed in bioassays inhibitory effects on the growth of V. dahliae in vivo and in vitro. Based on symptom severity, enhanced resistance was found in a survey of BTD-S-transgenic lines. Besides, crude protein extracts from root tissues of BTD-S-transformed plants significantly restricted the growth of fungal hyphae and the germination of conidia. Also, fungal biomass over time determined by real-time PCR demonstrated the overgrowth of V. dahliae in wild-type plants 2-3 weeks after inoculation, while almost no fungal DNA was detected in aerial tissues of their transgenic progenitors. The result suggested that fungus failed to invade and progress acropetally up to establish a systemic infection in BTD-S-transgenic plants. Moreover, the assessment of basal defense responses was performed in the leaves of WT and BTD-S-transgenic plants. The mitigated oxidative stress and low antioxidase level in BTD-S-transgenic plants revealed that BTD-S acts via permeabilizing target microbial membranes, which is in a category different from hypersensitive response-dependent defense. Taken together, our results demonstrate that BTD-S is a promising gene to be explored for transgenic engineering for plant protection against Verticillium wilt.

  18. FXR agonist activity of conformationally constrained analogs of GW 4064

    Energy Technology Data Exchange (ETDEWEB)

    Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y.; Caldwell, Richard D.; Caravella, Justin A.; Chen, Lihong; Creech, Katrina L.; Deaton, David N.; Madauss, Kevin P.; Marr, Harry B.; McFadyen, Robert B.; Miller, Aaron B.; Navas, III, Frank; Parks, Derek J.; Spearing, Paul K.; Todd, Dan; Williams, Shawn P.; Wisely, G. Bruce; (GSKNC)

    2010-09-27

    Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

  19. Polymorphism in the Plasmodium falciparum chloroquine-resistance transporter protein links verapamil enhancement of chloroquine sensitivity with the clinical efficacy of amodiaquine

    Directory of Open Access Journals (Sweden)

    Warhurst David C

    2003-09-01

    Full Text Available Abstract Background Chloroquine accumulates in the acidic digestive vacuole of the intraerythrocytic malaria parasite, and prevents the detoxication of haematin released during haemoglobin digestion. Changes in protein PfCRT in the digestive vacuole membrane of growing intra-erythrocytic stages of Plasmodium falciparum are crucial for resistance. Expressed in yeast, PfCRT resembles an anion channel. Depressed anion channel function could increase intralysosomal pH to reduce entry of basic drug, or enhanced function could reduce drug interaction with target haematin. The most important resistance-associated change is from positively-charged lysine-76 to neutral threonine which could facilitate drug efflux through a putative channel. It has been proposed that the resistance-reversing effect of verapamil is due to hydrophobic binding to the mutated PfCRT protein, and replacement of the lost positive charge, which repels the access of 4-aminoquinoline cations, thus partially restoring sensitivity. Desethylamodiaquine, the active metabolite of amodiaquine, which has significant activity in chloroquine-resistance, may also act similarly on its own. Methods Changes in physicochemical parameters in different CQ-resistant PfCRT sequences are analysed, and correlations with drug activity on lines transfected with different alleles of the pfcrt gene are examined. Results and conclusions The results support the idea that PfCRT is a channel which, in resistant parasites, can allow efflux of chloroquine from the digestive vacuole. Activity of the chloroquine/verapamil combination and of desethylamodiaquine both correlate with the mean hydrophobicity of PfCRT residues 72-76. This may partly explain clinical-resistance to amodiaquine found in the first chloroquine-resistant malaria cases from South America and enables tentative prediction of amodiaquine's clinical activity against novel haplotypes of PfCRT.

  20. Laser Cladding of an Al-11.7Wt% Si Alloy on ZM5 Magnesium Alloy to Enhance the Corrosion Resistance

    Institute of Scientific and Technical Information of China (English)

    CHEN Chang-jun; WANG Mao-cai; WANG Dong-sheng

    2004-01-01

    Magnesium alloy is an important engineering materials, but the wider application is restricted by poor corrosion resistance. An attempt was made to enhance the corrosion resistance and microhardness of a Mg-Al base ZM5 alloy by laser cladding of Al-11.7Wt%Si alloy powder with thickness 1.1mm and 1.7mm. The microstructure, phase and corrosion properties were analyzed by scanning electron micrographic (SEM), electron probe microanalysis(EPMA), vicker hardness tester and corrosion measurement system, respectively. Microhardness of the cladding layer was enhanced to 150-375Hv as compared to 60-99Hv of the substrate. The corrosion potential (Ecorr) of the cladding sample was 80mv higher than the substrate, while the corrosion current (Icorr) was lower than the substrate.

  1. Laser Cladding of an Al-11.7Wt% Si Alloy on ZM5 Magnesium Alloy to Enhance the Corrosion Resistance

    Institute of Scientific and Technical Information of China (English)

    CHENChang-jun; WANGMao-cai; WANGDong-sheng

    2004-01-01

    Magnesium alloy is an important engineering materials, but the wider application is restricted by poor corrosion resistance. An attempt was made to enhance the corrosion resistance and microhardness of a Mg-Al base ZM5 alloy by laser cladding of A1-11.7Wt%Si alloy powder with thickness 1.1 mm and 1.7inm. The microstructure, phase and corrosion properties were analyzed by scanning electron micrographic (SEM), electron probe microanalysis(EPMA), vicker hardness tester and corrosion measurement system, respectively. Microhardness of the cladding layer was enhanced to 150-375Hv as compared to 60-99Hv of the substrate. The corrosion potential (Ecorr) of the cladding sample was 80mv higher than the substrate, while the corrosion current (lcorr) was lower than the substrate.

  2. Aliphatic acid-conjugated antimicrobial peptides--potential agents with anti-tumor, multidrug resistance-reversing activity and enhanced stability.

    Science.gov (United States)

    Deng, Xin; Qiu, Qianqian; Ma, Ke; Wang, Xuekun; Huang, Wenlong; Qian, Hai

    2015-07-28

    Compared with traditional therapeutics, antimicrobial peptides as novel anti-tumor agents have prominent advantages of higher specificity and circumvention of multi-drug resistance. In a previous study, we found that B1, an antimicrobial peptide derived from Cathelicidin-BF15, presented specific anti-tumor activity against several tumor cells. Since aliphatic chain-conjugated peptides have shown ameliorative activity and stability, we conjugated aliphatic acids with different lengths to the amino terminal of B1. All the conjugated peptides exhibited improved anti-tumor activity over B1. Further investigations revealed that the peptides were capable of disrupting the cell membrane, stimulating cytochrome c release into the cytosol, which results in apoptosis. The peptides also acted against multidrug resistant cells and had multidrug resistance-reversing effects. Additionally, conjugation of aliphatic acid enhanced the peptide stability in plasma. In summary, aliphatic acid-modified peptides might be promising anti-tumor agents in the future. PMID:26083110

  3. Folate decorated dual drug loaded nanoparticle: role of curcumin in enhancing therapeutic potential of nutlin-3a by reversing multidrug resistance.

    Science.gov (United States)

    Das, Manasi; Sahoo, Sanjeeb K

    2012-01-01

    Retinoblastoma is the most common intraocular tumor in children. Malfunctioning of many signaling pathways regulating cell survival or apoptosis, make the disease more vulnerable. Notably, resistance to chemotherapy mediated by MRP-1, lung-resistance protein (LRP) is the most challenging aspect to treat this disease. Presently, much attention has been given to the recently developed anticancer drug nutlin-3a because of its non-genotoxic nature and potency to activate tumor suppressor protein p53. However, being a substrate of multidrug resistance protein MRP1 and Pgp its application has become limited. Currently, research has step towards reversing Multi drug resistance (MDR) by using curcumin, however its clinical relevance is restricted by plasma instability and poor bioavailability. In the present investigation we tried to encapsulate nutlin-3a and curcumin in PLGA nanoparticle (NPs) surface functionalized with folate to enhance therapeutic potential of nutlin-3a by modulating MDR. We document that curcumin can inhibit the expression of MRP-1 and LRP gene/protein in a concentration dependent manner in Y79 cells. In vitro cellular cytotoxicity, cell cycle analysis and apoptosis studies were done to compare the effectiveness of native drugs (single or combined) and single or dual drug loaded nanoparticles (unconjugated/folate conjugated). The result demonstrated an augmented therapeutic efficacy of targeted dual drug loaded NPs (Fol-Nut-Cur-NPs) over other formulation. Enhanced expression or down regulation of proapoptotic/antiapoptotic proteins respectively and down-regulation of bcl2 and NFκB gene/protein by Fol-Nut-Cur-NPs substantiate the above findings. This is the first investigation exploring the role of curcumin as MDR modulator to enhance the therapeutic potentiality of nutlin-3a, which may opens new direction for targeting cancer with multidrug resistance phenotype. PMID:22470431

  4. Folate decorated dual drug loaded nanoparticle: role of curcumin in enhancing therapeutic potential of nutlin-3a by reversing multidrug resistance.

    Directory of Open Access Journals (Sweden)

    Manasi Das

    Full Text Available Retinoblastoma is the most common intraocular tumor in children. Malfunctioning of many signaling pathways regulating cell survival or apoptosis, make the disease more vulnerable. Notably, resistance to chemotherapy mediated by MRP-1, lung-resistance protein (LRP is the most challenging aspect to treat this disease. Presently, much attention has been given to the recently developed anticancer drug nutlin-3a because of its non-genotoxic nature and potency to activate tumor suppressor protein p53. However, being a substrate of multidrug resistance protein MRP1 and Pgp its application has become limited. Currently, research has step towards reversing Multi drug resistance (MDR by using curcumin, however its clinical relevance is restricted by plasma instability and poor bioavailability. In the present investigation we tried to encapsulate nutlin-3a and curcumin in PLGA nanoparticle (NPs surface functionalized with folate to enhance therapeutic potential of nutlin-3a by modulating MDR. We document that curcumin can inhibit the expression of MRP-1 and LRP gene/protein in a concentration dependent manner in Y79 cells. In vitro cellular cytotoxicity, cell cycle analysis and apoptosis studies were done to compare the effectiveness of native drugs (single or combined and single or dual drug loaded nanoparticles (unconjugated/folate conjugated. The result demonstrated an augmented therapeutic efficacy of targeted dual drug loaded NPs (Fol-Nut-Cur-NPs over other formulation. Enhanced expression or down regulation of proapoptotic/antiapoptotic proteins respectively and down-regulation of bcl2 and NFκB gene/protein by Fol-Nut-Cur-NPs substantiate the above findings. This is the first investigation exploring the role of curcumin as MDR modulator to enhance the therapeutic potentiality of nutlin-3a, which may opens new direction for targeting cancer with multidrug resistance phenotype.

  5. Exploring prospects of β3-adrenoceptor agonists and inverse agonists for colon mobility control

    Directory of Open Access Journals (Sweden)

    Maria Grazia Perrone

    2013-07-01

    Full Text Available Inverse agonists are useful active ingredient of drugs clinically used to treat diseases mainly involving receptors endowed with non-endogenous agonist induced activity (constitutive or basal activity. SP-1e and SP-1g are the first two potent and highly selective β3-adrenoceptor inverse agonists [EC50=181 nM (IA=- 64% and 136 nM (IA=-73%, respectively], which their peculiar activity seems due to the absolute configurations of the two stereogenic centres present in each molecule. Rat proximal colon motility measurements allowed their further pharmacological characterization and pA2 values determination by Schild analysis (7.89 and 8.16, respectively. The purpose of our work is a further characterization of our novel β3-adrenoceptor agonists (SP-1a-d, SP-1f,1h and inverse agonists (SP-1e and SP-1g on rat proximal colon motility and a confirmation of their inverse agonist nature in a more complex system like the functional test on rat proximal colon. Male Wistar rats segment of the proximal colon were placed in organ baths containing Krebs solution. Muscle tension was recorded isotonically. Cumulative β3-AR agonists doses experiments were performed for each test compound: isoprenaline, BRL37344, SP-1a-d, SP-1f and SP-1h were dissolved in Krebs. The EC50 values of each agonists and pA2 of inverse agonists were determined. SP- 1a-d, SP-1f and SP-1h in rat colon have a muscle relaxing effect thus confirming their partial agonist activity found in CHO-K1 cell line. SP-1e and SP-1g behaved as antagonists with pA2 values of 7.89 and 8.16, respectively. In conclusion, experiments carried out by using isolated rat proximal colon allowed us to determine the pA2 values of the two β3-AR inverse agonists and add knowledge on the behavior of a novel set of compounds and their possible value as agents useful whenever is necessary to also control the colon motility.

  6. Enhanced resistance to fluoroquinolones in laboratory-grown mutants & clinical isolates of Shigella due to synergism between efflux pump expression & mutations in quinolone resistance determining region

    Directory of Open Access Journals (Sweden)

    Neelam Taneja

    2015-01-01

    Full Text Available Background & objectives: There is a worldwide emergence of fluoroquinolone resistance in Shigella species. To understand the molecular mechanisms associated with fluoroquinolone resistance, naturally occurring fluoroquinolone-resistant strains and laboratory-induced spontaneous mutants of Shigella spp. were used and the relative contributions of acrAB-tolC efflux pumps, gyrase and topoisomerase target gene mutations towards fluoroquinolone resistance were determined. Methods: Eight Shigella flexneri and six S. dysenteriae clinical isolates were studied. Three consecutive mutants resistant to ciprofloxacin for S. flexneri SFM1 (≥0.25 µg/ml, SFM2 (≥4 µg/ml and SFM3 (≥32 µg/ml were selected in 15 steps from susceptible isolates by serial exposure to increasing concentrations of nalidixic acid and ciprofloxacin. Similarly, two mutants for S. dysenteriae SDM1 (≥0.25 µg/ml and SDM2 (≥4 µg/ml were selected in eight steps. After PCR amplification sequence analyses of gyrase and topoisomerase target genes were performed. Expression of efflux genes acrA, acrB, acrR and tolC was measured using real-time PCR. Results: Mutations were observed in gyrA Ser [83]→Leu, Asp [87]→Asn/Gly, Val [196]→Ala and in parC Phe [93]→Val, Ser [80]→Ile, Asp [101]→Glu and Asp [110]→Glu. Overall, acrA and acrB overexpression was associated with fluoroquinolone resistance ( p0 <0.05; while tolC and acrR expression levels did not. Interpretation & conclusions: Fluoroquinolone resistance in Shigella spp. is the end product of either a single or a combination of mutations in QRDRs and/ or efflux activity. Novel polymorphisms were observed at Val [196]→Ala in gyrA in clinical isolates and Phe [93]→Val, Asp [101]→Glu, Asp [110]→Glu and in parC in majority of laboratory-grown mutants.

  7. Fluoxetine does not alter the ability of dopamine D1 and D2 agonists to substitute for cocaine in squirrel monkeys

    OpenAIRE

    Soto, Paul L; Katz, Jonathan L.

    2008-01-01

    Fluoxetine has been shown to enhance several behavioral effects of cocaine, including its discriminative-stimulus effects. An interaction between increased serotonergic and dopaminergic actions produced by blockade of serotonin and dopamine reuptake, is one possible mechanism for the enhancement. The present study investigated the effects of fluoxetine on the cocaine-like discriminative-stimulus effects of the D2-like agonists quinpirole and (-)-NPA, and the D1-like agonist SKF 82958 in squir...

  8. Toll-Like Receptor 9 Agonists for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Davide Melisi

    2014-08-01

    Full Text Available The immune system has acquired increasing importance as a key player in cancer maintenance and growth. Thus, modulating anti-tumor immune mediators has become an attractive strategy for cancer treatment. Toll-like receptors (TLRs have gradually emerged as potential targets of newer immunotherapies. TLR-9 is preferentially expressed on endosome membranes of B-cells and plasmacytoid dendritic cells (pDC and is known for its ability to stimulate specific immune reactions through the activation of inflammation-like innate responses. Several synthetic CpG oligonucleotides (ODNs have been developed as TLR-9 agonists with the aim of enhancing cancer immune surveillance. In many preclinical models, CpG ODNs were found to suppress tumor growth and proliferation both in monotherapy and in addition to chemotherapies or target therapies. TLR-9 agonists have been also tested in several clinical trials in patients with solid tumors. These agents showed good tolerability and usually met activity endpoints in early phase trials. However, they have not yet been demonstrated to significantly impact survival, neither as single agent treatments, nor in combination with chemotherapies or cancer vaccines. Further investigations in larger prospective studies are required.

  9. Conservation Research and Development/ New Ultra-Low Carbon High Strength Steels with Improved Bake Hardenability for Enhanced Stretch Formability and Dent Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Anthony J. DeArdo; C. Isaac Garcia

    2003-12-15

    Conservation Research and Development/New Ultra-Low Carbon High Strength Steels with Improved Bake Hardenability for Enhanced Stretch Formability and Dent Resistance. The experimental work can be divided into four phases. In each phase, the materials were received or designed, processed and tested, to evaluate the BH increment or response, as a function of compositions and processing conditions. Microstructural characterization by various techniques was performed in order to gain insights into the mechanisms of flow stress increment by bake hardening.

  10. Interfacial Electrode-Driven Enhancement of the Switching Parameters of a Copper Oxide-Based Resistive Random-Access Memory Device

    Science.gov (United States)

    Sangani, L. D. Varma; Kumar, Ch. Ravi; Krishna, M. Ghanashyam

    2016-01-01

    The characteristics of an Au/Cu x O/Au bipolar resistive random-access memory device are reported. It is demonstrated that switching parameters of this device structure can be enhanced by introducing an interfacial Al layer between the Au top electrode and the Cu x O-based dielectric layer. The set and reset voltages are, respectively, between -2.5 V to -6.0 V and +1.2 V to +3.0 V for the Al-based device. In contrast, the range of values are -0.5 V to -2.5 V and +0.5 V to +1.5 V for the set and reset voltages in the absence of Al. The Al-based device has a higher low resistance state value of 5-6 KΩ as compared to the 0.3-0.5 KΩ for the Au-based device, which leads to a 12 times lower power dissipation factor and lower reset current of 370 μA. Endurance studies carried out over 50 switching cycles show less than 2% variation in both the low resistance and high resistance values. The conduction is ohmic at low values of bias and non-ohmic at higher bias voltage which shows that the enhanced behaviour is a result of the formation of an insulating aluminum oxide layer at the Al-Cu x O interface.

  11. Gd-based upconversion nanocarriers with yolk-shell structure for dual-modal imaging and enhanced chemotherapy to overcome multidrug resistance in breast cancer

    Science.gov (United States)

    Pan, Yuanwei; Zhang, Ling'e.; Zeng, Leyong; Ren, Wenzhi; Xiao, Xueshan; Zhang, Jichao; Zhang, Lili; Li, Aiguo; Lu, Guangming; Wu, Aiguo

    2015-12-01

    Multidrug resistance (MDR) of cancers is still a major challenge, and it is very important to develop visualized nanoprobes for the diagnosis and treatment of drug resistant cancers. In this work, we developed a multifunctional delivery system based on DOX-encapsulated NaYF4:Yb/Er@NaGdF4 yolk-shell nanostructures for simultaneous dual-modal imaging and enhanced chemotherapy in drug resistant breast cancer. Using the large pore volume of the nanostructure, the delivery system had a high loading efficiency and excellent stability. Also, an in vitro and in vivo toxicity study showed the good biocompatibility of the as-prepared yolk-shell nanomaterials. Moreover, by nanocarrier delivery, the uptake of DOX could be greatly increased in drug resistant MCF-7/ADR cells. Compared with free DOX, the as-prepared delivery system enhanced the chemotherapy efficacy against MCF-7/ADR cells, indicating the excellent capability for overcoming MDR. Furthermore, core-shell NaYF4:Yb/Er@NaGdF4 improved the upconversion luminescence (UCL) performance, and the designed delivery system could also be applied for simultaneous UCL and magnetic resonance (MR) imaging, which could be a good candidate as a dual-modal imaging nanoprobe. Therefore, we developed a multifunctional yolk-shell delivery system, which could have potential applications as a visualized theranostic nanoprobe to overcome MDR in breast cancer.

  12. Low-dose radiation enhances susceptibility to cisplatin in resistant ovarian cancer cells via downregulation of ERCC1 and Bcl-2

    Institute of Scientific and Technical Information of China (English)

    Xiaoran Liu; Donghai Liang; Tao Jiang; Qing Dong; Hongsheng Yu 

    2016-01-01

    Objective Ovarian cancer is one of the leading causes of mortality in patients with malignant gyneco-logical tumors. After surgical intervention for ovarian cancer, cisplatin (DDP)-based chemotherapy is the first-line treatment. However, a major chal enge to treating ovarian cancer is the development of chemore-sistance. Thus, the first aim of this study was to determine whether low-dose radiation could enhance the susceptibility of resistant ovarian cancer cel s to DDP. The second aim was to provide new strategies for treating DDP-resistant ovarian cancer by examining its mechanism. Methods A cel counting kit-8 (CCK8) assay was performed to measure cel proliferation. Flow cytometry was utilized to quantify the apoptosis of DDP-resistant ovarian cancer cel s (SKOV3/DDP) using Annexin V and propidium iodide staining. Real-time quantitative (qPCR) was used to analyze the messenger RNA (mRNA) expression levels of excision repair cross complementing-group 1 (ERCC1) and B-cel lymphoma 2 (Bcl-2) in SKOV3/DDP. Results The IC50 values of the control, conventional-dose, and low-dose groups were 9.367 ± 0.16, 9.289 ± 0.16, and 3.847 ± 0.15, respectively (P Conclusion Low-dose radiation enhanced the sensitivity of resistant ovarian cancer cel s to DDP, pos-sibly by decreasing the DNA repair capacity of tumor cel s and promoting apoptosis.

  13. Enhancement of glass-forming ability and bio-corrosion resistance of Zr-Co-Al bulk metallic glasses by the addition of Ag

    International Nuclear Information System (INIS)

    A novel Ni and Cu-free Zr-based bulk metallic glass (BMG) system with enhancement of glass-forming ability (GFA) and bio-corrosion resistance was prepared by copper mold casting by the addition of Ag. It was found that the addition of Ag can considerably enhance the glass-forming ability, as indicated by the increase of the critical glass dimension from 3 mm diameter of the ternary system to over 10 mm in the alloy of Zr53Co18.5Al23.5Ag5. The bio-corrosion behaviors of the Zr-based BMGs in phosphate buffered solution (PBS) were investigated by electrochemical polarization at 310 K. It was found that the addition of appropriate amount of Ag can enhance the corrosion resistance of the BMGs. The X-ray photoelectron spectroscopy (XPS) indicated that the formation of an Al2O3-enriched passive film is mainly responsible for the high corrosion resistance of Ag-bearing alloy in phosphate buffered solution.

  14. Isoflavone Agonists of IRF-3 Dependent Signaling Have Antiviral Activity against RNA Viruses

    OpenAIRE

    Bedard, Kristin M.; Wang, Myra L.; Proll, Sean C.; Loo, Yueh-Ming; Michael G Katze; Gale, Michael; Iadonato, Shawn P.

    2012-01-01

    There is a growing need for novel antiviral therapies that are broad spectrum, effective, and not subject to resistance due to viral mutations. Using high-throughput screening methods, including computational docking studies and an interferon-stimulated gene 54 (ISG54)-luciferase reporter assay, we identified a class of isoflavone compounds that act as specific agonists of innate immune signaling pathways and cause activation of the interferon regulatory factor (IRF-3) transcription factor. T...

  15. Enhancing Activity of Anticancer Drugs in Multidrug Resistant Tumors by Modulating P-Glycoprotein through Dietary Nutraceuticals.

    Science.gov (United States)

    Khan, Muhammad; Maryam, Amara; Mehmood, Tahir; Zhang, Yaofang; Ma, Tonghui

    2015-01-01

    Multidrug resistance is a principal mechanism by which tumors become resistant to structurally and functionally unrelated anticancer drugs. Resistance to chemotherapy has been correlated with overexpression of p-glycoprotein (p-gp), a member of the ATP-binding cassette (ABC) superfamily of membrane transporters. P-gp mediates resistance to a broad-spectrum of anticancer drugs including doxorubicin, taxol, and vinca alkaloids by actively expelling the drugs from cells. Use of specific inhibitors/blocker of p-gp in combination with clinically important anticancer drugs has emerged as a new paradigm for overcoming multidrug resistance. The aim of this paper is to review p-gp regulation by dietary nutraceuticals and to correlate this dietary nutraceutical induced-modulation of p-gp with activity of anticancer drugs. PMID:26514453

  16. Ectopic Expression of Hrf1 Enhances Bacterial Resistance via Regulation of Diterpene Phytoalexins, Silicon and Reactive Oxygen Species Burst in Rice

    Science.gov (United States)

    Zhong, Weigong; Yang, Jie; Okada, Kazunori; Yamane, Hisakazu; Zhang, Lei; Wang, Guang; Wang, Dong; Xiao, Shanshan; Chang, Shanshan; Qian, Guoliang; Liu, Fengquan

    2012-01-01

    Harpin proteins as elicitor derived from plant gram negative bacteria such as Xanthomonas oryzae pv. oryzae (Xoo), Erwinia amylovora induce disease resistance in plants by activating multiple defense responses. However, it is unclear whether phytoalexin production and ROS burst are involved in the disease resistance conferred by the expression of the harpinXoo protein in rice. In this article, ectopic expression of hrf1 in rice enhanced resistance to bacterial blight. Accompanying with the activation of genes related to the phytoalexin biosynthesis pathway in hrf1-transformed rice, phytoalexins quickly and consistently accumulated concurrent with the limitation of bacterial growth rate. Moreover, the hrf1-transformed rice showed an increased ability for ROS scavenging and decreased hydrogen peroxide (H2O2) concentration. Furthermore, the localization and relative quantification of silicon deposition in rice leaves was detected by scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometer (EDS). Finally, the transcript levels of defense response genes increased in transformed rice. These results show a correlation between Xoo resistance and phytoalexin production, H2O2, silicon deposition and defense gene expression in hrf1-transformed rice. These data are significant because they provide evidence for a better understanding the role of defense responses in the incompatible interaction between bacterial disease and hrf1-transformed plants. These data also supply an opportunity for generating nonspecific resistance to pathogens. PMID:22970151

  17. IGF-1R and ErbB3/HER3 contribute to enhanced proliferation and carcinogenesis in trastuzumab-resistant ovarian cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Jia, Yanhan [Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071 (China); Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Zhang, Yan [Department of Gynaecology and Obstetrics, PLA General Hospital, Beijing 100853 (China); Qiao, Chunxia; Liu, Guijun [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Zhao, Qing [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Department of Gynaecology and Obstetrics, PLA General Hospital, Beijing 100853 (China); Zhou, Tingting; Chen, Guojiang [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Li, Yali [Department of Gynaecology and Obstetrics, PLA General Hospital, Beijing 100853 (China); Feng, Jiannan; Li, Yan [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Zhang, Qiuping, E-mail: qpzhang@whu.edu.cn [Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071 (China); Peng, Hui, E-mail: p_h2002@hotmail.com [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Beijing 100850 (China)

    2013-07-12

    Highlights: •We established trastuzumab-resistant cell line SKOV3/T. •SKOV3/T enhances proliferation and in vivo carcinogenesis. •IGF-1R and HER3 genes were up-regulated in SKOV3/T based on microarray analysis. •Targeting IGF-1R and/or HER3 inhibited the proliferation of SKOV3/T. •Therapies targeting IGF-1R and HER3 might be effective in ovarian cancer. -- Abstract: Trastuzumab (Herceptin®) has demonstrated clinical potential in several types of HER2-overexpressing human cancers. However, primary and acquired resistance occurs in many HER2-positive patients with regimens. To investigate the possible mechanism of acquired therapeutic resistance to trastuzumab, we have developed a preclinical model of human ovarian cancer cells, SKOV3/T, with the distinctive feature of stronger carcinogenesis. The differences in gene expression between parental and the resistant cells were explored by microarray analysis, of which IGF-1R and HER3 were detected to be key molecules in action. Their correctness was validated by follow-up experiments of RT-PCR, shRNA-mediated knockdown, downstream signal activation, cell cycle distribution and survival. These results suggest that IGF-1R and HER3 differentially regulate trastuzumab resistance and could be promising targets for trastuzumab therapy in ovarian cancer.

  18. Ectopic expression of Hrf1 enhances bacterial resistance via regulation of diterpene phytoalexins, silicon and reactive oxygen species burst in rice.

    Directory of Open Access Journals (Sweden)

    Wenqi Li

    Full Text Available Harpin proteins as elicitor derived from plant gram negative bacteria such as Xanthomonas oryzae pv. oryzae (Xoo, Erwinia amylovora induce disease resistance in plants by activating multiple defense responses. However, it is unclear whether phytoalexin production and ROS burst are involved in the disease resistance conferred by the expression of the harpin(Xoo protein in rice. In this article, ectopic expression of hrf1 in rice enhanced resistance to bacterial blight. Accompanying with the activation of genes related to the phytoalexin biosynthesis pathway in hrf1-transformed rice, phytoalexins quickly and consistently accumulated concurrent with the limitation of bacterial growth rate. Moreover, the hrf1-transformed rice showed an increased ability for ROS scavenging and decreased hydrogen peroxide (H(2O(2 concentration. Furthermore, the localization and relative quantification of silicon deposition in rice leaves was detected by scanning electron microscopy (SEM and energy-dispersive X-ray spectrometer (EDS. Finally, the transcript levels of defense response genes increased in transformed rice. These results show a correlation between Xoo resistance and phytoalexin production, H(2O(2, silicon deposition and defense gene expression in hrf1-transformed rice. These data are significant because they provide evidence for a better understanding the role of defense responses in the incompatible interaction between bacterial disease and hrf1-transformed plants. These data also supply an opportunity for generating nonspecific resistance to pathogens.

  19. Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability

    Directory of Open Access Journals (Sweden)

    Xiaolin Zhang

    2016-10-01

    Full Text Available Metronidazole (MNZ is an effective agent that has been employed to eradicate Helicobacter pylori (H. pylori. The emergence of broad MNZ resistance in H. pylori has affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention concentration (MPC, plays an important role in selecting or enriching resistant mutants and regulating therapeutic effects. A strategy to reduce the MPC that can not only effectively treat H. pylori but also prevent resistance mutations is needed. H. pylori is highly resistant to lysozyme. Lysozyme possesses a hydrolytic bacterial cell wall peptidoglycan and a cationic dependent mode. These effects can increase the permeability of bacterial cells and promote antibiotic absorption into bacterial cells. In this study, human lysozyme (hLYS was used to probe its effects on the integrity of the H. pylori outer and inner membranes using as fluorescent probe hydrophobic 1-N-phenyl-naphthylamine (NPN and the release of aspartate aminotransferase. Further studies using a propidium iodide staining method assessed whether hLYS could increase cell permeability and promote cell absorption. Finally, we determined the effects of hLYS on the bactericidal dynamics and MPC of MNZ in H. pylori. Our findings indicate that hLYS could dramatically increase cell permeability, reduce the MPC of MNZ for H. pylori, and enhance its bactericidal dynamic activity, demonstrating that hLYS could reduce the probability of MNZ inducing resistance mutations.

  20. Hydrophobicity attainment and wear resistance enhancement on glass substrates by atmospheric plasma-polymerization of mixtures of an aminosilane and a fluorocarbon

    Energy Technology Data Exchange (ETDEWEB)

    Múgica-Vidal, Rodolfo, E-mail: rodolfo.mugica@alum.unirioja.es [Department of Mechanical Engineering, University of La Rioja, c/ Luis de Ulloa 20, 26004, Logroño, La Rioja (Spain); Alba-Elías, Fernando, E-mail: fernando.alba@unirioja.es [Department of Mechanical Engineering, University of La Rioja, c/ Luis de Ulloa 20, 26004, Logroño, La Rioja (Spain); Sainz-García, Elisa, E-mail: elisa.sainzg@unirioja.es [Department of Mechanical Engineering, University of La Rioja, c/ Luis de Ulloa 20, 26004, Logroño, La Rioja (Spain); Pantoja-Ruiz, Mariola, E-mail: mpruiz@ing.uc3m.es [Materials Science and Engineering Department, IAAB, Materials Performance Group, University Carlos III of Madrid, Av. Universidad 30, 28911, Leganés, Madrid (Spain)

    2015-08-30

    Graphical abstract: - Highlights: • APTES and PFH were used to coat glass by non-thermal atmospheric jet plasma. • A mixture of 75% of APTES and 25% PFH produced the best sample of this work. • Hydrophobicity was achieved by changes in surface morphology and chemistry. • Wear resistance was enhanced by the formation of siloxane groups. - Abstract: Mixtures of different proportions of two liquid precursors were subjected to plasma-polymerization by a non-thermal atmospheric jet plasma system in a search for a coating that achieves a hydrophobic character on a glass substrate and enhances its wear resistance. 1-Perfluorohexene (PFH) was chosen as a low-surface-energy precursor to promote a hydrophobic character. Aminopropyltriethoxysilane (APTES) was chosen for its contribution to the improvement of wear resistance by the formation of siloxane bonds. The objective of this work was to determine which of the precursors’ mixtures that were tested provides the coating with the most balanced enhancement of both hydrophobicity and wear resistance, given that coatings deposited with fluorocarbon-based precursors such as PFH are usually low in resistance to wear and coatings deposited with APTES are generally hydrophilic. The coatings obtained were analyzed by Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Fourier Transform Infra-Red (FTIR) spectroscopy, X-ray Photoelectron Spectroscopy (XPS), static Water Contact Angle (WCA) measurements, tribological ball-on-disc tests and contact profilometry. A relationship between the achievement of a hydrophobic character and the modifications to roughness and surface morphology and the incorporation of fluorocarbon groups in the surface chemistry was observed. Also, it was seen that the wear resistance was influenced by the SiOSi content of the coatings. In turn, the SiOSi content appears to be directly related to the percentage of APTES used in the mixture of precursors. The best conjunction of

  1. The hrpZ gene of Pseudomonas syringae pv. phaseolicola enhances resistance to rhizomania disease in transgenic Nicotiana benthamiana and sugar beet.

    Science.gov (United States)

    Pavli, Ourania I; Kelaidi, Georgia I; Tampakaki, Anastasia P; Skaracis, George N

    2011-01-01

    To explore possible sources of transgenic resistance to the rhizomania-causing Beet necrotic yellow vein virus (BNYVV), Nicotiana benthamiana plants were constructed to express the harpin of Pseudomonas syringae pv. phaseolicola (HrpZ(Psph)). The HrpZ protein was expressed as an N-terminal fusion to the PR1 signal peptide (SP/HrpZ) to direct harpin accumulation to the plant apoplast. Transgene integration was verified by mPCR in all primary transformants (T0), while immunoblot analysis confirmed that the protein HrpZ(Psph) was produced and the signal peptide was properly processed. Neither T0 plants nor selfed progeny (T1) showed macroscopically visible necrosis or any other macroscopic phenotypes. However, plants expressing the SP/HrpZ(Psph) showed increased vigor and grew faster in comparison with non-transgenic control plants. Transgenic resistance was assessed after challenge inoculation with BNYVV on T1 progeny by scoring of disease symptoms and by DAS-ELISA at 20 and 30 dpi. Transgenic and control lines showed significant differences in terms of the number of plants that became infected, the timing of infection and the disease symptoms displayed. Plants expressing the SP/HrpZ(Psph) developed localized leaf necrosis in the infection area and had enhanced resistance upon challenge with BNYVV. In order to evaluate the SP/HrpZ-based resistance in the sugar beet host, A. rhizogenes-mediated root transformation was exploited as a transgene expression platform. Upon BNYVV inoculation, transgenic sugar beet hairy roots showed high level of BNYVV resistance. In contrast, the aerial non-transgenic parts of the same seedlings had virus titers that were comparable to those of the seedlings that were untransformed or transformed with wild type R1000 cells. These findings indicate that the transgenically expressed SP/HrpZ protein results in enhanced rhizomania resistance both in a model plant and sugar beet, the natural host of BNYVV. Possible molecular mechanisms

  2. The hrpZ gene of Pseudomonas syringae pv. phaseolicola enhances resistance to rhizomania disease in transgenic Nicotiana benthamiana and sugar beet.

    Directory of Open Access Journals (Sweden)

    Ourania I Pavli

    Full Text Available To explore possible sources of transgenic resistance to the rhizomania-causing Beet necrotic yellow vein virus (BNYVV, Nicotiana benthamiana plants were constructed to express the harpin of Pseudomonas syringae pv. phaseolicola (HrpZ(Psph. The HrpZ protein was expressed as an N-terminal fusion to the PR1 signal peptide (SP/HrpZ to direct harpin accumulation to the plant apoplast. Transgene integration was verified by mPCR in all primary transformants (T0, while immunoblot analysis confirmed that the protein HrpZ(Psph was produced and the signal peptide was properly processed. Neither T0 plants nor selfed progeny (T1 showed macroscopically visible necrosis or any other macroscopic phenotypes. However, plants expressing the SP/HrpZ(Psph showed increased vigor and grew faster in comparison with non-transgenic control plants. Transgenic resistance was assessed after challenge inoculation with BNYVV on T1 progeny by scoring of disease symptoms and by DAS-ELISA at 20 and 30 dpi. Transgenic and control lines showed significant differences in terms of the number of plants that became infected, the timing of infection and the disease symptoms displayed. Plants expressing the SP/HrpZ(Psph developed localized leaf necrosis in the infection area and had enhanced resistance upon challenge with BNYVV. In order to evaluate the SP/HrpZ-based resistance in the sugar beet host, A. rhizogenes-mediated root transformation was exploited as a transgene expression platform. Upon BNYVV inoculation, transgenic sugar beet hairy roots showed high level of BNYVV resistance. In contrast, the aerial non-transgenic parts of the same seedlings had virus titers that were comparable to those of the seedlings that were untransformed or transformed with wild type R1000 cells. These findings indicate that the transgenically expressed SP/HrpZ protein results in enhanced rhizomania resistance both in a model plant and sugar beet, the natural host of BNYVV. Possible molecular

  3. The hrpZ gene of Pseudomonas syringae pv. phaseolicola enhances resistance to rhizomania disease in transgenic Nicotiana benthamiana and sugar beet.

    Science.gov (United States)

    Pavli, Ourania I; Kelaidi, Georgia I; Tampakaki, Anastasia P; Skaracis, George N

    2011-01-01

    To explore possible sources of transgenic resistance to the rhizomania-causing Beet necrotic yellow vein virus (BNYVV), Nicotiana benthamiana plants were constructed to express the harpin of Pseudomonas syringae pv. phaseolicola (HrpZ(Psph)). The HrpZ protein was expressed as an N-terminal fusion to the PR1 signal peptide (SP/HrpZ) to direct harpin accumulation to the plant apoplast. Transgene integration was verified by mPCR in all primary transformants (T0), while immunoblot analysis confirmed that the protein HrpZ(Psph) was produced and the signal peptide was properly processed. Neither T0 plants nor selfed progeny (T1) showed macroscopically visible necrosis or any other macroscopic phenotypes. However, plants expressing the SP/HrpZ(Psph) showed increased vigor and grew faster in comparison with non-transgenic control plants. Transgenic resistance was assessed after challenge inoculation with BNYVV on T1 progeny by scoring of disease symptoms and by DAS-ELISA at 20 and 30 dpi. Transgenic and control lines showed significant differences in terms of the number of plants that became infected, the timing of infection and the disease symptoms displayed. Plants expressing the SP/HrpZ(Psph) developed localized leaf necrosis in the infection area and had enhanced resistance upon challenge with BNYVV. In order to evaluate the SP/HrpZ-based resistance in the sugar beet host, A. rhizogenes-mediated root transformation was exploited as a transgene expression platform. Upon BNYVV inoculation, transgenic sugar beet hairy roots showed high level of BNYVV resistance. In contrast, the aerial non-transgenic parts of the same seedlings had virus titers that were co